Approach to HRCT Diagnosis and Findings of Lung Disease

Transcription

S E C T I O N
II
Approach to HRCT Diagnosis
and Findings of Lung Disease
The high-resolution computed tomography (HRCT) detection and diagnosis of diffuse lung disease is
primarily based on the recognition of (a) a limited number of specific abnormal findings, (b) specific
combinations or patterns of these abnormalities, (c) one or more specific distributions of abnormal
findings, and (d) the use of basic history and clinical information.
HRCT FINDINGS OF LUNG DISEASE
Abnormal HRCT findings, which have been enumerated over the last 25 years, and their differential diagnosis are reviewed in the subsequent five chapters. These findings can be classified in general terms as:
1. linear and reticular opacities;
2. multiple nodules and nodular opacities;
3. parenchymal opacification, including consolidation and ground-glass opacity;
4. air-filled cystic lesions, including lung cysts, cystic lung disease, emphysema, and dilated bronchi
(bronchiectasis); and
5. decreased lung attenuation, including mosaic perfusion, mosaic attenuation, and air trapping on
expiratory scans.
(Continued)
#152201 Cust: LWW Au: Webb Pg. No. 71
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COMBINATIONS AND PATTERNS OF HRCT ABNORMALITIES
The diagnosis or differential diagnosis of diffuse lung disease is often based on the recognition of
specific combinations of HRCT abnormalities, representing specific patterns of disease. For example,
in a patient with honeycombing visible on HRCT, idiopathic pulmonary fibrosis may be a likely diagnosis, but if honeycombing is associated with mosaic perfusion or air trapping, hypersensitivity pneumonitis should be suggested instead. On the other hand, mosaic perfusion or air trapping associated
with bronchiectasis suggests airways disease. Furthermore, in some patients, ancillary abnormalities
such as lymph node enlargement, mediastinal and cardiac abnormalities, or abnormalities in the upper abdomen may be helpful.
DISTRIBUTION OF HRCT ABNORMALITIES
When attempting to reach a diagnosis or differential diagnosis of lung disease using HRCT, the
predominant distribution of abnormalities must be considered along with their appearance and morphology, and the combination or pattern or abnormal findings present. Although abnormalities in
patients with a diffuse lung disease may involve the entire lung to an equal degree, a specific predominance in one or more regions is often discernable. Many lung diseases show specific regional
distributions, or a predominance in relation to specific lung structures, a fact that is related to their
underlying histology, pathogenesis, and pathophysiology.
In different diseases, abnormalities may predominate in relation to:
1.one lung. Many lung diseases are diffuse, and involve both lungs to an equal or nearly equal
degree. On the other hand, some diseases may be asymmetrical, predominating in one lung, or
may show this finding in some cases. A few lung diseases can be unilateral.
2.the lung in cross section, as displayed on transaxial HRCT images. In different diseases, abnormalities may predominate in (a) the peripheral or subpleural lung, (b) the lung periphery, but
with relative sparing of the immediate subpleural regions, or (c) central or peribronchovascular regions, sparing the supleural lung, or maybe (d) diffuse, equally involving the entire cross
section of lung.
3.the upper-, mid-, or lower lungs. This predominance may be ascertained by comparing the severity of abnormal findings on transaxial scans through the upper-, mid-, and lower lung regions,
or by using two-dimensional reconstructions from volumetric imaging.
4.the anterior or posterior lung as seen on transaxial images or sagittal reconstructions.
5.the secondary pulmonary lobule or lobular structures, being centrilobular, bronchiolar, perilobular, involving the interlobular septa, or lobular.
6.specific lung structures, such as the pleura (visceral or parietal), bronchi, or vascular structures,
or a combination of specific lung structures. For example, some patients with nodular lung
disease may show a preponderance of nodules in relation to bronchi and peribronchovascular
regions, the subpleural lung, and interlobular septa; this combination is termed a lymphatic or
perilymphatic distribution. It is typical of sarcoidosis and a few other diseases.
It is important to keep in mind that predominance in more than one of the regions described
above may be identified in any given case; as when identifying specific HRCT abnormalities, a specific
combination of these may be suggestive of a particular diagnosis or differential diagnosis. For example, in a patient with sarcoidosis, a perilymphatic distribution of nodules on HRCT is usually associated with upper-lobe predominance, and the abnormalities may be symmetrical or asymmetrical.
Also, significant variations in classical patterns of lung involvement can be seen in individual
patients. A specific diagnosis that otherwise seems likely should not be excluded because of an atypical distribution of abnormalities.
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CLINICAL FINDINGS
Although history and other clinical findings can be of great value in suspecting or diagnosing a specific disease, in clinical practice, many HRCT studies are performed and interpreted with little or no
clinical information available. Patients may be referred for HRCT without having seen a local physician or pulmonologist, or prior to their first appointment. However, even in such cases, some basic
clinical information useful in diagnosis is often available. Such basic history as whether the patient’s
symptoms are acute or chronic, or whether a fever is present, can be helpful. These will be stressed in
the subsequent chapters, as specific findings and patterns are reviewed.
For example, in a patient with HRCT showing ground-glass opacity as the predominant HRCT
abnormality, knowing whether symptoms are acute or chronic can limit an otherwise lengthy and nonspecific differential diagnosis. In a patient with ground-glass opacity and acute symptoms, the most
likely diagnoses include pulmonary edema or hemorrhage, atypical pneumonia, aspiration, or diffuse
alveolar damage; in a similar patient with progressive or chronic symptoms, the differential diagnosis
is long, and includes such diseases as hypersensitivity pneumonitis, nonspecific interstitial pneumonia
(NSIP), desquamative interstitial pneumonia (DIP), respiratory bronchiolitis-interstitial lung disease
(RB-ILD), lymphoid interstitial pneumonia (LIP), organizing pneumonia (OP), eosinophilic lung disease, alveolar proteinosis, lipoid pneumonia, and invasive pulmonary mucinous adenocarcinoma.
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3
HRCT Findings: Linear
and Reticular Opacities
I M P O R T A N T
T O P I C S
INTERLOBULAR SEPTAL THICKENING 74
HONEYCOMBING 82
INTRALOBULAR INTERSTITIAL THICKENING
(INTRALOBULAR LINES) 89
PARENCHYMAL BANDS 97
NONSPECIFIC RETICULATION 92
SUBPLEURAL CURVILINEAR LINE 98
THE INTERFACE SIGN 92
NORMAL RETICULAR OPACITIES IN THE
ELDERLY 100
TRACTION BRONCHIECTASIS AND TRACTION
BRONCHIOLECTASIS 93
Abbreviations Used in This Chapter
AIP
ARDS
COPD
CWP
DAD
DIP
HP
IP
IPF
LIP
NSIP
OP
RB-ILD
UIP
PERIBRONCHOVASCULAR INTERSTITIAL
THICKENING 94
acute interstitial pneumonia
acute respiratory distress syndrome
chronic obstructive pulmonary disease
coal worker’s pneumoconiosis
diffuse alveolar damage
desquamative interstitial pneumonia
hypersensitivity pneumonitis
interstitial pneumonia
idiopathic pulmonary fibrosis
lymphoid interstitial pneumonia
nonspecific interstitial pneumonia
organizing pneumonia
respiratory bronchiolitis-interstitial lung disease
usual interstitial pneumonia
Thickening of the lung interstitium by fluid, fibrous tissue, or because of cellular infiltration usually results in an
increase in reticular or linear opacities on high-resolution
computed tomography (HRCT). Reticular abnormalities identifiable on HRCT are generally characterized as
belonging to one of three recognizable patterns, which
can sometimes be seen together. These are (a) interlobular
septal thickening, (b) honeycombing, and (c) intralobular
interstitial thickening, also described as intralobular lines
by its HRCT appearance (Fig. 3-1). The first two of these
are most easily recognized and have a limited differential
diagnosis. The last is less specific.
SUBPLEURAL INTERSTITIAL THICKENING 98
DISTRIBUTION OF RETICULAR OPACITIES IN THE
DIAGNOSIS OF LUNG DISEASE 100
Additional findings that may be seen in isolation or
associated with one or more of these reticular patterns
include traction bronchiectasis, the interface sign, peribronchovascular interstitial thickening, parenchymal
bands, subpleural interstitial thickening, and subpleural
lines (Fig. 3-1).
Interlobular Septal Thickening
On HRCT, numerous clearly visible interlobular septa
almost always indicate the presence of an interstitial
abnormality; only a few septa should be visible in normal
patients (see Chapter 2). Septal thickening can be seen
in the presence of interstitial fluid, cellular infiltration,
infiltration by other materials such as amyloid, lymphatic
dilatation or proliferation, or fibrosis.
Interlobular septal thickening can be diagnosed if visible linear opacities can be seen to outline what can be
recognized as pulmonary lobules because of their characteristic size and shape. Within the peripheral lung,
thickened septa 1 to 2 cm in length may outline part of
or an entire lobule and are usually seen extending to the
pleural surface, being roughly perpendicular to the pleura
(Figs. 3-1 to 3-14) (1–8). Lobules at the pleural surface
may have a variety of appearances, but they are often longer than they are wide, resembling a cone or truncated
cone. Within the central lung, thickened septa usually outline lobules that are 1 to 2.5 cm in diameter and appear
polygonal, or sometimes hexagonal, in shape (Fig. 3-2).
Lobules delineated by thickened septa commonly contain
a visible dotlike or branching centrilobular pulmonary
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C hapter 3 HRCT Findings: Linear and Reticular Opacities
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Interlobular septal
thickening
Parenchymal
bands
Centrilobular
peribronchovascular
interstitial thickening
Peribronchovascular
Intralobular interstital
thickening
Fissure thickening
due to subpleural
Traction
bronchiectasis
Peripheral
honeycombing
Honeycombing
producing a
subpleural line
Bronchiectasis
“signet ring sign”
Subpleural line
without honeycombing
FIGU RE 3-1 Linear and reticular opacities visible on HRCT.
A
B
FIGU RE 3-2 Smooth interlobular septal thickening in two patients with pulmonary edema. A: The reticular pattern can be recognized as interlobular septal thickening
because the lines outline recognizable pulmonary lobules. A lobule in the anterior lung outlined by interlobular septa (yellow arrows) shows dotlike pulmonary artery branches
in its center (red arrows). Small nodular opacities (blue arrows) seen in relation to some septa represent pulmonary vein branches seen in cross section. B: Smooth thickening of
numerous interlobular septa is visible in the upper lobe. Smooth peribronchovascular interstitial thickening (appearing as peribronchial cuffing or bronchial wall thickening) is also
present. This finding is commonly associated with interlobular septal thickening.
