Revisiting the pattern approach

to interstitial lung disease on

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

T
he 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, findings can be a challenging task. A lung interstitium and the various pat-
early, subtle pathological changes are solution to this problem is to revisit the terns of its possible derangement. The
often overlooked or poorly character- basic pattern approach to interstitial anatomy of the lung interstitium as
ized. Due to a confusing and often lung disease as first described by Fel- encountered on the routine chest radi-
changing classification system, it is son,1 and then review the major disease ograph is largely imperceptible unless
easy to become overwhelmed by the entities that best fit into these recogniz- a pathologic process is overriding and
vast array of diseases that affect the able patterns. We will review the pat- there is abnormal thickening. Concep-
lung interstitium, and developing a dif- tern approach for the evaluation of tually, the lung interstitium can be
ferential diagnosis based on isolated interstitial lung disease on chest radi- divided into 3 main parts: the axial
ography, and we present the most com- interstitium (or peribronchovascular
Dr. Perrin is a Diagnostic Radiology mon disease entities for each pattern. interstitium) which contains the bron-
Resident, Department of Radiology, In addition, the HRCT correlation for chovascular bundles; the centrilobular
University of South Florida College of some patterns will be discussed to interstitium, which contains the alveoli
Medicine, Tampa, FL; Dr. Ulano is an enhance understanding. and capillaries for gas exchange; and
Intern, Lahey Clinic Medical Center, the peripheral interstitium which con-
Burlington, MA, and Tufts University
School of Medcine, Boston, MA; and Dr. Evaluating patterns of ILD tains the pulmonary venules, lymphat-
Hazelton is Chair and Associate Profes- The first step to radiographic evalu- ics and interlobular septae. The
sor, Department of Radiology, Univer- ation of interstitial lung disease begins peripheral interstitium interdigitates
sity of South Florida College of with a fundamental working knowl- with the centrilobular interstitium
Medicine, Tampa, FL. edge of the pertinent anatomy of the through the interlobular septae to

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 INTERSTITIAL LUNG DISEASE

divide the centrilobular interstitium

into discrete units known as secondary Table 1. Pattern Approach to Interstitial Lung Disease.
pulmonary lobules. Through this inter- Diagnosis Radiographic and clinical clues
digitation, the venules and lymphatics Linear pattern
in the peripheral interstitium are able Interstitial pulmonary edema Changes rapidly
to drain the secondary lobules of the
Lymphangitic carcinomatosis May be asymmetric
centrilobular interstitium. Nodular septal thickening
Although this conceptualization is
helpful, it is important to remember Interstital pneumonia May be asymmetric
that any disease that affects the lung
affects the interstitium at some level: Nodular pattern
the intimate relationship of the lung Metastases History of cancer
interstitium and the airways cannot be Sarcoidosis Upper- and mid-lung zone distribution
overstated. The lung interstitium has a Lymphadenopathty
limited response to injury and usually
exhibits thickening of some or all of its Miliary tuberculosis or fungal infections Very tiny nodules
components. It is from these basic
anatomic concepts of the lung intersti- Hypersensitivity pneumonitis Indistinct nodules
tium that the patterns of interstitial
Langerhans-cell histiocytosis Upper-lung zone distribution
lung disease emerge. Classically, the Concurrent cysts
patterns of interstitial disease encoun- Lung hyperinflation
tered in conventional radiography rep-
resent abnormal thickening due to Silicosis or coal workers’ Upper-lung zone distribution
pathologic infiltration of the intersti- pneumoconiosis Egg-shell lymph node calcifications
tium at some level, depending on the Occupational history
nature of the disease process. The pat- Reticular Pattern
terns have been divided into the broad Idiopathic pulmonary fibrosis Small lung volumes
categories of linear, nodular and reticu- Peripheral reticular opacities
lar.2,3 (Table 1)
Collagen vascular diseases Small lung volumes
The linear pattern Peripheral reticular opacities
Clavicular erosions
The linear pattern on chest radiog-
Dilated esophagus
raphy consists of thin linear opacities Skin calcifications
which are either 2 to 6 cm long within
the lungs oriented radially toward the Asbestosis Small lung volumes
hila or 1 to 2 cm long at right angles to, Peripheral reticular opacities
and in contact with, the lateral pleural Pleural plaques
surfaces. These linear opacities have
Langerhans-cell histiocytosis Nodules
been referred to as Kerley A and Ker- Diffuse reticular (cystic) pattern
ley B lines, respectively,4 although the Upper-lung zone distribution
descriptors “septal thickening” or Pulmonary hyperinflation
“septal lines” are now preferred for the
latter.5 Histologically, this linear pat- Lymphangioleiomyomatosis Young female
tern represents thickening of either the Diffuse reticular (cystic) pattern
Pulmonary hyperinflation
bronchovascular/axial interstitium
Tuberous sclerosis
(Kerley A) or the peripheral intersti-
tium (Kerley B).6,7 The linear opacities Emphysema with concurrent fibrotic Older patient
may be single or multiple, regional or interstitial lung disease Peripheral reticular pattern
diffuse, and short or long, depending Hyperlucent lungs
on the etiology and severity of disease. Pulmonary hyperinflation
The most common cause of the linear
Bronchiectasis Ring shadows (central reticular pattern)
pattern is hydrostatic pulmonary Tram lines
edema (Figure 1), but other etiologies Bronchi larger than adjacent artery
include lymphangitic carcinomatosis

