- Email: [email protected]
Radiographic approach to multifocal consolidation
Radiographic Approach to Multifocal Consolidation Kristina M. Kjeldsberg, Karen Oh, Kathleen A. Murray, and George Cannon Consolidation in the lung is seen on radiographs or computed tomography (CT) as increased areas of attenuation that obscure the underlying pulmonary vasculature. There are numerous causes of multifocal consolidative opacities. If the symptoms are acute (days to weeks), the most common causes include edema, pneumonia, and hemorrhage. Depending on the patient's history, signs, and symptoms, the less common causes such as radiation pneumonitis or acute eosinophilic syndrome may be considered. If the symptoms are more chronic (weeks to months), the differential may include alveolar proteinosis, neoplasms such as lymphoma or bronchoalveolar cell carcinoma, granulomatous or inflammatory conditions, and lipoid pneumonia. In this article, we review and discuss characteristic radiographic and clinical findings that can aid the radiologist in prioritizing the differential considerations when faced with multifocal parenchymal consolidative disease.
Copyright 2002, Elsevier Science (USA). All rights reserved.
HIS ARTICLE addresses the approach to multiple areas of consolidative opacities seen in the lung parenchyma on chest radiograph or computed tomography (CT). Consolidation is seen as areas of increased lung attenuation with obscuration of underlying pulmonary vessels.1 Air bronchograms are often present. Diseases that cause consolidation are characterized by replacement of air in the alveoli by fluid, cells, protein, tissue, or some other material (essentially water, pus, blood, cells, or protein). 2'3 Most diseases are associated with filling of alveoli but diseases that produce an extensive confluent interstitial abnormality may also result in this finding. 2'4 We, therefore, find the distinction between airspace and interstitial disease patterns to be misleading, especially because both processes are often present. Consolidation that is lobar or segmental in distribution is characteristic of bacterial pneumonia. In addition, consolidation can result from the confluence of multiple illdefined 5- to 10-mm acinar nodules, as seen with varicella pneumonia and noncardiogenic pulmonary edema owing to fat emboli. 5 There are a number of diseases that manifest with a predominantly consolidative process. A useful approach that narrows the differential considerations is to separate etiologies into 2 major groups based on the duration of the patient's presenting respiratory symptoms. Acute symptoms are
T
From the Department of Radiology, and the School of Medicine, University of Utah Health Sciences Center, Salt Lake City, UT. Address reprint requests to Kathleen A. Murray, MD, Shriners Hospital for Children, Fairfax Road at Virginia Street, Salt Lake City, UT 84103;e-mail: [email protected] Copyright 2002, Elsevier Science (USA). All rights reserved. 0887-2171/02/2304-0001535.00/0 doi: l O.1053/sult.2002.3 3979 288
defined as occurring over days to weeks, whereas chronic symptoms last weeks to months. The plain radiographic appearance combined with the clinical history is usually sufficient to limit the differential diagnosis. In some cases, high-resolution CT (HRCT) may contribute to patient management by more clearly defining accompanying abnormalities, such as lymphadenopathy, pleural effusions, ill-defined nodular opacities, or a tree-in-bud pattern. HRCT can help further delineate the extent and distribution of disease and guide further diagnostic evaluation such as bronchoscopy and/or biopsy. ACUTE SYMPTOMS
The 3 most common causes of acute consolidation are edema, pneumonia, and pulmonary hemorrhage. 6 Less-common causes include radiation pneumonitis and acute eosinophilic syndrome.
Pulmonary Edema Pulmonary edema is one of the most common causes of acute consolidation on chest radiographs. It has traditionally been classified as being either cardiogenic (hydrostatic) or noncardiogenic (increased permeability).7 Hydrostatic edema. Hydrostatic pulmonary edema is usually seen with left ventricular heart failure, resulting from elevated pressures in the pulmonary capillaries. Radiographic findings include indistinctness of blood vessel margins, peribronchial cuffing, pleura/effusions, thickening of fissures (subpleural edema), and thickening of the interlobular septa (Kerley A and B lines) (Fig 1). The cardiac silhouette is often enlarged. As hydrostatic pressures increase, alveolar fluid accumulates, resulting in the development of symmetric, ground-glass, and consolidative opacities, often within the lower lobes medially. As it progresses,
Seminars in Ultrasound, CT, and MRI, Vol 23, No 4 (August), 2002: pp 288-301
iii!iiiiii~i
Fig 1. Hydrostatic edema. (A) Posteroanterior and (B) lateral chest radiographs in a 69-year-old man with known coronary artery disease, shortness of breath, and paroxysmal nocturnal dyspnea show features of congestive heart failure and hydrostatic edema. The cardiac silhouette is enlarged, and pulmonary vasculature is engorged and indistinct. Kerley A lines (large arrow) and B lines (small arrow) are seen. The Kerley A lines radiate from the hila and are seen less commonly than Kerley B lines. The Kerley A lines are particularly prominent in this case.
290
consolidation worsens superiorly and peripherally. In our experience, the classic bat wing distribution seen centrally near the hila is uncommon. An unusual manifestation of hydrostatic edema can result from acute mitral valve regurgitation. This is well described as focal consolidation in the right upper lobe, caused by the orientation of the regurgitant jet of blood flow that is oriented toward the right superior pulmonary vein. Furthermore, cephalization of blood flow is rarely seen in the acute setting. Its presence is an excellent indication of underlying chronic pulmonary venous hypertension. 7 A clue to the diagnosis of hydrostatic edema is rapid clearing with treatment. Other causes of hydrostatic edema include volume overload owing to renal failure or aggressive fluid resuscitation, pulmonary venoocclusive disease, decreased oncotic pressure as seen with hypoalbuminemia, mitral stenosis, left ventricular aneurysm, acute myocardial infarction, and acute arrhythmia. Permeability edema. Noncardiogenic or permeability edema results from disruption of the capillary endothelium with leakage of plasma into the surrounding lung tissue. Acute respiratory distress syndrome (ARDS) is classically thought to be the prototype of permeability edema. It is now clear that permeability edema results in a spectrum of disease, with ARDS being the most severe form. 7
The barriers to the formation and spread of edema are the capillary endothelium and the alveolar epithelium. Different degrees of damage to each can account for the varying clinical and radiographic appearances of permeability edema. Diffuse alveolar damage results when the alveolar epithelium is disrupted] Permeability edema can occur without diffuse alveolar damage. Examples include edema secondary to interleukin-2 or OKT3 therapy, transfusion reactions, and in milder forms of the hantavirus pulmonary syndrome. In most of these cases, endothelial injury predominates and epithelial injury is minimal, resulting in confinement of most of the edema to the interstitium. Therefore, the radiographic appearance may resemble hydrostatic edema with vascular indistinctness, thickened bronchial walls and fissures, septal lines, and pleural effusions. Additionally, the edema and symptoms usually change rapidly. 7 ARDS is the severest form of permeability edema, in which the determining factor is the
KJELDSBERG ET AL
alveolar epithelial injury (diffuse alveolar damage). The edema in the interstitium is allowed to escape into the alveoli, thus, the interstitial abnormalities are typically not seen on the radiograph. Radiographic findings include bilateral, widespread, patchy, ill-defined ground-glass and consolidative opacities, usually without pleural effusions, septal thickening, bronchial cuffing, or subpleural thickening (Figs 2 and 3). Air bronchograms appear to be more commonly seen than with hydrostatic edema] Consolidation seen predominantly in the dependent regions is often seen. It is thought that this dependent consolidation protects the posterior lung regions from the deleterious effects of mechanical ventilation, thus, offering an explanation for the striking anterior distribution of fibrosis resulting from ARDS. 8 The patient is almost always intubated owing to severe hypoxia, and resolution of the edema is slow. ARDS can develop from a number of causes. It may be idiopathic, which has been referred to as acute interstitial pneumonia, 9 or may be owing to a number of causes. A mnemonic used at our institution for some of the more common etiologies is DRIP DEATH: Drugs (heroin, chemotherapy), Renal failure, Inhalational (smoke, toxic gases)/Idiopathic, Pancreatitis, Drowning, Emboli (fat, amniotic), ARDS (idiopathic), Trauma (neurogenic, airway obstruction, shock)/Transfusions, and Highaltitude pulmonary edema (Table 1).