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s e c t i o n II Approach to HRCT Diagnosis and Findings of Lung Disease
FIGURE 3-3 Smooth interlobular septal thickening in a patient with pulmonary
edema. A coronal reconstruction shows smoothly thickened interlobular septa (arrows),
which are most evident in the peripheral lung. Thickening of the peribronchovascular
interstitium and subpleural interstitial thickening are present.
artery. The characteristic relationship of the interlobular
septa and centrilobular artery is often of value in identifying each of these structures.
The terms septal lines or septal thickening (Figs. 3-1
to 3-14) may also be used to describe interlobular septal
A
FIGURE 3-4 Smooth interlobular septal thickening in a patient with lymphangitic
carcinoma. This appearance is indistinguishable from pulmonary edema. thickening (9,10), and these terms are preferred to earlier descriptions such as peripheral lines, short lines,
and interlobular lines (4,8,11). Similarly, although
thickened septa outlining one or more pulmonary lobules have been described as producing a “large reticular
B
FIGU RE 3-5 A–C: Interlobular septal thickening in a patient with
lymphangitic spread of breast carcinoma. Diffuse, smooth interlobular septal
thickening outlines numerous pulmonary lobules, primarily in the right
lung. In addition to septal thickening, there is increased prominence of the
peribronchovascular interstitium, mostly easily recognized as bronchial wall
thickening (B, arrow). A small pneumothorax is visible on the right because of a
recent thoracentisis.
C
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FIGU RE 3-6 Smooth interlobular septal thickening in a child with
lymphangiomatosis. Mediastinal widening is also present.
FIGU RE 3-8 Interlobular septal thickening in alveolar proteinosis. Thickened
septa are associated with ground-glass opacity. The combination of interlobular septal
thickening and ground-glass opacity in the same lung region is typical of alveolar
proteinosis and is termed crazy paving.
pattern” (1,12) or “polygons” (13), and, if they can
be seen contacting the pleural surface, as “peripheral
arcades” or “polygonal arcades” (4), the terms interlobular septal thickening, septal thickening, and septal
lines are considered more specific in describing these
appearances (9,14).
Thickening of the interlobular septa is commonly seen
in patients with interstitial lung diseases (15,16), but may
also be seen in normal elderly patients (17) and otherwise
normal smokers. The presence of septal thickening is of
little diagnostic value when other HRCT abnormalities
are also visible (15). However, when visible as an isolated
or predominant abnormality, this finding has a limited
differential diagnosis (Table 3-1). Septal thickening can
be smooth, nodular, or irregular in contour in different pathologic processes (2,18–21). A simple algorithm
(Fig. 3-15) based on the recognition of these findings may
be useful for diagnosis.
Regardless of the cause or appearance of septal thickening, this finding is often associated with peribronchial
interstitial thickening and subpleural interstitial thickening, which are described later.
A
Smooth Septal Thickening
B
FIGU RE 3-7 Smooth interlobular septal thickening in Erdheim–Chester
disease, a non-Langerhans cell histiocytosis that can result in lung infiltration along
lymphatics. A: Thickening of numerous interlobular septa is visible on HRCT.
B: Sagittal lung slice after lung removal for transplantation. Thickened interlobular
septa are most evident in the upper lobes. Histology showed a combination of fibrosis
and histiocytic infiltration. (Courtesy of Kevin O. Leslie MD, Mayo Clinic, Scottsdale.)
Smooth septal thickening is usually seen in patients with
venous, lymphatic, or infiltrative diseases (19). Specifically, it may be seen in the presence of pulmonary edema
or hemorrhage (Figs. 3-2 and 3-3) (22–25), pulmonary
veno-occlusive disease (22,24,26,27), lymphangitic spread
of carcinoma (Figs. 3-4 and 3-5) (4,7,28), lymphoma,
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A
B
FIGU RE 3-9 “Beaded” or nodular septal thickening in two patients with sarcoidosis. A: Interlobular septa in the upper lobe are nodular in appearance (arrows); this has
been termed the beaded septum sign. B: Numerous nodules are visible within interlobular septa (arrows). The nodules are too numerous to represent normal pulmonary veins.
A
B
FIGURE 3-10 Nodular interlobular septal thickening in
C
D
lymphangitic spread of carcinoma. A–C: Nodular interlobular
septal thickening in a patient with metastatic colon carcinoma.
Nodules are clearly visible within the septa outlining a lobule in
the lung apex (arrows, A). D: Nodular septal thickening (arrows)
shown in a lung specimen of a patient with lymphangitic spread
of carcinoma.
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A
FIGU RE 3-12 Irregular interlobular septal thickening in patients with
fibrotic sarcoidosis. Numerous irregularly thickened interlobular septa (arrows)
are associated with lung fibrosis and distortion of lung architecture. Some nodules
remain visible.
(34), some pneumonias (35), and in a small percentage
of patients with pulmonary fibrosis. Smooth interlobular
septal thickening, regardless of its cause, is often associated with smooth peribronchovascular and subpleural
interstitial thickening, which is most easily recognized
as thickening of fissures. As discussed below, perilobular abnormalities in patients with organizing pneumonia
(OP) can mimic smooth interlobular septal thickening
(Fig. 3-14) (36).
In many diseases associated with smooth septal thickening, the thickening is diffuse. The primary exception is
lymphangitic spread of neoplasm, in which the abnormality may be unilateral or bilateral, asymmetrical, patchy,
and upper- or lower lobe predominant. Also, in patients
with diffuse septal thickening, or conditions such as pulmonary edema, in which a basal predominance may be
seen, often thickened septa are best defined in the apices
and upper lobes, as interlobular septa are best developed
in this region.
Smooth septal thickening may also be seen in association with ground-glass opacity, a pattern termed crazy
paving (see Chapter 5). This pattern is typical of alveolar
proteinosis (Fig. 3-8) but has a long differential diagnosis,
which is reviewed in Chapter 5 (37–42).
B
C
FIGU RE 3-11 Irregular interlobular septal thickening in patients with
fibrotic HP. A and B: Irregular interlobular septal thickening is visible (arrows) in
less-abnormal regions, but in areas with severe fibrosis, septa are more difficult to
recognize. C: In a different patient with chronic HP with fibrosis, well-defined septa
are visible in less-abnormal regions at the lung bases (red arrows), but are more
difficult to recognize and more irregular in contour in more severely involved regions
(yellow arrows).
leukemia, and lymphoproliferative diseases; lymphangiomatosis (Fig. 3-6) (29,30); congenital pulmonary lymphangiectasia (31,32), interstitial infiltration associated
with amyloid (33), Erdheim-Chester disease (Fig. 3-7)
Nodular Septal Thickening
Nodular or “beaded” septal thickening occurs in l ymphatic
or infiltrative diseases, including lymphangitic spread of
carcinoma and lymphoma (4,7,28), lymphoproliferative
disease such as lymphoid interstitial pneumonia (LIP)
(43–45), sarcoidosis (46–49), silicosis or coal worker’s
pneumoconiosis (CWP) (50), and amyloidosis or lightchain deposition disease (33,51) (Figs. 3-9 and 3-10).
Nodular septal thickening is most appropriately considered along with other nodular patterns of diffuse lung
disease. Septal nodules are often associated with a so-called
“perilymphatic” or “lymphatic” distribution of nodules, in
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A
B
FIGU RE 3-13 Irregular septal thickening in UIP. A: Irregular reticular opacities (arrows) are visible
in the peripheral lung in a patient with pulmonary fibrosis related to treatment with methotrexate. These
may represent irregularly thickened septa or perilobular fibrosis. B: Irregular interlobular septal thickening or
perilobular fibrosis (arrows) in a patient with IPF. C: Histologic section in a patient with IPF. Irregular bands of
fibrosis (arrows) are visible within the periphery of lobules, involving the interlobular septa.
C
A
B
FIGU RE 3-14 A perilobular pattern in OP. A and B: Thickened interlobular septa and thicker arcades are visible (arrows) in a patient with OP related to dematomyositis.
Areas of consolidation are also present.
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TABLE 3-1 Differential Diagnosis of Interlobular Septal Thickening
Diagnosis
Comments
Lymphangitic carcinomatosis, lymphoma, leukemia
Common; predominant finding in most; usually smooth; sometimes nodular
Lymphoproliferative disease (e.g., LIP)
Smooth or nodular; other abnormalities (i.e., nodules) typically present
Lymphangiomatosis
Rare, smooth
Congenital pulmonary lymphangiectasia
Rare, smooth
Pulmonary edema
Common; predominant finding in most; smooth; ground-glass opacity can be present
Pulmonary hemorrhage
Smooth; associated with ground-glass opacity
Erdheim-Chester disease
Rare, smooth
Pneumonia (e.g., viral, Pneumocystis carinii)
Smooth; associated with ground-glass opacity
Sarcoidosis
Common; usually nodular or irregular; conglomerate masses of fibrous tissue with traction
bronchiectasis typical in end stage
IPF or other cause of UIP
Sometimes visible but not common; appears irregular; intralobular thickening and
honeycombing usually predominates
NSIP
With findings of ground-glass opacity and reticulation
Silicosis/CWP; talcosis
Occasionally visible; usually nodular; irregular in end-stage disease
Asbestosis
Sometimes visible; irregular
HP (chronic)
Uncommon; irregular reticular opacities and honeycombing usually predominate
Amyloidosis
Smooth or nodular
OP
Perilobular pattern; thick, ill-defined “septal thickening”
Elderly patients
Some septal thickening normal
which abnormalities occur primarily in relation to pulmonary lymphatics (9,14,30,47). In addition to septal nodules,
a perilymphatic pattern is associated with interstitial thickening or nodules involving (a) the subpleural regions, (b) the
peribronchovascular interstitium in a perihilar location, and
(c) the centrilobular peribronchovascular interstitium. This
pattern is most typical of patients with sarcoidosis, silicosis,
lymphangitic spread of carcinoma or other neoplasms, and
lymphoproliferative disease. Nodular patterns of diffuse
lung disease are discussed in detail in the next chapter.
Nodular septal thickening in sarcoidosis, silicosis, and
CWP is usually best seen in the upper lobes and parahilar regions, because of the tendency of these diseases to
predominate in the upper lobes, but this is not always
the case. Lymphoproliferative disease is often diffuse in
distribution or basal predominant. Lymphangitic spread
Interlobular septal thickening
Irregular
(lung distortion)
Smooth
Thick septa
predominant
Sarcoidosis
Asbestosis
UIP
Fibrotic HP
Edema
Lymphangitic tumor
Lymphoproliferative disease
Lymphangiectasia
Amyloidosis
Pulmonary veno-occlusive disease
Erdheim-Chester disease
OP
Nodular
Ground-glass opacity
predominant
“Crazy-paving”
differential
diagnosis
Perilymphatic
diseases;
Sarcoidosis
Lymphangitic tumor
Lymphoproliferative disease
Silicosis and CWP
Amyloidosis
FIGU RE 3-15 Algorithmic approach to the diagnosis of interlobular septal thickening.
