The Core Curriculum: Cardiopulmonary Imaging, 1st Edition (2004)

Chapter 14. Diffuse Lung Disease

Imaging has a number of important goals in the patient with diffuse lung disease:

1. Differential diagnosis;

2. Specific diagnosis, if possible;

3. Delineation of extent of disease—may influence choice or locus of therapy, such as in outpatient pneumonia, and may allow subsequent evaluation of response to therapy;

4. Location of disease—may be helpful if biopsy becomes necessary for diagnosis;

5. Demonstration of associated abnormalities (such as in the mediastinum and upper abdomen)

The major diagnostic imaging tools that are generally applied to patients with diffuse lung disease are the chest radiograph (CXR) and chest high resolution computed tomography (HRCT). This chapter focuses on patterns of abnormality using these imaging tools, diagnosis and differential diagnosis (including mnemonics), and the advantages and disadvantages of CXR and HRCT. The radiographic part of this chapter is largely the work of Barry Gross, who as a disciple of Benjamin Felson is more than well qualified for this. The discussion that follows echoes true to the teaching “at the alternator” and comes from teaching conferences for which he has been applauded by his trainees. The second part of this chapter on HRCT focuses on the specific disease processes and patterns of abnormality as they relate to HRCT interpretation.

Chest Radiograph and Pattern Recognition of Diffuse Lung Disease

There has been a great deal of concern over the past few years about plagiarism in academic circles, especially among historians. I am hoping to dance around that subject by telling everyone in no uncertain terms that everything I know about pattern recognition I learned from Ben Felson. It is, of course, far less than he knew about it. Still, this is the best new material you can get from Ben and me in the twenty-first century.

As I was taught, I do not discuss alveolar (or airspace) and interstitial diseases; I simply discuss CXR patterns of abnormality. There is an interesting overlap of diseases that produce given CXR patterns, some alveolar, some interstitial, and many mixed in anatomic distribution.

Still, the goal of using a CXR is to generate an appropriate differential diagnosis, and this we can often do. Let us consider various patterns of diffuse lung disease, considering how to recognize the pattern and then how to generate a differential diagnosis.

Table 14.1: Chest Radiographic Findings of Alveolar Disease

Air bronchograms (Fig. 14.1) (and the smaller air alveolograms)
Ill-defined or fuzzy margins
Characteristic distribution
   Focal alveolar disease respects anatomic barriers (lobar or segmental distribution)
   Diffuse alveolar disease (“butterfly” or “batwing” appearance; reverse batwing)
Changes rapidly
Coalescence—when two adjacent areas of alveolar disease approach each other, they tend to blend together
Alveolar nodules—relatively large (1 cm or so), ill-defined nodules with a tendency to coalesce (Fig. 14.3)

Alveolar Disease

The radiographic hallmarks of alveolar disease are listed in Table 14.1. They include air bronchograms and ill-defined borders. Structures in the lungs are usually well outlined because of air in the alveoli; when the alveoli are filled with abnormality, there is nothing left to provide sharp margination. Alveolar disease may also have a characteristic distribution. For example, focal alveolar disease generally respects the anatomic barriers in the lungs, such as the pleural fissures, therefore demonstrating a lobar or segmental distribution (Fig. 14.1). Other characteristic distributions of more diffuse disease include the “butterfly” or “batwing” appearance (Fig. 14.2), predominantly occupying the central perihilar regions, typical of pulmonary edema, and a reverse batwing appearance of eosinophilic pneumonia. Areas of alveolar disease often coalesce together to form larger areas of alveolar disease (Fig. 14.3). Temporally speaking, alveolar disease processes often change quickly from day to day or even hour to hour.

Air bronchograms and ill-defined edges are the hallmark of alveolar disease.

Figure 14.1 Airspace disease in pneumonia, demonstrating air bronchograms and lobar distribution. Posteroanterior chest radiograph reveals branching lucencies (arrows) surrounded by right upper lobe airspace disease. Note that disease stops abruptly at its caudal margin, where the minor fissure resides.

Figure 14.2 Diffuse airspace disease in a “butterfly” distribution, a result of pulmonary hemorrhage in chronic renal failure. Peripheral margins of abnormality are poorly defined.

When alveolar disease is present, the key diagnostic question to ask is whether it is acute or chronic. The answer to that question may be supplied by history; a patient may be able to tell you that he or she was fine until yesterday (acute) or has been symptomatic for 4 months (chronic). Furthermore, a patient who is seriously ill (e.g., an intensive care unit patient) virtually always has acute disease; an asymptomatic patient with significant CXR evidence of alveolar disease usually has chronic abnormality. Old radiographs are another avenue for determining acuteness or chronicity. However, they are sometimes misleading (Fig. 14.4).

Establishing whether alveolar disease is acute or chronic changes the differential diagnosis.

Acute alveolar disease has an easy differential diagnosis, as listed in Table 14.2. It is blood or pus or water. Some radiologists like to add cells so they can include adult respiratory distress syndrome in the differential diagnosis; because I think of adult respiratory distress syndrome along the lines of noncardiogenic pulmonary edema, I get to the same end point by a different route. Cells from lymphoma or bronchoalveolar cell carcinoma also fall under that category. Blood or pus or water means that we should consider pulmonary hemorrhage, pneumonia, and edema. Pulmonary hemorrhage is a relatively uncommon cause and is often (although not always) associated with hemoptysis or anemia. Practically speaking, acute alveolar disease is usually pneumonia or pulmonary edema. Finally, some would add a category for protein to cover diseases such as alveolar proteinosis or silicoproteinosis.

Figure 14.3 Alveolar nodules caused by bronchoalveolar carcinoma, best visualized in the right upper lobe. Nodules become confluent in the right mid-lung, and there are air bronchograms at the cephalad margin of confluent abnormality.

Figure 14.4 Misleading assessment of disease chronicity via old films. A. Posteroanterior chest radiograph 12-12: widespread parenchymal abnormality with confluent airspace disease in the right lower lung. B. Posteroanterior chest radiograph 1-18, 37 days after A: even more airspace disease, seemingly chronic. Clinically, disease had resolved between A and B, and each episode was thought to represent an acute drug reaction to administered antibiotics. After cessation of antibiotic therapy, the chest radiograph was normal on 1-20.

It used to be that pneumonia was relatively focal most of the time, and edema was usually diffuse. In the era of acquired immunodeficiency syndrome (Chapter 6), pneumonia can also be diffuse. Edema is often a result of congestive heart failure, which may produce associated cardiomegaly, but there are a number of causes of noncardiogenic edema (Table 10.11) (Fig. 14.5). Furthermore, edema may have unusual distributions (Table 10.12); it may be unilateral (Fig. 14.6) in the upper lobes (with pulmonary hypertension caused by chronic pulmonary emboli) or irregularly irregular (especially in chronic obstructive pulmonary disease). The bottom line is I make my best guess, but I leave it to the clinician caring for the patient to apply my radiographic input to the rest of the available clinical data and thereby to come up with the best diagnosis.

As for chronic alveolar disease, allow me to introduce you to the first of my mnemonics, as listed in Table 14.3. A few words about using mnemonics are in order. I do not want someone to regurgitate such a list at me, demonstrating a complete inability to think and to synthesize information. I want this to be a safety net that allows you to remember the key entities to consider with a given pattern. As you run down the checklist mentally, you should be considering the applicability of each diagnosis to the patient and the pattern at hand. Is the patient a 70-year-old woman? Alveolar proteinosis is generally seen in men from ages 20 to 50, but sarcoidosis is sufficiently widely distributed in the population that almost any age and either gender is perfectly compatible. Is the disease predominantly basilar? That is good for lipoid pneumonia (Fig. 14.7) and desquamative interstitial pneumonitis (DIP), whereas tuberculosis (TB) and fungus are often in the upper lobes, especially with reactivation of previously dormant disease. Are there associated lymph nodes or pleural effusions? If so, lymphoma is a good diagnosis; if not, bronchoalveolar cell carcinoma is a much better bet.

Table 14.2: Differential Diagnosis of Acute Alveolar Disease (“Blood, Pus, Water, Cells, Protein”)

Blood: pulmonary hemorrhage
Plus: pneumonia
Water: edema (cardiogenic and non cardiogenic)
Cells: bronchoalveolar cell carcinoma, lymphoma
Protein: alveolar proteinosis

Figure 14.5 Neurogenic pulmonary edema. The patient was found unconscious.

A few more words about mnemonics come to mind. DIP is pretty uncommon; it is really there because “Dallas” is better known than “Allas.” When I have visited other programs I have been told about other mnemonics (as a way to include eosinophilic pneumonia, for instance; I will have more to say about that diagnosis later in this chapter). The best mnemonic is the one you can remember. If you want to include more diagnoses on your checklist, suit yourself. My goal is to include the most common diagnoses, the ones I really do not want to forget. If the answer is not on my list of common entities, I can always consult Gamuts in Radiology (1) for more ideas. A variant mnemonic was “STAPLE” for chronic alveolar disease, which some of our residents in the 1980s learned at the Armed Forces Institute of Pathology (sarcoid, TB/fungus, alveolar cell carcinoma, proteinosis, lymphoma, eosinophilic pneumonia, I believe). To the “TB, fungus, Dallas” mnemonic, one of our residents added “Wins Big” for Wegener granulomatosis and bronchiolitis obliterans organizing pneumonia (more correctly now known as cryptogenic organizing pneumonia [COP]).

