Chest Radiology: The Essentials, 2nd Edition

Chapter 10. Upper Lung Disease, Infection, and Immunity

Learning Objectives

1. List an appropriate differential diagnosis for upper lung disease seen on chest radiography or computed tomography (CT).

2. Describe the radiographic classification of sarcoidosis.

3. State the three most common locations (Garland triad) for adenopathy to occur in the chest of patients with sarcoidosis.

4. List four common etiologies of “eggshell” calcified lymph nodes in the chest.

5. Recognize progressive massive fibrosis secondary to silicosis on chest radiography and CT.

6. Recognize and describe the typical appearance of cystic fibrosis on chest radiography and CT.

7. Describe the radiologic manifestations of primary pulmonary tuberculosis.

8. Name the most common segmental sites of involvement for reactivation tuberculosis in the lung.

9. Define a Ghon lesion (calcified pulmonary parenchymal granuloma) and Ranke complex (calcified node and Ghon lesion); recognize both on a chest radiograph and CT and describe their significance.

10.   Suggest the possibility of radiation as a cause of new upper lung opacification on a chest radiograph of a patient with evidence of mastectomy and/or axillary node dissection or known head and neck cancer.

11.   Describe the acute and chronic phases of radiation-caused changes in the lungs, including the time course and typical chest radiograph and CT appearances.

12.   Recognize the typical appearance of irregular lung cysts on chest CT of a patient with Langerhans cell histiocytosis.

13.   Name the major categories of disease that cause chest radiographic or CT abnormalities in the immunocompromised patient.

14.   Other than typical bacterial infection, name two important infections and two important neoplasms to consider in patients with acquired immunodeficiency syndrome (AIDS) and chest radiographic or CT abnormalities.

15.   Describe the typical chest radiographic and CT appearances of Kaposi sarcoma.

16.   Describe the chest radiograph and CT appearances of Pneumocystis jiroveci pneumonia.

17.   Name four important etiologies of hilar and mediastinal lymphadenopathy in patients with AIDS.

18.   Describe the time course and chest radiographic appearance of a blood transfusion reaction.

19.   Describe the chest radiographic and CT appearances of a miliary pattern and provide a differential diagnosis.

20.   Name and describe the types of pulmonary Aspergillus disease.

21.   Identify an intracavitary fungus ball on chest radiography and CT.

22.   Name the most common pulmonary infections that occur after solid organ (e.g., liver, renal, lung, cardiac) and bone marrow transplantation.

23.   Describe the chest radiographic and CT findings of posttransplant lymphoproliferative disorders.

Pulmonary infections are a major cause of morbidity and mortality, especially in immunocompromised patients. Immunocompromised patients have altered immune mechanisms and are predisposed to opportunistic infections. Numerous factors are associated with an immunocompromised state, including but not limited to diabetes; renal or liver failure; advanced age; bone marrow or solid organ transplantation; acquired immunodeficiency syndrome (AIDS); presence of access lines (e.g., intravenous lines, endotracheal tubes, chest tubes); splenectomy, hospital environment (predisposing to nosocomial pneumonia); underlying malignancy; drug therapy (e.g., steroids, chemotherapy); and immune deficiencies (e.g., hypogammaglobulinemia). Some of the clinically important infections and other diseases seen in immunocompetent and immunocompromised patients tend to have an upper lung–predominant distribution (e.g., mycobacterial and fungal disease). Recognition of an upper lung distribution of disease helps the clinician to form an appropriate differential diagnosis. This chapter begins with a discussion of upper lung disease, including infectious and noninfectious causes, and continues with a review of the disorders that occur in immunocompromised individuals and their radiographic appearances.

Upper Lung Disease

Upper lung refers to the upper one third of the lung, which includes the majority of the upper lobes and the uppermost portion of the superior segments of the lower lobes. In the normal upright lung, blood flow and ventilation predominate in the lung base; in many lung disorders, however, the greatest degree of abnormality occurs in the upper lung. Alterations in ventilation–perfusion, lymphatic flow, metabolism, and mechanics are proposed as pathogenic factors in upper lung localization of lung disease (1). Two mnemonics, “SHRIMP” and “CASSET,” can be used to recall common and uncommon disorders occurring in the upper lungs (Table 10-1). Because it may be difficult to appreciate a predominantly upper lung distribution of disease on chest radiography, it is useful to consider the differential diagnoses given in Table 10-1, even if the disease appears diffuse, any time the upper lungs are as affected as much or more than the middle and lower lungs.

TABLE 10-1 UPPER LUNG DISEASE

“SHRIMP”
Sarcoidosis
Histiocytosis, Langerhan cell
Radiation pneumonitis (cancers of head/neck and breast)
Infection (tuberculous, fungal)
Metastasesa
Pneumoconiosesb (silicosis, coal miner's)
“CASSET”
Cystic fibrosis
Ankylosing spondylitis
Silicosis
Sarcoidosis
Eosinophilic granulomatosis (Langerhan cell histiocytosis)
Tuberculous, fungal infection

a See Chapter 7.
b See Chapter 3.

Sarcoidosis

Sarcoidosis is a common systemic disease of unknown etiology characterized by widespread development of noncaseating granulomas. These granulomas are nonspecific and resemble those in many other granulomatous processes, except for tuberculosis, a disease in which caseous necrosis of granulomas is usually seen. Sarcoidosis is ten times more common in African-Americans than in Caucasians (2). Most patients who present with sarcoidosis are between the ages of 20 and 40, but the disease occurs as early as 1 year and as late as 80 years of age (3). The disease is two to three times more common in African-American women than in African-American men (3). The lung is the most commonly involved organ in patients with sarcoidosis and accounts for most of the morbidity and mortality, with an overall mortality rate between 2.2% and 7.6% (3).

Sarcoidosis can be classified according to its appearance on the chest radiograph (Table 10-2) (4). Patients commonly, but not necessarily, progress through each class, and the class at presentation can, but does not always, correlate with prognosis (5). Forty-five percent to 65% of patients are class I at the time of presentation. Lymphadenopathy is the most common intrathoracic manifestation of sarcoidosis and occurs in 75% to 80% of patients at some point in their illness (6). The classic pattern of lymphadenopathy is bilateral hilar and right paratracheal nodal enlargement, the so-called Garland triad or 1-2-3 sign (Figs. 10-1 and 10-2), although any mediastinal nodes can be and frequently are involved. The hilar lymph nodes are usually symmetric in appearance and can be massively enlarged (“potato nodes”) but are usually clear of the cardiac borders, a feature that helps distinguish sarcoidosis from lymphomatous lymphadenopathy, as the latter usually abuts the cardiac margins. Of patients with class I disease at initial examination, about 60% go on to complete resolution (7), with parenchymal disease occurring in the remaining patients. Nodal calcification is seen in up to 20% of cases (8), and in some of these cases (approximately 5%), the calcification is of a peripheral “eggshell” pattern (Figs. 10-3 and 10-4). Eggshell calcification is largely limited to sarcoidosis and silicosis, but it can be seen in other disorders (Table 10-3) (9).

TABLE 10-2 CLASSIFICATION OF SARCOIDOSIS ON CHEST RADIOGRAPHY

0

Normal chest radiograph

I

Hilar or mediastinal nodal enlargement only

II

Nodal enlargement and parenchymal disease

III

Parenchymal disease only

IV

End-stage lung (pulmonary fibrosis)

FIGURE 10-1. Sarcoidosis. Posteroanterior (PA) chest radiograph of a 31-year-old woman with class I sarcoidosis shows right paratracheal (arrowheads) and bilateral hilar (arrows) lymphadenopathy. This pattern of lymphadenopathy is classic for sarcoidosis and is referred to as the 1-2-3 sign or Garland triad.

Parenchymal disease is seen on chest radiography at the time of presentation in approximately half of patients with sarcoidosis. Radiographic patterns of parenchymal disease include reticulonodular opacities, ill-defined opacities that have an appearance of alveolar filling, large nodules, and lung fibrosis. Reticulonodular opacities are the most common pattern, seen in 75% to 90% of patients with parenchymal disease; the opacities are usually bilaterally symmetric with a distribution predominantly in the middle and upper lungs (10) (Fig. 10-5). In 10% to 20% of patients, opacities with airspace features develop, which can be ill defined or focal, nodular, and well defined. The term alveolar sarcoid refers to this pattern, although the “airspace” disease represents an interstitial process that compresses and obliterates alveoli. Alveolar sarcoid generally consists of bilateral, multifocal, poorly defined opacities showing a predilection for the peripheral lungs (11) (Fig. 10-6). The peripheral distribution is particularly well seen with computed tomography (CT).

 

FIGURE 10-2. Sarcoidosis. A: CT of a 23-year-old woman shows ill-defined nodules in a bronchovascular distribution (arrow) in the right upper lobe. B: CT with mediastinal windowing shows right hilar lymphadenopathy (arrow). C: CT at the level of the inferior pulmonary veins shows left hilar lymphadenopathy (arrow). D: CT at the level of the lower lobe pulmonary arteries shows subcarinal lymphadenopathy (arrow).