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of neoplasm has a variable distribution, and may be
diffuse or localized.
Irregular Septal Thickening
In patients who have interstitial fibrosis, septal thickening visible on HRCT is often irregular in appearance and
associated with distortion of lung architecture (Figs. 3-11
to 3-13) (52–56). Although interlobular septal thickening can be seen on HRCT in association with fibrosis
and honeycombing (11), it is not usually a predominant
feature (5,57,58). Generally speaking, in the presence of
significant fibrosis and honeycombing, distortion of lung
architecture makes the recognition of thickened septa
difficult, except in less-involved lung regions (Fig. 3-11).
Among patients with pulmonary fibrosis and “end-stage”
lung disease, the presence of interlobular septal thickening on HRCT is most frequent in patients with sarcoidosis
(Fig. 3-12) (56% of patients) and is less common in those
with usual interstitial pneumonia (UIP) of various causes
(Fig. 3-13), asbestosis, and hypersensitivity pneumonitis
(HP) (Fig. 3-11) (58). The frequency of septal thickening
and fibrosis in patients with sarcoidosis reflects the tendency of active sarcoid granulomas to involve the interlobular septa.
In patients with idiopathic pulmonary fibrosis (IPF)
or UIP of other cause, irregular reticular opacities are
often visible on HRCT, which appear to represent thickened interlobular septa. However, this finding usually
correlates with the presence of fibrosis predominantly
affecting the periphery of acini and the secondary lobule
rather than the septa themselves (30,57). Nonetheless, the
HRCT appearance is similar to that of irregular septal
thickening (Fig. 3-13).
In patients with irregular interlobular septal thickening resulting from fibrosis, other findings such as honeycombing, traction bronchiectasis, and the distribution
of abnormalities are usually most valuable in differential
diagnosis.
The Perilobular Pattern
Pulmonary disease occurring predominantly in relation
to interlobular septa and the periphery of lobules has
been termed perilobular (10,19,36,59,60). Johkoh et al.
(41,60) emphasized that a perilobular distribution of disease may reflect abnormalities of the peripheral alveoli
and subpleural interstitium in addition to thickening of
interlobular septa (Fig. 3-13). Peripheral lobular fibrosis
may result in irregular reticular opacities, which mimic
the appearance of interlobular septal thickening.
A peripheral lobular or “perilobular” distribution of
abnormalities has been reported in as many as half of
patients with OP (36). These abnormalities result in an
appearance (on HRCT) of arcuate or polygonal opacities, which are less well defined, and may be thicker,
than thickened interlobular septa, and may be associated with areas of ground-glass opacity or consolidation
(Fig. 3-14). Although the histologic correlates of this pattern are unclear, it is likely related to OP involving distal
airspaces.
HONEYCOMBING
Extensive interstitial fibrosis that results in alveolar disruption and bronchiolectasis produces the classic and
characteristic appearance of honeycombing or honeycomb lung (61). Pathologically, honeycombing is defined
by the presence of small air-containing cystic spaces,
generally lined by bronchiolar epithelium and having
thickened walls composed of dense fibrous tissue. Honeycombing indicates the presence of end-stage lung and
can be seen in a number of diseases leading to end-stage
pulmonary fibrosis (58,62).
Honeycombing produces a characteristic cystic
appearance on HRCT, and when present, allows a confident diagnosis of lung fibrosis (Table 3-2) (5,52,61). On
HRCT, the cystic spaces of honeycombing usually range
from 3 mm to 1 cm in diameter, although they can be as
large as several centimeters in diameter; they are characterized by clearly definable walls 1 to 3 mm in thickness (5,52) (Figs. 3-1 and 3-16 to 3-19). The cysts are
air-filled and appear lucent in comparison to normal lung
parenchyma. Although there is some overlap between
the appearances of fine honeycombing and intralobular
interstitial thickening, if the spaces between the lines (i.e.,
the holes) appear to be air-filled (i.e., black), rather than
having the density of lung parenchyma, honeycombing
is likely present. Honeycombing has been described by
Zerhouni et al. as producing an “intermediate reticular
pattern” to distinguish it from the larger pattern seen with
interlobular septal thickening and the smaller pattern visible with intralobular interstitial thickening (12).
Honeycomb cysts often predominate in the peripheral and
subpleural lung regions regardless of their cause, and perihilar lung can appear normal despite the presence of extensive
peripheral abnormalities (Fig. 3-16). It must be emphasized
that unless cysts are visible in the immediate subpleural lung,
honeycombing cannot be diagnosed with certainty. Airfilled cysts that are not subpleural may represent traction
bronchiectasis, emphysema, pneumatoceles, or a cystic lung
disease such as lymphangiomyomatosis or Langerhans cell
TABLE 3-2 HRCT Characteristics of Honeycomb Cysts
Thick, easily seen walls
Air-filled (i.e., black)
Usually 3–10 mm in diameter
Immediately subpleural in location
They occur in clusters or layers and share walls (multiple layers are
seen in late disease)
Nonbranching
Associated with other findings of fibrosis (traction bronchiectasis,
irregular reticulation, volume loss, lung distortion)
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A
B
FIGU RE 3-16 A — C: Honeycombing in IPF. A: HRCT
C
A
shows honeycomb cysts in the peripheral and subpleural regions.
They are air-filled and have a thick and easily recognizable wall. Note
that the cysts occur in several layers and are generally less than
1 cm in diameter. B: Resected left lung at a similar level in a different
patient with IPF shows honeycomb cysts, which are most extensive
in the posterior and peripheral lung. C: Sagittal lung slice in a patient
with IPF shows honeycombing (arrows) in the posterior subpleural
lung. (Courtesy of Martha Warnock, MD.)
B
FIGU RE 3-17 A and B: Honeycombing in a patient with IPF (prone HCRT). Honeycombing results in cysts of various sizes, which have a peripheral predominance.
The cysts have thick and clearly defined walls. In areas of honeycombing, lobular anatomy cannot be resolved because of architectural distortion.
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A
B
FIGU RE 3-18 A–C: Honeycombing in rheumatoid lung disease.
HRCT shows honeycomb cysts with a distinct subpleural predominance.
The cysts are generally smaller than 1 cm in diameter and share walls.
Other findings of fibrosis include irregular thickening of the left major
fissure (B, arrow) and traction bronchiectasis (C, arrow).
C
A
B
FIGURE 3-19 Honeycombing in association
with paraseptal emphysema in a patient with IPF. A: Some cysts in
the lung periphery, particularly in the left lung, likely reflect paraseptal
emphysema, rather than lung fibrosis. The cysts are larger than 1 cm. B and
C: More typical honeycombing is visible in the posterior right lung base.
Emphysema and honeycombing may occur in combination in some patients,
and their distinction on any one slice may be difficult. Emphysema, however,
predominates in the upper lobes and honeycombing predominates in the
lower lobes. In the presence of emphysema, honeycomb cysts may be larger
than is typical.
C
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TABLE 3-3 Comparison of HRCT Features of
Paraseptal Emphysema and Honeycombing
Paraseptal
Emphysema
Honeycombing
Layers
One layer
One or more layers
Associated findings
Centrilobular
emphysema,
bullae in some
Traction
bronchiectasis,
reticulation
Distribution
Upper-lobe
predominant
Lower-lobe
predominant in
most
Size
Often >1 cm
Usually <1 cm
Overall lung volume
Increased
Decreased
histiocytosis. Also, a basal predominance is usually present, a
finding that is helpful in distinguishing honeycombing from
paraseptal emphysema, in which subpleural cysts are visible.
In early honeycombing, only a few isolated subpleural
cysts may be seen, but it is best to reserve a diagnosis
of honeycombing for scans showing clusters, groups, or
rows of clearly defined subpleural cysts with easily recognized walls (Figs. 3-16 to 3-18). It is generally a good
idea to be conservative when describing this finding as
it means that pulmonary fibrosis is present, and it is an
essential criterion in the diagnosis of UIP and IPF (10,63).
A reasonable, but admittedly arbitrary, rule of thumb
would be that honeycombing can be diagnosed if at least
three air-filled (black) cysts, 3 to 10 mm in diameter, with
thick, recognizable walls, are seen in a row or cluster in a
subpleural location (Fig. 3-17).
Extensive subpleural honeycomb cysts share walls
and often occur in several contiguous layers (Figs. 3-16
to 3-18). This latter finding can allow honeycombing to
be distinguished from subpleural emphysema (paraseptal
emphysema); in paraseptal emphysema, subpleural cysts
usually occur in a single layer (Table 3-3). But also keep in
mind that paraseptal emphysema and honeycombing may
coexist; in such patients, the cystic spaces of honeycombing may appear larger than usual, and it may be difficult
to determine where emphysema stops and honeycombing
begins (Fig. 3-19). The differentiation of honeycombing and
paraseptal emphysema is further discussed in Chapter 6.
Lung consolidation or infiltration in a patient with emphysema or cystic lung disease can mimic the appearance of
honeycombing.
Honeycombing is usually associated with other findings of lung fibrosis, such as volume loss, architectural
distortion, intralobular lines, traction bronchiectasis,
traction bronchiolectasis, and irregular subpleural interstitial thickening. Subpleural cysts seen in the absence of
other findings of fibrosis likely represent another abnormality such as emphysema. Significant interlobular septal
thickening is not commonly visible in association with
honeycombing, except in patients with sarcoidosis (58).
In patients with HRCT findings of septal thickening, the
presence of honeycombing distinguishes fibrosis from
other causes of reticulation, such as pulmonary edema or
lymphangitic spread of carcinoma.
Significance of Honeycombing
The presence of honeycombing on HRCT is indicative of
significant lung fibrosis and, in many cases, will lead to
a diagnosis of UIP and a consideration of its most common causes, including IPF (Figs. 3-16, 3-17, and 3-20)
(15,64,65); collagen-vascular diseases (66), most notably
rheumatoid arthritis (Fig. 3-18) (67) and scleroderma
(68); drug-related fibrosis; asbestosis and other pneumoconioses (69,70); chronic HP; diffuse alveolar damage
(DAD) resulting from acute respiratory distress syndrome
Honeycombing
Subpleural, posterior,
lower lobe predominant;
no atypical findings
Upper-, mid-lung, or
peribronchial
predominance
Atypical findings
also present
(GGO, nodules,
consolidation, cysts,
mosaic perfusion,
air trapping)
IPF (70%)
Collagen-vascular disease
Drug-related fibrosis
Asbestosis
Chronic HP
Sarcoidosis (rare)
Fibrotic NSIP (rare)
Chronic HP
Sarcoidosis
Radiation
Fibrotic ARDS
IPF
Interstitial pneumonias
other than UIP
(NSIP, OP, LIP, DIP)
Chronic HP
Sarcoidosis
Cystic lung disease
FIGU RE 3-20 Algorithmic approach to the differential diagnosis of honeycombing.
