Revisiting the pattern approach to interstitial lung disease on chest radiography.
Article Type: Clinical report
Subject: Lung diseases (Diagnosis)
Lung diseases (Care and treatment)
Radiography, Medical (Usage)
Radiography, Medical (Health aspects)
Authors: Perrin, Scott D.
Ulano, Adam
Hazelton, Todd R.
Pub Date: 12/01/2009
Publication: Name: Applied Radiology Publisher: Anderson Publishing Ltd. Audience: Academic Format: Magazine/Journal Subject: Health Copyright: COPYRIGHT 2009 Anderson Publishing Ltd. ISSN: 0160-9963
Issue: Date: Dec, 2009 Source Volume: 38 Source Issue: 12
Geographic: Geographic Scope: United States Geographic Code: 1USA United States
Accession Number: 231313776
Full Text: The excellent contrast afforded by the air-tissue interface of the lungs lends itself to diagnostic radiographic evaluation of multiple pathologic processes. However, given the confusion that often exists with regard to diffuse lung diseases, the art of interpreting the chest radiograph for the detection and characterization of interstitial disease has become less appreciated. The inability of some radiologists to properly recognize and differentiate interstitial lung diseases on chest radiography is unfortunate as this is often the initial screening test for patients with dyspnea. In many cases, early, subtle pathological changes are often overlooked or poorly characterized. Due to a confusing and often changing classification system, it is easy to become overwhelmed by the vast array of diseases that affect the lung interstitium, and developing a differential diagnosis based on isolated findings can be a challenging task. A solution to this problem is to revisit the basic pattern approach to interstitial lung disease as first described by Felson, (1) and then review the major disease entities that best fit into these recognizable patterns. We will review the pattern approach for the evaluation of interstitial lung disease on chest radiography, and we present the most common disease entities for each pattern. In addition, the HRCT correlation for some patterns will be discussed to enhance understanding.

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Evaluating patterns of ILD

The first step to radiographic evaluation of interstitial lung disease begins with a fundamental working knowledge of the pertinent anatomy of the lung interstitium and the various patterns of its possible derangement. The anatomy of the lung interstitium as encountered on the routine chest radiograph is largely imperceptible unless a pathologic process is overriding and there is abnormal thickening. Conceptually, the lung interstitium can be divided into 3 main parts: the axial interstitium (or peribronchovascular interstitium) which contains the bronchovascular bundles; the centrilobular interstitium, which contains the alveoli and capillaries for gas exchange; and the peripheral interstitium which contains the pulmonary venules, lymphatics and interlobular septae. The peripheral interstitium interdigitates with the centrilobular interstitium through the interlobular septae to divide the centrilobular interstitium into discrete units known as secondary pulmonary lobules. Through this interdigitation, the venules and lymphatics in the peripheral interstitium are able to drain the secondary lobules of the centrilobular interstitium.

Although this conceptualization is helpful, it is important to remember that any disease that affects the lung affects the interstitium at some level: the intimate relationship of the lung interstitium and the airways cannot be overstated. The lung interstitium has a limited response to injury and usually exhibits thickening of some or all of its components. It is from these basic anatomic concepts of the lung interstitium that the patterns of interstitial lung disease emerge. Classically, the patterns of interstitial disease encountered in conventional radiography represent abnormal thickening due to pathologic infiltration of the interstitium at some level, depending on the nature of the disease process. The patterns have been divided into the broad categories of linear, nodular and reticular. (2,3) (Table 1)

The linear pattern

The linear pattern on chest radiography consists of thin linear opacities which are either 2 to 6 cm long within the lungs oriented radially toward the hila or 1 to 2 cm long at right angles to, and in contact with, the lateral pleural surfaces. These linear opacities have been referred to as Kerley A and Kerley B lines, respectively, (4) although the descriptors "septal thickening" or "septal lines" are now preferred for the latter. (5) Histologically, this linear pattern represents thickening of either the bronchovascular/axial interstitium (Kerley A) or the peripheral interstitium (Kerley B). (6,7) The linear opacities may be single or multiple, regional or diffuse, and short or long, depending on the etiology and severity of disease. The most common cause of the linear pattern is hydrostatic pulmonary edema (Figure 1), but other etiologies include lymphangitic carcinomatosis (Figure 2), and atypical interstitial pneumonias such as those caused by mycoplasma, chlamydia, cytomegalovirus (CMV), and respiratory syncytial virus (RSV). (4) Interstitial pulmonary edema tends to be symmetric in distribution while atypical infections and lymphangitic carcinomatosis may be asymmetrical. A linear pattern with nodular interstitial thickening strongly suggests a diagnosis of lymphangitic carcinomatosis. In addition, clinical history is often helpful in determining the etiology as fever, cough and patient age would suggest pneumonia while an improvement in symptoms after a trial of diuretics in a patient with known cardiac disease would suggest congestive heart failure (CHF). No improvement in symptoms after treatment with diuretics or antibiotics should raise suspicion for lymphangitic carcinomatosis.