Pneumonia The most common cause of a focal, acute consolidative opacity, often without significant volume loss, is bacterial pneumonia. 1° Plain radiographs in combination with clinical findings are able to diagnose most cases (Fig 4). CT can contribute by revealing that the pneumonia is more widespread, showing an obstructing central mass, showing evidence of early necrosis or cavitation, or detecting an effusion or empyema. 11 Lobar consolidation with expansion of the lobe is most consistent with bacterial pneumonia, such as pneumococcal (Streptococcal pneumoniae) or Kleb-
siella pneumoniae.l° The development of cavitation suggests Staphylococcus aureus, a gram-negative, nosocomial, or fungal source. If lymphadenopathy is present, tubercular or fungal sources must be considered. Varicella pneumonia is a viral pneumonia caused by the varicella-zoster virus and can have conflu-
MULTIFOCAL CONSOLIDATION
291
Fig 2. ARDS. Portable supine chest radiograph in a 26-year-old woman with renal failure and uremia shows an enlarged cardiac silhouette and diffuse ground-glass and consolidative opacities. Air bronchograms(arrows) are seen in the upper lobes, Typically, the opacities are dependently located (the posterior aspects of all lobes are dependent when the patient is supine), Edema actually protects these areas from the deleterious effects of mechanical ventilation.
ence of multiple ill-defined 5- to 10-ram acinar nodules, similar to the pattern seen in fat embolization syndrome (Fig 5). Aspiration pneumonia usually presents as consolidation in the dependent regions of the lung. A tree-in-bud pattern seen on HRCT supports the diagnosis of aspiration pneumonia in the appropriate clinical scenario. In our experience, this treein-bud pattern may be recognized on chest radiographs in moderate to severe cases as thick reticular opacities with associated ill-defined 3- to 4-mm nodules and airway thickening. It is less common for pneumonia to cause diffuse or extensive confluent consolidative opacities. When present, the immunocompetency of the patient should be considered. ~2 Opportunistic organisms that should be considered in this patient population include Pneumocystis carinii, tuberculosis, fungai infections (including cryptococcosis and aspergillosis), cytomegalovirus, and Nocardia asteroides. If the patient is an immunocompetent individual, viral pneumonia as well as severe overwhelming pneumoncoccal pneumonia may show extensive multifocal abnormalities.
Pulmonary Hemorrhage A variety of disorders can result in bleeding into the lung. Clinically, the patient may present with hemoptysis, dyspnea, and anemia. Radiographic features are generally not helpful in determining the cause. Radiographs and CT show patchy or diffuse ground-glass opacity, consolidation, or both. 13 Opacities tend to be more pronounced centrally, with sparing of the costophrenic angles. Rapid clearing in 2 to 3 days is expected and can be helpful in limiting the differential. 14 Interlobular septal thickening may be seen a few days after an acute episode as hemosiderin-laden macrophages accumulate in the interstitium. 13 Diffuse pulmonary hemorrhage can result from multiple diseases. Goodpasture's Syndrome is an anti-basement membrane antibody disease typically occurring in young white men. Renal disease is usually, but not always, present. 13 Wegener's granulomatosis (Fig 6) is usually seen in older men and usually presents with upper airway involvement with sinusitis, rhinitis, and otitis. The majority of patients with active disease have a positive
292
KJELDSBERG ET AL
Fig 3. ARDS. Anteroposterior chest radiograph in an 18year-old man who sustained extensive trauma several days earlier. He has multiple pelvic and long bone fractures. This pattern of multiple, confluent, ill-defined nodules resulting in diffuse consolidation occurring 48 to 72 hours after trauma is characteristic of fat embolization syndrome. Patients with fat embolization may also exhibit confusion and skin petichiae as a manifestation of multiorgan involvement.
antineutrophil cytoplasmic antibody test. 14 Cavitary nodules can also occur, Systemic lupus erythematosus (SLE) most often occurs in younger women (Fig 7). There may be coexistent pleural or pericardial effusions. Idiopathic pulmonary hemosiderosis is most commonly seen in young children and young adults, and is sometimes associated with celiac disease or immunoglobulin-A gammopathy. 13 Other causes of diffuse pulmonary hemorrhage include coagulopathies caused by thrombo-
Table 1. Causes of ARDS D R I P
Drugs (heroin, chemotherapy) Renal failure Inhalational (smoke, toxic gases) or idiopathic Pancreatitis
D E A T
Drowning Emboli (fat, amniotic) ARDS (idiopathic) Trauma (neurogenic, airway obstruction, shock) or transfusions High-altitude pulmonary edema
H
Fig 4. Lobar pneumonia. (A) Posteroanterior and (B) lateral chest radiographs show focal consolidation (arrows) in the anteromedial segment of the left lower lobe. This 33-year-old woman had acute onset of productive cough, fevers, and chills. This pattern is characteristic of community-acquired bacterial pneumonia.
cytopenia, disseminated intravascular coagulation, or thrombotic thrombocytopenic purpura) 5 When pulmonary hemorrhage is focal or multifocal rather than diffuse, the systemic diseases are less likely compared with localized disease. In focal or multifocal disease, pulmonary embolism, aspiration of blood, pulmonary contusion, bronchi-
MULTIFOCAL CONSOLIDATION
Fig 5. Varicella pneumonia. Posteroanterior chest radiograph in this 34-year-old man with hemophilia and human immunodeficiency virus shows diffuse consolidation, with ill-defined confluent nodules. The appearance is very similar to fat embolization syndrome (see Fig 3); therefore, the history is crucial to making the appropriate diagnosis.
Fig 6. Wegener's granulomatosis. Portable anteroposterior chest radiograph in the intensive care unit on this 3g-yearold man with hemoptysis and respiratory failure. Extensive regions of peripheral consolidation are seen. When peripheral and wedge-shaped, Wegener's granulomatosis consolidation can mimic thromboembolic disease. Although more common in older men, Wegener's granulomatosis can also occur in younger individuals. This patient has known disease and has had renal failure, treated with kidney transplantation.
293
Fig 7. SLE. Portable anteroposterior chest radiograph in a 27-year-old woman with sudden onset of shortness of breath and hemoptysis shows central consolidative opacities, with sparing of the costophrenic angles. In this case, a history of gross hematuria, anemia, and a markedly elevated sedimentation rate all helped direct the clinician and the radiologist to the diagnosis of SLE. Note the enlarged cardiac silhouette, indicating a pericardial effusion, which is also seen in SLE.
ectasis, tumors, or localized infections should be considered. 13'15 Pulmonary embolism with or without infarction can be seen as a pleural-based wedge-shaped opacity (Fig 8). The term Hampton's hump was initially described as a sign of pulmonary infarction seen predominantly in the lower lung zones. Air bronchograms are rarely present. As infarctions resolve, the opacity clears from the periphery first like a melting ice cube. 16 Pulmonary embolism mimics include Wegener's granulomatosis, invasive aspergillosis, and cocaine-induced pulmonary vasoconstriction (Fig 9). Radiation pneumonitis. Radiation pneumonitis is a well-known complication of radiation therapy to the chest. It is variably seen at doses between 30 and 40 Gy, and is almost always seen at doses over 40 Gy. Depending on the dose, radiographic changes can be seen as early as 1 week but usually do not occur until 6 to 8 weeks after therapy. CT shows various patterns, ranging from homogeneous to patchy consolidations. The key to recognizing this is noting the nonanatomic delineation of disease (which defines the radiation port). CT is able to detect these parenchymal abnormalities earlier than radiographs. These areas often show improvement with steroid therapy, x7
294
KJELDSBERG ET AL
to l0 days with extensive diffuse consolidations on the radiograph. 1~'19 Release of eosinophilic granules during an inflammatory response results in acute lung injury. The reported common radiographic findings in acute eosinophilic pneumonia resemble pulmonary edema with areas of ground-glass and consolidative opacities, interlobular septal thickening, and pleural effusions (Fig 10). Unlike chronic eosinophilic pneumonia, the opacities have no peripheral
Fig 8. Thromboembolic disease. (A) Anteroposterior chest radiograph in a 37-year-old woman with acute shortness of breath shows volume loss and opacity in the right lower lobe, This is a large peripheral wedge-shaped opacity, (B) CT angiogram shows a large embolus (arrow) in the descending right pulmonary artery,
Acute eosinophilic pneumonia. Also known as Loeffler's Syndrome, acute eosinophilic pneumonia is an idiopathic disease that can result in acute respiratory failure. Elevated levels of eosinophils usually are obtained in bronchoalveolar lavage (BAL) fluid. Patients present over 1 to 5 days with an acute febrile illness, myalgias, pleuritic chest pain, and profound hypoxemia. There is no identifiable inciting agent recovered. BAL is essential in the diagnosis because, unlike chronic eosinophilic pneumonia, peripheral blood eosinophilia is rare. The diagnosis should be considered in patients with progressive clinical deterioration over 5
Fig 9. Pulmonary hemorrhage secondary to cocaine, (A) Anteroposterior chest radiograph in a 50-year-old man with shortness of breath and hemoptysis shows peripheral wedgeshaped consolidation and patchy ill-defined opacities. The cardiac size is large. Note the similarities of this case with Wegener's granulomatosis (see Fig 6). The patient admits to occasional use of cocaine, (B) CT image shows multiple peripheral wedge opacities and the patchy areas of increased attenuation typical of alveolar hemorrhage. There was no CT evidence of thromboembolic disease,
MULTIFOCAL CONSOLIDATION
295
Neoplasm, Granulomatous processes, Inflammatory diseases, and Old [ANGIO]) to help recall the diseases that characteristically present with chronic consolidation (Table 2). Bronchopulmonary foregut malformation (sequestration) may also be considered in younger patients with focal consolidation. Alveolar Proteinosis
Figure 10. Eosinophilic pneumonia (acute). (A) Anteroposterior chest radiograph in a 26-year-old man with acute symptoms over 5 days shows symmetric, diffuse, ground-glass and consolidative opacities, with a somewhat central distribution. Bronchoscopy revealed almost all eosinophils.