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TABLE 3-4 Differential Diagnosis of Honeycombing
Diagnosis
Comments
IPF
Common (70%); peripheral, basal, and subpleural predominance
Common; any collagen-vascular disease but most common in rheumatoid arthritis and scleroderma
Many drugs possible; may be indistinguishable from other causes
Asbestosis
Common in advanced disease; peripheral, basal, and subpleural predominance
HP (chronic)
Common in advanced disease; may be peripheral, patchy, or diffuse; midlung predominance common
DAD in the ARDS
Honeycombing in some; may be anterior
Pleuroparenchymal fibroelastosis
Upper-lobe, peripheral predominance; pleural thickening
Radiotherapy
Localized to the radiation port
Sarcoidosis
A few percent of cases; may be peripheral or patchy; upper-lobe predominance common; associated
with peribronchovascular fibrosis
NSIP (fibrotic)
Uncommon and minimal extent; other findings usually predominate
Other idiopathic IPs (i.e., DIP, RB-ILD,
OP, AIP, LIP)
Uncommon and minimal extent; other findings usually predominate
Silicosis/CWP, other pneumoconioses
Uncommon
(ARDS) or radiotherapy; fibrosis in some smokers
(71,72); and in association with interstitial pneumonias
(IPs) other than UIP (Table 3-4).
For example, in a study of HRCT appearances of 129
proven cases of idiopathic IP, admittedly including atypical cases requiring biopsy for diagnosis, honeycombing
was visible in 71% of patients with UIP, 39% of patients
with desquamative interstitial pneumonia (DIP), 30% of
patients with acute interstitial pneumonia (AIP), 26% of
patients with nonspecific interstitial pneumonia (NSIP),
and 13% of patients with OP (73). Honeycombing with
a basal predominance was found in 59% of patients with
UIP, 26% of patients with DIP, 22% of patients with NSIP,
and 4% of patients with OP (73). However, honeycombing
is significantly less extensive in patients with IPs other than
UIP (15). In a study by Sumikawa et al. (15), the extent of
honeycombing averaged 4.4% of lung parenchyma in UIP;
0.3% and 0.6% in patients with cellular and fibrotic NSIP,
respectively; 0.7% in DIP or respiratory bronchiolitis-
interstitial lung disease (RB-ILD); and 0.2% in LIP.
In a survey of patients with end-stage lung (58), subpleural honeycombing was present in 96% of patients
with UIP associated with IPF or rheumatoid arthritis, in
100% of asbestosis patients, in 44% of those with sarcoidosis, and in 75% of those with chronic HP (58,74).
Honeycombing is relatively uncommon and limited in
extent in patients with NSIP (75–77), but may be seen in
a few percent of patients with fibrotic NSIP (65).
The distribution of honeycombing is of value in differential diagnosis (Fig. 3-20). Honeycombing in patients
with IPF and asbestosis is usually most severe in the subpleural lung regions and at the lung bases (63). The honeycombing in chronic HP may be most marked in the
subpleural lung regions, but is more often patchy in distribution, and tends to be most severe in the midlung
zones with relative sparing of the lung bases (58,74).
Honeycombing in sarcoidosis often has an upper-lobe
predominance. In patients who have pulmonary fibrosis
resulting from ARDS (78), findings of fibrosis and honeycombing on follow-up HRCT had a striking anterior
distribution. This distribution of reticular opacities and
lung fibrosis is unusual in other diseases. Lung fibrosis
limited to anterior lung regions probably reflects the fact
that patients with ARDS typically develop posterior lung
atelectasis and consolidation during the acute phase of
their disease; it is believed that consolidation protects
the posterior lung regions from the effects of mechanical
ventilation, including high ventilatory pressures and high
oxygen tension (78).
Honeycombing in the Diagnosis
of UIP and IPF
In patients who present with clinical features of UIP and
lack a history of collagen-vascular disease or exposure to
dusts, organic antigens, or drugs, the presence of a predominantly subpleural and basal distribution of fibrosis
and honeycombing on HRCT can be sufficiently characteristic of IPF to obviate biopsy (63,79–81). HRCT findings,
including the presence of honeycombing with a subpleural
and basal predominance, have been shown to be highly
accurate in making this diagnosis (58,63,82–90). In a
study by Hunninghake et al. (89) of 91 patients with idiopathic IP, clinical, physiologic, chest radiographic, and CT
features were prospectively recorded; 54 patients (59%)
received a pathologic diagnosis of UIP/IPF. On multivariate analysis, lower-lung honeycombing (odds ratio, 5.36)
and upper-lung irregular lines (odds ratio, 6.28) were the
only independent predictors of UIP/IPF. Using only these
two factors, a diagnosis of UIP/IPF could be established
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TABLE 3-5 HRCT Findings Predicting a UIP Pattern
(All are Necessary)
Basal and subpleural-predominant distribution
Reticular opacities, traction bronchiectasis (i.e., findings supportive of
fibrosis)
Honeycombing
Absence of inconsistent findings (see Table 3-6)
with a sensitivity of 74%, a specificity of 81%, and a positive predictive value of 85%.
A recent paper (63) presented the cooperative statement of the American Thoracic Society, European Respiratory Society, Japanese Respiratory Society, and Latin
American Thoracic Association regarding the diagnosis
of UIP and IPF. The numerous authors concluded that,
in the absence of a lung biopsy, a clinical diagnosis of IPF
can be solely based on the presence of a UIP pattern on
HRCT and the absence of a history of diseases or exposures usually associated with this pattern (i.e., collagen
disease, drugs, dusts, or organic antigens). Keep in mind
that the differential diagnosis of a UIP pattern is shorter
than the differential diagnosis of honeycombing, and typically includes IPF, collagen-vascular diseases, asbestosis,
drug reactions, and sometimes HP.
The authors, in turn, specify that the HRCT diagnosis of
a UIP pattern should be based on four criteria, all of which
must be present (Table 3-5, Fig. 3-21) (63). These are:
6.mosaic perfusion or air trapping, bilateral and in
three or more lobes (Fig. 3-22), and
7. segmental or lobar consolidation.
The presence, extent, and progression of honeycombing are important in determining the prognosis of patients
with IPF and other interstitial lung diseases (91,92). A
recent study (92) assessed the prognostic implications of
CT and physiologic variables at baseline and on sequential evaluation in patients with fibrosing IP, both idiopathic and associated with collagen vascular disease.
A
1. the presence of a basal and subpleural predominance
of abnormalities,
2.
reticular opacities with or without traction
bronchiectasis,
3. honeycombing, and
4. the absence of findings inconsistent with the diagnosis.
This combination of four findings predicts a pathologic
diagnosis of UIP in 95% to 100% of cases. However, that
not all cases of UIP will meet these criteria. These criteria
are specific, but likely not sensitive. A HRCT diagnosis of
a “possible UIP pattern” is based on the same criteria, but
with honeycombing being absent.
The same authors describe HRCT findings that are
considered inconsistent with a UIP pattern (63). Each of
these findings is typical of an IP other than UIP or a different lung disease (Table 3-6). Any one of these findings
is sufficient for determining that HRCT is inconsistent
with a UIP pattern. These findings include:
1. an upper- or midlung predominance of abnormalities
(Fig. 3-11C),
2.a peribronchovascular predominance of abnormalities (Fig. 3-12),
3.extensive ground-glass opacity, exceeding reticulation in extent,
4. profuse micronodules, bilateral and upper lobe,
5. discrete cysts, not representing honeycombing,
87
B
C
FIGU RE 3-21 A UIP pattern in a patient with IPF. A–C: Fibrosis
is characterized by reticular opacities, traction bronchiectasis, and areas of
honeycombing (arrows). The honeycomb cysts are seen in rows and clusters.
Findings of fibrosis predominate in the bases and subpleural regions. No atypical
findings are present.
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TABLE 3-6 Features Inconsistent with a UIP Pattern
HRCT feature
Likely alternative diagnoses
Ground-glass opacity outside areas of fibrosis, exceeding reticulation
NSIP, HP, other IPs
Mosaic perfusion/air trapping
HP
Centrilobular nodules
HP
Perilymphatic nodules
Sarcoidosis, pneumoconioses
Peripheral fibrosis with only minimal honeycombing, subpleural sparing
NSIP
Upper-lobe distribution of abnormalities
Sarcoidosis, pneumoconioses, HP
Parahilar, peribronchovascular predominance
NSIP, HP, sarcoidosis, pneumoconioses
Lower-lobe distribution of findings, not subpleural-predominant
HP, NSIP
The only independent predictors of mortality were the
baseline extent of honeycombing and progression of honeycombing on follow-up studies (p = 0.001 and 0.002,
respectively). Neither baseline nor serial change in physiologic variables, nor the presence of collagen vascular disease, was predictive of rate of survival.
Variability in the Diagnosis
of Honeycombing
Although it may seem that honeycombing should be easily diagnosed, with good interobserver agreement, this
is not always the case. Subtle or early honeycombing
B
A
C
D
FIGU RE 3-22 HRCT inconsistent with UIP and IPF in a patient with chronic HP and honeycombing. A and B: Inspiratory images show reticulation, traction
bronchiectasis, and honeycombing (arrows) in the subpleural lung. C and D: Dynamic expiratory images at the same levels show air trapping in multiple lobules (arrows) in three
lobes, a finding inconsistent with UIP.
DESIGN SERVICES OF
may be difficult to distinguish from pure reticulation or
traction bronchiectasis, and other abnormalities such as
paraseptal emphysema and cystic lung diseases may be
confused with this finding (93). In a recent study (93)
assessing interobserver variability in the diagnosis of
honeycombing, five experts scored 80 HRCT images for
the presence of honeycombing using a 5-point scale (5 =
definitely present to 1 = definitely absent) to establish
a reference standard. Forty-three observers, a number of
whom were expert thoracic radiologists, subsequently
scored the HRCT using the same scoring system. Their
agreement with the reference standard was only moderate (weighted k values: 0.40–0.58); of note, agreement
among the five study experts as to the presence of honeycombing was only slightly better (k value = 0.45–
0.67). On a case-by-case basis, observers agreed that
honeycombing was present in 21 of the 80 (26%) cases
and agreed that honeycombing was absent in 18 (22%).
They disagreed as to the presence of honeycombing in
23 images (29%); these cases included honeycombing
mixed with traction bronchiectasis, large cysts, and
fibrosis with superimposed emphysema. The remaining
18 images (22%) did not fulfill the criteria of the previous three categories.