Mnemonics are only helpful if you can remember them.

Figure 14.6 Postoperative pulmonary vein thrombosis causing unilateral left pulmonary edema.

Table 14.3: Mnemonic for the Differential Diagnosis of Chronic Alveolar Disease (“TB, Fungus, Dallas”)

TB, Fungus
Desquamative interstitial pneumonitis
Alveolar cell carcinoma
Lymphoma
Lipoid pneumonia
Alveolar proteinosis
Sarcoidosis

TB, tuberculosis.

Figure 14.7 Lipoid pneumonia, particularly involving right lower lung. Computed tomography demonstrates fat attenuation filling the alveoli (F). There is an associated M. fortuitum empyema (E).

Miliary Nodules

Turning to the patterns generally thought of as “interstitial,” we start with miliary nodules. They are small nodules (under 5 mm in size) that are very uniform in size and sharply defined. Even when they are extremely numerous they do not tend to become confluent. As I often tell residents, the result is the sense that with a pair of tweezers and a lot of patience, you could pick nodules off the radiograph for hours on end. The mnemonic for miliary lung disease is listed in Table 14.4.

Most tumors that metastasize to the lungs do so a little at a time—one metastasis in January, three in February, two in April, five in May—so that the radiographic picture is nodules varying in size. At the time of detection it would be unusual to have a large number of lesions all under 5 mm in size. The exception would be a very vascular primary neoplasm that could release a shower of metastases all at once. Miliary metastases are mainly seen with thyroid carcinomas; renal cell carcinoma is the next most common source (Fig. 14.8). However, I like to teach that in a given patient, the most likely primary neoplasm to produce a given finding is that patient’s neoplasm. Miliary nodules in a patient with duodenal leiomyosarcoma could indicate opportunistic infection, but if they prove to be malignant, they will probably be metastatic duodenal leiomyosarcoma (Fig. 14.9).

Table 14.4: Mnemonic for the Differential Diagnosis of Miliary Lung Disease (“TB, Fungus, SHRIMP”)

TB, Fungus
Sarcoid
Histiocytosis X (eosinophilic granuloma)
Rheumatoid lung
Idiopathic pulmonary fibrosis (usual interstitial pneumonitis)
Metastases
Pneumoconiosis (especially silicosis)

TB, tuberculosis.

Miliary nodules are most commonly due to infection or metastases.

Usual interstitial pneumonitis (UIP) is on the list not because it tends to cause miliary nodules, but because with diffuse lung disease it is sometimes difficult to decide if the abnormality is the opaque areas (miliary nodules) or the lucent zones in between (honeycombing, see below). On HRCT, which provides better anatomic resolution, UIP is definitely not miliary. Small miliary nodules may also be seen in secondary hemosiderosis due to longstanding mitral valvular disease.

Calcified miliary nodules are a special category. They usually result from histoplasmosis or chickenpox pneumonia. Less commonly, they are seen with silicosis and hemosiderosis. At the far end of the spectrum is alveolar microlithiasis (Fig. 14.10), where tiny calcifications become so numerous they may simulate very opaque alveolar disease; microlithiasis occurs in families, although the inheritance pattern is difficult to discern. Affected patients are often surprisingly asymptomatic.

Figure 14.8 Miliary metastases. A. Thyroid carcinoma. B. Renal cell carcinoma.

Honeycombing

This is a pattern of clustered cystic spaces, ranging from 1 to 10 mm in size. Honeycombing tends to occur at the periphery of the lungs, although that may not be easy to appreciate with the CXR. It should also be noted that diseases that do not result in honeycombing at HRCT may nevertheless have a CXR appearance that looks like honeycombing (e.g., lymphangiomyomatosis, with cysts rather than honeycombing at HRCT). The mnemonic for honeycombing is given in Table 14.5. In deference to me, some of our former residents used to make this HIPSARDS, adding amyloidosis (I was previously obsessed with that disease); because it almost never causes honeycombing, and I am no longer obsessed with amyloidosis, I do not prefer that version.

Figure 14.9 Unusual miliary metastases. Close-ups of (A) right and (B) left lungs demonstrate fine miliary nodules in a patient with duodenal leiomyosarcoma, subsequently proven to be metastases.

Figure 14.10 Alveolar microlithiasis. Innumerable extremely opaque nodules, resulting in markedly increased opacity of the lungs. (Courtesy of Dr. Michael Streiter, Huntington, NY.)

As previously mentioned, differential diagnosis requires more than a simple recollection of the applicable mnemonic. Disease distribution can be a very helpful piece of ancillary information. A quick glance at a lateral radiograph will convince you that the lungs are somewhat triangular; they are much larger at the bases than at the apices. As a result, disease that is truly uniformly distributed from apices to bases will look somewhat worse at the bases on the CXR. However, some diseases are virtually limited to the lung bases, whereas others will more prominently affect the upper lungs. Examples of upper lung diseases are listed in Table 14.6 and include TB, fungus, sarcoid, ankylosing spondylitis, primary adenocarcinoma of lung, typical emphysema, respiratory bronchiolitis (RB), eosinophilic granuloma (the last four associated with cigarette smoking), and silicosis (and most other inhalational diseases). Lower lung diseases are listed in Table 14.7 and include anything related to blood flow (such as metastases, pulmonary emboli, and most miliary nodules), collagen vascular diseases other than ankylosing spondylitis (RDS in the listed mnemonic), aspiration and lipoid pneumonia, asbestosis, UIP, and emphysema secondary to α1-antitrypsin deficiency. Please note that this list includes a number of conditions that do not cause honeycombing. Still, honeycombing with upper lung predominance usually boils down to Langerhans cell histiocytosis (a.k.a. eosinophilic granuloma), sarcoidosis, or silicosis (Fig. 14.11); honeycombing with lower lung predominance is often collagen vascular disease, UIP, or asbestosis (Fig. 14.12).

Table 14.5: Mnemonic for the Differential Diagnosis of Honeycombing (“HIPS RDS”)

Histiocytosis X (eosinophilic granuloma)
Idiopathic pulmonary fibrosis or Iatrogenic (drug-induced lung disease)
Pneumoconiosis
Sarcoidosis
Rheumatoid lung
Dermatomyositis
Scleroderma

In my experience most drug-induced lung disease is diffuse or at least not lower lung predominant, although amiodarone-induced lung toxicity tends to be basilar. This sometimes allows me to sort out the disease (such as rheumatoid arthritis) from the effect of its treatment (sometimes treated with methotrexate, which can also result in honeycomb lung). Among the collagen vascular diseases, scleroderma in particular is sometimes limited to the extreme lung bases (Fig. 14.13).

Table 14.6: Upper Lung Predominant Diseases

Granulomatous disease
   Tuberculosis
   Fungal infection
   Sarcoidosis
Ankylosing spondylitis
Smoking-related lung diseases
   Primary adenocarcinoma of lung
   Centrilobular emphysema
   Respiratory bronchiolitis
   Langerhans cell histiocytosis (a.k.a. eosinophilic granuloma)
Occupational lung disease
   Silicosis
   Coal workers’ pneumoconiosis

 

Gender can also be helpful in sorting among differential diagnostic possibilities. Langerhans cell histiocytosis (a.k.a. eosinophilic granuloma) used to have a significant male predilection (9:1); because it is a cigarette-smoking related disease, it no longer has a pronounced gender preference, likely due to the profound increase in women smoking over the last few decades. Sarcoid has something of a female predominance, but it is so ubiquitous that this turns out not to be helpful in differential diagnosis (many males are also affected). Diseases with continuing significant male predominance include rheumatoid lung (even though rheumatoid arthritis itself has a strong female predominance), ankylosing spondylitis, alveolar proteinosis, silicosis, and asbestosis. Female gender is more typical of lymphangiomyomatosis, dermatomyositis, and scleroderma.

Table 14.7: Lower Lung Predominant Diseases

Metastases
Pulmonary emboli and most miliary nodules
Collagen vascular diseases
   Rheumatoid arthritis
   Dermatomyositis
   Scleroderma
Aspiration, including lipoid pneumonia
Asbestosis
Usual interstitial pneumonia
Panlobular emphysema (secondary to α1-antitrypsin deficiency)

Figure 14.11 Upper lobe honeycombing. A. Eosinophilic granuloma. B. Sarcoid.

Figure 14.12 Lower lobe honeycombing. A. Rheumatoid lung. B. Usual interstitial pneumonitis.

Figure 14.13 Extreme basilar distribution of honeycombing in scleroderma. A. Posteroanterior chest radiograph and (B) close-up of lung bases.