predominance. Mediastinal lymphadenopathy, pericardial effusion, and cardiomegaly are not seen. Radiographic findings and symptoms improve rapidly after administration of intravenous corticosteroids.18'19 CHRONIC SYMPTOMS
Chronic consolidative opacities are defined as being present for weeks to months. Patients often present with clinical symptoms that are more insidious in onset, such as chronic cough, shortness of breath, malaise, or dyspnea on exertion. Because the symptoms persist or worsen, the patient usually has had recurrent visits to their physician. The severity of the disease rarely warrants hospitalization; therefore, it is the outpatient facilities and clinicians that usually encounter these more unusual diseases. A useful generalization is chronic or recurrent symptoms should increase the pretest probability of underlying lung or pulmonary vascular disease. When the radiographic abnormality is predominately consolidative in appearance, then the more unusual diseases should be considered. The common diseases to present as a chronic consolidative process will be reviewed. It is important to realize that many will require tissue sampling, but clues to help reduce the differential among the multiple diseases are discussed. As with many differential diagnoses in radiology, we use a pneumonic (Alveolar proteinosis,
Pulmonary alveolar proteinosis (PAP) is characterized by proteinaceous material filling the alveoli. This material is lipid-rich and periodic acidSchiff positive. Most patients who are affected are between 20 and 50 years of age, 2° with men outnumbering women by up to 4:1. Initial presenting symptoms include shortness of breath with activity and/or a mild nonproductive cough. Low-grade fever may be present with the disease, though usually indicates superinfection.2°'2I N. asteroides has been traditionally cited as an associated infection. 22 The diagnosis is usually made with transbronchial biopsy and BAL, in which milky fluid is obtained. BAL is also considered therapeutic, with some patients showing no recurrence after lavage. Repeated BAL may be needed for those who recur, though up to 38% did not recur after the first therapeutic lavage in a Mayo Clinic series. 21 PAP can be seen in the primary or idiopathic form without associated disease process, or in the secondary form. Secondary PAP can the seen with pulmonary infection, hematologic malignancies, or exposure to inhaled chemicals. 2°'21 Although symptoms are usually chronic and insidious in onset, secondary PAP has recently been reported to cause acute respiratory failure, especially in patients with hematologic malignancy. 23 Radiographic findings of PAP include consolidative or ground-glass opacities. The typical radiograph shows bilateral patchy consolidation, more concentrated in the lung bases and perihilar regions. 2°'24 HRCT shows patchy consolidative opacities with sharp delineation from the surround-
Table 2. Causes of Chronic Lung Consolidation
A N G I O
Alveolar proteinosis Neoplasm Granulomatous processes Inflammatory diseases Old (occurring in the elderly: aspiration, lipoid pneumonia)
296
KJELDSBERG ET AL
nary symptoms, is characteristic of PAP. The crazy-paving pattern is described in a number of acute, subacute, and chronic diseases, but is essentially always present in PAP though variably present in other processes. 2
Neoplasms
Fig 11. Pulmonary alveolar proteinosis. (A) Posteroanterior radiograph in a 30-year-old woman with dyspnea and chronic cough for 2 months shows bilateral areas of groundglass and consolidative opacity. In alveolar proteinosis, these findings typically are worse in the perihilar regions and lung bases. Often the chest radiograph shows much more opacity than would be expected for the concomitant mild symptoms. (B) HRCT in the same patient shows the patchy geographic increase in density that is seen in this disease. The interlobular septa are thickened, giving the crazy-paving appearance of a cobblestone street typically associated with alveolar proteinosis. Although this pattern can be seen in other diseases, the clinical signs and symptoms help lead the radiologist to the correct diagnosis.
ing normal lung tissue, giving a typical geographic appearance. The intra- and interlobular septa are thickened in a polygonal pattern, also described as crazy-paving (Fig 11). 20,24 This pattern, when seen in the patient with chronic and often mild pulmo-
Lymphoma and bronchoalveolar carcinoma are 2 neoplasms that may present as chronic consolidations. Both are similar in appearance to the typical community-acquired pneumonia, but do not resolve with antibiotic treatment and have a more insidious onset than most types of pneumonia. Lymphoma may be primary or secondary, though secondary spread from extrathoracic lymphoma is more common. Radiographically, lymphoma shows air bronchograms with multiple or solitary nodules and/or areas of consolidation (Fig 12). 25,26 Pleural effusions or lymphadenopathy may be present as well, with adenopathy more common in Hodgkin's lymphoma. 26 A reticular pattern similar to lymphangitic carcinomatosis may also be seen on radiographs and HRCT. 25'26 Bronchoalveolar carcinoma appears similar to lymphoma, with air bronchograms, patchy areas of consolidation, or nodular opacities (Fig 13). 27,28 Interlobular septal thickening (crazy-paving) may be present, though is uncommon. 27 Ground-glass opacities may result from lepidic (butterfly-like) spread of tumor, with diffuse lung involvement likely secondary to hematogenous spread. 27'28 Postobstructive consolidative pattern from a primary lung tumor can result in a drowned lung appearance. There may be volume loss distal to the tumor. However, the distal lung may be expanded instead, and fluid-filled bronchi may serve as a clue to a more central obstruction.
Granulomatous Etiologies This group of infections tends to be more insidious in onset, causing more chronic consolidations than the typical community-acquired pneumonia. Aspergillosis, tuberculosis, and other fungal infections such as coccidiomycosis may present with consolidation. Invasive aspergillosis is seen most frequently in severely immunocompromised hosts, for example, in patients with neutropenia, corticosteroid therapy, and acquired immune deficiency syndrome. 29 The most common radiographic findings are cavitary upper lobe disease,
MULTIFOCAL CONSOLIDATION
297
Fig 13. Bronchoalveolar carcinoma. Posteroanterior radiograph in this immunocompetent, 46-year-old man with several months of nonproductive cough shows right upper lobe consolidation, This is radiographically indistinguishable from pneumonia, but the history is not consistent with this diagnosis. This pattern, in conjunction with chronic cough, is consistent with tumor, including bronchoalveolar carcinoma and lymphoma. Patients with bronchoalveolar carcinoma may produce copious amounts of clear sputum.
Fig 12. Lymphoma. (A) Posteroanterior and (B) lateral radiographs of a 48-year-old man show a large consolidative opacity in the left upper lobe as well as hilar and mediastinal adenopathy. This patient had recurrent non-Hodgkin's lymphoma. The left upper lobe resembles extensive pneumonia (which sometimes coexists with parenchymal tumor), but the bilateral adenopathy should be a clue directing the radiologist to an underlying lymphoma.
focal consolidation, or bilateral patchy consolidation (Fig 14). 29 The semi-invasive form of Aspergillosis strikes patients with underlying medical histories of chronic illness, advanced age, corticosteroid use, or chronic obstructive pulmonary disease. 3° The symptoms are chronic, with weakness, cough, and
Fig 14. Primary tuberculosis. Posteroanterior radiograph shows left upper lobe consolidation in this 16-year-old patient. The mediastinum is enlarged from adenopathy. The combination of a slow-to-resolve pneumonia and adenopathy is highly suggestive of primary tuberculosis or other fungal infection.
298
KJELDSBERG ET AL
Fig 15. Alveolar sarcoid. This 24-year-old man presented with a chronic cough of 6 months duration. (A) Posteroanterior radiograph shows patchy, ill-defined opacities bilaterally. Mediastinal and hilar adenopathy are present. (B) HRCT in the same patient shows nodular, consolidative opacities with air bronchograms. Subsequent open biopsy procedure revealed alveolar sarcoid.
fever. This form also presents with mainly upper lobe consolidation, often with cavitation and possibly with nodular opacities. Histology shows Aspergillus organisms, intra-alveolar hemorrhage, active inflammation, and tissue necrosis in the areas of consolidation. The radiographic findings can be indistinguishable from tuberculosis, though tuberculosis is usually associated with lymphadenopathy as well. Alveolar sarcoid is the noninfectious granulomatous etiology that should be considered (Fig 15). As with other forms of sarcoid, adenopathy is often (but not always) present. 33
Fig 16. BOOP. (A) Portable anteroposterior radiograph in a 68-year-old woman with respiratory distress shows bilateral lower lobe consolidation. A chest tube has been placed on the right after open biopsy. (B) HRCT in this patient shows multiple small nodules and ground-glass opacities in the lung bases. The open-lung biopsy showed BOOP. (C) Two months later, HRCT shows marked progression of disease.