Sarcoid granulomas may resolve completely or heal by fibrosis. Pulmonary fibrosis occurs in approximately 20% of patients with sarcoidosis, and the radiologic features are considered by some authors to be almost pathognomonic. The findings consist of permanent, coarse, linear opacities radiating laterally from the hilum into adjacent upper and middle lungs. Bullae can form in the upper lungs. The hila are pulled upward and outward, and vessels and fissures are distorted. The fibrosis is occasionally so severe that massive parahilar opacities in the middle and upper lungs, resembling those of progressive massive fibrosis of silicosis, are seen.

FIGURE 10-3. Sarcoidosis. CT shows precarinal lymphadenopathy with rim calcification (arrow). This pattern of calcification is referred to as “eggshell” calcification and is commonly seen with sarcoidosis.

CT can define the anatomic location of parenchymal sarcoid granulomas much more accurately (12,13,14). The most common finding of sarcoidosis on CT is multiple, 1- to 5-mm nodules, usually with irregular margins, in a lymphatic distribution (bronchovascular margins, along interlobular septa, subpleurally, and in the center of secondary pulmonary lobules) (Fig. 10-7). Septal thickening from sarcoidosis has a beaded appearance, a feature that helps distinguish it from pulmonary edema, in which the septal thickening is typically smooth. Patchy ground-glass opacities are seen in about 50% of patients with sarcoidosis and rarely may be the only CT abnormality (Fig. 10-8). Fibrosis is better characterized on CT than on chest radiography. CT can show findings of sarcoidosis when the chest radiograph is normal, and patients can have a normal CT study yet have sarcoidosis proved by lung biopsy (13).

TABLE 10-3 COMMON CAUSES OF “EGGSHELL” CALCIFICATION OF NODES IN THE CHEST

“SIT”
Sarcoidosis
Silicosis
Infection (tuberculous, fungal)
Treated lymphoma

FIGURE 10-4. Sarcoidosis. A: PA chest radiograph of a 37-year-old man shows bilateral upper lobe nodular disease and hilar enlargement (class II). B: CT shows nodules of varying size along the fissures (straight solid arrow) and bronchovascular bundles (dashed arrow) and in a subpleural location (curved solid arrow). C: CT with mediastinal windowing shows central calcification of right paratracheal lymph nodes (arrow). D: CT at a lower level shows calcification of right hilar nodes (arrow).

FIGURE 10-5. Sarcoidosis. PA chest radiograph shows reticulonodular opacities scattered diffusely throughout the upper and middle lungs. Parenchymal disease without lymphadenopathy indicates class III sarcoidosis.

FIGURE 10-6. Sarcoidosis. A: PA chest radiograph of a 28-year-old man with mild shortness of breath shows right paratracheal and bilateral hilar lymphadenopathy and bilateral peripheral areas of consolidation (arrows). B: CT shows multifocal opacities in the periphery of the left lung (arrows). This pattern of sarcoidosis is referred to as alveolar sarcoid, although pathologically it is seen to be an interstitial process.

Fungus balls (mycetomas) can develop in cystic areas that develop from sarcoidosis, and sarcoidosis is the second most common predisposing condition (after tuberculosis) leading to the development of mycetoma (15). Hemoptysis resulting from mycetoma formation can be life threatening. Mycetomas occur in the upper lobes and should be suspected when new opacities are seen in an area of chronic cystic or bullous disease, especially when they are accompanied by new apical pleural or extrapleural opacity on chest radiography. There are myriad other atypical features of sarcoidosis, including pleural effusions, pleural thickening, cavitary nodules, bronchostenosis, pulmonary artery hypertension from periarterial granulomatosis (Fig. 10-9), cor pulmonale, and pneumothorax from chronic fibrosis.

FIGURE 10-7. Sarcoidosis. CT of a 40-year-old man shows ill-defined nodules in a bronchovascular distribution (arrows).

Silicosis

Silicosis is a disease of the lungs caused by inhalation of dust containing silicon dioxide, or silica, the predominant constituent of the earth's crust. Silica dust is prevalent in mining, quarrying, and tunneling operations. Occupations associated with the development of silicosis include mining of heavy metals, the pottery industry, sandblasting, foundry work, and stonemasonry. When silica particles are inhaled, they are deposited in the alveoli and engulfed by alveolar macrophages, where they are acted on by lysosomal enzymes. The affected macrophage dies and liberates mediators (leading to stimulation of collagen production) and the silica particles. The silica particles are then free to be taken up by other macrophages, and the cycle continues, leading to progressive lung disease even without continued occupational exposure to silica. Silicosis can be classified as simple silicosis, complicated silicosis, acute silicosis, or Caplan syndrome. Coal worker's pneumoconiosis, caused by inhalation of coal dust, is different pathologically from silicosis, but it produces chest radiographic findings similar to and often indistinguishable from those of silicosis.

FIGURE 10-8. Sarcoidosis. CT image of a 46-year-old woman with mild shortness of breath shows bilateral areas of abnormal opacification distributed along the central and peripheral bronchovascular bundles (straight arrows). Some of the opacities are of ground-glass attenuation, allowing visualization of underlying bronchial and vascular markings. Note small nodules along the right major fissure (arrowheads), in the center of secondary pulmonary lobules (curved arrows), and in a peripheral subpleural location (open arrow). All of these findings illustrate a perilymphatic distribution, which is typical of sarcoidosis.

FIGURE 10-9. Sarcoidosis. PA (A) and lateral (B) chest radiographs of a 69-year-old man with class IV sarcoidosis show enlarged pulmonary arteries (arrows) secondary to pulmonary arterial hypertension. Note diffuse upper and middle lung reticulonodular opacities, and note also the upward retraction of the hila. C: CT shows bilateral central areas of pulmonary fibrosis with thickening of bronchovascular bundles and traction bronchiectasis. Note parenchymal bands on right (arrows).

Patients with simple silicosis are usually asymptomatic. Between 10 and 20 years' exposure is usually necessary before the chest radiograph becomes abnormal (16). The chest radiograph shows multiple nodules, 1 to 10 mm in diameter, with a diffuse but upper lung–predominant distribution (Fig. 10-10). Occasionally, the nodules may calcify. Enlargement of mediastinal and hilar nodes is common and is occasionally associated with eggshell calcification similar to that seen with sarcoidosis.

Complicated silicosis refers to progression of simple silicosis, where the nodules become confluent and larger than 1 cm. On chest radiography, these opacities are seen predominantly in the periphery of the upper lungs, which, over time, tend to migrate toward the hilum as the fibrotic process progresses. These conglomerate masses, which can reach several centimeters in size and contain obliterated blood vessels and bronchi, are referred to as progressive massive fibrosis (Fig. 10-11). The conglomerate masses are often surrounded by paracicatricial emphysema, which is best appreciated on chest CT. As conglomeration of the nodules occurs, the lungs gradually lose volume, and cavitation of the masses can occur. Patients who have advanced to this stage are at increased risk of active tuberculosis, and this diagnosis should be suspected when a new area of cavitation is seen on chest radiography.

Acute silicosis is a rare condition related to heavy acute exposure to silica in enclosed spaces with minimal or no protection. Histologically, the appearance is identical to that of pulmonary alveolar proteinosis; hence the term silicoproteinosis is used. The disease is rapidly progressive, often leading to death as a result of respiratory failure. The chest radiographic pattern is that of nonspecific diffuse airspace disease or ground-glass opacities, with a perihilar distribution and air bronchograms identical to the radiographic findings of pulmonary edema.

Caplan syndrome consists of the presence of large necrobiotic rheumatoid nodules superimposed on a background of simple silicosis. The syndrome is a manifestation of rheumatoid lung disease and is seen in both coal worker's pneumoconiosis and silicosis.

 

FIGURE 10-10. Simple silicosis. A: PA chest radiograph of a foundry worker shows numerous bilateral ill-defined tiny nodules, creating an overall increase in lung opacity. B: On CT, the nodules are much better appreciated. C: CT with mediastinal windowing shows densely calcified hilar (solid arrows) and subcarinal (dashed arrow) lymph nodes.

FIGURE 10-11. Complicated silicosis. A: CT of a 52-year-old man who had spent many years working in a sand pit shows calcification of hilar (long arrows) and subcarinal (short arrows) nodes. B: CT with lung windowing shows “progressive massive fibrosis” in the right upper lobe (long straight arrows) and early conglomeration of nodules in the superior segments of the lower lobes (curved arrows). Multiple parenchymal bands are seen on the right (short straight arrows).

 

FIGURE 10-12. Langerhans cell histiocytosis. PA (A) and lateral (B) chest radiographs of a 32-year-old male cigarette smoker show bilateral reticular interstitial opacities and thin-walled cysts (arrows). Note increased lung volumes. C: CT shows bilateral thin-walled cysts, with rounded and irregular shapes (straight arrows), and ill-defined nodules (curved arrows).