Small Irregular Opacities

This pattern is also referred to as reticulonodular. It describes a complex combination of lines, dots, and spaces and is something of a wastebasket term for thousands of entities that involve the interstitium of the lungs. Although any “interstitial” disease can manifest this way, I particularly try to remember four common entities, as listed in Table 14.8: lymphangitic metastases (Fig. 14.14), sarcoidosis, collagen vascular disease, and pneumoconiosis. It is worth remembering that from a pattern recognition standpoint, this is a less helpful descriptor than miliary or honeycombing.

Table 14.8: Differential Diagnosis of Small Irregular Opacities (a.k.a. Reticulonodular Pattern)

Lymphangitic metastases
Sarcoidosis
Collagen vascular disease
Pneumoconiosis

Bronchial Abnormality

This is a pattern of abnormality of the bronchi, characterized by bronchial enlargement or bronchial wall thickening as manifestations of bronchiectasis, discussed in greater detail in Chapter 15. Bronchial abnormality can be mistaken for honeycombing because enlarged bronchi may result in apparent cystic spaces. However, such bronchi may contain fluid, and they tend not to cluster to quite the same extent as do that honeycomb cysts. Furthermore, careful review of frontal and lateral radiographs will generally demonstrate that abnormal bronchi have a different appearance depending on whether they are viewed in short axis (where they often resemble cystic spaces) or long axis (where their appearance often simulates railroad or tram tracks). As treatment for cystic fibrosis improves and patients survive further and further into adulthood, cystic fibrosis is a more and more common cause of bronchial abnormality (Fig. 14.15).

Bronchiectasis may instead be postinflammatory or congenital (Kartagener syndrome). Bronchial wall thickening is also sometimes seen in asthma and chronic bronchitis.

Bronchiectasis can mimic honeycombing on chest radiographs.

Figure 14.14 Small irregular opacities in lymphangitic spread of uterine sarcoma. Posteroanterior chest radiograph reveals lines, dots, and circles.

Figure 14.15 Bronchial pattern of cystic fibrosis. (A) Posteroanterior chest radiograph and (B) lateral chest radiograph demonstrate thick-walled bronchi (arrows) and tram tracks (arrowheads).

Figure 14.16 Unusual cause of multiple nodules. A. Posteroanterior chest radiograph at initial presentation: several lung nodules are best visualized in the right lower lung. B. Posteroanterior chest radiograph 31 months after A: growing bilateral nodules (N), although growth rate is less than typically seen with lung metastases. Biopsy revealed benign metastasizing leiomyomatosis (pulmonary fibroleiomyomatous hamartomas).

Multiple Nodules and Cavitary Nodules

This is a pattern characterized by nodules of varying size. Unlike alveolar nodules, the nodules considered here are sharply outlined. Unlike miliary nodules, they are not uniform in size and they often range well above the 5 mm limit for miliary nodules. The important entities in the differential diagnosis are metastases, metastases, metastases, metastases, and granulomas. This reinforces the fact that metastatic disease is numerically the most common cause and also the most important cause (based on effect on patient outcome) to remember. There are numerous other causes, including Wegener granulomatosis, hamartomas, and arteriovenous malformations; if you have a special interest in the less common causes, this is a good time to go to the Gamut book (Fig. 14.16). Cavitary nodules have a separate mnemonic, as listed in Table 14.9. This mnemonic can be used for a single cavity or for multiple cavities.

In the context of multiple cavities, cancer usually means squamous cell carcinoma metastases. Sarcoma metastases actually have a greater tendency to cavitate, but they are less common (Fig. 14.17). Apart from Wegener granulomatosis, rheumatoid nodules may also cavitate. Vascular reminds us that both bland and septic emboli may cavitate. Infection refers to bacterial lung abscesses and to infections like TB and fungus with a predilection for cavitation. A variety of traumatic lesions presents with cavitations (including laceration, contusion, and pneumatocele). Although congenital abnormalities that cavitate (such as bronchogenic cyst and sequestration) are usually single lesions, they may on occasion be multiple (Box 14.1).

Table 14.9: Mnemonic for the Differential Diagnosis of Cavitary Lung Nodules (“CAVITY”)

Cancer
Autoimmune
Vascular
Infection
Trauma
Young (for congenital abnormalities)

Figure 14.17 Cavitary metastatic osteosarcoma. A. Computed tomography december 3rd: peripheral left upper lobe metastasis (M). B.Computed tomography 8 weeks after A: lesion has cavitated in the interval.

Box 14.1: Summary of Mnemonics

·      Chronic alveolar disease—TB, fungus, DALLAS

·      Miliary nodules—TB, fungus, SHRIMP

·      Honeycombing—HIPS RDS

·      Cavitary nodule(s)—CAVITY

Figure 14.18 Calcified lung nodules (H). This patient also had gastric leiomyosarcoma; together with these calcified hamartomas, this constitutes ⅔ of Carney triad (the other element in the triad is extraadrenal pheochromocytoma, or paraganglioma).

Calcified nodules usually indicate benign disease. Several such nodules are often seen in old TB or histoplasmosis. Hamartomas also calcify and are sometimes multiple, as in Carney triad (Fig. 14.18). However, metastases may also calcify. This is particularly likely after chemotherapy has been administered. De novo calcification (or ossification) of metastases is usually a manifestation of sarcomas, especially osteosarcoma (Fig. 14.19). Calcification of lesser magnitude is occasionally seen in adenocarcinoma metastases from the breast or gastrointestinal tract (Fig. 14.20).

Pointers in Pattern Recognition

It takes practice to become proficient at recognizing these patterns and generating differential diagnoses. Personal experience indicates that it is worthwhile to make the effort. Your ability to make diagnoses using pattern recognition will rapidly outstrip that of clinicians, who generally rely on the history and physical examination as guides to the interpretation of the chest radiograph. In practical terms, it is important to know that it is generally easier to recognize a pattern in areas of moderate profusion than in areas of extreme profusion. What I am saying is that although alveolar disease is the pattern that is particularly likely to demonstrate areas of confluent disease, any pattern becomes harder to recognize if you pile on too much of it.

When lung abnormality is extensive, look at the areas least involved to help identify the pattern of abnormality.

It will assist you enormously to acknowledge one more pattern: “I don’t know.” Some patients have disease that is not easily sorted into one of the above patterns of abnormality (sometimes the problem is with the pattern, sometimes it is with you as the interpreter of the pattern). In any event, pretending that you know what the pattern is will lead to erroneous differential diagnoses and loss of confidence in the system, both on your part and on the part of your referring clinicians.

Figure 14.19 Grossly calcified metastasis. Obvious calcification is seen in this metastatic osteosarcoma, especially on the lateral view.

How should you handle a radiograph that demonstrates two (or more) patterns of abnormality (Box 14.2)? There are different answers to that question that apply to different circumstances. If possible, you should try to examine their lists of differential diagnosis for points of overlap (Fig. 14.21). This may result in a very short list of diagnostic possibilities. If one pattern is far more widespread, it is probably better to go with the predominant pattern. If you recognize one pattern and not the other, you should go with the pattern you recognize. If you know a mnemonic (or at least the differential diagnosis) for one and not the other, you should obviously go with the pattern whose differential diagnosis you know. If one pattern has a reasonably focused differential diagnosis and the other is small irregular opacities, go with the pattern with a better differential diagnosis.

Figure 14.20 Computed tomography demonstration of calcification in metastatic colon carcinoma.

I generally approach a radiograph demonstrating two patterns as an example of Osler’s Rule (I have also heard this called Occam’s Razor): “No matter how you pinch and squeeze, it’s got to fit just one disease.” It is also worthwhile to remember Hictum’s Dictum: “A patient can have as many diseases as he damn well pleases” (Fig. 14.22).

Although this kind of organized analysis will usually work best, there are two other approaches to CXR diagnosis that are sometimes helpful. The first is the “Aunt Minnie” approach. If you happen to have an Aunt Minnie, when she walks in the room you are unlikely to think to yourself, “This is a 65-year-old woman who is 30 pounds overweight, walks with a limp, and wears outrageous color combinations—it is probably my Aunt Minnie.” Instead, her overall presentation is sufficiently unique that you get an immediate gestalt impression of her as Aunt Minnie. Similarly, some radiographic presentations are uniquely characteristic of diagnostic entities, and these are labeled as “Aunt Minnies” (Figs. 14.23 and 14.24).

Box 14.2: How to Deal with Two Different Patterns

·      Cross-check the differential diagnoses

·      Go with the predominant pattern

·      Go with the pattern you recognize

·      Go with the pattern whose differential you know

·      Go with the more specific pattern

·      Remember Hictum’s dictum

 

A second approach is to take into account the patient’s clinical presentation and to look for typical radiographic manifestations (Box 14.3). In a patient with severe inherited anemia, this approach makes extramedullary hematopoiesis an important diagnostic consideration for any posterior mediastinal mass. In a patient with prior left upper quadrant abdominal trauma, this makes splenosis a consideration for any left pleural mass(es). Another illustrative example is shown in Fig. 14.25.