89
Intralobular Interstitial
Thickening (Intralobular Lines)
Intralobular interstitial thickening results in a fine reticular pattern on HRCT, with the visible lines separated by
a few millimeters (Fig. 3-1) (52). Lung regions showing
this finding characteristically show a fine lace- or netlike
appearance (Figs. 3-1 and 3-23 to 3-28).
Intralobular interstitial thickening is a
nonspecific
finding; it may be associated with interstitial
fibrosis
(Figs. 3-23 to 3-26) or interstitial infiltration or inflammation in the absence of fibrosis (Figs. 3-27 and 3-28).
The presence of intralobular interstitial thickening is
described using the term intralobular lines (10,52). This
finding is responsible for the “small reticular pattern”
originally described by Zerhouni et al. (12). Intralobular
lines may be seen in isolated or associated with interlobular septal thickening or honeycombing.
In patients with intralobular interstitial thickening
resulting from fibrosis, intralobular bronchioles may be
visible in the peripheral lung (Figs. 3-1 and 3-23). This is
not a normal finding, and it results from a combination
of bronchiolar dilatation (i.e., traction bronchiolectasis)
and thickening of the peribronchiolar interstitium that
A
B
FIGU RE 3-23 Intralobular interstitial thickening and traction bronchiolectasis in a patient with IPF. A: Prone HCRT shows a fine network of lines in the lung periphery.
Intralobular bronchioles (arrows) are visible throughout the peripheral lung as a result of fibrosis and traction bronchiolectasis. B: Histologic specimen in a patient with IPF shows
fibrosis, intralobular interstitial thickening, and bronchiolecstasis (br.) (Courtesy of Martha Warnock, MD.)
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FIGU RE 3-24 Intralobular interstitial thickening in a patient with early IPF.
On a supine scan, fine reticular opacities are visible posteriorly. This abnormality
reflects intralobular interstitial thickening.
A
surrounds them (52,57). Traction bronchiectasis, dilatation of large bronchi occurring because of fibrosis, may
also be seen (Figs. 3-25 and 3-26). Traction bronchiectasis
and traction bronchiolectasis are described in more detail
below.
Intralobular interstitial thickening as perceived on
HRCT reflects thickening of the distal peribronchovascular
B
A
C
FIGURE 3-26 Prone scans in a patient with IPF. A: Abnormal reticulation
representing intralobular interstitial thickening predominates in the subpleural lung. B: At
a lower level, fibrosis is more extensive. Traction bronchiectasis and bronchiolectasis are
predominant features. Also, note the irregular thickening of the major fissure (large arrow)
and irregular interlobular septal thickening. C: Typically, traction bronchiectasis and bronchiolectasis are characterized by irregular, varicose, or cockscrew appearance (arrows).
B
FIGU RE 3-25 Prone scans in a patient with fibrotic NSIP. A and B: Abnormal reticulation represents intralobular interstitial thickening. Traction bronchiectasis
(arrows) is easily seen.
interstitial tissues and the intralobular interstitium. As
an isolated finding, it is most commonly seen in patients
with pulmonary fibrosis (Figs. 3-23 to 3-27). In patients
who have IPF or other causes of UIP, such as rheumatoid arthritis, scleroderma, or other collagen-vascular
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91
FIGU RE 3-27 Cellular NSIP with intralobular interstitial thickening and
ground-glass opacity. Ground-glass opacity predominates in the posterior lung, with
subpleural sparing typical of NSIP. Fine reticular opacities in association with the
ground-glass represent intralobular lines.
diseases, fibrosis tends to predominantly involve alveoli
in the periphery of acini, resulting in a “peripheral acinar
distribution” of interstitial fibrosis (30,57); this histologic
finding correlates with the presence of intralobular lines
on HRCT.
Intralobular lines, resulting in a fine reticular p
attern,
can also be seen in patients with NSIP or other IPs
(Table 3-7) (Figs. 3-25, 3-27, and 3-29) (15,73,75-77,94).
In NSIP, the presence of intralobular lines or irregular
linear opacities correlated with the presence of interstitial fibrosis and was often associated with bronchial or
bronchiolar dilatation (traction bronchiectasis or bronchiolectasis) (75,95). In a study of HRCT appearances
of various idiopathic IPs, intralobular lines were visible
in 97% of patients with UIP, 93% of patients with NSIP,
78% of patients with DIP, 71% of patients with OP, and
F I G U R E 3-28 Pulmonary hemorrhage with intralobular interstitial
thickening and ground-glass opacity. Patchy ground-glass opacity and intralobular
lines represent focal pulmonary hemorrhage.
70% of patients with AIP (73). Intralobular lines are also
common in asbestosis (96).
Intralobular interstitial thickening can be seen in the
absence of significant fibrosis in patients with a variety
of infiltrative or inflammatory lung diseases (Table 3-7)
(Figs. 3-27 to 3-29) (97). When this is the case, traction
bronchiectasis and other manifestations of fibrosis are
less evident or absent, and ground-glass opacity may be
visible instead. Intralobular interstitial thickening may
be seen in association with interlobular septal thickening in patients with diseases such as pulmonary edema,
TABLE 3-7 Differential Diagnosis of Intralobular Interstitial Thickening
Diagnosis
Comments
Common (97%); often associated with honeycombing
HP (chronic)
Common; associated with other findings of fibrosis
Asbestosis
Common; associated with other findings of fibrosis
NSIP
Common (93%); ground-glass opacity (cellular NSIP) or traction
bronchiolectasis (fibrotic NSIP) commonly visible
Other idiopathic IPs (i.e., DIP, OP, AIP)
Common (70%); other findings (i.e., traction bronchiolectasis, ground-glass
opacity, consolidation also present)
Smooth or nodular; associated with septal thickening
Pulmonary edema
Smooth; associated with septal thickening and ground-glass opacity
Pulmonary hemorrhage
Pneumonia (e.g., viral, Pneumocystis carinii)
Alveolar proteinosis
Other causes of septal thickening, lung fibrosis, or lung infiltration
See interlobular septal thickening, honeycombing, crazy paving differential
diagnoses
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Intralobular lines
Traction bronchiectasis
also present
Septal thickening
also present
Ground-glass opacity
also present
Fibrosis
Septal thickening
differential
diagnosis
Infiltrative or
inflammatory
disease
Consider
causes of
honeycombing
and fibrotic lung
disease
“Crazy paving”
differential diagnosis;
e.g., edema
Hemorrhage
Atypical infections
Interstitial pneumonias
HP
Adenocarcinoma
FIGU RE 3-29 Algorithmic approach to the differential diagnosis of intralobular lines.
pulmonary hemorrhage, atypical pneumonia, lymphangitic spread of carcinoma, and other infiltrative processes
such as cellular NSIP (7). In the absence of traction bronchiectasis or bronchiolectasis, the differential diagnosis
of this finding is identical to that of interlobular septal
thickening.
Intralobular lines may also be seen in patients with
ground-glass opacity or the pattern of crazy paving, in
association with diseases such as pulmonary edema or
hemorrhage (25), some pneumonias (e.g., Pneumocystis
jiroveci, cytomegalovirus), IPs such as NSIP and OP, HP,
invasive mucinous adenocarcinoma, and alveolar proteinosis (Figs. 3-8 and 3-29).
NONSPECIFIC RETICULATION
Generally speaking, if a reticular pattern visible on
HRCT cannot be characterized as representing interlobular septal thickening, honeycombing, or intralobular
interstitial thickening (intralobular lines), the nonspecific terms “reticulation,” “reticular pattern,” or “reticular opacities” can be used to describe the abnormality
present (10).
Reticular opacities 1 to 3 mm thick, that cannot be
characterized as representing one of these patterns, are
often visible in patients with interstitial disease, representing bands of fibrosis or other causes of interstitial
infiltration (9). Such opacities may represent poorly
characterized irregular interlobular septal thickening,
poorly characterized areas of honeycombing, bands of
fibrous tissue in the periphery of pulmonary lobules or
bridging the lobule from the centrilobular region to the
lobular periphery, or thickening of the intralobular interstitium by fibrous tissue or because of inflammation or
infiltration.
This finding is nonspecific and may be seen in a v ariety
of diseases, including those associated with inflammation or fibrosis, including UIP and NSIP (73,75–77), and
in a percentage of cigarette smokers (71,72). In patients
who have UIP, irregular reticulation may be seen instead
of honeycombing, particularly in early cases or in less
abnormal regions (i.e., in the upper lobes of patients with
IPF); in patients with NSIP, reticulation is more common
than honeycombing.
THE INTERFACE SIGN
The presence of irregular interfaces between the aerated
lung parenchyma and bronchi, vessels, or visceral
pleural surfaces has been termed the interface sign by
Zerhouni et al. (1,12) (Figs. 3-1 and 3-30). The interface sign is nonspecific and is commonly seen in patients
with an interstitial abnormality, regardless of its cause.
In the original description of the interface sign, this finding was visible in 89% of patients with interstitial lung
disease (12).
The interface sign is generally associated with an
increase in lung reticulation; the presence of thin linear
opacities contacting the bronchi, vessels, or pleural surfaces is responsible for their having an irregular or
spiculated appearance on HRCT (Fig. 3-30). The linear
opacities producing the interface sign may represent
thickened interlobular septa, intralobular lines, or irregular scars (Fig. 3-1). The interface sign is most frequently
visible in patients with fibrotic lung disease, but it may
also be seen in patients with infiltrative diseases, inflammatory disease, and pulmonary edema. Nishimura et al.
(57) reported the presence of irregular pleural surfaces
and irregular vessel margins in 94% and 98%, respectively, of patients with IPF. In virtually all cases showing
DESIGN SERVICES OF
FIGU RE 3-30 The interface sign in fibrotic sarcoidosis. The irregular
appearance of the fissure and the edges of vessels reflects the presence of
increased lung reticulation, whether due to intralobular lines, septal thickening,
or honeycombing.
the interface sign, other, more specific, abnormal findings
will also be visible on HRCT.
TRACTION BRONCHIECTASIS
AND TRACTION BRONCHIOLECTASIS
In patients with lung fibrosis and a reticular pattern visible on HRCT, bronchial dilatation is commonly present,
resulting from traction by fibrous tissue on the bronchi
walls. This is termed traction bronchiectasis (Figs. 3-1
and 3-31); it typically results in irregular bronchial dilatation with the abnormal bronchus appearing varicose
or “corkscrew” (52,98). Traction bronchiectasis usually
involves the segmental and subsegmental bronchi and is
most commonly visible in the perihilar regions in patients
with significant lung fibrosis (Figs. 3-25 and 3-26) (49,99).
It can also affect small peripheral bronchi or bronchioles
(Fig. 3-23), an occurrence termed traction bronchiolectasis.