Langerhans Cell Histiocytosis

Langerhans cell histiocytosis (LCH), also referred to as histiocytosis X or eosinophilic granuloma, is a granulomatous disorder of unknown cause characterized by the presence within the granulomas of a histiocyte, the Langerhans cell. The disease is equally prevalent in male and female patients, it is unusual in African-Americans (17), and 95% of adult patients are cigarette smokers (17). In most patients, symptoms appear in the third or fourth decades, but the disease can occur in teenagers and those over age 60. The diagnosis can be made in asymptomatic patients with abnormal chest radiographs. Pneumothorax is a classic manifestation of LCH, and the frequency of pneumothorax as the initial manifestation is as high as 14% (18). The pneumothoraces are commonly recurrent and may be bilateral. Approximately one third of patients with LCH improve, one third remain stable, and one third deteriorate (18).

The chest radiograph of patients with LCH shows a diffuse, symmetric, reticulonodular pattern or, less commonly, a solely nodular pattern. Both patterns have a predominantly middle and upper lung distribution. The nodules are usually ill defined, vary in size from 1 to 15 mm, and are often innumerable but can be few in number. Large nodules can mimic metastases. With time, small cystic airspaces develop, and larger airspaces up to 5 cm in diameter will form only rarely. Because of the development of these abnormal airspaces, lung volume does not decrease with time but often increases. Pleural effusion and hilar or mediastinal nodal enlargement are uncommon.

CT of the lungs shows cysts and nodules, often in combination (19,20) (Fig. 10-12). Cysts range in diameter from 1 to 30 mm or more and, unlike centrilobular emphysema, usually have very thin discrete walls and no centrilobular core structure. Some cysts have bizarre shapes, which can help to distinguish them from the uniformly round cysts that are typical of lymphangioleiomyomatosis. Nodules are typically 1 to 5 mm in diameter, have irregular margins, and may be cavitary. The disease is thought to progress from solid nodules to cavitary nodules to cysts, although this is controversial. End-stage disease can resemble that of generalized centrilobular pulmonary emphysema.

Radiation Pneumonitis

Radiation injury to the lung is most commonly seen after radiation therapy for breast cancer, lung cancer, and Hodgkin disease. On the chest radiograph, the changes of radiation pneumonitis are almost always confined to the field of irradiation. The first change is a diffuse haze in the irradiated region, with obscuration of the normal vascular markings. Patchy opacities appear, which may coalesce into a nonanatomic but geometric area of pulmonary opacification. These radiographic changes usually appear about 8 weeks after treatment, depending on the radiation dose and dosing interval (21); peak reaction occurs at 3 to 4 months. With time, the opacities become more linear or reticular, and fibrous contraction and distortion of lung architecture occurs. The fibrosis and contraction continue over a 12- to 18-month period. When only the apices of the lung are affected by radiation, such as with treatment for head and neck neoplasms, the radiographic changes do not appear geometric but ill defined and patchy (Fig. 10-13). When bilateral apical airspace opacities are seen on chest radiography, radiation pneumonitis should be considered in the appropriate patient population. Radiation of the axilla, an adjuvant treatment for patients with breast cancer who have undergone lumpectomy or mastectomy, can result in ipsilateral peripheral upper lung patchy airspace opacities (Fig. 10-14).

FIGURE 10-13. Radiation pneumonitis. A: PA chest radiograph of a 60-year-old woman 3 months after radiation treatment to the neck for a piriform sinus carcinoma. Subtle areas of abnormal opacification are seen at both apices (arrows). B: PA chest radiograph obtained 2 months later shows progression of apical opacities (arrows). C: CT shows bilateral apical airspace disease without anatomic or geographic distribution. Bronchoscopic biopsy of the right apex was negative for organisms, and the opacities gradually resolved without treatment on follow-up chest radiographs.

Tuberculosis

Once a disease of childhood, more than half of cases of initial infection with Mycobacterium tuberculosis, or primary tuberculosis (TB), are now seen in the adult population (22). In primary tuberculous infections, the pulmonary focus and lymphadenopathy may resolve without a trace, or they may leave a focus of caseous necrosis, scarring, or calcification. Several terms are used to describe the form of tuberculosis that develops after a primary infection under the influence of established hypersensitivity including reactivation TBpostprimary TB, and secondary TB.

The predominant radiographic feature of primary TB is the presence of hilar lymphadenopathy (usually unilateral) and mediastinal lymphadenopathy contiguous to the affected hilum. Lymphadenopathy is less common and milder in adults than in children, with the exception of immunocompromised adults, especially those with AIDS. On CT, the enlarged nodes typically have a low-density center with rim enhancement (Fig. 10-15) (23). The pulmonary foci of primary TB are randomly distributed throughout the lungs, and they range from small, occasionally imperceptible, ill-defined parenchymal opacities to segmental or lobar consolidation, often with an appearance similar to that of other bacterial pneumonias (Figs. 10-16 and 10-17). The incidence of cavitation varies between 10% and 30% (22). Hilar or mediastinal lymph node calcification is observed in 35% of cases (24). Pleural effusions are not uncommon, are generally unilateral, and are usually, but not always, associated with some identifiable pulmonary parenchymal disease (Fig. 10-18). Bronchial stenosis, bronchial occlusions, and polypoid endobronchial tuberculous lesions may be seen on CT.

 

FIGURE 10-14. Radiation pneumonitis. A: Normal baseline PA chest radiograph of a 71-year-old woman. B: PA chest radiograph obtained 11 months later shows interval right mastectomy for treatment of breast cancer (note hyperlucent right lower hemithorax) and surgical clips in the right axilla. Note new abnormal areas of nonsegmental opacification in the periphery of the right upper lobe (arrows) from recent radiation to the axilla.

FIGURE 10-15. Primary tuberculosis. CT shows low-density subcarinal nodes with partial rim enhancement (arrow).

FIGURE 10-16. Primary tuberculosis. PA chest radiograph shows diffuse nodular airspace disease.

 

FIGURE 10-17. Primary tuberculosis. A: PA chest radiograph of a 71-year-old man with fever, hemoptysis, and weight loss shows bilateral patchy airspace opacities, with areas of cavitation in the upper lobes (arrows). Sputum contained numerous M. tuberculosis organisms. B: PA chest radiograph taken 9 months later shows changes of healing in upper lobes consisting of linear opacities (straight arrow) and thin-walled cavities (curved arrows). C: PA chest radiograph 2 months after (B) shows new right apical pleural thickening (solid arrows) and increased opacification of the right upper lobe. A fungus ball (aspergilloma) is seen within a right upper lobe cavity (open arrows). D: CT shows fungus ball in right upper lobe cavity (arrows). Note the cystic changes of healed TB in left upper lobe.

FIGURE 10-18. Primary tuberculosis. PA chest radiograph of a 39-year-old man shows abnormal right upper lobe opacification (curved arrows) and a large loculated right pleural effusion (straight arrows). Freely layering pleural fluid collects inferiorly, within the most gravity-dependent portion of the pleural space, in upright positioning, and the pleural fluid in this case tracks superiorly along the chest wall.

 

FIGURE 10-19. Reactivation tuberculosis. A: PA chest radiograph of a 44-year-old man shows a partially calcified opacity in the right upper lobe (arrows), which was unchanged in comparison with multiple prior chest radiographs and thus consistent with prior TB infection of indeterminate activity. B: PA chest radiograph obtained 6 years later shows a new cavity in the right upper lobe (arrows). Sputum contained M. tuberculosis organisms.

The earliest chest radiographic findings of reactivation TB consist of one or more ill-defined patchy opacities, with or without small satellite foci in the adjacent lung, occurring in the posterior segments of the upper lobes in the majority of patients and in the superior segment of the lower lobes in most of the remainder of patients. This distribution of disease is very helpful in suggesting the diagnosis of reactivation TB. Cavitation with or without the presence of air–fluid levels is a distinct feature of reactivation TB and indicates a high likelihood of active infection (Figs. 10-19, 10-20, 10-21). The presence of cavitation implies that the disease is highly contagious, and patients with cavitary disease should be placed under immediate infective precautions (respiratory isolation) on the basis of radiographic findings alone. With healing, the chest radiograph shows gradually increasing definition of the lung opacities, development of fibrosis in the surrounding lung, contraction and volume loss of the affected segment or lobe with fissural displacement or distortion of the vascular structures in the hilum, bronchiectasis, and calcification (Fig. 10-22). Fluid levels in cavities disappear, and the cavities either disappear or persist with a smooth inner wall.