MULTIFOCAL CONSOLIDATION
299
dations and normal lung volumes, often with a patchy peripheral distribution (Fig 16). 31"32 Ground-glass opacities may be present and air bronchograms can be seen in the consolidated areas. Lymphocytes and neutrophils are the predominant cellular components on BAL. With these radiographic findings, the differential diagnosis includes BOOP, eosinophilic pneumonia, lymphoma, and bronchoalveolar carcinoma. Clinical history and laboratory results may differentiate eosinophilic pneumonia from BOOP, though BAL or biopsy may be required. Clinically, chronic eosinophilic pneumonia is associated with a wide variety of causative agents, including neoplasms, asthma, allergic disorders, collagen vascular disorders, sarcoidosis, and parasitesY As with BOOP, fever, cough, and malaise are the presenting symptoms. Eosinophil levels will often be elevated in the peripheral blood smear. Radiographic findings include chronic peripheral consolidations that clear rapidly with steroid therapy (Fig 17). "Old"
This is to remind us of the diseases that affect the elderly population, including chronic aspiration
Fig 17. Chronic eosinophilic pneumonia. (A) Posteroanteriot radiograph in a 44-year-old woman with a progressive cough shows bilateral peripheral, midlung peripheral consolidative opacities, consistent with eosinophilic pneumonia. The striking peripheral location of poorly defined opacities should suggest this entity, which will respond to steroids. The peripheral blood smear shows eosinophilia. (B) CT image of a different patient with eosinophilic pneumonia also shows the peripheral consolidation,
Inflammatory Etiologies Bronchiolitis obliterans with organizing pneumonia (BOOP) is included in this category. Patients present with subacute onset of fever, cough, malaise. 31 It is associated with multiple inciting factors, including rheumatoid arthritis, bone marrow grafting, or as a reaction to various drugs. BOOP or organizing pneumonia manifests with multifocal areas of immature fibroblasts in the lung parenchyma, and can be seen after an infectious pneumonia has been treated. 32 Radiographic features include bilateral consoli-
Fig 18. Lipoid pneumonia. Posteroanterior radiograph shows extensive bibasilar areas of consolidation. There is no adenopathy. A mild nonproductive cough was present. The minimal symptoms, with fairly marked dependent opacities, are the clues to this diagnosis. If performed, CT can document the low density of the aspirated lipid material.
300
KJELDSBERG ET AL
and lipoid pneumonia. Both present with chronic consolidative opacities. Chronic aspiration has a bibasilar and dependant lobe predominance of consolidation. The distribution reflects the pattern of deposition in the upright patient, with material more often settling in the right middle lobe or right lower lobe because of the straighter path of the bronchus. Gravity will also cause settling of material in the left lower lobe bronchus, In the supine patient, the consolidation may be in the superior segments of the lower lobes because of the dependent position of the bronchi leading to the superior segments. On HRCT, illdefined centrilobular opacities may be seen, with filling of the terminal bronchioles with aspirated material (tree-in-bud).34 In the chronic setting, bronchiectasis, fibrosis, and architectural distortion may result from repeated aspiration and/or infection. In lipoid p n e u m o n i a , the radiographic pattern of i n v o l v e m e n t is similar to chronic aspiration. A history of chronic aspiration or inhalation of a
large quantity of animal, vegetable, or petrol e u m - b a s e d oils or fats may be elicited from the patient after careful questioning. Lung inflammation results from the hydrolyzed free fatty acids, creating a foreign-body reaction. B A L may reveal lipid-laden macrophages. The radiographic findings show bibasilar consolidation or mass-like opacities that have areas of low-attenuation on CT (Fig 18). 35 Fibrosis and architectural distortion may result with reticular opacities on HRCT.
CONCLUSION Consolidative opacities in the lung, as seen on radiographs and/or CT, can represent a diagnostic challenge. By combining the knowledge of the duration of the patient' s respiratory symptoms and the radiographic appearance, we have found that the differential can be significantly focused and can aid the clinicians in determining the etiology and further treatment.
REFERENCES
1. Webb WR, Muller NL, Naidich DP: Standardizedterms for high resolution computed tomography of the lung: A proposed glossary. J Thorac Imaging 8:167-185, 1993 2. WebbWR, Muller NL, Naidich DP: High-ResolutionCT of the Lung (ed 3), Philadelphia,PA, LippincottWilliams and Wilkins, 2001, pp 136-137 3. NaldichDP, ZerhouniEA, HutchinsGM, et al: Computed tomography of the pulmonaryparenchyma: Part 1. Distal airspace disease. J Thorac Imaging 1:39-53, 1985 4. Leung AN, Miller RR, Muller NL: Parenchymalopacification in chronic infiltrativelung diseases: CT-pathologiccorrelation. Radiology 188:209-214, 1993 5. Arakawa H, Kurihara Y, Nakajima Y: Pulmonary fat emboli syndrome:CT findingsin six patients. J Comput Assist Tomogr 24:24-29, 2000 6. Collins J, Stern EJ: Chest Radiology. The Essentials. Philadelphia,PA, LippincottWilliamsand Wilkins, 1999,pp 49 7. Ketai LH, GodwinJD: A new view of pulmonaryedema and acute respiratory distress syndrome. J Thorac Imaging 13:147-171, 1998 8. Webb WR, Muller NL, NaidichDP: High-ResolutionCT of the Lung (ed 3). Philadelphia,PA, LippincottWilliams and Wilkins, 2001, pp 415 9. Webb WR, Muller NL, Naidich DP: High-ResolutionCT of the Lung (ed 3). Philadelphia,PA, LippincottWilliams and Wilkins, 2001, pp 386 10. Collins J, Stern EJ: Chest Radiology. The Essentials. Philadelphia,PA, LippincottWilliamsand Wilkins, 1999,pp 53 11. Hommeyer SH, Godwin JD, Takasugi JE: Computed tomography of air-space disease. Radiol Clin North Am 29: 1065-1084, 1991
12. Webb WR, Muller NL, Naidich DP: High-Resolution CT of the Lung (ed 3). Philadelphia, PA, LippincottWilliams and Wilkins, 2001, pp 396 13. Webb WR, Muller NL, Naidich DP: High-Resolution CT of the Lung (ed 3). Philadelphia,PA, LippincottWilliams and Wilkins, 2001, pp 408 14. Collins J, Stern EJ: Chest Radiology. The Essentials. Philadelphia,PA, LippincottWilliamsand Wilkins, 1999,pp 51 15. Primack SL, Miller RR, Muller NL: Diffuse pulmonary hemorrhage: Clinical, pathologic, and imaging features. AJR Am J Roentgenol 164:295-300, 1995 16. Collins J, Stem EJ: Chest Radiology. The Essentials. Philadelphia, PA, Lippincott Williams and Wilkins, 1999, pp 183 17. Ikezoe J, Takashima S, Morimoto S, et al. CT appearance of acute radiation-inducedinjury in the lung. AJR Am J Roentgenol 150:765-770, 1988 18. King MA, Pope-Harman AL, et al: Acute eosinophilic pneumonia: Radiologic and clinical features. Radiology 203: 715-719, 1997 19. CheonJE, Lee KS, et al: Acute eosinophilicpneumonia: Radiographic and CT findings in six patients. AJR Am J Roentgenol 167:1195-1199, 1996 20. Wang BM, Stern EJ, Schmidt RA, et al: Diagnosing pulmonary alveolar proteinosis. Chest 111:460-466, 1997 21. Prakash U, Barham S, Carpenter H, et al: Pulmonary alveolar proteinosis: Experience with 34 cases and review. Mayo Clin Proc 62:499-518, 1987 22. PasqualJ, GomezAguinagaMA, Vidal R, et al: Alveolar proteinosis and nocardiosis: A patient treated by bronchopulmonary lavage. Postgrad Med J 65:674-677, 1989
MULTIFOCAL CONSOLIDATION
23. Gacouin A, Le Tulzo Y, Suprin E, et al: Acute respiratory failure caused by secondary alveolar proteinosis in a patient with acute myeloid leukemia: A case report. Intensive Care Med 24:265-267, 1998 24. Webb WR, Muller NL, Naidich DP: High-Resolution CT of the Lung (ed 3). Philadelphia, PA, Lippincott Williams and Wilkins, 2001, pp 390-393 25. Lee KS, Kim Y, Primack SL: Imaging of pulmonary lymphomas. AJR Am J Roentgenol 168:339-345, 1997 26. Au V, Leung AN: Radiologic manifestations of lymphoma in the thorax. AJR Am J Roentgenol 168:93-98, 1997 27. Akira M, Atagi S, Kawahara M, et al: High-resolution CT findings of diffuse bronchioloalveolar carcinoma in 38 patients. AJR Am J Roentgenol 173:1623-1629, 1999 28. Lee KS, Kim Y, Han J, et al: Bronchioloalveolar carcinoma: Clinical, histopathologic, and radiologic findings. Radiographics 17:1345-1357, 1997 29. Staples C, Kang E, Wright J, et al: Invasive pulmonary
301
aspergillosis in AIDS: Radiographic, CT, and pathologic findings. Radiology 196:409-414, 1995 30. Franquet T, Muller N, Gimenez A, et al: Semiinvasive pulmonary aspergillosis in chronic obsa-uctive pulmonary disease: Radiologic and pathologic findings in nine patients. AJR Am J Roentgenol 174:51-56, 2000 31. Cordier J. Organising pneumonia. Thorax 55:318-328, 2000 32. McAdams H, Rosado-de-Christenson M, Wehunt W, et al: The alphabet soup revisited: The chronic interstitial pneumonias in the 1990s. Radiographics 16:1009-1033, 1996 33. Collins J, Stern E: Chest Radiology: The Essentials. Philadelphia, PA, Lippincott Williams and Wilkins, 1999, pp 178-184 34. Collins J, Blankenbaker D, Stem EJ: CT patterns of bronchiolar disease: What is tree-in-bud? AJR Am J Roentgenol 171:365-370, 1998 35. Lee KS, Muller NL, Hale V, et al: Lipoid pneumonia: CT findings. J Comput Assist Tomogr 19:48-51, 1995
Copyright 2002, Elsevier Science (USA). All rights reserved.