Figure 14.21 Cross-checking multiple patterns. A. Posteroanterior chest radiograph May 25th: widespread lung nodules and left hilar lymph node enlargement (N). B. Close-up of right perihilar lung two days later: progression of nodules, now with confluence and air bronchograms (arrows). Histoplasmosis is a diagnosis in the differential for nodules, airspace disease, and thoracic lymph node enlargement (and the correct diagnosis).

Figure 14.22 Multiple patterns, multiple diseases. A. Posteroanterior chest radiograph: extensive parenchymal abnormality. B. Close-up of right lung base: honeycombing. C. Close-up of right lung apex: miliary nodules. Patient was known to have rheumatoid lung, accounting for honeycombing, but autopsy revealed miliary tuberculosis resulting from chronic steroid therapy for rheumatoid disease, with reactivation of old tuberculosis.

Figure 14.23 Silicosis. Typical appearance of progressive massive fibrosis with upper lobe conglomerate masses. Underlying lungs demonstrate small nodules, and there is emphysematous destruction of upper peripheral lungs adjacent to conglomerate masses.

The CXR has a number of positive features for assessment of diffuse lung disease. It is widely available and inexpensive. Resultant patient radiation doses are very low. Perhaps most importantly, we (collectively) have an enormous backlog of experience using this tool in this situation. That is how we know that although TB is a common cause of miliary nodules, we do not see calcified miliary nodules after TB.

On the other hand, CXR has disadvantages in the assessment of diffuse lung disease. It is neither sensitive nor specific. Real abnormalities may be missed, and in many patients a final diagnosis cannot be established. Disease is not always well localized on the CXR, limiting our ability to guide endoscopists to the best locations for transbronchial lung biopsy in specific patients. Disease activity is also not generally something we can assess. It is thus hard to predict which patients with interstitial lung disease (ILD) will respond to steroids. Although that seems like a trivial distinction, the numerous complications associated with steroid therapy should persuade you otherwise. Finally, associated findings in the mediastinum, axillae, bones, and upper abdomen that might help to explain the etiology of lung disease are generally not well visualized.

Figure 14.24 Eosinophilic pneumonia. Asthmatic with recurrent episodes of dyspnea. A. Posteroanterior chest radiograph, April 1st: subtle abnormality at periphery of left upper lung (E). B. Posteroanterior chest radiograph fifteen days later: left upper lung abnormality has blossomed. Peripheral airspace disease, especially in the upper lungs of atopic patients, is typical. C. Posteroanterior chest radiograph 5-21: complete resolution of abnormality. D. Posteroanterior chest radiograph 9-2: recurrence at periphery of both upper lungs (E), also a typical feature if steroid therapy is discontinued.

Box 14.3: Other Tools in the Pattern-Gamut Approach

Gamuts in radiology*

“Aunt Minnies”

Expected abnormalities given the clinical diagnosis

Footnote

*Reader and Felson’s Gamuts in radiology: Comprehensive lists of roentegen differential diagnosis, 3rd ed. New York, Springer-Verlag, 1993.

Figure 14.25 Unknown from the Chest Club of Southeastern Michigan. A. Chest radiograph 6-92: patchy right perihilar opacity. B.Chest radiograph 11-92: more obvious chronic middle lobe airspace disease (C). C. Chest radiograph 2-92: before there was middle lobe disease there was free intraperitoneal gas (G). Because of the possibility of peritoneal dialysis, metastatic calcification of lung was added to the chronic alveolar differential diagnosis for this patient. D. Computed tomography: high-attenuation middle lobe abnormality (C) confirms metastatic calcification of lung. (Courtesy of Dr. David Spizarny, Detroit, MI)

High Resolution Computed Tomography Approach to Interstitial Lung Diseases

Technique

HRCT is a sampling tool for evaluating the lung parenchyma, during which images are obtained at thin collimation, typically 1 or 1.5 mm (2). HRCT differs from most thoracic CT examinations in two ways. First, during most thoracic CT examinations the entire thoracic volume is captured during the CT acquisition, such as when looking for lung metastases. In contrast, HRCT images are obtained at intervals spaced throughout the lungs. Techniques range from an image every 1 cm to clusters of images at predefined anatomic levels, such as the aortic arch, the carina, and just above the diaphragm. Second, HRCT images are reconstructed using a high spatial frequency reconstruction algorithm that enhances edges, thereby emphasizing the borders of fine lines and nodules, similar (if not identical to) a bone algorithm. In contrast, most thoracic CT examinations use an algorithm for reconstruction that creates a smoother image that is more pleasing to the eye. HRCT images are inherently noisy and suffer from quantum mottle; this usually has little effect on the images reviewed on lung window settings. However, this noise is readily apparent when reviewing on soft tissue window settings. Most HRCT examinations are performed at inspiration. Images are often obtained at expiration to evaluate for air trapping that indicates small airway disease. Prone images are useful to exclude lung disease in areas of dependent opacity that is commonly seen in the subpleural posterior portion of the lower lobes, created by atelectasis. This finding is more common with increasing age and in current or former smokers than nonsmokers (3).

HRCT differs from conventional CT in that it samples the lung for pattern and distribution of abnormality.

Prone images are useful to distinguish subpleural basilar lung disease from dependent atelectasis.

Figure 14.26 Line drawing of a secondary pulmonary lobule. The borders of the lobule are the interlobular septa. At the center of each lobule is a bronchiole and a pulmonary artery branch (blue). The pulmonary vein branches (red) run in the interlobular septa. The lymphatics (green) are found in the interlobular septa and within the central or axial interstitium that surrounds the bronchovascular bundles. (From 

Kazerooni EA. High-resolution CT tomography of the lungs. AJR Am J Roentgenol 2001;177:501–519

, with permission.)

Anatomy

The smallest anatomic unit visible on HRCT is the secondary pulmonary lobule (Fig. 14.26). The walls of these lobules are made up of the interlobular septa, which are typically not seen unless abnormal; they are below the resolution limit of HRCT. The interlobular septa correspond to Kerley B lines on chest radiographs. The occasional visible septum may be normal. The lower limit of resolution on HRCT is approximately 0.1 mm, which is the width of the interlobular septa. Structures 0.2 to 0.3 mm thick can be routinely identified on HRCT. The diameter of the pulmonary artery supplying each lobule is 1 mm, and the diameter of the intralobular acinar arteries is 0.5 mm; both are therefore readily seen on HRCT. Bronchi are visible based on their wall thickness. The 1.0 mm diameter bronchiole supplying the lobule has an approximately 0.15 mm wall, at the limit of HRCT resolution, and is barely if at all visible on HRCT images.

Clinical Indications

The clinical indications for HRCT are summarized in Table 14.10. HRCT is more sensitive and specific for the detection and diagnosis of ILD than both chest radiography and conventional CT (4,5,6,7,8,9). HRCT is the test of choice for finding and characterizing bronchiectasis. It should be used in cases of suspected diffuse infiltrative lung disease when the chest radiograph is normal or when the pattern of abnormality is unclear on chest radiographs. In cases when the pattern is well characterized at radiography, such as a miliary pattern, HRCT is unlikely to provide additional useful information. Individuals with infiltrative lung diseases, such as usual or nonspecific interstitial pneumonitis (NSIP), benefit further from HRCT, because findings such as ground glass opacity tend to indicate more active and potentially reversible disease against which aggressive, often toxic, pharmaceuticals may be used. In contrast, individuals with predominantly honeycombing have end-stage fibrosis, are unlikely to respond to medical therapy and have a very poor prognosis. HRCT is often repeated over the course of therapy to measure the impact of the therapy. Finally, HRCT can be used to guide the surgeon to the areas of ground glass opacity and away from honeycombing during surgical lung biopsy, thereby improving the ability to characterize the underlying disease process.

Table 14.10: Clinical Indications for HRCT

Detect and evaluate bronchiectasis
Evaluation of suspected lung disease when chest radiography is normal
Clarify pattern of abnormality from chest radiography to narrow differential diagnosis
Evaluate disease activity
Predict response to therapy and survival
Guide type and location of biopsy
Evaluate effectiveness of medical therapy

Definitions of Idiopathic Interstitial Pneumonias

The definitions of disease used here are taken from new consensus classification of idiopathic interstitial pneumonias developed by the American Thoracic Society and European Respiratory Society, published in 2002 (10). This classification comprises the clinicopathologic entities in the order of relative frequency, as listed in Table 14.11 (11,12). Each clinical-radiologic diagnosis is paired with a histologic pattern. The clinical terms are most appropriate for clinical description, which includes radiology. The latter terms are used to describe biopsy specimens. COP was formerly known as idiopathic bronchiolitis obliterans organizing pneumonia.