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The linear pattern, as viewed with high resolution computed tomography (HRCT), is often referred to as interlobular septal thickening. The normal interlobular septum is approximately 0.1 mm in thickness and is occasionally visible on normal scans. The interlobular septae outline the secondary pulmonary lobule and represent the HRCT equivalent of Kerley B lines. (7) Abnormal thickening can be described as smooth, beaded or irregular.5 Causes of smooth septal thickening include pulmonary edema and atypical interstitial pneumonias. Lymphangitic carcinomatosis may cause either beaded or smooth septal thickening. (7)

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The nodular pattern

The nodular pattern on chest radiography is characterized by multiple small, discrete, rounded opacities that range in diameter from 2 to 10 mm. (4,5,7) The differential diagnosis for the nodular pattern can be separated into 3 main categories based on etiology: nodular metastases, nodular pneumoconioses and the granulomatous diseases. The most common malignancies resulting in this pattern are thyroid, breast and renal-cell carcinoma, with the nodules measuring up to 10 mm in diameter. (4)

The nodular pneumoconioses include silicosis (Figures 3) and coal worker's pneumoconiosis (CWP). In these diseases, the nodules are small and have sharp borders. When present, peripheral "egg shell" calcification of hilar and mediastinal lymph nodes is virtually pathognomonic for these entities. (4) Clinical history, particularly occupational history, is helpful in diagnosis. Miners, sandblasters, ceramic workers, and manufacturers of paint and varnishes have significantly increased risk.

Granulomatous diseases include pulmonary sarcoidosis (Figure 4) hypersensitivity pneumonitis (HP), Langerhans-cell histiocytosis (Figure 5, formerly known as pulmonary histiocytosis X or eosinophilic granuloma), and miliary infections caused by tuberculosis, cryptococcosis, coccidiomycosis, and histoplasmosis.

Pulmonary sarcoidosis is the most common of the granulomatous diseases. (4) Over 90% of patients have an abnormal chest radiograph where the disease is generally divided into 4 radiographic stages. Stage I presents with lymphadenopathy. Stage II is characterized by lymphadenopathy and nodular lung disease. Stage III exhibits nodular lung disease but little evidence of lym phadenopathy. Stage IV demonstrates lung fibrosis that can resemble advanced tuberculosis. As the radiographic stage increases, the disease prognosis worsens. (6)

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It may be helpful to separate the differential diagnoses of nodular lung disease by lung zone predominance. Both silicosis and CWP generally appear in the upper-lung zones. Sarcoidosis and LCH typically have upper- and middle-lung zone predominance. HP, metastases and miliary infections typically have a diffuse or disseminated appearance. (4)

Nodules are typically easier to identify and accurately diagnose on HRCT. With HRCT, nodules can be further described according to margins (smooth vs. irregular), presence or absence of cavitations, and distribution. (7,9) While patterns of nodule distribution can be difficult to appreciate radiographically, Raoof et al. describe an algorithmic approach to diagnosis on HRCT which can be used to better characterize diffuse nodular lung disease. (10) Based on their distribution with respect to the secondary pulmonary lobule on HRCT, nodules can be classified as affecting the central structures (centrilobular nodules) or affecting peripheral structures (perilymphatic nodules), and a more specific diagnosis may be achievable.

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The reticular pattern

The reticular pattern as seen on chest radiography and computed tomography (CT or HRCT) is depicted by numerous, small, linear opacities which, by summation, have been described as a lace-like or net-like in appearance. (4,5) The reticular pattern can be divided into 3 distinct groups, each of which suggests different diagnoses: peripheral reticular pattern with small lung volumes, diffuse reticular/cystic pattern with normal or increased lung volumes, and airway/central reticular pattern.