HIS ARTICLE addresses the approach to multiple areas of consolidative opacities seen in the lung parenchyma on chest radiograph or computed tomography (CT). Consolidation is seen as areas of increased lung attenuation with obscuration of underlying pulmonary vessels.1 Air bronchograms are often present. Diseases that cause consolidation are characterized by replacement of air in the alveoli by fluid, cells, protein, tissue, or some other material (essentially water, pus, blood, cells, or protein). 2'3 Most diseases are associated with filling of alveoli but diseases that produce an extensive confluent interstitial abnormality may also result in this finding. 2'4 We, therefore, find the distinction between airspace and interstitial disease patterns to be misleading, especially because both processes are often present. Consolidation that is lobar or segmental in distribution is characteristic of bacterial pneumonia. In addition, consolidation can result from the confluence of multiple illdefined 5- to 10-mm acinar nodules, as seen with varicella pneumonia and noncardiogenic pulmonary edema owing to fat emboli. 5 There are a number of diseases that manifest with a predominantly consolidative process. A useful approach that narrows the differential considerations is to separate etiologies into 2 major groups based on the duration of the patient's presenting respiratory symptoms. Acute symptoms are
T
From the Department of Radiology, and the School of Medicine, University of Utah Health Sciences Center, Salt Lake City, UT. Address reprint requests to Kathleen A. Murray, MD, Shriners Hospital for Children, Fairfax Road at Virginia Street, Salt Lake City, UT 84103;e-mail: [email protected] Copyright 2002, Elsevier Science (USA). All rights reserved. 0887-2171/02/2304-0001535.00/0 doi: l O.1053/sult.2002.3 3979 288
defined as occurring over days to weeks, whereas chronic symptoms last weeks to months. The plain radiographic appearance combined with the clinical history is usually sufficient to limit the differential diagnosis. In some cases, high-resolution CT (HRCT) may contribute to patient management by more clearly defining accompanying abnormalities, such as lymphadenopathy, pleural effusions, ill-defined nodular opacities, or a tree-in-bud pattern. HRCT can help further delineate the extent and distribution of disease and guide further diagnostic evaluation such as bronchoscopy and/or biopsy. ACUTE SYMPTOMS
The 3 most common causes of acute consolidation are edema, pneumonia, and pulmonary hemorrhage. 6 Less-common causes include radiation pneumonitis and acute eosinophilic syndrome.
Pulmonary Edema Pulmonary edema is one of the most common causes of acute consolidation on chest radiographs. It has traditionally been classified as being either cardiogenic (hydrostatic) or noncardiogenic (increased permeability).7 Hydrostatic edema. Hydrostatic pulmonary edema is usually seen with left ventricular heart failure, resulting from elevated pressures in the pulmonary capillaries. Radiographic findings include indistinctness of blood vessel margins, peribronchial cuffing, pleura/effusions, thickening of fissures (subpleural edema), and thickening of the interlobular septa (Kerley A and B lines) (Fig 1). The cardiac silhouette is often enlarged. As hydrostatic pressures increase, alveolar fluid accumulates, resulting in the development of symmetric, ground-glass, and consolidative opacities, often within the lower lobes medially. As it progresses,
Seminars in Ultrasound, CT, and MRI, Vol 23, No 4 (August), 2002: pp 288-301
iii!iiiiii~i
Fig 1. Hydrostatic edema. (A) Posteroanterior and (B) lateral chest radiographs in a 69-year-old man with known coronary artery disease, shortness of breath, and paroxysmal nocturnal dyspnea show features of congestive heart failure and hydrostatic edema. The cardiac silhouette is enlarged, and pulmonary vasculature is engorged and indistinct. Kerley A lines (large arrow) and B lines (small arrow) are seen. The Kerley A lines radiate from the hila and are seen less commonly than Kerley B lines. The Kerley A lines are particularly prominent in this case.
290
consolidation worsens superiorly and peripherally. In our experience, the classic bat wing distribution seen centrally near the hila is uncommon. An unusual manifestation of hydrostatic edema can result from acute mitral valve regurgitation. This is well described as focal consolidation in the right upper lobe, caused by the orientation of the regurgitant jet of blood flow that is oriented toward the right superior pulmonary vein. Furthermore, cephalization of blood flow is rarely seen in the acute setting. Its presence is an excellent indication of underlying chronic pulmonary venous hypertension. 7 A clue to the diagnosis of hydrostatic edema is rapid clearing with treatment. Other causes of hydrostatic edema include volume overload owing to renal failure or aggressive fluid resuscitation, pulmonary venoocclusive disease, decreased oncotic pressure as seen with hypoalbuminemia, mitral stenosis, left ventricular aneurysm, acute myocardial infarction, and acute arrhythmia. Permeability edema. Noncardiogenic or permeability edema results from disruption of the capillary endothelium with leakage of plasma into the surrounding lung tissue. Acute respiratory distress syndrome (ARDS) is classically thought to be the prototype of permeability edema. It is now clear that permeability edema results in a spectrum of disease, with ARDS being the most severe form. 7
The barriers to the formation and spread of edema are the capillary endothelium and the alveolar epithelium. Different degrees of damage to each can account for the varying clinical and radiographic appearances of permeability edema. Diffuse alveolar damage results when the alveolar epithelium is disrupted] Permeability edema can occur without diffuse alveolar damage. Examples include edema secondary to interleukin-2 or OKT3 therapy, transfusion reactions, and in milder forms of the hantavirus pulmonary syndrome. In most of these cases, endothelial injury predominates and epithelial injury is minimal, resulting in confinement of most of the edema to the interstitium. Therefore, the radiographic appearance may resemble hydrostatic edema with vascular indistinctness, thickened bronchial walls and fissures, septal lines, and pleural effusions. Additionally, the edema and symptoms usually change rapidly. 7 ARDS is the severest form of permeability edema, in which the determining factor is the
KJELDSBERG ET AL
alveolar epithelial injury (diffuse alveolar damage). The edema in the interstitium is allowed to escape into the alveoli, thus, the interstitial abnormalities are typically not seen on the radiograph. Radiographic findings include bilateral, widespread, patchy, ill-defined ground-glass and consolidative opacities, usually without pleural effusions, septal thickening, bronchial cuffing, or subpleural thickening (Figs 2 and 3). Air bronchograms appear to be more commonly seen than with hydrostatic edema] Consolidation seen predominantly in the dependent regions is often seen. It is thought that this dependent consolidation protects the posterior lung regions from the deleterious effects of mechanical ventilation, thus, offering an explanation for the striking anterior distribution of fibrosis resulting from ARDS. 8 The patient is almost always intubated owing to severe hypoxia, and resolution of the edema is slow. ARDS can develop from a number of causes. It may be idiopathic, which has been referred to as acute interstitial pneumonia, 9 or may be owing to a number of causes. A mnemonic used at our institution for some of the more common etiologies is DRIP DEATH: Drugs (heroin, chemotherapy), Renal failure, Inhalational (smoke, toxic gases)/Idiopathic, Pancreatitis, Drowning, Emboli (fat, amniotic), ARDS (idiopathic), Trauma (neurogenic, airway obstruction, shock)/Transfusions, and Highaltitude pulmonary edema (Table 1).
Pneumonia The most common cause of a focal, acute consolidative opacity, often without significant volume loss, is bacterial pneumonia. 1° Plain radiographs in combination with clinical findings are able to diagnose most cases (Fig 4). CT can contribute by revealing that the pneumonia is more widespread, showing an obstructing central mass, showing evidence of early necrosis or cavitation, or detecting an effusion or empyema. 11 Lobar consolidation with expansion of the lobe is most consistent with bacterial pneumonia, such as pneumococcal (Streptococcal pneumoniae) or Kleb-
siella pneumoniae.l° The development of cavitation suggests Staphylococcus aureus, a gram-negative, nosocomial, or fungal source. If lymphadenopathy is present, tubercular or fungal sources must be considered. Varicella pneumonia is a viral pneumonia caused by the varicella-zoster virus and can have conflu-
MULTIFOCAL CONSOLIDATION
291
Fig 2. ARDS. Portable supine chest radiograph in a 26-year-old woman with renal failure and uremia shows an enlarged cardiac silhouette and diffuse ground-glass and consolidative opacities. Air bronchograms(arrows) are seen in the upper lobes, Typically, the opacities are dependently located (the posterior aspects of all lobes are dependent when the patient is supine), Edema actually protects these areas from the deleterious effects of mechanical ventilation.
ence of multiple ill-defined 5- to 10-ram acinar nodules, similar to the pattern seen in fat embolization syndrome (Fig 5). Aspiration pneumonia usually presents as consolidation in the dependent regions of the lung. A tree-in-bud pattern seen on HRCT supports the diagnosis of aspiration pneumonia in the appropriate clinical scenario. In our experience, this treein-bud pattern may be recognized on chest radiographs in moderate to severe cases as thick reticular opacities with associated ill-defined 3- to 4-mm nodules and airway thickening. It is less common for pneumonia to cause diffuse or extensive confluent consolidative opacities. When present, the immunocompetency of the patient should be considered. ~2 Opportunistic organisms that should be considered in this patient population include Pneumocystis carinii, tuberculosis, fungai infections (including cryptococcosis and aspergillosis), cytomegalovirus, and Nocardia asteroides. If the patient is an immunocompetent individual, viral pneumonia as well as severe overwhelming pneumoncoccal pneumonia may show extensive multifocal abnormalities.