The branching or irregular tubular appearance of traction
bronchiectasis or bronchiolectasis should be distinguished
from honeycombing whenever possible. As reviewed
above, the diagnosis of honeycombing should be limited to
cases showing rows, layers, or clusters of thick-walled air
cysts in the immediate subpleural lung. In a patient with
fibrosis, thick-walled, air-filled cysts separated from the
pleural surface often represent traction bronchiectasis or
traction bronchiolectasis.
The presence of traction bronchiectasis usually indicates that lung fibrosis is present, and the differential diagnosis includes a large number of fibrotic lung diseases.
Common lung diseases associated with fibrosis and traction bronchiectasis, but without visible honeycombing,
93
FIGU RE 3-31 Traction bronchiectasis and traction bronchiolectasis in
pulmonary fibrosis. A thin lung slice from a patient with IPF shows honeycombing in
the posterior lung. Irregular dilatation of bronchi (traction bronchiectasis) having a
varicose or corkscrew appearance (red arrows) reflects the presence of lung fibrosis.
Dilatation of bronchioles (traction bronchiolectasis, blue arrows) in less-abnormal
lung regions also reflects surrounding lung fibrosis.
include fibrotic NSIP, end-stage sarcoidosis, and chronic
HP, but keep in mind that UIP may also result in lung
fibrosis without honeycombing. When honeycombing is
also present, UIP is most likely.
Some patients with cellular NSIP and other inflammatory lung diseases can show bronchial dilatation
resembling traction bronchiectasis that resolves with the
resolution of the lung disease. Often, bronchial dilatation in these patients is cylindrical rather than irregular and varicose, and findings of inflammation such as
ground-glass opacity or consolidation predominate in the
abnormal regions. Likely, a decrease in lung compliance
associated with interstitial infiltration results in bronchial
dilatation in these cases.
In patients with lung fibrosis and intralobular interstitial thickening, intralobular bronchioles may be visible
because of their dilatation (traction bronchiolectasis) and
surrounding fibrous tissue (Fig. 3-23). The differential
diagnosis of this finding is that of lung fibrosis. Akira
et al. (69) found traction bronchiolectasis to be more
common in patients with IPF (78%) than in those with
asbestosis (20%). In some cases, the HRCT pattern of
intralobular lines can reflect the presence of very small
honeycomb cysts or dilated bronchioles associated with
surrounding lung fibrosis. Nishimura et al. (57) reviewed
46 cases of IPF with UIP, correlating findings on CT with
appearances of lung histology from open biopsy specimens or autopsy. Visibility of centrilobular bronchioles
in association with a fine reticulation or increased lung
attenuation was found in 96% of cases, indicating the
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presence of bronchiolar dilatation, fibrosis, and “microscopic” honeycombing, with dilated bronchioles or small
cysts measuring approximately 1 mm in diameter (57).
PERIBRONCHOVASCULAR
INTERSTITIAL THICKENING
Central bronchi and pulmonary arteries are surrounded
and enveloped by a strong connective tissue sheath, termed
the peribronchovascular interstitium, extending from the
level of the pulmonary hila into the peripheral lung. In the
lung periphery, the peribronchovascular interstitium surrounds centrilobular arteries and respiratory bronchioles
(Fig. 2-1) (100). The peribronchovascular interstitium has
been termed the axial interstitium by Weibel (101).
Thickening of the perihilar peribronchovascular interstitium occurs in many diseases that cause a generalized
interstitial abnormality (Table 3-8) (2,4,7,102). Peribronchovascular interstitial thickening is common in patients
with lymphangitic spread of carcinoma (4,7,103); lymphoma (104); leukemia (105); lymphoproliferative disease such as LIP (43–45); interstitial pulmonary edema
(23,106); diseases that result in a perilymphatic distribution of nodules (e.g., sarcoidosis) (49); and in many
diseases that result in pulmonary fibrosis, particularly sarcoidosis, which has a propensity to involve the peribronchovascular interstitium (48,107). Peribronchovascular
interstitial thickening has also been reported in as many
as 65% of patients with NSIP (75) and 19% of patients
with chronic HP (74).
Because the thickened peribronchovascular interstitium
cannot be distinguished from the underlying opacity of
the bronchial wall or pulmonary artery, this abnormality
is usually perceived on HRCT as an increase in bronchial
wall thickness or an increase in diameter of pulmonary
artery branches (Fig. 3-32) (7). Apparent bronchial wall
thickening is the easier of these two findings to recognize. This finding is exactly equivalent to “peribronchial
cuffing” seen on plain chest radiographs in patients with
an interstitial abnormality. In patients with pulmonary
interstitial emphysema, air is commonly seen within the
peribronchovascular interstitium, outlining vessels and
bronchi (Fig. 3-32D) (108–110).
Peribronchovascular interstitial thickening is commonly present in patients with interlobular septal thickening, and as with septal thickening, it can appear smooth,
nodular, or irregular in different diseases (Figs. 3-2 to 3-5)
(100). Smooth peribronchovascular interstitial thickening is most typical of patients with lymphangitic spread
of carcinoma or lymphoma (Fig. 3-33) and interstitial
pulmonary edema (23,106), but can be seen in patients
with fibrotic lung disease as well. Nodular thickening of
the peribronchovascular interstitium is particularly common in sarcoidosis (Fig. 3-34) and lymphangitic spread of
carcinoma. The presence of irregular peribronchovascular
interstitial thickening, as an example of the interface sign,
is most frequently seen in patients with adjacent lung fibrosis. Extensive peribronchovascular fibrosis can also result
in the presence of large conglomerate masses of fibrous
tissue (Fig. 3-35). This can occur in patients with sarcoidosis, silicosis, tuberculosis, and talcosis, (49,107,111) and
is discussed in greater detail in Chapter 4.
Peribronchovascular interstitial thickening is easy
to diagnose if it is marked; in this instance, bronchial
walls appear several millimeters thick, and bronchovascular structures may show evidence of the interface
sign or nodules. However, the diagnosis of minimal
peribronchovascular thickening can be difficult and is
quite subjective, particularly if the abnormality is diffuse and symmetric. Although the thickness of the wall
of a normal bronchus should measure from one-sixth to
one-tenth of its diameter (see Chapter 2) (112), and in
several HRCT studies, a veraged about 0.2 of the bronchial diameter (113,114), there are no reliable criteria
as to what represents the upper limit of normal for the
combined thickness of bronchial wall and the surrounding interstitium (115). Furthermore, these measurements
vary, depending on the lung window chosen, and too
low a window mean can make normal bronchi or vessels appear abnormal. However, in many patients with
peribronchovascular interstitial thickening, and particularly in patients with lymphangitic spread of carcinoma
TABLE 3-8 Differential Diagnosis of Peribronchovascular Interstitial Thickening
Diagnosis
Comments
Common; smooth or nodular; may be the only abnormality
Lymphoproliferative disease (e.g., LIP)
Smooth or nodular; other abnormalities typically present
Pulmonary edema
Common; smooth
Sarcoidosis
Common; usually nodular or irregular; conglomerate masses of fibrous tissue with traction
bronchiectasis typical in end stage
Common; often irregular; associated with traction bronchiectasis; other findings of fibrosis
predominate
NSIP
Silicosis/CWP, talcosis
Conglomerate masses
HP (chronic)
Sometimes visible; often irregular; associated with traction bronchiectasis
DESIGN SERVICES OF
Paired bronchi and arteries
of similar size
(bronchoarterial ratio < 1)
Smooth
Nodular
Irregular
Peribronchovascular
Normal
Signet ring
sign
Bronchiectasis
FIGURE 3-32 Differentiation of peribronchovascular interstitial thickening and bronchiectasis. A: In a normal subject, bronchi are uniformly thin-walled and appear
approximately equal in diameter to adjacent pulmonary arteries. B: In the presence of peribronchovascular interstitial thickening, there appears to be an increase in bronchial wall
thickness and a corresponding increase in the diameter of pulmonary artery branches. The contours of the bronchi and vessels can appear smooth, nodular, or irregular in different
diseases. C: In bronchiectasis, bronchi are usually thick walled and appear larger than adjacent pulmonary arteries. This results in the so-called signet ring sign. D: CT with 3-mm
collimation in a patient with pulmonary interstitial emphysema. Air is visible within the peribronchovascular interstitial sheath, outlining pulmonary arteries (large black arrows) and
bronchi (small black arrow). Air also surrounds pulmonary veins.
FIGU RE 3-33 Peribronchovascular interstitial thickening. In a patient with
unilateral lymphangitic spread of carcinoma including the left lung, there is smooth
thickening of the peribronchovascular interstitium manifested as peribronchial cuffing
(arrows); this appearance is easily contrasted with that of normal bronchi in the right
lung. Note that the left-sided pulmonary artery branches appear similar in diameter to
the cuffed bronchi because the thickened interstitium surrounds them as well. Small
intrapulmonary vessels on the left also appear more prominent than those on the normal
side because of perivascular interstitial thickening. Interlobular septal thickening and
subpleural nodules are also visible on the left.
95
DESIGN SERVICES OF
96
and confusion between these two is not often a problem
in clinical practice. In addition, several HRCT findings
allow these two entities to be differentiated (Fig. 3-32).
First, peribronchovascular interstitial thickening is
often associated with other findings of interstitial disease, such as septal thickening, irregular reticulation,
intralobular lines, honeycombing, or the interface sign,
whereas bronchiectasis usually is not. Second, in patients
with bronchiectasis, the abnormal thick-walled and
dilated bronchi often appear much larger than the adjacent pulmonary artery branches, with a bronchoarterial
ratio exceeding 1 (see Chapter 2) (Fig. 3-36). This results
in the appearance of large ring shadows, each associated
FIGU RE 3-34 Nodular peribronchovascular interstitial thickening in a
patient with sarcoidosis. Numerous small nodules surround the central bronchi and
vessels.
and sarcoidosis, this abnormality is unilateral or patchy,
sparing some areas of lung. In such patients, normal
and abnormal lung regions can easily be contrasted
(Fig. 3-33). As a rule, bronchial walls in corresponding regions of one or both lungs should be similar in
thickness.
Bronchial wall thickening occurring in patients with
true bronchiectasis or chronic obstructive pulmonary
disease (COPD) produces an abnormality that closely
mimics the HRCT appearance of peribronchovascular
interstitial thickening. However, airway diseases and
interstitial diseases can usually be distinguished on the
basis of symptoms or pulmonary function abnormalities,
A
B
FIGU RE 3-35 Peribronchovascular interstitial thickening in end-stage
sarcoidosis, with conglomerate masses of fibrous tissue surrounding the central
vessels and bronchi. Bronchi appear dilated and thick walled because of surrounding
fibrosis and traction bronchiectasis. Note that the vessels and bronchi appear to be of
similar diameter.