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INTERSTITIAL LUNG DISEASE

A B

FIGURE 2. Lymphangitic carcinomatosis. Chest radiograph (A) demonstrating beaded septal

thickening caused by lymphangitic spread of carcinoma. Correlated computed tomography (CT,
B) image demonstrating beaded septal thickening caused by lymphangitic spread of carcinoma.

A B

FIGURE 1. Interstitial pulmonary edema.

Chest radiograph demonstrating interstitial
pulmonary edema with characteristic thick-
ening of the axial interstitium (Kerley A lines
denoted by the thin arrows) and peripheral
interstitium (Kerley B lines denoted by the
thick arrows).
FIGURE 3. Silicosis. Chest radiograph (A) demonstrating small discrete nodules discrete
nodules in the bilateral upper lobes. In addition there is egg-shell calcification of a left hilar
lymph node. CT image (B) demonstrating small discrete centrilobular nodules in the bilateral
upper lungs.

(Figure 2), and atypical interstitial pneu-
monias such as those caused by myco-
plasma, chlamydia, cytomegalovirus
(CMV), and respiratory syncytial virus
(RSV).4 Interstitial pulmonary edema
tends to be symmetric in distribution
while atypical infections and lymphan-
gitic carcinomatosis may be asymmet-
rical. A linear pattern with nodular
interstitial thickening strongly suggests
a diagnosis of lymphangitic carcino-
matosis. In addition, clinical history is
often helpful in determining the etiol-
ogy as fever, cough and patient age
would suggest pneumonia while an
improvement in symptoms after a trial
of diuretics in a patient with known car-
diac disease would suggest congestive
heart failure (CHF). No improvement in
symptoms after treatment with diuretics
or antibiotics should raise suspicion for
lymphangitic carcinomatosis.
The linear pattern, as viewed with
high resolution computed tomography
(HRCT), is often referred to as inter-
lobular septal thickening. The normal
interlobular septum is approximately
0.1 mm in thickness and is occasion-
ally visible on normal scans. The inter-
lobular 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 intersti-
tial pneumonias. Lymphangitic carci-
nomatosis may cause either beaded or
smooth septal thickening.7
The nodular pattern
The nodular pattern on chest radiog-
raphy 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 nodu-
lar 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 in-
clude 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 enti-
ties.4 Clinical history, particularly occu-
pational history, is helpful in diagnosis.
Miners, sandblasters, ceramic workers,
and manufacturers of paint and var-
nishes have significantly increased risk.
Granulomatous diseases include
pulmonary sarcoidosis (Figure 4)
hypersensitivity pneumonitis (HP),
Langerhans-cell histiocytosis (Fig-
ure 5, formerly known as pulmonary
histiocytosis X or eosinophilic granu-
loma), and miliary infections caused
by tuberculosis, cryptococcosis, coc-
cidiomycosis, 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

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 INTERSTITIAL LUNG DISEASE

A B C

FIGURE 4. (A) Stage II pulmonary sarcoidosis: Chest radiograph demonstrating sarcoidosis with medi-
astinal lymphadenopathy and associated parenchymal disease. (B) Stage III pulmonary sarcoidosis:
Chest radiograph demonstrating parenchymal involvement with lack of associated lymphadenopathy.
(C) Pulmonary sarcoidosis: Selected axial CT image demonstrating nperilymphtic nodules..

A B

FIGURE 5. Langerhans-cell histiocytosis (eosinophilic granuloma). Chest radiograph (A)

demonstrates reticulonodular opacities with upper-lobe predominance. A selected CT image
(B) demonstrates centrilobular nodularity.
FIGURE 6. Idiopathic pulmonary fibrosis.
Chest radiograph demonstrates peripheral
and basilar interstitial disease.