Pulmonary Hemorrhage A variety of disorders can result in bleeding into the lung. Clinically, the patient may present with hemoptysis, dyspnea, and anemia. Radiographic features are generally not helpful in determining the cause. Radiographs and CT show patchy or diffuse ground-glass opacity, consolidation, or both. 13 Opacities tend to be more pronounced centrally, with sparing of the costophrenic angles. Rapid clearing in 2 to 3 days is expected and can be helpful in limiting the differential. 14 Interlobular septal thickening may be seen a few days after an acute episode as hemosiderin-laden macrophages accumulate in the interstitium. 13 Diffuse pulmonary hemorrhage can result from multiple diseases. Goodpasture's Syndrome is an anti-basement membrane antibody disease typically occurring in young white men. Renal disease is usually, but not always, present. 13 Wegener's granulomatosis (Fig 6) is usually seen in older men and usually presents with upper airway involvement with sinusitis, rhinitis, and otitis. The majority of patients with active disease have a positive
292
KJELDSBERG ET AL
Fig 3. ARDS. Anteroposterior chest radiograph in an 18year-old man who sustained extensive trauma several days earlier. He has multiple pelvic and long bone fractures. This pattern of multiple, confluent, ill-defined nodules resulting in diffuse consolidation occurring 48 to 72 hours after trauma is characteristic of fat embolization syndrome. Patients with fat embolization may also exhibit confusion and skin petichiae as a manifestation of multiorgan involvement.
antineutrophil cytoplasmic antibody test. 14 Cavitary nodules can also occur, Systemic lupus erythematosus (SLE) most often occurs in younger women (Fig 7). There may be coexistent pleural or pericardial effusions. Idiopathic pulmonary hemosiderosis is most commonly seen in young children and young adults, and is sometimes associated with celiac disease or immunoglobulin-A gammopathy. 13 Other causes of diffuse pulmonary hemorrhage include coagulopathies caused by thrombo-
Table 1. Causes of ARDS D R I P
Drugs (heroin, chemotherapy) Renal failure Inhalational (smoke, toxic gases) or idiopathic Pancreatitis
D E A T
Drowning Emboli (fat, amniotic) ARDS (idiopathic) Trauma (neurogenic, airway obstruction, shock) or transfusions High-altitude pulmonary edema
H
Fig 4. Lobar pneumonia. (A) Posteroanterior and (B) lateral chest radiographs show focal consolidation (arrows) in the anteromedial segment of the left lower lobe. This 33-year-old woman had acute onset of productive cough, fevers, and chills. This pattern is characteristic of community-acquired bacterial pneumonia.
cytopenia, disseminated intravascular coagulation, or thrombotic thrombocytopenic purpura) 5 When pulmonary hemorrhage is focal or multifocal rather than diffuse, the systemic diseases are less likely compared with localized disease. In focal or multifocal disease, pulmonary embolism, aspiration of blood, pulmonary contusion, bronchi-
MULTIFOCAL CONSOLIDATION
Fig 5. Varicella pneumonia. Posteroanterior chest radiograph in this 34-year-old man with hemophilia and human immunodeficiency virus shows diffuse consolidation, with ill-defined confluent nodules. The appearance is very similar to fat embolization syndrome (see Fig 3); therefore, the history is crucial to making the appropriate diagnosis.
Fig 6. Wegener's granulomatosis. Portable anteroposterior chest radiograph in the intensive care unit on this 3g-yearold man with hemoptysis and respiratory failure. Extensive regions of peripheral consolidation are seen. When peripheral and wedge-shaped, Wegener's granulomatosis consolidation can mimic thromboembolic disease. Although more common in older men, Wegener's granulomatosis can also occur in younger individuals. This patient has known disease and has had renal failure, treated with kidney transplantation.
293
Fig 7. SLE. Portable anteroposterior chest radiograph in a 27-year-old woman with sudden onset of shortness of breath and hemoptysis shows central consolidative opacities, with sparing of the costophrenic angles. In this case, a history of gross hematuria, anemia, and a markedly elevated sedimentation rate all helped direct the clinician and the radiologist to the diagnosis of SLE. Note the enlarged cardiac silhouette, indicating a pericardial effusion, which is also seen in SLE.
ectasis, tumors, or localized infections should be considered. 13'15 Pulmonary embolism with or without infarction can be seen as a pleural-based wedge-shaped opacity (Fig 8). The term Hampton's hump was initially described as a sign of pulmonary infarction seen predominantly in the lower lung zones. Air bronchograms are rarely present. As infarctions resolve, the opacity clears from the periphery first like a melting ice cube. 16 Pulmonary embolism mimics include Wegener's granulomatosis, invasive aspergillosis, and cocaine-induced pulmonary vasoconstriction (Fig 9). Radiation pneumonitis. Radiation pneumonitis is a well-known complication of radiation therapy to the chest. It is variably seen at doses between 30 and 40 Gy, and is almost always seen at doses over 40 Gy. Depending on the dose, radiographic changes can be seen as early as 1 week but usually do not occur until 6 to 8 weeks after therapy. CT shows various patterns, ranging from homogeneous to patchy consolidations. The key to recognizing this is noting the nonanatomic delineation of disease (which defines the radiation port). CT is able to detect these parenchymal abnormalities earlier than radiographs. These areas often show improvement with steroid therapy, x7
294
KJELDSBERG ET AL
to l0 days with extensive diffuse consolidations on the radiograph. 1~'19 Release of eosinophilic granules during an inflammatory response results in acute lung injury. The reported common radiographic findings in acute eosinophilic pneumonia resemble pulmonary edema with areas of ground-glass and consolidative opacities, interlobular septal thickening, and pleural effusions (Fig 10). Unlike chronic eosinophilic pneumonia, the opacities have no peripheral
Fig 8. Thromboembolic disease. (A) Anteroposterior chest radiograph in a 37-year-old woman with acute shortness of breath shows volume loss and opacity in the right lower lobe, This is a large peripheral wedge-shaped opacity, (B) CT angiogram shows a large embolus (arrow) in the descending right pulmonary artery,
Acute eosinophilic pneumonia. Also known as Loeffler's Syndrome, acute eosinophilic pneumonia is an idiopathic disease that can result in acute respiratory failure. Elevated levels of eosinophils usually are obtained in bronchoalveolar lavage (BAL) fluid. Patients present over 1 to 5 days with an acute febrile illness, myalgias, pleuritic chest pain, and profound hypoxemia. There is no identifiable inciting agent recovered. BAL is essential in the diagnosis because, unlike chronic eosinophilic pneumonia, peripheral blood eosinophilia is rare. The diagnosis should be considered in patients with progressive clinical deterioration over 5
Fig 9. Pulmonary hemorrhage secondary to cocaine, (A) Anteroposterior chest radiograph in a 50-year-old man with shortness of breath and hemoptysis shows peripheral wedgeshaped consolidation and patchy ill-defined opacities. The cardiac size is large. Note the similarities of this case with Wegener's granulomatosis (see Fig 6). The patient admits to occasional use of cocaine, (B) CT image shows multiple peripheral wedge opacities and the patchy areas of increased attenuation typical of alveolar hemorrhage. There was no CT evidence of thromboembolic disease,
MULTIFOCAL CONSOLIDATION
295
Neoplasm, Granulomatous processes, Inflammatory diseases, and Old [ANGIO]) to help recall the diseases that characteristically present with chronic consolidation (Table 2). Bronchopulmonary foregut malformation (sequestration) may also be considered in younger patients with focal consolidation. Alveolar Proteinosis
Figure 10. Eosinophilic pneumonia (acute). (A) Anteroposterior chest radiograph in a 26-year-old man with acute symptoms over 5 days shows symmetric, diffuse, ground-glass and consolidative opacities, with a somewhat central distribution. Bronchoscopy revealed almost all eosinophils.