Pitfalls

To interpret HRCT images, it is important to understand the pitfalls (13,14,15). Unfamiliarity with these pitfalls may cause the interpretation of images as abnormal when the findings can best be attributed to an artifact or interpretation as normal when there is really disease present. These pitfalls can be divided into patient related, technical, and interpretive or cognitive pitfalls, as listed in Table 14.12, with several examples illustrated in Figs. 14.27,14.2814.29 and 14.30. A window width that is too narrow or a level that is too low falsely thickens bronchial walls and creates false ground glass opacity by making normal parenchymal structures appear too opaque, whereas a width that is too wide may mask diseases that are characterized by reduced attenuation, including emphysema and cystic lung disease (Fig. 14.29). Serial examinations should always be viewed at the same window width–level combinations to avoid reporting disease as better or worse when it is really an artifact of viewing settings. Although there is no single standard window and level combination, appropriate window width lies between 1,000 and 2,000 Hounsfield units and an appropriate level between -500 and -700 Hounsfield units. Normal lung attenuation is between -600 and -700 Hounsfield units.

Table 14.11: Classification of Idiopathic Interstitial Pneumonias

Clinical Diagnosis Pattern

Histologic

Idiopathic pulmonary fibrosis/cryptogenic fibrosing alveolitis

Usual interstitial pneumonia

Nonspecific interstitial pneumonia

Nonspecific interstitial pneumonia

Cryptogenic organizing pneumonia

Organizing pneumonia

Acute interstitial pneumonia (Chapter 10)

Diffuse alveolar damage

Respiratory bronchiolitis-interstitial lung disease

Respiratory bronchiolitis

Desquamative interstitial pneumonia

Desquamative interstitial pneumonia

Lymphocytic interstitial pneumonia (Chapter 13)

Lymphocytic interstitial pneumonia

Table 14.12: Pitfalls in the Interpretation of HRCT

Patient related

·   Motion artifact (respiratory and/or cardiovascular) creates pseudobronchiectasis, pseudo–ground glass opacity and star artifacts

·   Dependent atelectasis mimics or hides early subpleural lung disease

·   Image noise in large patients and through the shoulders

·   Technical

·   Viewing images at incorrect window width and level

·   Failure to obtain expiratory images (thereby missing small airway disease)


Interpretive/cognitive

·   Failure to detect bronchiectasis due to mucous plugging

·   Failure to recognize diffuse air trapping on expiratory images

·   Interstitial edema due to left heart failure mimics infiltrative lung diseases

·   Edema superimposed on emphysema may mimic honeycombing

·   Mosaic perfusion (airway, vascular, or infiltrative lung disease)

·   Septal lines and ground glass opacity may be interpreted as an idiopathic interstitial pneumonitis, with infection such as cytomegalovirus or Pneumocystis carinii unrecognized

Figure 14.27 HRCT pitfall: Dependent opacity. A. On the supine image there is dependent subpleural ground glass opacity, which can be either be dismissed as dependent opacity or identified as disease, neither of which can be stated confidently without prone images.B. On the prone image the abnormality persists, confirming the presence of interstitial lung disease. If the abnormality had resolved, it indicates dependent opacity, a mimic of lung disease.

 

Major Patterns of Abnormality

The major patterns of abnormality encountered on HRCT are listed in Table 14.13. As with chest radiographs, these patterns of abnormality may overlap in one examination. It is important to focus on the major or predominant pattern of abnormality when trying to generate a differential diagnosis or a specific diagnosis. For example, a thickened septal line or two can be found on just about any HRCT examination; hence, every disease (as well as normal) could be listed under a gamut for “thickened septal lines.” However, to do so would not be practical or useful. Reticular abnormality refers to thickening of inter- and intralobular septa, which when extensive and due to fibrosis form honeycombing. These findings represent abnormal peripheral or “septal” interstitium. There is also a central or axial interstitial compartment, and bronchovascular thickening represents the central equivalent of septal lines. Thickening may be either smooth (as in interstitial pulmonary edema), irregular (as in fibrosis), or nodular (as in lymphangitic tumor spread). Primary nodular abnormality is divided up based on the type and distribution of nodules. Centrilobular nodules that characterize subacute hypersensitivity pneumonitis or RB-associated ILD (RB-ILD) are caused by peribronchiolar inflammation and/or fibrosis. Abnormality that is characterized predominantly by a change in the attenuation of the lung may be either increased, decreased, or mosaic attenuation.

Figure 14.28 HRCT pitfall: Extensive image noise due to large body habitus and relative photon starvation if thin section image, further exaggerated by the use of an edge-enhancing algorithm, rendering this examination nondiagnostic.

Figure 14.29 HRCT pitfall: Incorrect window level and width for image viewing. A. High resolution computed tomography image at the incorrect window settings appears to demonstrate extensive ground glass opacity, consolidation and septal lines. B. In reality, the patient has severe emphysema.

Figure 14.30 Interstitial edema manifesting on HRCT as smooth septal lines and ground glass opacity that is gravity dependent in distribution, with ill-defined vessel margins, and subpleural edema with smoothly thickened right major fissure.

Table 14.13: Patterns of High-Resolution CT Abnormality

Reticular abnormality

·   Septal lines
   –Smooth
   –Irregular
   –Nodular

·   Honeycombing

·   Bronchovascular thickening


Nodular abnormality

·   Miliary

·   Centrilobular

·   Perilymphatic


Altered attenuation

·   Increased attenuation
   –Ground glass opacity
   –Consolidation

·   Decreased attenuation
   –Cysts
   –Emphysema

·   Mosaic attenuation
   –Primary vascular
   –Primary airway
   –Patchy infiltrative lung disease

CT, computed tomography.

Predominantly Reticular Diseases

Pulmonary Edema

Interstitial edema appears on chest radiographs as Kerley B lines, which represents edema within the interlobular septa of the “septal” or peripheral interstitial compartment, peribronchial cuffing with perivascular indistinctness due to edema within the central or axial interstitial compartment, and pulmonary vascular redistribution (Fig. 14.30).

The same appearance is seen on HRCT (Table 14.14). Thickened septa in interstitial edema are smooth and usually most severe in a gravity-dependent distribution (16,17). Alveolar opacities are the hallmark of alveolar edema on radiographs; on HRCT this appears as ground glass opacity and even consolidation. Pleural effusions and thickening of fissures may also be a clue that the septal thickening is due to edema and not fibrosis. Edema superimposed on black holes in the lung caused by emphysema may create “pseudo-honeycombing.” Note that the distribution will usually be gravity dependent and less subpleural than pulmonary fibrosis. When the major clinical consideration is edema versus ILD, such as UIP or NSIP, repeating the HRCT after diuresis and treatment of heart failure can be useful to demonstrate that the findings have resolved.

Smooth septal lines in a gravity-dependent distribution should raise the possibility of interstitial pulmonary edema.

Table 14.14: HRCT Findings of Pulmonary Edema

Interlobular septal thickening
Peribronchovascular interstitial thickening
Increased vascular caliber
Pleural effusion
Thickening of pleural fissures
Ground glass opacity

From Storto ML, Kee ST, Golden JA, et al. Hydrostatic pulmonary edema: high-resolution CT findings.AJR Am J Roentgenol 1995;165:817–820, with permission.

Lymphangitic Carcinomatosis

Like edema, lymphangitic spread of tumor involves both the peripheral and central interstitial compartments. Involvement of the peripheral compartment is characterized by irregular, nodular, or “beaded” interlobular septa that form polygons and subpleural micronodules (Table 14.15Fig. 14.31) (18,19,20,21). Involvement of the central compartment is characterized by irregular and nodular thickening of the bronchovascular core structures within the secondary lobule and thickening of the central bronchovascular bundles as they extend toward the hila of the lungs. This represents what is known as a perilymphatic distribution of disease. Thick or nodular fissures are common. Early on, these findings may be related to tumor thrombi in lymphatic vessels, accompanied by edema (19). Other findings, such as enlarged lymph nodes and pleural effusions, may accompany the lung findings.

Polygon formation by thick and nodular septal lines are the hallmarks of lymphangitic carcinomatosis.

The radiologic findings of lymphangitic carcinomatosis may change slowly or even remain stable for several months, particularly when chemotherapy is being administered. Therefore, stability should not be used to exclude this diagnosis (20). In addition to pulmonary embolism due to a hypercoagulable state, HRCT should be considered in cancer patients with new shortness of breath and a normal chest radiograph to evaluate for radiographically occult lymphangitic carcinomatosis (22). Up to 25% of patients with lymphangitic tumor spread in the lungs may have a normal chest radiograph. In one series, the mean survival of patients with lymphangitic carcinomatosis ranged from 11 to 30 months (median, 13 months).

Table 14.15: HRCT Findings of Lymphangitic Carcinomatosis

Irregular, nodular, or “beaded” interlobular septa
Polygons
Subpleural micronodules
Irregular or nodular thickening of bronchovascular core structures in secondary pulmonary lobules
Thickening of central bronchovascular bundles
Pleural effusion
Thickening and nodularity of pleural fissures
Enlarged thoracic lymph nodes

From references 181920 and 21, with permission.

Figure 14.31 Lymphangitic tumor spread in the left lung secondary to bronchogenic carcinoma with nodular and beaded thickened septa forming polygons.