Other patterns of reactivation TB include lobar pneumonia, diffuse bronchopneumonia, endobronchial TB, tuberculoma formation, miliary TB, and tuberculous pleuritis. A calcified lymph node may erode into an adjacent airway, becoming a broncholith, and be associated with hemoptysis or postobstructive atelectasis or pneumonia. Broncholiths can be suggested when a previously documented nodal calcification on chest radiography has disappeared or changed position. On rare occasion, a patient can cough up pieces of a calcified broncholith, a phenomenon referred to as lithoptysis. Tuberculomas are discrete tumorlike foci of TB in which there is a fine balance between inflammation and healing. The margins of a tuberculoma are usually well circumscribed. Tuberculomas may be single or multiple, are occasionally as large as 5 cm in diameter, and may grow slowly over an extended period of time. Calcification develops in the central caseous core with time and may be seen radiographically, but it is better characterized with CT. When the calcification is dense and assumes the majority of the volume of the tuberculoma as seen on chest radiography, the diagnosis of a benign inactive granuloma can be assumed. Such a parenchymal tuberculoma, known as a Ghon lesion, in combination with calcified nodes, is referred to as a Ranke complex. Miliary TB, which results from hematogenous dissemination of disease, is an uncommon but serious complication of both primary and reactivation TB. The chest radiograph shows innumerable 2- to 3-mm nodules likened to millet seeds in size and appearance. The nodules are uniformly distributed and equal in size. Because there is a threshold below which the nodules are imperceptible, miliary TB can be present in patients with a “normal” chest radiograph. Miliary TB does not leave residual calcifications.

FIGURE 10-20. Reactivation tuberculosis. A: PA chest radiograph of a 30-year-old man from Africa who had been treated for tuberculosis 10 years earlier shows elevation of the minor fissure, right apical pleural opacity, and ill-defined opacities throughout the right lung. B: CT shows a thin-walled cavity, thickening of the bronchovascular bundles, and ill-defined nodules in the superior segment of the right lower lobe.

FIGURE 10-21. Reactivation tuberculosis. PA chest radiograph of a 28-year-old man with a prior history of right middle and lower lobectomy and right pleurodesis, currently taking steroids for severe asthma, shows right apical pleural opacity and a thin-walled cyst (arrow) in the right upper lung. Both were new findings compared with prior chest radiographs. B: CT shows the cyst and surrounding ill-defined nodules in the posterior right upper lobe.

FIGURE 10-22. Healed tuberculosis. A: CT shows calcified nodules in the right upper lobe (arrows). B: CT with lung windowing shows a thin-walled cyst. The mural nodule along the anterior cyst wall and the nodule posterior to the cyst represent the calcified nodules seen in (A). C: CT at a more inferior level shows bronchiectasis (solid arrow) and a second thin-walled cyst (dashed arrow). The findings were unchanged in comparison with multiple CT scans obtained during the prior 3 years.

A number of mycobacteria other than M. tuberculosis can cause pulmonary infection. These atypical mycobacteria are common in the natural environment, and numerous species exist, including M. kansasii and M. avium-intracellulare; the latter is a very important pathogen in human immunodeficiency virus (HIV)–infected individuals. The classic features of atypical mycobacterial infections of the lung are those of a chronic indolent fibrocavitary process, usually involving one or both apical regions of the lungs in a middle-aged or older individual with underlying chronic obstructive pulmonary disease (25), or in chronic lower lung bronchiectasis. In many cases, the radiographic features are indistinguishable from those of reactivation TB. The lesions have the same predilection for the posterior aspects of the upper lobes or the superior segments of the lower lobes as reactivation TB. Cavitation occurs in up to 96% of patients with atypical mycobacterial infection (26).

FIGURE 10-23. Noninvasive pulmonary aspergillosis. A: Baseline PA chest radiograph of a 79-year-old woman with class IV sarcoidosis shows retraction of the hila bilaterally, bilateral upper lobe fibrosis, and tenting of the hemidiaphragms from upper lobe volume loss. B: PA chest radiograph taken 2 years later shows increased right apical pleural thickening (curved arrow) and a fungus ball (aspergilloma) in the right upper lobe cavity (straight arrow). C: CT shows opacity within the right upper lobe cavity, representing vascular granulation tissue and fungal organisms. A small amount of air is seen within the cavity (arrows).

Aspergillus Lung Disease

Fungi of the genus Aspergillus are ubiquitous saprophytes that are commonly laboratory contaminants but on occasion can become human pathogens. Infection is acquired primarily through the respiratory tract. Exposure to Aspergillus is almost universal, yet the nonimmunocompromised patient usually does not develop Aspergillus infection (27).

Aspergillosis represents a spectrum of diseases based on the degree of immune impairment at one end of the spectrum and hypersensitivity at the other end of the spectrum (28). Four basic types of pulmonary aspergillosis are (i) noninvasive (saprophytic), (ii) semi-invasive, (iii) invasive, and (iv) allergic.

Noninvasive pulmonary aspergillosis refers to colonization of a pre-existing cavity or cystic area in the lung with Aspergillus organisms, creating a “fungus ball” or mycetoma. Prior tuberculous infection, emphysematous bullae, sarcoidosis (Fig. 10-23), or other processes, such as ankylosing spondylitis, that result in cavities, cysts, or cystic bronchiectasis, can lead to mycetoma formation (29,30). In noninvasive aspergillosis, the fungus causes the development of vascular granulation tissue within the cavity wall, which can lead to hemoptysis. With peripheral cavities, there is also a pleural response to the presence of the organism, leading to marked pleural thickening and extrapleural fatty hypertrophy as clues to the chronic inflammation. Chest radiography and CT typically show a mobile, intracavitary mass, usually in an upper lobe (Figs. 10-24 and 10-25). Specific therapy is not required for patients with an asymptomatic aspergilloma; however, this type of aspergillosis can cause massive hemoptysis that can sometimes lead to death. Bronchial artery embolization, surgery, or instillation of amphotericin B into the aspergilloma cavity can be used to treat patients with an aspergilloma and hemoptysis.

FIGURE 10-24. Noninvasive pulmonary aspergillosis. A: Supine CT image of a 41-year-old man with hemoptysis shows a thin-walled cavity in the left upper lobe containing an ovoid mass of soft tissue attenuation. B: Prone CT image shows movement of the mass to the dependent aspect of the cavity. Movement of an intracavitary fungus ball with change in patient positioning is typical of noninvasive aspergillosis.

Semi-invasive pulmonary aspergillosis refers to a chronic, indolent form of Aspergillus infection that leads to cavity formation and then a classic aspergilloma. This form of aspergillosis tends to occur in patients with depressed immune systems (e.g., those with a neoplasm, those who have undergone radiation, those who are of advanced age or debilitated, those with diabetes or chronic obstructive lung disease, or those on chronic corticosteroid therapy) (31). The disease typically begins as an upper lung opacity on chest radiography, which, over a period of weeks to months, gradually develops cavitation with formation of an “air crescent sign.” As the disease progresses, extensive apical pleural thickening develops. As cavitation progresses, a thick-walled cavity often becomes thin walled, containing a mycetoma (Fig. 10-26). Therapy is the same as for noninvasive aspergillosis.

FIGURE 10-25. Noninvasive pulmonary aspergillosis. A: PA chest radiograph of a 14-year-old girl with a thin-walled cavity in the right upper lobe (long arrows) containing a fungus ball (short arrows). B: PA chest radiograph after change in patient position shows movement of the mobile fungus ball.

Invasive pulmonary aspergillosis is the most pathologically aggressive form of aspergillosis and occurs in severely immunocompromised patients (Fig. 10-27). Chest radiographs show a solitary pulmonary nodule or mass, or multifocal opacities. In some cases, multiple poorly defined nodules (likely representing infarcts) are seen and extend to the periphery of the lungs. In patients with leukemia, cavitation of the nodules develops as the neutrophil count recovers from the chemotherapy-induced nadir (32). Cavitation leads to the air crescent sign, which is seen as a crescent-shaped collection of air between the cavity wall and the intracavitary contents. In contrast to noninvasive and semi-invasive forms of aspergillosis, in which a fungus ball occupies the cavity, in invasive aspergillosis the central mass within the cavity is almost always necrotic lung and not an aspergilloma. Early in the course of infection during bone marrow aplasia, before air crescent formation or cavitation, CT often shows the CT “halo sign,” a zone of ground-glass opacification surrounding the pulmonary nodule or mass. In patients with acute leukemia, the presence of the CT halo sign (representing a zone of hemorrhage) strongly suggests the diagnosis of invasive aspergillosis (Fig. 10-28) (33). Intravenous amphotericin B remains the frontline therapy for invasive aspergillosis. Patients who do not respond to therapy usually die of the disease.

FIGURE 10-26. Semi-invasive pulmonary aspergillosis. A: PA chest radiograph of a 49-year-old woman with hemoptysis shows a rounded opacity (arrows) within a right upper lobe cavity. There is retraction of the right hilum along with elevation of the right hemidiaphragm. B: CT shows a fungus ball within the right upper lobe cavity. Note severe changes of emphysema in the left lung.