Peripheral reticular pattern with small lung volumes

The peripheral reticular pattern demonstrates lucent spaces, which are typically <5 mm in diameter. It is always seen at the edges of the lung and usually has a basilar predominance. (4) The diseases in this category are characterized by small lung volumes, the most common of which is idiopathic pulmonary fibrosis (IPF), as seen in Figure 6. However, this entity often remains a diagnosis of exclusion. (11) Other common causes include collagen vascular diseases (Figure 7) such as rheumatoid disease and scleroderma. (12) Clinical history, such as age and symptoms, and laboratory findings such as elevated rheumatoid factor or antinuclear antibodies (ANA) may be helpful. Other radiologic findings such as clavicular erosions in RA and esophageal dilation in scleroderma may also offer significant clues to the diagnosis. (4) Asbestosis, cryptogenic organizing pneumonia (COP), and pulmonary drug toxicity (Figure 8) can also demonstrate this pattern. (7) The idiopathic pneumonias such as desquamative interstitial pneumonia (DIP), acute interstitial pneumonia (AIP), nonspecific interstitial pneumonia (NSIP), and lymphoid interstitial pneumonia (LIP) may have features consistent with the peripheral reticular pattern. However, they will often have other findings, such as consolidation in AIP or nodules and cysts in LIP. (13,14) The peripheral reticular pattern is uncommon in sarcoidosis. (11)

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Reticular (cystic) pattern with normal or increased lung volumes

The diffuse reticular pattern is characterized by global involvement of the lungs and is often referred to as a cystic pattern. The disease processes are characterized by normal and/or increased lung volumes and include: emphysema with concurrent pulmonary fibrosis (Figure 9), Langerhans-cell histiocytosis (Figure 10), and lymphangioleiomyomatosis (Figure 11), which is histologically identical to pulmonary involvement in tuberous sclerosis (TS). (7)

Langerhans-cell histiocytosis is best characterized by preservation of lung volume with reticulonodular opacities in the upper- and middle-lung zones of a smoking patient with sparing of the costophrenic angles. HRCT demonstrates bizarre-shaped cysts with irregular centrilobular nodules of the distal airways. In comparison, lymphangiomyomatosis (LAM) shows larger thin-walled cysts that are diffusely distributed in the lungs and eventually involve the entire lung parenchyma. Also, LAM can result in hyperinflation of the lungs in the later stages of the disease.

Airway (central reticular)pattern

The airway pattern, or central reticular pattern, typically spares the periphery of the lungs and may demonstrate larger spaces (5 to 10 mm) than those caused by the peripheral and diffuse reticular patterns. The most common cause of this pattern is bronchiectasis. (4) On radiography, bronchiectasis appears as nontapering bronchi, as well as dilated bronchi, which are larger than the adjacent pulmonary artery branch. Bronchiectasis is often associated with bronchial wall thickening. When viewed face on, dilated bronchi appear as thickened rings, while those viewed in-plane appear as thickened parallel lines. Based on etiology, diffuse bronchiectasis can be divided into congenital and acquired diseases. Congenital causes include cystic fibrosis (CF, Figure 12), immotile cilia syndrome (Kartagener's syndrome), hyper-IgE syndrome, and common-variable immunodeficiency. Some of the acquired causes of diffuse bronchiectasis include allergic bronchopulmonary aspergillosis (Figure 13), fibrosis with traction bronchiectasis, aspiration, extrinsic bronchial obstruction, and toxin inhalation. (11)

Conclusion

Conceptualization of the interstitial anatomy of the lung aids the radiologist in understanding of the basic patterns of interstitial lung disease which allows for more accurate recognition and characterization of these disorders. While the evaluation of a chest radiograph with suspected interstitial lung disease is often viewed as a formidable task by many radiologists, a firm understanding of the pattern-based approach to characterization of diffuse lung diseases is important. A summary of this pattern approach for chest radiography is provided in Table 1. Utilizing this approach, it is often possible to establish a relevant differential diagnosis while still recommending further evaluation with HRCT to better characterize distribution and extent of the lung parenchymal abnormality.

References

(1.) Felson, B. A new look at pattern recognition of diffuse pulmonary disease. AJR Am J Roentgenol. 1979;133:183-189.

(2.) Heitzman ER, Markarian B, Berger I, Dailey E. The secondary pulmonary lobule: A practical concept for interpretation of chest radiographs. Radiology. 1969; 93:507-519.

(3.) Brown KK, Schwarz MI. Classifying interstitial lung disease: Remembrance of things past. Chest. 2006;130:1289-1291.

(4.) Miller WT. Chest radiographic evaluation of diffuse infiltrative lung disease: Review of a dying art. Eur J Radiol. 2002;44:182-197.