FIGU RE 3-36 Bronchiectasis with the signet ring sign. A: Thick-walled and
dilated bronchi (large arrows) appear larger than the adjacent pulmonary artery
branches (small arrows). This appearance is termed the signet ring sign and is typical
of bronchiectasis. B: In another patient, upper-lobe bronchiectasis is present, with
several good examples of the signet ring sign (arrows). The signet ring sign indicates
that the bronchoarterial ratio is abnormally increased.
DESIGN SERVICES OF
with a small, rounded opacity, a finding that has been
termed the signet ring sign, and is considered to be diagnostic of bronchiectasis (116–120). In patients with peribronchovascular interstitial thickening, however, the size
relationship between the bronchus and artery is maintained, and they appear to be of approximately equal
size. The diagnosis and appearances of bronchiectasis
and bronchial wall thickening is discussed in greater
detail in Chapter 6.
Diseases that cause peribronchovascular interstitial thickening often result in prominence of the centrilobular artery, which normally appears as a dot,
Y-shaped, or X-shaped branching opacity. This finding
reflects thickening of the intralobular component of the
peribronchovascular interstitium, also termed the cen
trilobular interstitium (Fig. 2-1) (2,4,8,12). On HRCT,
linear, branching, or dotlike centrilobular opacity may be
seen (Fig. 3-1).
Thickening of the centrilobular interstitium is often
associated with interlobular septal thickening or intralobular interstitial thickening (Fig. 3-1) but sometimes
occurs as an isolated abnormality. Centrilobular interstitial thickening is common in patients with lymphangitic
spread of carcinoma or lymphoma (4,7) and interstitial
pulmonary edema (23,121). In patients with lung fibrosis, centrilobular interstitial thickening is common but
almost always associated with honeycombing, traction
bronchiolectasis, or intralobular lines. However, it is
significantly more extensive in patients with NSIP than
UIP (15).
PARENCHYMAL BANDS
The term parenchymal band has been used to describe
a nontapering, reticular opacity, usually 1 to 3 mm
in thickness and up to 5 cm in length, seen in patients
with atelectasis, pulmonary fibrosis, or other causes of
interstitial thickening, and often associated with pleural thickening (Figs. 3-1, 3-36, and 3-37) (8–10,122). A
parenchymal band is often peripheral and generally contacts the visceral pleural surface, which may be thickened
and retracted inward.
In some patients, these bands represent contiguous
thickened interlobular septa and have the same significance and differential diagnosis as septal thickening (11).
When parenchymal bands can be identified as thickened
septa, the use of a separate term to describe this finding
is unjustified; the term septal thickening should suffice.
However, parenchymal bands visible on HRCT can
also represent areas of peribronchovascular fibrosis,
coarse scars, or atelectasis associated with lung infiltration or pleural fibrosis (Figs. 3-37 and 3-38) (11,123).
These nonseptal bands are often several millimeters thick
and irregular in contour and are associated with significant distortion of adjacent lung parenchyma and bronchovascular structures (124).
Parenchymal bands may be seen in various diseases,
and have been reported as most common in patients
97
FIGU RE 3-37 Parenchymal bands in a patient with asbestos. A prone scan
shows both thick and thin bands. These may be seen in relation to visceral pleural
thickening, representing scars or atelecstasis.
with asbestos-related lung and pleural disease (Fig. 3-37),
sarcoidosis with interstitial fibrosis (49), silicosis associated with progressive massive fibrosis and conglomerate masses, tuberculosis, and lung disease associated
with ankylosing spondylitis (53,125–127) (Table 3-9). In
patients with asbestos exposure, multiple parenchymal
bands are common; in one study (8), multiple parenchymal
FIGU RE 3-38 Parenchymal band in a patient with otherwise normal lungs.
This likely represents an isolated scar.
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98
TABLE 3-9 Differential Diagnosis of Parenchymal Bands
Diagnosis
Comments
Asbestosis
Multiple parenchymal bands common; smooth; associated with thickened pleura
Sarcoidosis
Common; associated with septal thickening
Silicosis/CWP
In association with progressive massive fibrosis and emphysema
Tuberculosis
Associated with scarring
Common; often irregular; associated with traction bronchiectasis; other findings of fibrosis predominate
NSIP
Silicosis/CWP, talcosis
Conglomerate masses
HP (chronic)
Sometimes visible; often irregular; associated with traction bronchiectasis
Ankylosing spondylitis
Apical
bands were seen in 66% of asbestos-exposed patients.
In patients with asbestos-related disease, parenchymal
bands can reflect thickened interlobular septa, indicating
pulmonary fibrosis, or, more often, areas of atelectasis
and focal scarring occurring in association with visceral
pleural thickening or pleural plaques. In asbestos-exposed
patients, parenchymal bands are frequently associated
with areas of thickened pleura and have a basal predominance (8,123). They may precede the development of
rounded atelectasis.
SUBPLEURAL INTERSTITIAL THICKENING
Usually, thickening of the interlobular septa within
the peripheral lung is associated with thickening of
the subpleural interstitium (1,2); both the septa and the
subpleural interstitium are part of the peripheral interstitial fiber system described by Weibel (Fig. 2-1) (101).
Subpleural interstitial thickening can be difficult to

recognize in locations where the lung contacts the chest
wall or mediastinum but is easy to see adjacent to the
major fissures (Figs. 3-1 to 3-3). Because two layers of the
subpleural interstitium are seen adjacent to each other in
this location, any subpleural abnormality appears twice
as abnormal as it does elsewhere. Thus, thickening of the
fissure visible on HRCT often represents subpleural interstitial thickening. If the thickening is smooth, it may be
difficult to distinguish from fissural fluid. If the interface
sign is present and the thickening is irregular in appearance (1,12), or if the thickening is nodular, an interstitial
abnormality is more easily diagnosed.
In general, the differential diagnosis of subpleural
interstitial thickening is the same as that of interlobular
septal thickening, although subpleural interstitial thickening is more common than septal thickening in patients
with IPF or UIP of any cause. The presence of subpleural interstitial fibrosis with irregular or “rugged” pleural
surfaces has been reported by Nishimura et al. (57) as
a common finding in IPF, correlating with the presence
of fibrosis predominantly affecting the lobular periphery;
this finding was present in 94% of the cases of IPF that he
studied. A subpleural predominance of fibrosis can also
be seen in patients with collagen-vascular diseases and
drug-related fibrosis (30).
Nodular thickening of the subpleural interstitium can
also be seen, and it has the same differential diagnosis
as nodular septal thickening (47). Remy-Jardin et al.
(47) reported the appearance of subpleural micronodules, defined as 7 mm or less in diameter, on HRCT in
patients with sarcoidosis, CWP, lymphangitic spread of
carcinoma, and LIP, and in a small percentage of normal
subjects. Subpleural nodules are described further in the
next chapter.
SUBPLEURAL CURVILINEAR LINE
A curvilinear opacity a few millimeters or less in t hickness,
less than 1 cm from the pleural surface and paralleling the pleura, is termed a subpleural line or subpleural
curvilinear line (9,10). It is a nonspecific indicator of atelectasis, fibrosis, inflammation, or even edema. It was first
described in patients with asbestosis (128).
It was originally suggested that a subpleural line
reflected the presence of fibrosis associated with honeycombing (128), and in some patients, a confluence of
honeycomb cysts can result in a somewhat irregular subpleural line (Figs. 3-39 to 3-42). A subpleural line representing fibrosis is much more common in patients who
have asbestosis than in those who have IPF or other causes
of UIP (54,83). Indeed, the presence of a subpleural line in
nondependent lung has been reported in as many as 41%
of patients with clinical findings of asbestosis (8). However, the presence of this finding is nonspecific and can be
seen in a variety of lung diseases (Fig. 3-1). The presence
of subpleural lines has also been reported as common
in patients with scleroderma who have interstitial disease (Fig. 3-41) (129,130); this may reflect the common
occurrence of NSIP in patients with scleroderma and the
tendency of NSIP to spare the immediate subpleural lung
(Fig. 3-42). Subpleural lines may also be seen in ankylosing spondylitis (53).
DESIGN SERVICES OF
99
A
FIGU RE 3-39 Subpleural line in a patient with asbestosis. An illdefined subpleural line (arrows) on a prone scan reflects subpleural fibrosis and
honeycombing. Other findings of pulmonary fibrosis are also present.
A subpleural line also has been reported to occur as
a result of the confluence of peribronchiolar interstitial abnormalities in patients with asbestosis, representing early fibrosis with associated alveolar flattening and
collapse (11,96). In these patients, honeycombing was
not present. Also, in patients with asbestos exposure,
a subpleural line may be seen adjacent to focal pleural
thickening or plaques. These most likely represent focal
atelectasis or localized areas of scarring.
It is common to see a subpleural line or focal areas
of reticulation adjacent to thoracic spine osteophytes or
other causes of chest wall distortion, such as prominent
healed rib fractures or at the site of postsurgical lung hernia. The subpleural line or reticulation reflects the presence of localized alveolar collapse and fibrosis (131). In
addition, in some patients with asbestos exposure, a subpleural line may be seen adjacent to pleural plaques, representing focal atelectasis.
A subpleural line can also be seen in normal patients
as a result of atelectasis within the dependent lung (e.g.,
the posterior lung when the patient is positioned supine);
the presence of dependent atelectasis has been confirmed
experimentally (132). Also, a thicker, less well-defined
B
C
FIGU RE 3-40 Bilateral subpleural lines (arrows) in a patient with early IPF.
FIGU RE 3-41 Subpleural lines in a patient with scleroderma who likely has
NSIP. Supine (A) and prone (B). HRCT shows bilateral subpleural lines (arrows).
C: Sagittal reconstruction also shows a posterior subpleural line.
DESIGN SERVICES OF
100
DISTRIBUTION OF LINEAR AND
RETICULAR OPACITIES IN THE DIAGNOSIS
OF LUNG DISEASE
FIGU RE 3-42 Subpleural line in a patient with NSIP. On an axial HRCT
obtained in the prone position, bilateral subpleural lines are visible. In this patient, this
may reflect the tendency of NSIP to spare the immediate subpleural lung.
When attempting to reach a diagnosis or differential diagnosis of lung disease using HRCT, the overall distribution
of pulmonary abnormalities should be considered along
with their morphology, HRCT appearance, and distribution relative to lobular structures (3,59,84,135). Many
lung diseases show specific regional distributions or preferences, a fact that is likely related to their underlying
pathogenesis and pathophysiology (136).
An important caveat to keep in mind when reading the
following section is that significant variations in classical
patterns of lung involvement can be seen in individual
patients. A specific diagnosis should not be excluded
because of an atypical distribution of abnormalities.
Central Lung Versus Peripheral Lung
subpleural opacity, a so-called dependent density (8) or
dependent opacity (133) can also be seen in normal subjects as a result of volume loss. In a study by Lee et al.