predominance. Mediastinal lymphadenopathy, pericardial effusion, and cardiomegaly are not seen. Radiographic findings and symptoms improve rapidly after administration of intravenous corticosteroids.18'19 CHRONIC SYMPTOMS
Chronic consolidative opacities are defined as being present for weeks to months. Patients often present with clinical symptoms that are more insidious in onset, such as chronic cough, shortness of breath, malaise, or dyspnea on exertion. Because the symptoms persist or worsen, the patient usually has had recurrent visits to their physician. The severity of the disease rarely warrants hospitalization; therefore, it is the outpatient facilities and clinicians that usually encounter these more unusual diseases. A useful generalization is chronic or recurrent symptoms should increase the pretest probability of underlying lung or pulmonary vascular disease. When the radiographic abnormality is predominately consolidative in appearance, then the more unusual diseases should be considered. The common diseases to present as a chronic consolidative process will be reviewed. It is important to realize that many will require tissue sampling, but clues to help reduce the differential among the multiple diseases are discussed. As with many differential diagnoses in radiology, we use a pneumonic (Alveolar proteinosis,
Pulmonary alveolar proteinosis (PAP) is characterized by proteinaceous material filling the alveoli. This material is lipid-rich and periodic acidSchiff positive. Most patients who are affected are between 20 and 50 years of age, 2° with men outnumbering women by up to 4:1. Initial presenting symptoms include shortness of breath with activity and/or a mild nonproductive cough. Low-grade fever may be present with the disease, though usually indicates superinfection.2°'2I N. asteroides has been traditionally cited as an associated infection. 22 The diagnosis is usually made with transbronchial biopsy and BAL, in which milky fluid is obtained. BAL is also considered therapeutic, with some patients showing no recurrence after lavage. Repeated BAL may be needed for those who recur, though up to 38% did not recur after the first therapeutic lavage in a Mayo Clinic series. 21 PAP can be seen in the primary or idiopathic form without associated disease process, or in the secondary form. Secondary PAP can the seen with pulmonary infection, hematologic malignancies, or exposure to inhaled chemicals. 2°'21 Although symptoms are usually chronic and insidious in onset, secondary PAP has recently been reported to cause acute respiratory failure, especially in patients with hematologic malignancy. 23 Radiographic findings of PAP include consolidative or ground-glass opacities. The typical radiograph shows bilateral patchy consolidation, more concentrated in the lung bases and perihilar regions. 2°'24 HRCT shows patchy consolidative opacities with sharp delineation from the surround-
Table 2. Causes of Chronic Lung Consolidation
A N G I O
Alveolar proteinosis Neoplasm Granulomatous processes Inflammatory diseases Old (occurring in the elderly: aspiration, lipoid pneumonia)
296
KJELDSBERG ET AL
nary symptoms, is characteristic of PAP. The crazy-paving pattern is described in a number of acute, subacute, and chronic diseases, but is essentially always present in PAP though variably present in other processes. 2
Neoplasms
Fig 11. Pulmonary alveolar proteinosis. (A) Posteroanterior radiograph in a 30-year-old woman with dyspnea and chronic cough for 2 months shows bilateral areas of groundglass and consolidative opacity. In alveolar proteinosis, these findings typically are worse in the perihilar regions and lung bases. Often the chest radiograph shows much more opacity than would be expected for the concomitant mild symptoms. (B) HRCT in the same patient shows the patchy geographic increase in density that is seen in this disease. The interlobular septa are thickened, giving the crazy-paving appearance of a cobblestone street typically associated with alveolar proteinosis. Although this pattern can be seen in other diseases, the clinical signs and symptoms help lead the radiologist to the correct diagnosis.
ing normal lung tissue, giving a typical geographic appearance. The intra- and interlobular septa are thickened in a polygonal pattern, also described as crazy-paving (Fig 11). 20,24 This pattern, when seen in the patient with chronic and often mild pulmo-
Lymphoma and bronchoalveolar carcinoma are 2 neoplasms that may present as chronic consolidations. Both are similar in appearance to the typical community-acquired pneumonia, but do not resolve with antibiotic treatment and have a more insidious onset than most types of pneumonia. Lymphoma may be primary or secondary, though secondary spread from extrathoracic lymphoma is more common. Radiographically, lymphoma shows air bronchograms with multiple or solitary nodules and/or areas of consolidation (Fig 12). 25,26 Pleural effusions or lymphadenopathy may be present as well, with adenopathy more common in Hodgkin's lymphoma. 26 A reticular pattern similar to lymphangitic carcinomatosis may also be seen on radiographs and HRCT. 25'26 Bronchoalveolar carcinoma appears similar to lymphoma, with air bronchograms, patchy areas of consolidation, or nodular opacities (Fig 13). 27,28 Interlobular septal thickening (crazy-paving) may be present, though is uncommon. 27 Ground-glass opacities may result from lepidic (butterfly-like) spread of tumor, with diffuse lung involvement likely secondary to hematogenous spread. 27'28 Postobstructive consolidative pattern from a primary lung tumor can result in a drowned lung appearance. There may be volume loss distal to the tumor. However, the distal lung may be expanded instead, and fluid-filled bronchi may serve as a clue to a more central obstruction.
Granulomatous Etiologies This group of infections tends to be more insidious in onset, causing more chronic consolidations than the typical community-acquired pneumonia. Aspergillosis, tuberculosis, and other fungal infections such as coccidiomycosis may present with consolidation. Invasive aspergillosis is seen most frequently in severely immunocompromised hosts, for example, in patients with neutropenia, corticosteroid therapy, and acquired immune deficiency syndrome. 29 The most common radiographic findings are cavitary upper lobe disease,
MULTIFOCAL CONSOLIDATION
297
Fig 13. Bronchoalveolar carcinoma. Posteroanterior radiograph in this immunocompetent, 46-year-old man with several months of nonproductive cough shows right upper lobe consolidation, This is radiographically indistinguishable from pneumonia, but the history is not consistent with this diagnosis. This pattern, in conjunction with chronic cough, is consistent with tumor, including bronchoalveolar carcinoma and lymphoma. Patients with bronchoalveolar carcinoma may produce copious amounts of clear sputum.
Fig 12. Lymphoma. (A) Posteroanterior and (B) lateral radiographs of a 48-year-old man show a large consolidative opacity in the left upper lobe as well as hilar and mediastinal adenopathy. This patient had recurrent non-Hodgkin's lymphoma. The left upper lobe resembles extensive pneumonia (which sometimes coexists with parenchymal tumor), but the bilateral adenopathy should be a clue directing the radiologist to an underlying lymphoma.
focal consolidation, or bilateral patchy consolidation (Fig 14). 29 The semi-invasive form of Aspergillosis strikes patients with underlying medical histories of chronic illness, advanced age, corticosteroid use, or chronic obstructive pulmonary disease. 3° The symptoms are chronic, with weakness, cough, and
Fig 14. Primary tuberculosis. Posteroanterior radiograph shows left upper lobe consolidation in this 16-year-old patient. The mediastinum is enlarged from adenopathy. The combination of a slow-to-resolve pneumonia and adenopathy is highly suggestive of primary tuberculosis or other fungal infection.
298
KJELDSBERG ET AL
Fig 15. Alveolar sarcoid. This 24-year-old man presented with a chronic cough of 6 months duration. (A) Posteroanterior radiograph shows patchy, ill-defined opacities bilaterally. Mediastinal and hilar adenopathy are present. (B) HRCT in the same patient shows nodular, consolidative opacities with air bronchograms. Subsequent open biopsy procedure revealed alveolar sarcoid.
fever. This form also presents with mainly upper lobe consolidation, often with cavitation and possibly with nodular opacities. Histology shows Aspergillus organisms, intra-alveolar hemorrhage, active inflammation, and tissue necrosis in the areas of consolidation. The radiographic findings can be indistinguishable from tuberculosis, though tuberculosis is usually associated with lymphadenopathy as well. Alveolar sarcoid is the noninfectious granulomatous etiology that should be considered (Fig 15). As with other forms of sarcoid, adenopathy is often (but not always) present. 33
Fig 16. BOOP. (A) Portable anteroposterior radiograph in a 68-year-old woman with respiratory distress shows bilateral lower lobe consolidation. A chest tube has been placed on the right after open biopsy. (B) HRCT in this patient shows multiple small nodules and ground-glass opacities in the lung bases. The open-lung biopsy showed BOOP. (C) Two months later, HRCT shows marked progression of disease.