It may be helpful to separate the dif-

FIGURE 7. Collagen vascular disease.
Chest radiograph demonstrates diffuse
interstitial thickening of the periphery and
in the lung bases as well as a dilated
esophagus.
stages. Stage I presents with lym-
phadenopathy. Stage II is characterized
by lymphadenopathy and nodular lung
disease. Stage III exhibits nodular lung
disease but little evidence of lym-
FIGURE 8. Drug-induced pneumonitis.
Chest radiograph shows increased reticular
interstitial thickening of the lung periphery
as well as the bronchovascular (axial) inter-
stitium and cardiomegaly.
phadenopathy. Stage IV demonstrates
lung fibrosis that can resemble
advanced tuberculosis. As the radi-
ographic stage increases, the disease
prognosis worsens.6
ferential diagnoses of nodular lung dis-
ease by lung zone predominance. Both
silicosis and CWP generally appear in
the upper-lung zones. Sarcoidosis and
LCH typically have upper- and mid-
dle-lung zone predominance. HP,
metastases and miliary infections typi-
cally have a diffuse or disseminated
appearance.4
Nodules are typically easier to iden-
tify and accurately diagnose on HRCT.
With HRCT, nodules can be further
described according to margins
(smooth vs. irregular), presence or
absence of cavitations, and distribu-
tion.7,9 While patterns of nodule distrib-
ution can be difficult to appreciate
radiographically, Raoof et al. describe
an algorithmic approach to diagnosis

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INTERSTITIAL LUNG DISEASE

on HRCT which can be used to better

characterize diffuse nodular lung dis-
ease.10 Based on their distribution with
respect to the secondary pulmonary
lobule on HRCT, nodules can be classi-
fied as affecting the central structures
(centrilobular nodules) or affecting
peripheral structures (perilymphatic
nodules), and a more specific diagnosis
may be achievable.

The reticular pattern

FIGURE 9. Emphysema with superimposed
IPF. Chest radiograph shows hyperinflation
with predominant peripheral and basilar
reticular interstitial pattern.
A appearance.4,5 The reticular pattern can
FIGURE 10. Langerhans-cell histiocytosis
(eosinophilic granuloma). Chest radiograph
demonstrates bilateral pneumothoracies
with parenchymal cysts.
B
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
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 char-
acterized by small lung volumes, the
FIGURE 11. Lymphangiomyomatosis. Chest radiograph (A) shows hyperinflated lungs with
faint cystic reticular pattern. CT image (B) demonstrates diffuse replacement of the lung
parenchyma with multiple thin-walled cysts of variable size.

A B

FIGURE 13. Allergic bronchopulmonary

aspergillosis. Chest radiograph shows dif-
fuse bronchiectasis with characteristic “Y-
FIGURE 12. Cystic fibrosis. Chest radiograph (A) demonstrating bronchiectasis with mucous shaped” configuration in the right upper
plugging. CT image (B) shows diffuse bronchiectasis with upper-lobe predominance. lung.

12 ■ APPLIED RADIOLOGY ©
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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 symp-
toms, and laboratory findings such as
elevated rheumatoid factor or antinu-
clear antibodies (ANA) may be help-
ful. 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 pul-
monary drug toxicity (Figure 8) can
also demonstrate this pattern.7 The
idiopathic pneumonias such as desqua-
mative interstitial pneumonia (DIP),
acute interstitial pneumonia (AIP),
nonspecific interstitial pneumonia
(NSIP), and lymphoid interstitial pneu-
monia (LIP) may have features consis-
tent 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 uncom-
mon in sarcoidosis.11
Reticular (cystic) pattern
with normal or increased
lung volumes
The diffuse reticular pattern is char-
acterized by global involvement of the
lungs and is often referred to as a cystic
pattern. The disease processes are char-
acterized by normal and/or increased
lung volumes and include: emphysema
with concurrent pulmonary fibrosis
(Figure 9), Langerhans-cell histiocyto-
sis (Figure 10), and lymphangioleiomy-
omatosis (Figure 11), which is histo-
logically identical to pulmonary in-
volvement 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
December 2009
costophrenic angles. HRCT demonstrates
bizarre-shaped cysts with irregular cen-
trilobular 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 reticu-
lar pattern, typically spares the periph-
ery 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 bronchi-
ectasis 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 ac-
quired 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 radiolo-
gist in understanding of the basic pat-
terns of interstitial lung disease which
allows for more accurate recognition
and characterization of these disorders.
While the evaluation of a chest radi-
ograph with suspected interstitial lung
www.appliedradiology.com
INTERSTITIAL LUNG DISEASE
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 radi-
ography is provided in Table 1. Utiliz-
ing this approach, it is often possible to
establish a relevant differential diagno-
sis while still recommending further
evaluation with HRCT to better char-
acterize distribution and extent of the
lung parenchymal abnormality.
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