(133), dependent lung opacity was significantly more
common at reduced lung volumes, with studies using spirometrically gated HRCT. Such normal posterior lines or
opacities are transient and disappear in the prone position. In a study of patients with asbestos exposure by
Aberle et al. (8), neither transient subpleural lines nor
transient dependent densities correlated with the clinical
suspicion of pulmonary fibrosis.
In patients with early interstitial lung disease, there
may be a greater tendency for atelectasis to develop in the
peripheral lung, resulting in the appearance of a subpleural line. As such, the presence of this abnormality could
reflect an increased closing volume (i.e., an increased tendency for the lung to collapse) that is known to occur as
a result of early interstitial lung disease. The association
of platelike atelectasis at the junction of “cortical” and
“medullary” lung regions, air trapping in the lung peripheral to the atelectasis, and decreased compliance of lung
because of interstitial infiltration was first reported by
Kubota et al. (134).
Some diseases have a central, perihilar, bronchocentric,
or peribronchovascular distribution (59,100), whereas
others favor the peripheral or subpleural parenchyma, or
lung cortex (Table 3-10).
Diseases associated with reticular opacities on HRCT
that can have a central or perihilar predominance include
end-stage sarcoidosis, silicosis, fibrotic NSIP, chronic HP
(137), and lymphangitic spread of carcinoma (138). In a
study by Grenier et al. (138), a predominantly central distribution of abnormalities was visible in 16% of patients
with sarcoidosis, 31% of patients with silicosis, and 8% of
those with lymphangitic spread of carcinoma. In another
study (84), a central or peribronchovascular predominance was seen in 70% of patients with sarcoidosis and
60% of patients with lymphangitic spread of carcinoma.
A predominantly peribronchial distribution of fibrosis is
considered inconsistent with UIP and IPF (63); in patients
TABLE 3-10 Predominance of Lung Disease on HRCT:
Central Lung Versus Peripheral Lung
Lung disease
Findings
Central lung
NORMAL RETICULAR OPACITIES
IN THE ELDERLY
Sarcoidosis
Peribronchovascular nodules; conglomerate
fibrosis with traction bronchiectasis
Silicosis
Conglomerate masses of fibrosis
The presence of fine reticular opacities in the peripheral,
posterior, lower lobes can be seen as a normal finding in
older subjects. In a study by Copley et al. (17), a limited
subpleural reticular pattern was identified in the majority (24 of 40, 60%) of individuals older than 75 years,
and was absent in a group younger than 55 years (p <
0.001) (17). The reticulation was fine or coarse, and was
unassociated with honeycombing or traction bronchiectasis. Interlobular septal thickening was also seen in some
patients. These findings are presumably due to an increase
in lung collagen in older patients.
Talcosis
Lymphangitic spread
of carcinoma
Peribronchovascular interstitial thickening
or nodules
HP
Peribronchovascular fibrosis in some
NSIP
Peribronchovascular fibrosis in some
Peripheral lung
UIP, IPF, collagen
diseases, asbestosis
Subpleural fibrosis; honeycombing
NSIP in 50%
Subpleural ground-glass opacity;
reticulation; subpleural sparing
DESIGN SERVICES OF
with HRCT findings of fibrosis, this distribution would
be more typical of NSIP (95), chronic HP, or sarcoidosis.
A peripheral, cortical, or subpleural predominance of
abnormalities is typical of UIP and has been reported in
nearly all patients with asbestosis (58); 81% to 94% of
patients with IPF (58,84,85); and a similar high percentage of patients with scleroderma, rheumatoid lung disease, or other collagen-vascular diseases. Other fibrotic
IPs, such as NSIP, commonly show a peripheral predominance, although subpleural sparing is present in about
half. A peripheral predominance of abnormalities is visible in approximately half of patients with OP and DIP
(58,84,138–141), although these entities uncommonly
present with a predominantly reticular pattern. Peripheral predominance is occasionally present in patients
with chronic HP and end-stage sarcoidosis, ranging
from a few percent to 20% in different studies. Subpleural predominance is also typical of diffuse amyloidosis,
although this disease is quite rare.
In a study by Silva et al. (137) of HRCT findings in patients with IPF, NSIP, and chronic HP with
fibrosis, patients with IPF and NSIP were more likely
to have peripheral predominance of abnormalities
(78% and 72%, respectively) (p< 0.001) and fibrosis
(100% and 92%, respectively) than those with chronic
HP (25% and 78%, respectively) (p< 0.002).
Upper Lung Versus Lower Lung
The relative extent and severity of abnormalities in the
upper lungs and midlungs and at the lung bases can be
determined on HRCT by using coronal or sagittal reconstruction of volumetric HRCT, or by comparing the severity of abnormalities on transaxial scans at different levels.
Some diseases tend to predominate in the upper lobes,
whereas others predominate in the mid- or lower lobes
(Table 3-11) (142).
Diseases that can result in reticular opacities and have
been recognized to have upper-lobe predominance on
HRCT include sarcoidosis, silicosis, and CWP chronic
HP (48,50,84,85,135,138,143–145), and Langerhans
cell histiocytosis, in the small percentage cases presenting
with reticulation. An upper-lobe predominance of abnormalities is present in nearly equal percentages of patients
with sarcoidosis (47%–50%) and silicosis (55%–69%),
whereas a lower-lobe predominance is present in less than
10% of patients with these diseases (85,138). According
to recent criteria, a predominantly upper- or midlung predominance of fibrosis is considered inconsistent with a
diagnosis of UIP and IPF (63); however, some patients
with a diagnosis of UIP may show this distribution. In
patients with HRCT findings of fibrosis, an upper- or
midlung predominance would be more typical of chronic
HP or sarcoidosis.
A basal distribution is most typical of lymphangitic
metastasis (46%), UIP, IPF (68%), collagen-vascular diseases such as rheumatoid lung disease and scleroderma
(80%), and asbestosis (3,5,8,58,84,85,122,138,141). A
101
Upper Lung Versus Lower Lung
Lung disease
Findings
Upper Lung
Sarcoidosis
Nodules, fibrosis, conglomerate
masses
Silicosis
Nodules, conglomerate masses
Talcosis
Chronic HP
Mid- to upper-lung
predominance typical
Langerhans cell histiocytosis
Reticulation in a few percent
Pleuroparenchymal fibroelastosis
Rare, reticulation traction
bronchiectasis, honeycombing;
pleural thickening
Lower Lung
Pulmonary edema
Septal thickening
Lymphangitic carcinoma and
lymphoproliferative diseases
Septal thickening
UIP, IPF, collagen diseases,
asbestosis
Subpleural fibrosis;
honeycombing
NSIP
Peripheral reticulation
Other IPs
Findings of fibrosis in a few
basal predominance of abnormalities is typical of fibrotic
NSIP (95). Pulmonary fibrosis of any cause has a basal
predominance in approximately 60% of cases (84,85).
Although HP may show an upper-lobe predominance, it
more often appears to be diffuse or preponderant in the
mid- (58,74) or lower lung zones (30%) (138).
In a study by Silva et al. (137) comparing the HRCT
findings in patients with IPF, NSIP, and chronic HP with
fibrosis, a lower-zone predominance of abnormalities was
more common in patients with IPF (83%) and NSIP (94%)
than in those with chronic HP (31%) (p < 0.001). Also,
although no significant difference was observed in the
frequency of honeycombing in patients with chronic HP
(64%) and IPF (67%), patients with IPF were more likely
to have basal predominance of honeycombing (52%) than
were those with chronic HP (11%) (p < 0.001).
Upper-lobe fibrosis was seen in all patients with
chronic HP, compared to 96% in IPF and 62% in NSIP
(p < 0.001), and although an upper-zone predominance
of abnormalities was uncommon, it was seen more frequently in patients with chronic HP (11%) than in those
with IPF (2%) or NSIP (0%) (p = 0.02) (137). Uniform
involvement of upper- and lower-lung zones was more
common in patients with chronic HP (58%) than in those
with IPF (15%) or NSIP (6%) (p < 0.001).
Anterior Lung Versus Posterior Lung
Some diseases produce their initial or most extensive
abnormalities in the posterior lung (Table 3-12). The
distinction between anterior and posterior, of course,
is easily made on HRCT. However, it is important to
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102
Posterior Lung Versus Anterior Lung
Lung disease
Findings
Posterior lung
UIP, NSIP
Fibrosis
Asbestosis
Fibrosis
Fibrosis
Silicosis
Fibrosis; conglomerate masses
Sarcoidosis
Fibrosis; conglomerate masses
Pulmonary edema
Septal thickening
Lymphangitic carcinoma and
lymphoproliferative disease
Septal thickening
HP
Findings of fibrosis
Anterior lung
Post-ARDS fibrosis
Subpleural fibrosis;
honeycombing; traction
bronchiectasis
Radiation fibrosis in some patients
(e.g., those with breast cancer)
Reticulation; volume loss;
traction bronchiectasis;
honeycombing in some
recognize the value of using both prone and supine scans
in this regard. Areas of increased attenuation that are
limited to the posterior lung on scans obtained in the
supine position can reflect normal dependent volume
loss; prone scans are essential in making a confident
diagnosis of early posterior lung disease. Although the
percentages vary in different series, a posterior preponderance of disease is particularly common in scleroderma
(60%), sarcoidosis (32%–36%), silicosis (31%–38%)
HP (23%), IPF (9%–21%) and other causes of UIP, and
NSIP (50,84,85,138,145). A posterior predominance of
abnormalities is also common in patients with asbestosis, lymphangitic carcinomatosis, and pulmonary edema
(3,8,84,85,122,138,141,145). In patients with pulmonary edema, the predominant abnormality is more appropriately referred to as dependent rather than posterior.
An anterior predominance of lung disease is unusual
but has been reported in adult survivors of ARDS (78).
In this study, HRCT was obtained during the acute illness
and at follow-up in 27 patients with ARDS. At follow-up
CT, a reticular pattern was the most prevalent abnormality (85%), with a striking anterior distribution. This finding was related to the duration of mechanical ventilation
and was inversely correlated with the extent of parenchymal opacification on scans obtained during the acute illness. Anterior lung fibrosis is common in patients having
radiation therapy for breast cancer.
Unilateral Disease Versus Bilateral Disease
A unilateral predominance of abnormalities is most typical of lymphangitic spread of carcinoma, which is often
asymmetric in distribution; this was seen in nearly 40%
of patients with lymphangitic spread of carcinoma in
one series (84). Asymmetry or unilateral predominance
of findings is also common in patients with sarcoidosis,
ranging from 9% to 21%. It is somewhat less frequent
in association with silicosis (2%–21%), IPF (3%–14%),
and HP (5%) (84,85). Drug reactions resulting in lung
fibrosis or other abnormalities may appear asymmetrical
or predominantly unilateral.
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