MULTIFOCAL CONSOLIDATION
299
dations and normal lung volumes, often with a patchy peripheral distribution (Fig 16). 31"32 Ground-glass opacities may be present and air bronchograms can be seen in the consolidated areas. Lymphocytes and neutrophils are the predominant cellular components on BAL. With these radiographic findings, the differential diagnosis includes BOOP, eosinophilic pneumonia, lymphoma, and bronchoalveolar carcinoma. Clinical history and laboratory results may differentiate eosinophilic pneumonia from BOOP, though BAL or biopsy may be required. Clinically, chronic eosinophilic pneumonia is associated with a wide variety of causative agents, including neoplasms, asthma, allergic disorders, collagen vascular disorders, sarcoidosis, and parasitesY As with BOOP, fever, cough, and malaise are the presenting symptoms. Eosinophil levels will often be elevated in the peripheral blood smear. Radiographic findings include chronic peripheral consolidations that clear rapidly with steroid therapy (Fig 17). "Old"
This is to remind us of the diseases that affect the elderly population, including chronic aspiration
Fig 17. Chronic eosinophilic pneumonia. (A) Posteroanteriot radiograph in a 44-year-old woman with a progressive cough shows bilateral peripheral, midlung peripheral consolidative opacities, consistent with eosinophilic pneumonia. The striking peripheral location of poorly defined opacities should suggest this entity, which will respond to steroids. The peripheral blood smear shows eosinophilia. (B) CT image of a different patient with eosinophilic pneumonia also shows the peripheral consolidation,
Inflammatory Etiologies Bronchiolitis obliterans with organizing pneumonia (BOOP) is included in this category. Patients present with subacute onset of fever, cough, malaise. 31 It is associated with multiple inciting factors, including rheumatoid arthritis, bone marrow grafting, or as a reaction to various drugs. BOOP or organizing pneumonia manifests with multifocal areas of immature fibroblasts in the lung parenchyma, and can be seen after an infectious pneumonia has been treated. 32 Radiographic features include bilateral consoli-
Fig 18. Lipoid pneumonia. Posteroanterior radiograph shows extensive bibasilar areas of consolidation. There is no adenopathy. A mild nonproductive cough was present. The minimal symptoms, with fairly marked dependent opacities, are the clues to this diagnosis. If performed, CT can document the low density of the aspirated lipid material.
300
KJELDSBERG ET AL
and lipoid pneumonia. Both present with chronic consolidative opacities. Chronic aspiration has a bibasilar and dependant lobe predominance of consolidation. The distribution reflects the pattern of deposition in the upright patient, with material more often settling in the right middle lobe or right lower lobe because of the straighter path of the bronchus. Gravity will also cause settling of material in the left lower lobe bronchus, In the supine patient, the consolidation may be in the superior segments of the lower lobes because of the dependent position of the bronchi leading to the superior segments. On HRCT, illdefined centrilobular opacities may be seen, with filling of the terminal bronchioles with aspirated material (tree-in-bud).34 In the chronic setting, bronchiectasis, fibrosis, and architectural distortion may result from repeated aspiration and/or infection. In lipoid p n e u m o n i a , the radiographic pattern of i n v o l v e m e n t is similar to chronic aspiration. A history of chronic aspiration or inhalation of a
large quantity of animal, vegetable, or petrol e u m - b a s e d oils or fats may be elicited from the patient after careful questioning. Lung inflammation results from the hydrolyzed free fatty acids, creating a foreign-body reaction. B A L may reveal lipid-laden macrophages. The radiographic findings show bibasilar consolidation or mass-like opacities that have areas of low-attenuation on CT (Fig 18). 35 Fibrosis and architectural distortion may result with reticular opacities on HRCT.
CONCLUSION Consolidative opacities in the lung, as seen on radiographs and/or CT, can represent a diagnostic challenge. By combining the knowledge of the duration of the patient' s respiratory symptoms and the radiographic appearance, we have found that the differential can be significantly focused and can aid the clinicians in determining the etiology and further treatment.
REFERENCES
1. Webb WR, Muller NL, Naidich DP: Standardizedterms for high resolution computed tomography of the lung: A proposed glossary. J Thorac Imaging 8:167-185, 1993 2. WebbWR, Muller NL, Naidich DP: High-ResolutionCT of the Lung (ed 3), Philadelphia,PA, LippincottWilliams and Wilkins, 2001, pp 136-137 3. NaldichDP, ZerhouniEA, HutchinsGM, et al: Computed tomography of the pulmonaryparenchyma: Part 1. Distal airspace disease. J Thorac Imaging 1:39-53, 1985 4. Leung AN, Miller RR, Muller NL: Parenchymalopacification in chronic infiltrativelung diseases: CT-pathologiccorrelation. Radiology 188:209-214, 1993 5. Arakawa H, Kurihara Y, Nakajima Y: Pulmonary fat emboli syndrome:CT findingsin six patients. J Comput Assist Tomogr 24:24-29, 2000 6. Collins J, Stern EJ: Chest Radiology. The Essentials. Philadelphia,PA, LippincottWilliamsand Wilkins, 1999,pp 49 7. Ketai LH, GodwinJD: A new view of pulmonaryedema and acute respiratory distress syndrome. J Thorac Imaging 13:147-171, 1998 8. Webb WR, Muller NL, NaidichDP: High-ResolutionCT of the Lung (ed 3). Philadelphia,PA, LippincottWilliams and Wilkins, 2001, pp 415 9. Webb WR, Muller NL, Naidich DP: High-ResolutionCT of the Lung (ed 3). Philadelphia,PA, LippincottWilliams and Wilkins, 2001, pp 386 10. Collins J, Stern EJ: Chest Radiology. The Essentials. Philadelphia,PA, LippincottWilliamsand Wilkins, 1999,pp 53 11. Hommeyer SH, Godwin JD, Takasugi JE: Computed tomography of air-space disease. Radiol Clin North Am 29: 1065-1084, 1991
12. Webb WR, Muller NL, Naidich DP: High-Resolution CT of the Lung (ed 3). Philadelphia, PA, LippincottWilliams and Wilkins, 2001, pp 396 13. Webb WR, Muller NL, Naidich DP: High-Resolution CT of the Lung (ed 3). Philadelphia,PA, LippincottWilliams and Wilkins, 2001, pp 408 14. Collins J, Stern EJ: Chest Radiology. The Essentials. Philadelphia,PA, LippincottWilliamsand Wilkins, 1999,pp 51 15. Primack SL, Miller RR, Muller NL: Diffuse pulmonary hemorrhage: Clinical, pathologic, and imaging features. AJR Am J Roentgenol 164:295-300, 1995 16. Collins J, Stem EJ: Chest Radiology. The Essentials. Philadelphia, PA, Lippincott Williams and Wilkins, 1999, pp 183 17. Ikezoe J, Takashima S, Morimoto S, et al. CT appearance of acute radiation-inducedinjury in the lung. AJR Am J Roentgenol 150:765-770, 1988 18. King MA, Pope-Harman AL, et al: Acute eosinophilic pneumonia: Radiologic and clinical features. Radiology 203: 715-719, 1997 19. CheonJE, Lee KS, et al: Acute eosinophilicpneumonia: Radiographic and CT findings in six patients. AJR Am J Roentgenol 167:1195-1199, 1996 20. Wang BM, Stern EJ, Schmidt RA, et al: Diagnosing pulmonary alveolar proteinosis. Chest 111:460-466, 1997 21. Prakash U, Barham S, Carpenter H, et al: Pulmonary alveolar proteinosis: Experience with 34 cases and review. Mayo Clin Proc 62:499-518, 1987 22. PasqualJ, GomezAguinagaMA, Vidal R, et al: Alveolar proteinosis and nocardiosis: A patient treated by bronchopulmonary lavage. Postgrad Med J 65:674-677, 1989
MULTIFOCAL CONSOLIDATION
23. Gacouin A, Le Tulzo Y, Suprin E, et al: Acute respiratory failure caused by secondary alveolar proteinosis in a patient with acute myeloid leukemia: A case report. Intensive Care Med 24:265-267, 1998 24. Webb WR, Muller NL, Naidich DP: High-Resolution CT of the Lung (ed 3). Philadelphia, PA, Lippincott Williams and Wilkins, 2001, pp 390-393 25. Lee KS, Kim Y, Primack SL: Imaging of pulmonary lymphomas. AJR Am J Roentgenol 168:339-345, 1997 26. Au V, Leung AN: Radiologic manifestations of lymphoma in the thorax. AJR Am J Roentgenol 168:93-98, 1997 27. Akira M, Atagi S, Kawahara M, et al: High-resolution CT findings of diffuse bronchioloalveolar carcinoma in 38 patients. AJR Am J Roentgenol 173:1623-1629, 1999 28. Lee KS, Kim Y, Han J, et al: Bronchioloalveolar carcinoma: Clinical, histopathologic, and radiologic findings. Radiographics 17:1345-1357, 1997 29. Staples C, Kang E, Wright J, et al: Invasive pulmonary
301
aspergillosis in AIDS: Radiographic, CT, and pathologic findings. Radiology 196:409-414, 1995 30. Franquet T, Muller N, Gimenez A, et al: Semiinvasive pulmonary aspergillosis in chronic obsa-uctive pulmonary disease: Radiologic and pathologic findings in nine patients. AJR Am J Roentgenol 174:51-56, 2000 31. Cordier J. Organising pneumonia. Thorax 55:318-328, 2000 32. McAdams H, Rosado-de-Christenson M, Wehunt W, et al: The alphabet soup revisited: The chronic interstitial pneumonias in the 1990s. Radiographics 16:1009-1033, 1996 33. Collins J, Stern E: Chest Radiology: The Essentials. Philadelphia, PA, Lippincott Williams and Wilkins, 1999, pp 178-184 34. Collins J, Blankenbaker D, Stem EJ: CT patterns of bronchiolar disease: What is tree-in-bud? AJR Am J Roentgenol 171:365-370, 1998 35. Lee KS, Muller NL, Hale V, et al: Lipoid pneumonia: CT findings. J Comput Assist Tomogr 19:48-51, 1995