Idiopathic Pulmonary Fibrosis

Idiopathic pulmonary fibrosis (10) may appear as a spectrum of abnormalities on HRCT, ranging from ground glass opacity early in the disease course to honeycombing in end-stage disease (Table 14.16). Subpleural lower lobe predominant honeycombing is highly specific for the diagnosis of idiopathic pulmonary fibrosis, a disease process referred to as UIP on histopathologic specimens (Fig. 14.32) (23,24). Traction bronchiectasis and bronchiolectasis accompany areas of honeycombing. Ground glass opacity as the predominant pattern on HRCT has a long differential diagnosis and includes most of the idiopathic interstitial pneumonias, including idiopathic pulmonary fibrosis (25). Reticular and honeycomb abnormalities develop over time in areas that were previously occupied by ground glass opacity. When ground glass opacity is the predominant pattern on HRCT, NSIP and DIP should be suspected.

Lower lobe predominant subpleural honeycombing is highly specific for idiopathic pulmonary fibrosis.

Table 14.16: HRCT Findings of Idiopathic Pulmonary Fibrosis

Distribution: peripheral, subpleural, basal
Reticular (septal lines)
Honeycombing
Traction bronchiectasis/bronchiolectasis
Architectural distortion
Focal ground glass
Volume loss
Enlarged thoracic lymph nodes
Differential diagnosis
   Asbestosis
   Collagen vascular disease
   Drug toxicity
   Chronic hypersensitivity pneumonitis

As the name implies, idiopathic pulmonary fibrosis is usually idiopathic in etiology. A similar pattern may also be seen with collagen vascular disease or drug toxicity (26,27). Rarely, idiopathic pulmonary fibrosis is familial. Patients usually present after the age of 50 years with slowly progressive shortness of breath and a nonproductive cough. Most patients with idiopathic pulmonary fibrosis are diagnosed fairly late in the course of the disease and already have honeycombing. The median survival is 2.5 to 3.5 years. Honeycombing represents fibrosis histopathologically and is irreversible (28,29). In contrast, ground glass opacity may represent more active inflammation and is thereby more responsive to therapy (30,31,32). The pathologic hallmark is heterogeneity and the presence of fibroblastic foci.

Figure 14.32 HRCT of idiopathic pulmonary fibrosis with subpleural honeycombing, irregular septal thickening, and traction bronchiectasis.

Honeycombing on HRCT represents irreversible fibrosis histologically.

Asbestosis

This is one of the most common pneumoconioses encountered radiologically, the others being silicosis and coal worker’s pneumoconiosis. Although pleural plaques indicate asbestos exposure (Fig. 17.29), the term asbestosis refers to the lung findings in asbestos-exposed individuals. The HRCT findings are listed in Table 14.17. Characteristic findings include inter- and intralobular septal thickening, subpleural and parenchymal bands (the latter akin to a Kerley A line on chest radiographs), and honeycombing in a subpleural posterior and basilar distribution, with or without pleural plaques (Fig. 14.33) (33,34,35). HRCT is often abnormal in asbestos-exposed individuals patients with normal chest radiographs. Individuals with an abnormal HRCT have lower forced vital capacity and poorer gas exchange than asbestos-exposed individuals with a normal HRCT. Individuals with an abnormal chest radiograph have a longer duration of exposure than those with a normal chest radiograph and abnormal HRCT (36,37,38).

Asbestosis is a basilar predominant reticular lung disease.

Table 14.17: HRCT Findings of Asbestosis

Distribution: peripheral, subpleural, basal
Reticular (septal lines)
Subpleural bands
Parenchymal bands
Honeycombing

Predominantly Nodular Diseases

Sarcoidosis

This is one of the more commonly encountered chronic infiltrative lung diseases. The clinical presentations, extrapulmonary manifestations, and staging of the disease are discussed in Chapter 13 (Table 13.12Figs. 13.3613.37, and 13.38). The characteristic HRCT findings are peribronchovascular and subpleural nodules in an upper lobe predominant distribution (Table 14.18Fig. 14.34) (39).

Figure 14.33 HRCT of asbestosis. A. Thickened interlobular septa along the periphery of the right lung (arrows)B. Subpleural band in the left lower lobe (arrow)C. Extensive pleural plaques of asbestos exposure, calcified on the right noncalcified diffuse thickening on the left.

The pathologic lesion of sarcoidosis is the noncaseating granuloma. The granulomas are typically located along lymphatics in the peribronchovascular sheath and to a lesser extent in subpleural and interlobular septal lymphatics (40). This anatomic distribution of abnormality is termed perilymphatic. Nodular upper lobe predominant disease is most commonly sarcoidosis. The major differential diagnosis is silicosis or coal worker’s pneumoconiosis if there is an appropriate exposure history. As the disease progresses, irregular opacities, architectural distortion, and honeycombing predominate, as small nodules coalesce into central mass-like opacities (Fig. 14.35) (41). Less common manifestations of pulmonary sarcoidosis include nummular or “coin-like” lesions that resemble metastases and alveolar sarcoidosis that may make the diagnosis challenging. Additional findings include bilateral hilar and mediastinal lymph node enlargement, seen to involve more anatomic locations on CT than at chest radiography.

Sarcoidosis is an upper lung predominant nodular lung disease.

Table 14.18: HRCT Findings of Sarcoidosis

Distribution: upper lung predominant
Bronchovascular thickening and peribronchovascular miliary nodules
Subpleural nodulse
Irregular mass-like opacities
Architectural distortion and hilar rotation
Honeycombing (late-stage advanced disease)
Multiple pulmonary nodules (uncommon as primary finding)
Alveolar consolidation (uncommon as primary finding)
Enlarged thoracic lymph nodes

Figure 14.34 HRCT of sarcoidosis. A. Small lung nodules surrounding the central bronchovascular structures, which themselves are thickened and beaded. B. Enlarged mediastinal lymph nodes.

Silicosis and Coal Worker’s Pneumoconiosis

Silicosis and coal worker’s pneumoconiosis both appear as 2 to 5-mm well-defined discrete nodules that are most extensive in the upper lobes. Over time the nodules may coalesce to form conglomerate masses or progressive massive fibrosis, leaving peripheral emphysema (Fig. 14.36) (42). When this occurs, the profusion of small nodules decreases as they coalesce to form the masses, and emphysema creates increased lucency. Nodules and masses may calcify, and there may be associated eggshell calcified lymph nodes. In early disease when radiographs are still normal, HRCT may reveal the radiographically occult tiny lung nodules. There may be associated lymph node enlargement, calcification of lung nodules, masses and lymph nodes, and a minor component of septal thickening (43,44,45). Pulmonary function test abnormalities in silicosis correlate more with the amount of underlying emphysema than with the profusion of lung nodules (46). Coalescence of small nodules or conglomerate masses are associated with significant lung volume reduction, reduced gas exchange, and greater airflow obstruction (47).

Silicosis is an upper lung predominant nodular lung disease.

Hypersensitivity Pneumonitis

The radiologic appearance depends on the acuity of the exposure. In the subacute stage, diffuse centrilobular nodules, with or without patchy ground glass opacity, and air trapping are seen on HRCT (Fig. 14.37) (48). Clinical history and serologic tests combined with this HRCT appearance are sufficient to make the diagnosis. The HRCT findings are due to a mononuclear cell bronchiolitis and cellular interstitial infiltrate, with poorly defined, scattered, non-necrotizing granulomas (48). Centrilobular nodules have been reported in 40% to 100% of patients with subacute hypersensitivity pneumonitis and patchy ground glass opacity in 52% to 100% (48,49,50). Ground glass opacity, centrilobular fuzzy nodules, and air trapping are the HRCT hallmarks of subacute hypersensitivity pneumonitis. The abnormality may be more severe in the mid and lower lungs than the lung apices. In a population-based study by Lynch et al. (51) of 31 symptomatic recreation center employees referred because of possible hypersensitivity pneumonitis, 11 were diagnosed with hypersensitivity pneumonitis. Chest radiography was abnormal in only one patient (9%). On contrast, HRCT was abnormal in five patients (45%); in each of these cases poorly defined centrilobular nodules were present.

Figure 14.35 HRCT end-stage sarcoidosis with central honeycombing and architectural distortion.

Figure 14.36 HRCT of silicosis with a central right lung conglomerate mass (arrow), bilateral small silicotic nodules (arrowheads) that coalesce centrally with peripheral emphysema.

Ground glass opacity, centrilobular fuzzy nodules, and air trapping are the HRCT hallmarks of subacute hypersensitivity pneumonitis.

The appearance of chronic hypersensitivity pneumonitis is less specific, appearing as fibrosis superimposed on patchy ground glass opacity and centrilobular nodules. It often spares the lung bases or appears patchy with air trapping, findings that can be used to distinguish chronic hypersensitivity pneumonia from UIP (Fig. 14.38) (52,53). Chronic HP and NSIP may be difficult to separate on HRCT. After the antigen that has provoked the lung injury is withdrawn from the patient’s environment, ground glass opacity and centrilobular nodules usually improve or resolve, whereas in patients with persistent antigen exposure the HRCT findings persist (49).