(5.) Hansell DM, Bankier AA, MacMahon H, et al. Fleischner society: Glossary of terms for thoracic Imaging. Radiology. 2008; 246: 697-722.

(6.) Kang EY, Grenier P, Laurent F, et al. Interlobular septal thickening. Patterns at high-resolution computed tomography. J Thorac Imaging. 1996;11: 260-264.

(7.) Hansel DM, Zelena AA, Muller NL. In: Adams A, Dixon A, eds. Grainger & Allison's Diagnostic Radiology. 5th ed. Philadelphia: Churchill Living stone;2008:357-408.

(8.) Collins J. CT signs and patterns of lung disease. Rad Clin N Am. 2001;39:1115-1135.

(9.) Gruden JF, Webb WR, Naidich DP, McGuiness G. Multinodular disease: Anatomic localization at thin-section CT: Multireader evaluation of a simple algorithm. Radiology. 1999; 210:711-720.

(10.) Raoof S, Amchentsev A, loannis V et al. Pictoral Essay: Multinodular Disease: A high-resolution CT scan diagnostic algorithm. Chest. 2006; 129:805-815.

(11.) Lynch DA, David Godwin J, Safrin S, et al. High-resolution computed tomography in idiopathic pulmonary fibrosis: diagnosis and prognosis. Am J Respir Crit Care Med. 2005; 172:488-493.

(12.) Parambil JG, Myers JL, Lindell RM, et al. Interstitial lung disease in primary Sjogren syndrome. Chest. 2006;130:1489-1495.

(13.) Elliot TL, Lynch DA, Newell JD Jr, et al. High-resolution computed tomography features of nonspecific interstitial pneumonia and usual interstitial pneumonia. J Comput Assist Tomogr. 2005;29: 339-345.

(14.) Sumikawa H, Johkoh T, Ichikado K, et al. Usual interstitial pneumonia and chronic idiopathic interstitial pneumonia: Analysis of CT appearance in 92 patients. Radiology. 2006; 241:258-266.

Scott D. Perrin, MD, Adam Ulano, MD, and Todd R. Hazelton, MD

Dr. Perrin is a Diagnostic Radiology Resident, Department of Radiology, University of South Florida College of Medicine, Tampa, FL; Dr. Ulano is an Intern, Lahey Clinic Medical Center, Burlington, MA, and Tufts University School of Medcine, Boston, MA; and Dr. Hazelton is Chair and Associate Professor, Department of Radiology, University of South Florida College of Medicine, Tampa, FL.
Table 1. Pattern Approach to Interstitial Lung Disease.

Diagnosis                        Radiographic and clinical clues

Linear pattern

Interstitial pulmonary edema     Changes rapidly
Lymphangitic carcinomatosis      May be asymmetric
                                 Nodular septal thickening
Interstital pneumonia            May be asymmetric

Nodular pattern

Metastases                       History of cancer
Sarcoidosis                      Upper- and mid-lung zone distribution
                                 Lymphadenopathty
Miliary tuberculosis or fungal   Very tiny nodules
  infections
Hypersensitivity pneumonitis     Indistinct nodules
Langerhans-cell histiocytosis    Upper-lung zone distribution
                                 Concurrent cysts
                                 Lung hyperinflation
Silicosis or coal workers'       Upper-lung zone distribution
pneumoconiosis                   Egg-shell lymph node calcifications
                                 Occupational history
Reticular Pattern

Idiopathic pulmonary fibrosis    Small lung volumes
                                 Peripheral reticular opacities
Collagen vascular diseases       Small lung volumes
                                 Peripheral reticular opacities
                                 Clavicular erosions
                                 Dilated esophagus
                                 Skin calcifications
Asbestosis                       Small lung volumes
                                 Peripheral reticular opacities
                                 Pleural plaques
Langerhans-cell histiocytosis    Nodules
                                 Diffuse reticular (cystic) pattern
                                 Upper-lung zone distribution
                                 Pulmonary hyperinflation
Lymphangioleiomyomatosis         Young female
                                 Diffuse reticular (cystic) pattern
                                 Pulmonary hyperinflation
                                 Tuberous sclerosis
Emphysema with concurrent        Older patient
fibrotic interstitial lung       Peripheral reticular pattern
disease                          Hyperlucent lungs
                                 Pulmonary hyperinflation
Bronchiectasis                   Ring shadows (central reticular
                                 pattern)
                                 Tram lines
                                 Bronchi larger than adjacent artery
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