Allergic bronchopulmonary aspergillosis(ABPA) is a form of hypersensitivity reaction to inhaled Aspergillus organisms. It is seen most commonly in patients with underlying asthma, it is seen in approximately 10% of patients with cystic fibrosis, and it is seen occasionally in patients with no known underlying pulmonary disease (34). The fungus grows noninvasively within the bronchi, releasing an antigen that causes host sensitization and a subsequent immunologic reaction. Mucus traps the organisms in the bronchi. Bronchiectasis either results from or is a predisposing factor to development of ABPA. Patients with ABPA typically present with symptoms of asthma. Typical radiographic findings consist of central bronchiectasis with mucoid material filling the bronchi. The appearance of mucus-filled bronchi on chest radiography has been variously described as finger in glove, rabbit ears, Mickey Mouse, toothpaste-shaped, and Y- or V-shaped opacities. The diagnosis of ABPA is based on major and minor criteria (35). Major criteria include asthma, blood eosinophilia, immediate skin reactivity to Aspergillus antigen, increased serum immunoglobulin E, transient or fixed pulmonary opacities on chest radiography, and central bronchiectasis. Minor criteria include fungal organisms in the sputum, history of expectoration of brown plugs or flecks, and delayed skin reactivity to fungal antigens. Because ABPA is an allergic disease, the primary treatment consists of corticosteroids.

FIGURE 10-27. Invasive pulmonary aspergillosis. A: PA chest radiograph of a 57-year-old woman with a transplanted heart shows focal airspace opacity in the left upper lobe (arrows). B: CT shows dense airspace opacity and surrounding halo of ground-glass opacity in the left upper lobe.

Bronchocentric granulomatosis, characterized histologically by necrotizing granulomas that may obstruct and destroy bronchioles, is a histopathologic pattern that is generally believed to represent a nonspecific response to a variety of forms of airway injury. Approximately half of all cases are associated with asthma and ABPA, and among these patients, bronchocentric granulomatosis may represent a histopathologic manifestation of fungal hypersensitivity. Aspergillus hyphae can be identified within the granulomas in up to 50% of patients. Although the imaging features may be similar to those of conventional ABPA, the lung involvement in bronchocentric granulomatosis is more commonly focal and peripheral (36).

FIGURE 10-28. Invasive pulmonary aspergillosis. CT of a 30-year-old woman with leukemia and fever shows an ill-defined nodule with a halo of ground-glass opacity in the right lung.

Cystic Fibrosis

Cystic fibrosis is an autosomal recessive disease involving chromosome 7 and characterized by dysfunction of exocrine glands, which form a thick, tenacious material. The incidence is 1 in 1,600 live births, with Caucasians affected most frequently. Organs involved include the lung, upper respiratory tract, pancreas, liver, gallbladder, and reproductive tract. The earliest chest radiographic findings include peribronchial inflammatory changes (peribronchial cuffing) and both atelectasis and hyperinflation. With progression of the disease, ring shadows and tram tracking are seen as signs of bronchiectasis, usually with an upper lobe predominance (Fig. 10-29). Not uncommonly, air–fluid levels can be seen in areas of cystic bronchiectasis. Small, ill-defined or tubular opacities occur as a result of mucus plugging in dilated airways (Figs. 10-30 and 10-31). Larger opacities usually represent pneumonia, most commonly caused by Staphylococcus aureus or Pseudomonas species. Bilateral hilar lymphadenopathy is common. Severe disease can lead to pulmonary arterial hypertension and cor pulmonale, which may be suggested when enlargement of the central pulmonary arteries and enlargement of the right heart, respectively, are seen on the chest radiograph. ABPA occurs in 10% of patients with cystic fibrosis, as discussed earlier in this chapter. Hypertrophic pulmonary osteoarthropathy, a disorder involving the long bones and joints, occurs in approximately 15% of patients with cystic fibrosis.

FIGURE 10-29. Cystic fibrosis. A: CT of a 29-year-old woman shows bilateral cystic bronchiectasis and thickening of bronchial walls. Small nodules in the left upper lobe likely represent mucoid-impacted bronchioles. B: CT at a more inferior level shows similar but less severe findings. Cystic fibrosis typically involves the upper lungs to a greater degree than the lower lungs.

FIGURE 10-30. Cystic fibrosis. CT of a 37-year-old woman shows bilateral bronchiectasis and mucoid-impacted airways (arrows).

Radiologic Abnormalities in Immunocompromised Patients

Infection is the leading cause of chest radiographic abnormalities in immunocompromised patients and is a direct result of a deficiency in immune defenses (e.g., immunoglobulin abnormalities, cell-mediated dysfunction, and phagocytic defense disorders) or a nonspecific reduction in host resistance (e.g., advanced age, alcoholism, diabetes, starvation or malnutrition, and cancer). In addition to infection, radiographic abnormalities in immunocompromised patients can result from many other causes, as listed in Table 10-4.

FIGURE 10-31. Cystic fibrosis and Mycobacterium avium infection. A: CT shows small nodular and linear branching opacities (arrow) in the left lower lobe, consistent with bronchiolar spread of mycobacterial disease. Note bronchiectasis in both upper lobes. B: CT at a more inferior level shows a markedly distended, mucoid-impacted bronchus in the right middle lobe (arrow). This finding is suggestive of ABPA, which patients with cystic fibrosis are predisposed to develop.

Infection

Bacterial agents are the most frequent causes of pneumonia in immunocompromised patients. Patients receiving steroids and patients with renal transplants are particularly susceptible to infection with Legionella organisms. L. pneumophila manifests as progressive parenchymal consolidation, sometimes with cavitation and pleural effusion. L. micdadei pneumonia results in well-circumscribed nodular densities with central cavitation (37). Nocardia asteroidesinfection occurs most commonly in immunosuppressed patients, including those with AIDS and solid organ transplants. Chest radiographs show lobar or multilobar areas of consolidation, or they show solitary or multiple ill-defined pulmonary nodules with a tendency to cavitate and invade surrounding structures such as the chest wall (38,39).

TABLE 10-4 CAUSES OF RADIOGRAPHIC ABNORMALITIES IN IMMUNOCOMPROMISED PATIENTS

Infection
  Bacterial (typical)
  Mycobacterial
  Fungal
  Viral (Cytomegalovirus pneumonia)
Neoplasm
  Lymphoma and other lymphoproliferative disorders
  Leukemia
  Metastases/recurrence of primary tumor
Transfusion reaction
Graft-versus-host disease (after bone marrow transplantation)
Radiation pneumonitis
  Acute
  Chronic
Adverse drug reaction
  Early (noncytotoxic)
  Late (cytotoxic)
Hemorrhage

TB in immunocompromised patients occurs most commonly in the AIDS population. In non-AIDS immunocompromised patients, TB is usually caused by reactivation of a dormant lesion. The radiographic features typically consist of apical and posterior segmental fibronodular disease in the upper lobes with or without cavitation (40). Infection with atypical mycobacteria can have a similar appearance, but there is a tendency toward increased cavitation relative to total lung involvement, thin-walled cavities with less dense surrounding parenchymal opacification, less bronchogenic and more contiguous spread, more involvement of the apical and anterior segments of the upper lobes, and marked pleural thickening over the involved areas of the lung (40).

A. fumigatus is an important fungal pathogen in immunocompromised patients, especially those with lymphoma or leukemia. The different types of Aspergillus lung disease were discussed earlier in this chapter.

Candida albicans is another fungal agent that causes pneumonia in a substantial number of patients with leukemia or lymphoma. Chest radiographs most commonly show diffuse bilateral nonsegmental patchy alveolar or mixed alveolar–interstitial opacities. A pattern of miliary opacities can also be seen (41).

Mucormycosis results from infection with one of the phycomycetes and has a 100% mortality rate in the absence of treatment. Patients susceptible to mucormycosis include those with leukemia or lymphoma and those with diabetes mellitus. Pathologically, mucormycosis is fungal vascular invasion resulting in infarction (42). The most common radiographic abnormality is a single pulmonary nodule, mass, or focus of consolidation, frequently with cavitation. This is usually accompanied by infection of the paranasal sinuses, brain, and meninges.

Cryptococcosis, discussed later in this chapter, is the most common fungal pulmonary infection in patients with AIDS. Widespread dissemination of the organisms causing blastomycosis, coccidiomycosis, and histoplasmosis can occur in immunocompromised patients, but radiodiagnostic features are lacking; attention is usually given to excluding more common opportunistic fungi.

The most common virus to cause pneumonia in immunocompromised patients is Cytomegalovirus (CMV). The radiographic appearances include diffuse interstitial opacities, often with a nodular pattern. Other important viruses, especially in patients with lymphoma, are the varicella-zoster virus and the herpes simplex virus.

Neoplasm

Patients with lymphoma or leukemia can have pulmonary involvement of their disease. Leukemic infiltration of the lungs, pleura, or mediastinum, although common pathologically, does not appear to be a cause of pulmonary symptoms and is rarely a cause of radiographic abnormalities. Radiographs and CT scans of the chest are often normal in pathologically proven cases. Diffuse pulmonary disease is more likely to represent pneumonia or hemorrhage than leukemic infiltration (43). Radiographically visible leukemic infiltrates are virtually confined to patients with high peripheral blast counts (44). Leukostasis—the accumulation of leukemic cells in small pulmonary blood vessels in patients with leukemia—can result in diffuse airspace opacities on chest radiography, which is felt to be caused by pulmonary edema rather than the accumulation of leukemic cells (45). Distinguishing pneumonia from pulmonary lymphoma can be difficult or impossible radiographically.

In patients with an underlying nonpulmonary primary malignancy, the development of multiple, well-circumscribed pulmonary nodules of varying sizes is highly suspicious for metastatic disease. Infection, especially from fungal agents, and septic emboli should be considered in the differential diagnosis.