Chronic hypersensitivity pneumonitis manifest with patchy reticular abnormality, bronchiectasis, and air trapping that is not in the subpleural lower lung distribution of idiopathic pulmonary fibrosis.

Chronic HP and NSIP may be difficult to separate on HRCT.

Figure 14.37 HRCT of hypersensitivity pneumonitis. A. Inspiratory image demonstrates diffuse ground glass opacity with intervening areas of abnormally low attenuation lung that could loosely be called a mosaic pattern. B. Expiratory image demonstrates exaggeration of the mosaic pattern, indicating a component of small airway disease that is commonly seen with hypersensitivity pneumonitis.

Figure 14.38 HRCT of chronic hypersensitivity pneumonitis. A. Inspiratory image demonstrates patchy areas of septal thickening and traction bronchiectasis, which are not in subpleural distribution like usual interstitial pneumonia. Nonspecific interstitial pneumonia can have this appearance as well. B. Expiratory image demonstrates a component of air-trapping (arrows).

Table 14.19: HRCT Findings of Respiratory Bronchiolitis-associated Interstitial Lung Disease

Distribution: diffuse or upper lung predominant
Centrilobular nodules
Patchy ground glass opacity
Bronchial wall thickening
Air trapping on expiration
Differential diagnosis
   Hypersensitivity pneumonitis
   Desquamative interstitial pneumonia
   Nonspecific interstitial pneumonia

Respiratory Bronchiolitis–Associated Interstitial Lung Disease

RB-ILD is a smoking-related lung disease, with onset usually between ages 30 and 50 years in individuals with an average cigarette smoking history of 30 pack-years. Onset at an earlier age is usually associated with a larger smoking history of shorter duration, such as two to three packs a day for at least 10 years. Men are affected twice as often as women (54,55). Patients with RB-ILD usually have mild slowly progressive dyspnea and a new or increasing chronic cough (10). Some patients are asymptomatic. This abnormality is often an incidental finding in resected lung specimens of patients with bronchogenic carcinoma, another smoking-related disease. Smoking cessation usually results in clinical and radiologic improvement; sometimes corticosteroids are required.

RB-ILD is a smoking-related lung disease characterized by upper lobe predominant centrilobular nodules.

The pathologic features of RB-ILD include the accumulation of pigmented macrophages in a bronchiolocentric distribution with peribronchiolar fibrosis, predominantly involving the first- and second-order respiratory bronchioles. This results in a pattern of centrilobular nodules that is either upper lung predominant or diffuse in distribution. It should be noted that RB-ILD and DIP are a spectrum pathologically, with DIP sharing the association with cigarette smoking as well as macrophage accumulation. The latter is diffuse in DIP and bronchiolocentric in RB-ILD. Other HRCT findings are listed in Table 14.19. There may be superimposed upper lung predominant centrilobular emphysema as well, another smoking-related lung disease (56). Chest radiographs demonstrate bronchial wall thickening and ground glass opacity but may be normal in 14% of patients (10).

Disease Characterized Predominantly by Altered Attenuation

Lung parenchymal attenuation can either be normal, increased (ground glass or consolidation), decreased (emphysema, cysts), or mixed, the so-called mosaic attenuation pattern. Emphysema is discussed in detail in Chapter 15 and so is not discussed here. A mosaic pattern may be seen with small airway disease (Chapter 15), with pulmonary embolism (Chapter 21) or patchy ground glass opacity secondary to an interstitial pneumonia, such as patchy DIP. Expiratory images that either reveal or exaggerate the mosaic pattern indicate small airway disease as the cause.

Abnormally Reduced Attenuation: Predominantly Cystic Lung Diseases

HRCT is very accurate for diagnosing cystic lung disease. Diseases in this category are listed in Table 14.20 and include Langerhans cell histiocytosis (a.k.a. eosinophilic granuloma) and lymphangioleiomyomatosis (LAM), which are both obstructive lung diseases that clinically present with shortness of breath. Other predominantly cystic disease are less common, such as chronic Pneumocystis carinii infection or very cavitary thin-walled metastases.

Table 14.20: HRCT Cystic Lung Diseases

Lymphangioleiomyomatosis
Tuberous sclerosis
Langerhans cell histiocytosis (a.k.a. eosinophilic granuloma)
Chronic Pneumocytis carinii infection
Very cavitary metastases

LAM is a very rare cystic lung disease with classic highly specific radiologic findings. This disease is characterized by uniformity and homogeneity. Uniformly sized cysts, uniformly distributed from lung apex to base and center to periphery, uniformly occur in women of childbearing age. Early in the disease the cysts are surrounded by normal lung parenchyma (Fig. 13.34). Over time, no normal parenchyma is visualized (Fig. 14.39) (5,57). The severity of the cysts measured visually or using attenuation-based quantitative CT corresponds to the severity of obstructive pulmonary function abnormalities, the impairment in gas exchange, and the reduction in exercise performance (58,59). The same disease process may also be seen in the lungs of patients with tuberous sclerosis, in which case men can also have the disease. LAM may be a forme fruste of tuberous sclerosis, because patients with LAM have an increased incidence of angiomyolipomas of the kidneys, one of the findings of tuberous sclerosis.

LAM is a disease of uniformity: uniformly sized cysts, uniformly throughout the lungs, and uniformly in women.

Figure 14.39 High resolution computed tomography of lymphangioleiomyomatosis demonstrates small lung cysts with well-defined walls separated by intervening areas of normal lung that were uniformly distributed through the lungs from apices to bases.

Langerhans cell histiocytosis (otherwise known as histiocytosis X or eosinophilic granuloma) is a cigarette smoking–related lung disease characterized by irregular cysts and nodules that is more severe in the upper lungs than the lower lungs. A history of cigarette smoking is reported in 90% to 100% of cases. Over time, the nodules give way to predominantly cystic lesions. When a combination of cysts and irregular nodules is identified, more severely involving the upper lungs than the lung bases, this diagnosis can be made with confidence (Fig. 14.40) (60,61,62). The abnormalities may resolve with smoking cessation, but if abnormality and symptoms persist, medical therapy such as corticosteroids may be used. Bone and pituitary gland involvement (diabetes insipidus) are uncommon. In one series of 48 patients, only 2 patients had pituitary involvement and 4 had bone lesions (63). Bronchoalveolar lavage can be used to suggest this diagnosis.

Langerhans cell histiocytosis is characterized by upper lung predominant irregularly shaped cysts and nodules and is a smoking-related lung disease.

Figure 14.40 HRCT of Langerhans cell histiocytosis. A. High resolution computed tomography image through the upper lobes demonstrates the characteristic irregular cysts and small nodules. B. Abnormality is less severe in the lower lungs.

In practice, there should be little difficulty distinguishing between LAM and Langerhans cell histiocytosis. The main differences are outlined in Table 14.21.

Table 14.21: Langerhans Cell Histiocytosis vs. Lymphangioleiomyomatosis

 

Langerhans Cell Histiocytosis

Lymphangioleiomyomatosis

Distribution

Upper lung predominant

Diffuse

Lung findings

Cysts and nodules

Cysts

Other findings

None

Chylous effusions

   

Lymph node enlargement

Cyst shape

Irregular

Round and smooth

Associations

Cigarette smoking

Tuberous sclerosis

Gender

Males > females

Females only

Disease Characterized Predominantly by Abnormally Increased Attenuation

Desquamative Interstitial Pneumonia

DIP was once thought to be due the intraalveolar accumulation of desquamated epithelial cells, hence the name. It is now known to be due to the intraalveolar accumulation of macrophages (64). DIP usually occurs in smokers aged 30 to 50 years and is twice as common in men as in women (10). When DIP occurs in nonsmokers there is usually second-hand smoke exposure. Symptoms include the gradual onset of dyspnea and dry cough over weeks or months and may progress to respiratory failure. DIP is fairly rare compared with UIP and NSIP.

The HRCT findings of DIP are listed in Table 14.22. The characteristic HRCT finding of DIP is ground glass opacity, which is lower lung predominant and subpleural in most cases (Fig. 14.41). In approximately one-fourth of cases the abnormality may be patchy. Reticular lines are a less prominent finding, usually confined to the lung bases (65). Intraalveolar macrophages create the ground glass opacity, and septal fibrosis creates the reticular lines. In DIP the intraalveolar macrophage accumulation is diffuse, whereas in RB-ILD it is bronchiolocentric. Honeycombing is uncommon. With treatment, ground glass opacity usually resolves (31,66).

DIP manifests on HRCT with ground glass opacity that is usually more severe in the lower lungs (it is rarer than most of the interstitial pneumonias).