Certain populations of patients are predisposed to developing lymphoproliferative disorders, which can range from benign lymphoid hyperplasia to frank malignancy. This topic is discussed in the later sections on AIDS and lung transplantation.

Transfusion Reaction

Transfusion reactions are leukoagglutinin reactions that occur approximately 4 hours after blood transfusion. Acute reactions can be difficult to distinguish radiographically from volume overload with pulmonary edema (Fig. 10-32). True reactions are caused by an excess of antibodies in the donor serum directed against the recipient's white blood cells, leading to the abrupt onset of fever, chills, tachypnea, and tachycardia, coincident with the development of varying radiographic patterns of noncardiac pulmonary edema (46). The edema can persist for 24 to 48 hours, and it does not respond to diuresis but can respond to steroids.

Drug Reaction

Drug reactions can be categorized as cytotoxic (late) or noncytotoxic (early). The most common are cytotoxic reactions, which are well known in patients receiving a variety of chemotherapeutic agents (especially azathioprine, bleomycin, busulfan, cyclophosphamide, cytosine arabinoside, and methotrexate) (47). Between 2 and 6 months after completion of chemotherapy, the patient develops a cough, fever, and dyspnea. The chest radiograph shows either diffuse interstitial or hazy alveolar opacities (Fig. 10-33). Pleural effusions are uncommon. The resulting lung injury is compounded by chest radiation, oxygen therapy, and concurrent administration of other cytotoxic drugs. Two types of noncytotoxic drug reactions are hypersensitivity reactions and noncardiac pulmonary edema (47). Hypersensitivity reactions occur within hours or days of the initial administration of the drug. The patient develops an acute cough, fever, and dyspnea. Peripheral eosinophilia is often present. The chest radiograph typically shows nonspecific diffuse interstitial opacities that can progress to airspace disease.

FIGURE 10-32. Transfusion-related lung injury. PA chest radiograph of a woman with abrupt onset of fever, chills, tachypnea, and tachycardia 4 hours after blood transfusion shows bilateral interstitial lung disease with prominent Kerley lines.

Hemorrhage

Pulmonary hemorrhage can occur in patients who develop thrombocytopenia after treatment of leukemia or after bone marrow transplantation, and it can be associated with an underlying bleeding tendency, infection, or diffuse alveolar damage. Pulmonary hemorrhage is seen in approximately 75% of patients with leukemia at autopsy (48), and alveolar lung disease from pulmonary hemorrhage alone occurs in up to 40% of patients with leukemia (49). The chest radiograph initially shows focal or, more commonly, multifocal airspace opacities that are gradually replaced by interstitial opacities as the by-products of blood breakdown are cleared by alveolar macrophages and transported through the lymphatic system in the interstitial spaces of the lungs.

AIDS

The majority of patients with AIDS eventually suffer from one or more forms of pulmonary disease. The chest radiograph has an important function in detecting the presence of disease, and in some cases it strongly suggests a specific diagnosis. The distinct radiographic features of disorders seen in patients with AIDS are outlined in Tables 10-5 and 10-6.

The bacterial agents that most commonly cause pneumonia in AIDS patients are the same organisms that cause pneumonia in the population at large (Streptococcus pneumoniae and Haemophilus influenzae). Septic emboli, usually owing to S. aureus, occur most commonly in AIDS patients who are intravenous drug abusers or who have central venous catheters in place (Fig. 10-34). Other bacterial agents associated with AIDS include the Legionella organisms (Fig. 10-35), Mycoplasma species, and Rhodococcus equi(50). The radiographic findings of single or multiple segmental or lobar areas of consolidation are the same as those in non-AIDS patients. The diagnosis, however, can be confounded by the presence of coexistent infections or other disease processes.

 

FIGURE 10-33. Bleomycin toxicity. A: Anteroposterior (AP) supine chest radiograph of a 30-year-old woman with Hodgkin disease shows subtle bilateral hazy opacification of the lungs. B: CT shows bilateral diffuse ground-glass opacification. The underlying bronchovascular markings remain visible. Motion artifact is present because of the inability to suspend respiration during scanning.

TABLE 10-5 RADIOGRAPHIC FEATURES OF COMMON DISORDERS IN PATIENTS WITH AIDS

Pneumocystis jiroveci pneumonia
  Typically, NO effusions or lymphadenopathy
  Bilateral perihilar or diffuse alveolar or reticulonodular opacities
  Lung cysts, often multiseptated, with associated spontaneous pneumothorax
  Upper lung predominance in some cases

Mycobacterial disease
  Tuberculosis
    Can manifest as primary or reactivation disease
    Responds rapidly to therapy unless the strain is drug resistant
    Can be spread to normal healthy people
  Mycobacterium avium-intracellulare complex
    Newly acquired, not reactivation
    Not transmitted to normal, healthy people
    Does not respond rapidly to treatment

Kaposi sarcoma
  Most common malignancy in AIDS
  Nearly all patients have mucocutaneous lesions
  Bilateral perihilar opacities with bronchovascular distribution
  Poorly defined, “flame-shaped” parenchymal nodules
  Pleural effusions common
  Kerley B lines common

AIDS-related lymphoma
  Occurs with severe immunocompromise
  Solitary or multiple lung nodules or masses
  Pleural or pericardial effusions common
  Lymphadenopathy common
  Can be rapidly progressive

AIDS, acquired immunodeficiency syndrome.

Other than typical community-acquired bacterial disease, the two most important infections to consider in AIDS patients are mycobacterial disease and Pneumocystis jiroveci pneumonia (PCP). There has been an increase in incidence of TB as a result of the AIDS epidemic. TB in patients with AIDS usually represents a reactivation of a previously acquired disease (51), and it occurs with less severe degrees of immunocompromise than other opportunistic infections in HIV-infected patients. With lesser degrees of immunocompromise, TB usually manifests as cavitary disease involving the apicoposterior segments of the upper lobes and superior segments of the lower lobes, without lymphadenopathy. As the immunocompromise worsens, a form of TB resembling primary TB develops—even though the disease is usually reactivation TB—with prominent lymphadenopathy and dissemination of disease throughout the lungs, pleura, and other parts of the body (Figs. 10-36 and 10-37). Intrathoracic lymphadenopathy is not a feature of the diffuse lymphadenopathy syndrome found in HIV infection, and it signifies an active complication of HIV infection such as TB (52).

TABLE 10-6 HILAR AND MEDIASTINAL LYMPHADENOPATHY AND AIDS

Tuberculosisa
Mycobacterium avium-intracellulare complexa
Fungal (especially Cryptococcus)
Lymphomaa
Kaposi sarcoma
Bronchogenic carcinoma (? increased incidence in AIDS patients)

Lymphadenopathy is NOT a feature of Pneumocystis jiroveci pneumonia.
AIDS, acquired immunodeficiency syndrome.
a Bulky nodes are a common feature.

 

FIGURE 10-34. Septic emboli. CT of a 3-year-old girl with AIDS shows multiple ill-defined nodules with cavitation in a predominantly peripheral distribution (curved arrows). A “feeding vessel” leads to one of the nodules in the left upper lobe (straight arrow), indicating a hematogenous process. (Reprinted with permission from 

Kuhlman JE. Pulmonary manifestations of acquired immunodeficiency syndrome. Semin Roentgenol. 1994;29:242–274.

)

FIGURE 10-35. Legionella pneumonia. AP upright chest radiograph of a 27-year-old man with AIDS shows bilateral diffuse airspace opacity, a nonspecific pattern of parenchymal disease that can be seen with many types of pneumonias, pulmonary edema, and pulmonary hemorrhage.

FIGURE 10-36. Tuberculosis. A: PA chest radiograph of a 27-year-old man with AIDS shows an air–fluid level adjacent to the right hilum (straight arrow), fullness to the right infrahilar area, and abnormal opacity in the left lower lung (curved arrow). B: CT shows cavitation of a right hilar mass that communicates with a central bronchus (arrowhead). Small nodules in the periphery of the posterior segment of the right upper lobe (arrow) and larger nodules in the superior segment of the right lower lobe are consistent with endobronchial spread of TB. C: CT with mediastinal windowing shows low-attenuation paratracheal lymphadenopathy (arrows). D: CT at a level inferior to (C) shows low-attenuation right hilar and subcarinal lymphadenopathy (arrows). (Courtesy of Janet E. Kuhlman, MD, University of Wisconsin Hospital and Clinics, Madison.)

 

FIGURE 10-37. Tuberculosis. CT scan of a 49-year-old man with AIDS shows cavitary, ill-defined nodules (arrows) in the posterior segment of the right upper lobe and superior segment of the right lower lobe, along with peripheral small linear and nodular opacities bilaterally. (Courtesy of Janet E. Kuhlman, MD, University of Wisconsin Hospital and Clinics, Madison.)