Table 14.22: HRCT Findings of Desquamative Interstitial Pneumonia

Distribution: basal, peripheral predominance
Ground glass attenuation
Reticular lines
Differential diagnosis

·   Respiratory bronchiolitis-interstitial lung disease

·   Hypersensitivity pneumonitis

·   Infection, such as Pneumocystis carinii infection

Nonspecific Interstitial Pneumonia

NSIP is a recently recognized entity, characterized by a histologic pattern that does not fit into the classification of other interstitial pneumonias, such as UIP, DIP, and lymphoid interstitial pneumonia (LIP) (67). NSIP is often subdivided into cellular and fibrotic forms, the latter being more common (68). NSIP is a heterogeneous group of disorders and may be seen in association with collagen vascular diseases such as scleroderma, hypersensitivity pneumonitis, DIP, drug-induced pneumonitis, infection, and immunodeficiency, including human immunodeficiency virus infection (10). The age at onset is approximately 10 years younger than UIP, it may occur in children, and it has a better prognosis than UIP. There is no gender predominance. Patients present with gradually progressive dyspnea and dry cough, with up to half having weight loss. Most patients either stabilize or improve with therapy; a few die (10). Lymphocytosis may be seen on bronchoalveolar lavage.

The HRCT findings of NSIP are listed in Table 14.23. Ground glass attenuation predominates, with a letter component of irregular lines (Fig. 14.42) (30,32,68,69,70). Bronchiectasis is commonly seen in areas of ground glass attenuation. Ground glass attenuation corresponds to interstitial thickening pathologically due to inflammation and/or fibrosis. Cellular NSIP is predominantly inflammatory, whereas fibrotic NSIP is predominantly fibrotic. In the setting of bronchiectasis, ground glass opacity represents interstitial fibrosis. Unlike UIP, there are no fibroblastic foci. Honeycombing is very uncommon.

Ground glass opacity with traction bronchiectasis in a lower lung predominant distribution should raise the possibility of NSIP.

Figure 14.41 HRCT of desquamative interstitial pneumonia demonstrates extensive ground glass opacity that is more severe at the lung bases (A) than apices (B).

Lymphoid Interstitial Pneumonia

LIP is characterized by a diffuse lymphoid interstitial infiltrate of lymphocytes, plasma cells, histiocytes, and type 2 cell hyperplasia, dominated by alveolar septal involvement (10). This is in contrast to the peribronchiolar lymphocytic infiltration with germinal centers seen with follicular bronchiolitis (10). Care should be taken to distinguish between LIP and lymphoma histologically, the latter associated with destruction of alveolar architecture, Dutcher bodies, and infiltration of the pleura and along the lymphatics.

Table 14.23: HRCT Findings of Nonspecific Interstitial Pneumonia

Distribution: peripheral, subpleural, basal
Ground glass attenuation
Irregular lines
Consolidation
Differential diagnosis

·   Usual interstitial pneumonia

·   Desquamative interstitial pneumonia

·   Chronic organizing pneumonia

·   Hypersensitivity pneumonitis

Figure 14.42 HRCT of nonspecific intersitial pneumonia demonstrates basilar predominant ground glass opacity with mild traction bronchiectasis in the absence of honeycombing.

LIP is more common in women than men and may present at any age, but most often between 40 and 50 years (71). It has very gradual onset and progression of dyspnea with cough that usually occurs over a few years before clinical presentation, and symptoms are generally milder than other interstitial pneumonias. Idiopathic LIP is rare, with most cases associated with either collagen vascular or autoimmune diseases, as listed in Table 14.24. LIP is also associated with human immunodeficiency virus infection, usually in children. Over 75% of cases are associated with either a polyclonal or monoclonal gammopathy. Once thought to be a premalignant condition, many of the earlier described cases of LIP were reclassified as either low grade lymphoma or NSIP. Using the current histologic definition of LIP, malignant transformation is rare. LIP is less common than UIP and NSIP, and less is known about its natural history or responsiveness to therapy. Corticosteroids are the usual mode of treatment, and some cases may progress to fibrosis. Lymphocytes are seen at bronchoalveolar lavage.

Ground glass opacity and centrilobular nodules are the predominant finding on HRCT, with reticular abnormality in half of patients (72). Findings are usually diffuse in distribution. Perivascular cysts or honeycombing, nodules and diffuse consolidation have also been reported (73).

Table 14.24: Conditions Associated with Lymphocytic Interstitial Pneumonia

Collagen vascular disease
   Sjögren syndrome
   Rheumatoid arthritis
   Systemic lupus erythematosis
Infection
   Hepatitis B
   Pneumocystis carinii
   Ebstein-Barr virus
Immunologic disorders
   Hashimoto thyroiditis
   Chronic active hepatitis
   Primary biliary cirrhosis
   Myasthenia gravis
   Hypogammaglobulinemia
   Severe combined immunodeficiency
   Autoimmune hemolytic anemia
   Pernicious anemia
Drug induced/toxic exposure
HIV infection (in children)

HIV, human immunodeficiency virus.
Adapted from American Thoracic Society/European Respiratory Society International Multidisciplinary Consensus Classification of the Idiopathic Interstitial Pneumonias. Am J Respir Crit Care Med2002;165:277–304.

Cryptogenic Organizing Pneumonia

Previously know as bronchiolitis obliterans organizing pneumonia, COP is the preferred term, avoiding confusion with bronchiolitis obliterans (10). COP is characterized by organizing pneumonia within alveolar ducts and alveoli, with or without bronchiolar involvement. COP may be associated with many conditions, as listed in Table 14.25. COP has a mean age at onset of 55 years, occurs equally in men and women, and is twice as common in nonsmokers than smokers (74). Patients present with a short duration of dyspnea and cough, often less than 3 months, which may follow a lower respiratory tract infection. There may be systemic symptoms including sweats and chills, fever, and myalgias. At bronchoalveolar lavage there is a lymphocytosis.

Table 14.25: Conditions Associated with Cryptogenic Organizing Pneumonia

Idiopathic
Infection
Diffuse alveolar damage
Distal to obstruction
Aspiration pneumonia
Drug reaction
Fume and toxic exposures
Collagen vascular diseases
Hypersensitivity pneumonitis
Eosinophilic lung disease
Inflammatory bowel disease
Reparative reaction (to tumor, infection, etc.)

Adapted from American Thoracic Society/European Respiratory Society International Multidisciplinary Consensus Classification of the Idiopathic Interstitial Pneumonias. Am J Respir Crit Care Med2002;165:277–304.

Figure 14.43 HRCT of cryptogenic organizing pneumonia demonstrates multifocal bilateral patchy consolidation with air bronchograms.

Multifocal patchy consolidation (sometimes nodular) is the hallmark of COP.

COP usually responds quickly to corticosteroid therapy with resolution within a few weeks or few months.

At radiography and HRCT, the hallmark is patchy multifocal and often subpleural alveolar consolidation that does not resolve with antibiotic therapy (Fig. 14.43) (75). Less commonly there are discrete nodular opacities and ground glass opacity. The abnormality is commonly more severe in the lower lungs than the lung apices. The findings rapidly clear with corticosteroid therapy (76).

Pulmonary Alveolar Proteinosis

Pulmonary alveolar proteinosis (PAP) is a rare disease, characterized by excess surfactant production with the accumulation of phospholipoproteinaceous material within the alveoli that stains pink with periodic acid–Schiff stain. The phospholipids is mostly comprised of lecithin, which is the predominant component of surfactant, and surfactant specific proteins. Over 80% of individuals with PAP are aged 30 to 50 years, and the disease affects men three times more often than women. Patients usually present with dyspnea, cough, and hypoxemia and occasionally with low grade fever. PAP patients are at increased risk of infection with Aspergillus, Nocardia, Mycobacteria, Cryptococcus neoformans, Histoplasma capsulatum, P. carinii, and viruses, which may be due to the culture medium created by the phospholipoproteinaceous material and to impaired macrophage function and surfactant abnormalities, which impair host defenses by preventing surfactant from binding to infectious organisms so that they can be phagocytosed by macrophages. The first clinical presentation for patients is often due to the superimposed infection. Most cases are idiopathic; less commonly PAP is associated with chemical inhalation. Whole lung lavage with as many as 20 to 40 L of fluid is the mainstay of therapy, usually performed when dyspnea limits daily activities (77).

The characteristic findings of PAP on HRCT are diffuse or perihilar predominant ground glass opacity with superimposed septal lines that form polygons, giving the “crazy-paving” appearance (Fig. 14.44) (78). The former is due to the phospholipoproteinaceous material within the alveoli, and the latter is usually due to edema (77,79). The abnormality is usually symmetric and is usually out of proportion in extent and severity compared with mild clinical symptoms. The extent of HRCT abnormalities corresponds to the restrictive abnormality seen with pulmonary function testing. Progression to pulmonary fibrosis is rare. Uncommonly, PAP has been reported in children, in whom the appearance on HRCT may also include small miliary nodules (80).

Ground glass opacity with superimposed smooth septal lines forming polygons is the hallmark of alveolar proteinosis and is referred to as “crazy-paving.”

Figure 14.44 HRCT of pulmonary alveolar proteinosis demonstrates diffuse symmetric ground glass opacity with superimposed thickened septal lines, forming polygons and creating the “crazy-paving” appearance.

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