Numerous nontuberculous mycobacterial agents affect patients with AIDS, but M. avium-intracellulare predominates. Radiographs or CT scans of the chest show hilar and mediastinal lymphadenopathy with or without diffuse nodular or patchy alveolar parenchymal opacities (Figs. 10-38 and 10-39). Cavitation in pulmonary opacities is uncommon. The infection is extremely resistant to treatment.

The microbe that causes PCP in humans is a distinct phylogenetic fungal species called P. jiroveci (pronounced “yee-row-vet-zee”) (53). PCP has long been the most common serious AIDS-defining opportunistic infection in the United States. The introduction of highly active antiretroviral therapy (HAART) for the treatment of HIV infection has been accompanied by substantial reductions in mortality and the incidence of opportunistic infections, including PCP (53). Despite these advances, P. jiroveci remains a major pathogen in HIV-infected persons who either are not receiving or are not responding to HAART and among those who are unaware of their HIV status. PCP is also of clinical importance in people who are immunocompromised for reasons other than HIV, such as organ or bone marrow transplantation (Fig. 10-40) or after receiving chemotherapy for malignant diseases (Fig. 10-41) (53).

The chest radiograph is abnormal in more than 90% of patients with PCP; it most commonly shows diffuse opacity of the lung parenchyma, which is finely reticular in early stages but progresses to confluent airspace disease (54). Patients receiving aerosolized pentamidine show an increased tendency to develop focal parenchymal opacity, particularly in the upper lungs (55) (Fig. 10-42), although an apical predominance of disease can be seen even in patients not receiving pentamidine prophylaxis (56). Pneumatoceles can develop in patients with AIDS and PCP (Figs. 10-41 and 10-43), which can lead to pneumothorax. When the chest radiograph is normal, CT may show diffuse ground-glass opacities. Pleural effusions and lymphadenopathy are rare with PCP. As the disease evolves, CT can show calcification in hilar, mediastinal, and abdominal lymph nodes.

FIGURE 10-38. Mycobacterium avium pneumonia. A: CT of a 56-year-old man with AIDS shows an impacted bronchus in the right upper lobe (solid arrow), which is surrounded by small nodules, and bronchiectasis (dashed arrow). B: CT with mediastinal windowing shows bulky right paratracheal lymphadenopathy (arrow).

FIGURE 10-39. Mycobacterium avium pneumonia. CT of a man with AIDS shows bilateral small ill-defined nodules (arrows) in a predominantly peripheral distribution. (Reprinted with permission from 

Kuhlman JE. Pulmonary manifestations of acquired immunodeficiency syndrome. Semin Roentgenol. 1994;29:242–274.

)

FIGURE 10-40. Pneumocystis jiroveci pneumonia. CT of a 53-year-old man with a bone marrow transplant shows bilateral dense airspace and ground-glass opacities associated with airway dilatation. The distribution is predominantly central and upper lung.

FIGURE 10-41. Pneumocystis jiroveci pneumonia. A: PA chest radiograph of a 46-year-old man undergoing treatment for a brain tumor and acute shortness of breath shows a large left pneumothorax and shift of the mediastinum to the right. B: CT shows multiseptated cysts (arrow), left pneumothorax (P) after chest tube placement, and patchy ground-glass opacity (G). This constellation of findings is very suggestive of PCP.

FIGURE 10-42. Pneumocystis jiroveci pneumonia. PA chest radiograph of a 41-year-old man with AIDS, who had been treated with inhaled pentamidine, shows bilateral interstitial and alveolar opacities with an upper lung–predominant distribution.

Viruses, especially CMV, are an infrequent cause of clinical pneumonia in HIV-infected patients, even though CMV is often isolated from the lungs in patients with AIDS. To be able to name CMV as the cause of pneumonia in AIDS patients, CMV must be recovered by culture, CMV inclusion bodies must be identified in lavage or biopsy samples, and progressive pneumonia responding to an antiviral agent must be present. Viral pneumonias result in diffuse parenchymal opacities on chest radiography, similar in appearance to pulmonary edema of noncardiac origin, without substantial pleural effusions or lymphadenopathy (Fig. 10-44).

Numerous fungal agents can cause pneumonia in patients with AIDS. Cryptococcosis is the most common fungal pulmonary infection, and it usually coexists with cryptococcal meningitis. Chest radiographs show focal or diffuse reticular or reticulonodular opacities, a miliary nodular pattern (Fig. 10-45), or focal airspace opacities. Lymphadenopathy, pleural effusions, and cavitation are frequent findings (57).

Pulmonary aspergillosis occurs in the terminal stages of AIDS, usually when other opportunistic infections or AIDS-related malignancies are present.

FIGURE 10-43. Pneumocystis jiroveci pneumonia. CT of a 37-year-old man with AIDS shows a multiseptated cyst in the right lower lobe (arrow) and scattered ground-glass opacities.

FIGURE 10-44. Pneumocystis jiroveci pneumonia and Cytomegalovirus pneumonia. A: PA chest radiograph of a 60-year-old man with AIDS shows nonspecific diffuse bilateral interstitial and airspace opacities. B: CT shows nonspecific findings of bilateral dense airspace and ground-glass opacities associated with airway dilatation. Imaging of immunocompromised patients is often confounded by the presence of multiple ongoing disease processes.

FIGURE 10-45. Cryptococcal pneumonia. A: PA chest radiograph of a 43-year-old man with AIDS, fever, night sweats, and weight loss shows diffuse bilateral hazy opacity. B: Prior chest radiograph is normal. C: CT shows numerous randomly distributed miliary nodules.

FIGURE 10-46. Large-cell lung cancer. A: CT scout image of a 37-year-old man with AIDS and multiple distended neck and anterior chest veins shows a large right pleural effusion and collapse of most of the right lung. B: Axial CT shows extensive tumor infiltrating the mediastinum, resulting in slitlike narrowing of the superior vena cava (solid arrow), encasement of the right pulmonary artery (dashed arrow), and a large right pleural effusion.

The two most important malignancies to consider in patients with AIDS are Kaposi sarcoma and lymphoproliferative disease. There is also a possible increased incidence of bronchogenic cancer in patients with AIDS, which is highly aggressive and occurs in patients who are younger than those who have bronchogenic cancer without AIDS (Fig. 10-46). Kaposi sarcoma is the most common malignancy (58). Pulmonary Kaposi sarcoma is rare in the absence of cutaneous involvement, providing a helpful clue to the diagnosis. Chest radiographic findings are nonspecific, and Kaposi sarcoma, like other disorders in patients with AIDS, often coexists with opportunistic infections. Two patterns can be seen: (i) diffuse linear and reticular interstitial opacities (including Kerley B lines) or (ii) diffuse nodular opacities. A perihilar distribution predominates with both patterns, reflecting a bronchovascular distribution (59) (Fig. 10-47). The bronchovascular nodules can have a flame-shaped appearance. Pleural effusions are common and can be large. Hilar and mediastinal lymphadenopathy is common, although not bulky; the CT attenuation of these nodes can be relatively high after injection of intravenous contrast material because of the hypervascularity of Kaposi sarcoma.

FIGURE 10-47. Kaposi sarcoma. A: PA chest radiograph of a 49-year-old man with AIDS, cutaneous lesions, nonproductive cough, and shortness of breath shows bilateral ill-defined nodular thickening of the bronchovascular bundles. B: CT shows nodular bronchovascular thickening (solid arrow), septal thickening (Kerley lines; dashed arrow), and bilateral pleural effusions (E). The findings are very suggestive of Kaposi sarcoma.

Pulmonary lymphoma is the second most common intrathoracic malignancy associated with HIV infection (58). Most are of the B-cell Hodgkin type. These lymphomas are usually aggressive, widely disseminated, and almost always associated with extranodal disease. It is a later feature of AIDS that occurs in severely immunocompromised patients. The chest radiographic and CT appearances are similar to those of non–AIDS-related lymphomas, including pulmonary masses or nodules (Fig. 10-48), lymphadenopathy (Fig. 10-49), and pleural effusions (60). There is a strong association between the presence of the Epstein-Barr virus and lymphoproliferative disorders of many kinds in immunocompromised patients, including those with AIDS. The most common CT appearance in these patients is multiple nodules with a bronchovascular and subpleural distribution affecting predominantly the middle and lower lungs (61).

FIGURE 10-48. Large-cell lymphoma. CT of a man with AIDS and profound immunosuppression shows multiple circumscribed pulmonary nodules (arrows).

Lymphocytic interstitial pneumonia (LIP) is characterized by infiltration of the peribronchial interstitial tissues of the lung by mature polyclonal lymphocytes, plasma cells, and immunoblasts. Although LIP is usually a diffuse interstitial process with a basilar predominance, one or more nodular masses frequently develop (62). The diffuse interstitial pattern can be miliary in appearance, an appearance similar to that of miliary TB. LIP is more common in children than in adults and is an AIDS-defining illness in children. Other lymphoproliferative disorders seen in patients with AIDS include lymphocytic bronchiolitis and pulmonary lymphoid hyperplasia.

FIGURE 10-49. AIDS-related lymphoma. CT shows a large anterior mediastinal mass encasing the right brachiocephalic vein (curved arrow), displacing the left brachiocephalic vein laterally (straight arrow), and displacing the brachiocephalic artery (B), left common carotid artery (C), left subclavian artery (S), trachea (T), and esophagus (E) posteriorly. (Reprinted with permission from 

Kuhlman JE. AIDS-related tumors of the chest. In: Husband JES, Reznele RH, eds. Imaging in Oncology. Oxford, UK: ISIS Medical Media; 1998:1003–1018.

)

Bone Marrow Transplantation

Pulmonary infections occur in at least half of all patients after bone marrow transplantation and are the most significant cause of death in this patient population (63) (Fig. 10-50). Infections occurring in immunocompromised patients were discussed earlier in this chapter. [AU: Are BMT patients, AIDS patients, and lung transplant patients, then, not considered “immunocompromised”?]

Graft-versus-host disease (GVHD) results from the transplantation of immunocompetent donor lymphocytes that attack the recipient's tissues, especially the skin, liver, and gastrointestinal tract. Acute GVHD occurs 20 to 100 days after transplantation and involves primarily extrapulmonary organs. Chronic GVHD occurs at least 100 days after transplantation in approximately one third of patients surviving this long (64), and it results in lymphocytic infiltration of the airways and obliterative bronchiolitis. Chest radiograph and CT findings include diffuse patchy perihilar opacities, reflecting the airway distribution of disease. In severe cases, a diffuse interstitial pattern is seen. CT may be normal on inhalational images but may show air trapping on exhalational images, reflecting obliterative bronchiolitis.

Pulmonary veno-occlusive disease rarely occurs in patients after bone marrow transplantation but can lead to patient death. The pulmonary veins thrombose and develop intimal fibrosis, possibly as a result of pulmonary infection. Occlusion of the pulmonary veins leads to pulmonary venous and capillary congestion, pulmonary edema, alveolar hemosiderin deposits, pulmonary arterial hypertension, and right heart failure. Chest radiographs, when abnormal, show signs of pulmonary arterial hypertension (enlarged central pulmonary arteries) and, in some cases, interstitial and alveolar pulmonary edema (65). The left atrium is not enlarged, differentiating this entity from mitral valve disease and left atrial myxoma.

Pulmonary hemorrhage can occur in the absence of any evidence of a coagulopathy and in the absence of hemoptysis. It usually develops within 20 days of transplantation and is a fulminant condition with a 75% mortality rate. Chest radiographs most commonly show diffuse alveolar lung disease, although in some cases a pattern of reticular interstitial disease predominates (66).

Lung Transplantation

The first successful lung transplantation was performed in 1983. As of June 2004, 3,154 heart–lung and 19,296 lung transplantations had been performed [AU: Worldwide?] according to data from an international registry (67). Single lung transplantation is the preferred procedure for lung replacement because fewer donor organs are required compared with heart–lung or bilateral lung transplantation. Cystic fibrosis is the most common indication for bilateral lung transplantation because of the incidence of recurrent infections in the native lung after single lung transplantation and institution of immunosuppression.

In single lung transplantation, the chest is entered through the bed of the fifth rib. This avoids complications of a sternotomy, which is performed for heart–lung and double lung transplantation. The surgery involves pulmonary artery, bronchial, and donor–recipient left atrial cuff anastomoses (68). Bilateral lung transplantation involves sequential single lung transplants and is commonly performed via a “clamshell” approach through a lower sternotomy.

FIGURE 10-50. Respiratory syncytial virus pneumonia. A: Baseline PA chest radiograph of a 23-year-old man 21 days after bone marrow transplantation. B: PA chest radiograph taken 9 days later shows new bilateral interstitial and alveolar opacities. C: AP supine chest radiograph taken 4 days after (B) shows progression of diffuse parenchymal disease, correlating with the clinical onset of acute respiratory distress syndrome (ARDS). Note new endotracheal tube. The patient died from fulminant viral pneumonia and ARDS.

FIGURE 10-51. Streptococcal pneumonia. A: PA chest radiograph of a 40-year-old man with bilateral lung transplants shows bilateral patchy airspace opacities. B: CT shows airspace opacities that are not specific for any infectious organism. The findings can also be seen with acute rejection.

FIGURE 10-52. Staphylococcal pneumonia. A: PA chest radiograph of an 18-year-old woman with bilateral lung transplants shows diffuse bilateral interstitial and airspace opacities. B: CT shows multifocal dense airspace and ground-glass opacities and small cavitary nodules (arrow).

Infection is the leading cause of death in the lung transplant population, accounting for 48% of early postoperative mortality (69). Factors that increase the susceptibility to infection include immunosuppression, reduced mucociliary clearance, interruption of lymphatic drainage, and direct and constant contact of the transplant with the outside environment via the airways (70). Bacterial agents predominate in the first month after transplantation (Figs. 10-51 and 10-52), CMV infections occur mainly in the second and third months (Fig. 10-53), and fungal infections (Fig. 10-54) occur both early and later after transplantation (70,71,72,73). PCP is uncommon secondary to antibiotic prophylaxis. If CMV pneumonia develops, a fulminant course proceeding to respiratory failure and death within a few days can develop (74).

FIGURE 10-53. Cytomegalovirus pneumonia. A: PA chest radiograph of a 55-year-old man with a left lung transplant shows abnormal opacity in the left upper lobe. Note the hyperlucent and hyperexpanded native right emphysematous lung. B: CT shows ground-glass opacity involving only the left transplant lung and severe changes of emphysema in the native right lung.

Acute rejection may be observed at any point after transplantation, with the first episode occurring as early as 48 hours and most occurring in the first 100 days after surgery. Most recipients experience at least one episode (75). CT of the chest shows ground-glass opacification as the only significant finding (76). Chest radiograph and CT findings overlap with those of infection (77).

Reperfusion edema is seen within 24 hours after transplantation and resolves over a period of days to months, usually within 1 to 2 weeks. The radiographic appearance ranges from mild perihilar haze to dense consolidation, and it results from surgical trauma, ischemia, organ preservation, denervation, and lymphatic interruption (70). The diagnosis is one of exclusion and is characterized by all radiographic changes beginning soon after surgery that are not the result of left ventricular failure, rejection, fluid overload, infection, or atelectasis (75).

FIGURE 10-54. Invasive pulmonary aspergillosis. A: PA chest radiograph of a 35-year-old man with bilateral lung transplants shows multiple nodules, some with evidence of cavitation (arrow), in the right upper lung. B: CT shows a cavitary nodule in the right upper lobe with a halo of ground-glass opacity. There is a smaller thin-walled cavity in the left upper lobe.

Pleural effusions are common after lung transplantation, secondary to impaired fluid clearance through the lymphatics of the visceral pleura. Most effusions develop immediately following surgery and continue for up to 9 days, with output declining steadily during the first week (78). Pneumothoraces are evident on postoperative radiographs in 60% of patients; they are generally small and apical in location (79).

Chronic rejection is a major problem in patients surviving longer than 3 months, and it occurs in more than 50% of patients. Obliterative bronchiolitis represents the pathologic finding in chronic rejection. CT findings of bronchiectasis/bronchiolectasis, decreased vascular markings, and air trapping on exhalational scans are findings associated with obliterative bronchiolitis (71,72,80).

FIGURE 10-55. Posttransplant lymphoproliferative disorder. A: PA chest radiograph of a 32-year-old woman with bilateral lung transplants shows multiple pulmonary nodules (arrows). B: CT confirms multiple circumscribed pulmonary nodules (arrows). The nodule in the right lung is related to a bronchovascular bundle, a common pattern of distribution of nodules in patients with this disorder.

Posttransplantation lymphoproliferative disease, thought to be induced by the Epstein-Barr virus, manifests as a spectrum of lymphoproliferation that ranges from a mild, polyclonal lymphoid hyperplasia to frank lymphoma. Of all transplantation procedures, this disorder occurs most often after lung transplantation, with a prevalence of 5% to 20%, occurring most often within the first year after surgery (81). Intrathoracic involvement is most commonly characterized by the presence of discrete nodules, either solitary or multiple, with or without mediastinal lymphadenopathy (Fig. 10-55) (61,81,82). Bronchogenic carcinoma occurs after lung transplantation, most commonly in the native lung in patients with single lung transplantation for emphysema (Fig. 10-56) or idiopathic pulmonary fibrosis (83).

FIGURE 10-56. Squamous cell bronchogenic carcinoma. CT of a 65-year-old woman with a left lung transplant and a 35–pack-year history of cigarette smoking shows a right paravertebral mass (arrow). Note the severe changes of emphysema in the native right lung and normal perfusion to the left transplant lung.

Recurrence of disease has occurred in patients transplanted for sarcoidosis (most common), LCH, lymphangiomyomatosis, bronchioloalveolar carcinoma, desquamative interstitial pneumonitis, pulmonary alveolar proteinosis, giant cell interstitial pneumonitis, diffuse panbronchiolitis, talc granulomatosis, and bronchiectasis from aspiration (84). It is important to consider recurrence of native disease when new abnormalities are seen on chest radiography or CT in the appropriate clinical situation.

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