VINOTHKUMAR

2nd yr PG Resident
Dept of Radiology
 Interstitial lung diseases (ILD’s)represent a large number of
conditions that involve the parenchyma of lung- the alveoli,
the alveolar epithelium, the capillary endothelium, and the
spaces between these structures, as well as perivascular and
lymphatic tissues.

 There are numerous interstitial lung diseases, but in clinical

practice only about ten diseases account for approximately
90% of cases.

 Knowledge of both, the radiological and clinical appearance

of these more common interstitial lung diseases, is therefore
important for recognizing them in the daily practice and
including them in the differential diagnosis.
The Lung Interstitium
The interstitium of the lung is not normally visible
radiographic- ally; it becomes visible only when disease (e.g.,
edema, fibrosis, tumor) increases its volume and attenuation.
The interstitial space is defined as continuum of loose
connective tissue throughout the lung composed of three
subdivisions:
(i) the bronchovascular (axial), surrounding the bronchi,
arteries, and veins from the lung root to the level of the
respiratory bronchiole
(ii) the parenchymal (acinar), situated between the alveolar
and capillary basement membranes
(iii) the subpleural, situated beneath the pleura, as well as in
the interlobular septae.
 Secondary pulmonary lobules (also simply known as the
pulmonary lobules) range from 1 to 2.5 cm in size and are
marginated by connective tissue interlobular septa, which contain
pulmonary veins and lymphatics .

 Within the peripheral lung, interlobular septa are at the lower

limit of HRCT resolution. On clinical HRCT in normal patients, a
few interlobular septa often can be seen, but they tend to be
inconspicuous.

 The central portion of the secondary lobule, referred to as the

centrilobular region, contains the pulmonary artery and
bronchiolar branches that supply the lobule. The pulmonary
artery supplying a secondary lobule measures somewhat less than
1 mm in diameter and can be seen in normal lungs as a dot or
branching structure 5 to 10 mm from the pleural surface; the
centrilobular bronchiole normally is invisible.
 An acinus is the largest unit of lung structure in
which all airways participate in gas exchange.
Anatomically, it is located distal to a terminal
bronchiole and is supplied by a first-order
respiratory bronchiole.

 Acini average 7 to 8 mm in diameter. A

pulmonary lobule usually consists of a dozen
or fewer acini, although large lobules may
contain twice that number. Acini are not visible
on HRCT.
 CT protocols utilize thin collimation and high
spatial frequency reconstruction algorithms to
achieve an optimal spatial resolution and facilitate
an optimal assessment of interstitial and airspace
disease .
 This technique consists of a “step-and-shoot”
approach, in which 0.5- to 1 mm collimation scans
are obtained at 10 to 20 mm intervals, a small FOV,
and a high radiation dose per section.
 provides excellent image quality, free of partial
volume and projection artifacts, and combines high
sensitivity in the detection of ILD with high
accuracy in establishing the correct diagnosis.
 Thin collimation improves spatial resolution
and consequently enhances the detection of key
morphologic features in HRCT interpretation:
 thickened interlobular septa,
 ground-glass opacification,
 small nodules
 abnormally thickened or dilated airways.
A linear pattern is seen when there is
Kerley A lines
thickening of the interlobular septa,
producing Kerley lines.

Kerley B lines

Kerley A lines

The interlobular septa contain pulmonary

veins and lymphatics.

The most common cause of interlobular

septal thickening, producing Kerley A and B
lines, is pulmonary edema, as a result of Kerley B lines
pulmonary venous hypertension and
distension of the lymphatics.
• Pulmonary edema is the most common cause
• Mitral stenosis
• Lymphangitic carcinomatosis
• Malignant lymphoma
• Congenital lymphangiectasia
• Idiopathic pulmonary fibrosis
• Pneumoconiosis
• Sarcoidosis
A reticular pattern results from the summation
or superimposition of irregular linear
opacities.
The term reticular is defined as meshed, or in
the form of a network. Reticular opacities can be
described as fine, medium, or coarse, as the
width of the opacities increases.
 Edema
 Lymhangitic Mets
 UIP (Usual Interstitial Pneumonia)
 NSIP (Non-specific Interstitial Pneumonia)
 HP (Hypersensitivity Pneumonia)
 Asbestosis
 Honeycombing reflects extensive lung fibrosis
with alveolar destruction, and results in a
characteristic reticular appearance.
 On HRCT, honeycombing may be diagnosed
accurately by the presence of thick-walled, air-
filled cysts, usually measuring from 3 mm to 1 cm
in diameter.
 Typically, the cysts share walls and occur in
several layers at the pleural surface (
 Early honeycombing usually occurs in a subpleural
location, and scattered individual cysts rather than
layers of clusters of cysts may be seen
 When honeycombing is present, normal lung architecture is
distorted, and secondary lobules are difficult or impossible
to recognize. Associated findings of fibrosis, including
reticular opacities, traction bronchiectasis, and traction
bronchiolectasis, are usually present.
 The presence of honeycombing strongly predicts the
presence of usual interstitial pneumonia (UIP). The
differential diagnosis is that of UIP, and includes idiopathic
pulmonary fibrosis (IPF), which accounts for 60% to 70% of
cases of honeycombing; collagen-vascular diseases often
rheumatoid arthritis and scleroderma); fibrotic drug
reactions; asbestosis, chronic or end-stage hypersensitivity
pneumonitis; and, occasionally, sarcoidosis This appearance
also may be seen with nonspecific interstitial pneumonia
(NSIP).
 A nodular pattern consists of multiple round opacities,
generally ranging in diameter from 1 mm to 1 cm

 Nodular opacities may be described as miliary (1 to 2 mm,

the size of millet seeds), small, medium, or large, as the
diameter of the opacities increases

 A nodular pattern, especially with predominant

distribution, suggests a specific differential diagnosis
 feature of both interstitial and airspace disease.
 Perilymphatic nodules within the lung
interstitium, especially those related to the
lymphatic vessels, are seen in the interlobular
septa, subpleural and peribronchovascular
regions.
 Centriacinar nodules
 Random
 •Hematogenous infection
(TB etc)
 •Metastases

 •HP
 •RBILD
 •LCH
 Silicosis

 •Sarcoid
 •Lymphangitic mets
Sarcoidosis
 Inflammation of the
terminal bronchiole and
lobular pulmonary artery
 Small round opacity in the
center of a secondary
pulmonary lobule
Hematogenous metastases and nodular ILD. The PA chest
radiograph shows a diffuse pattern of nodules in metastatic
gastric carcinoma patient.
A reticulonodular pattern results from a combination of
reticular and nodular opacities.

This pattern is often difficult to distinguish from a purely

reticular or nodular pattern, and in such a case a
differential diagnosis should be developed based on the
predominant pattern.

If there is no predominant pattern, causes of both nodular

and reticular patterns should be considered.

Seen in sarcoidosis, berylliosis, pulmonary silicosis.

lymphangitis carcinomatosis.
A: PA chest radiograph, close-up of right upper lung, shows
reticulonodular ILD.
B: CT scan shows multiple circumscribed round pulmonary nodules, 2 to 3
mm in diameter.
 generalized increase in opacity that does not obscure
pulmonary vessels.
 include partial filling of the airspaces,
considerable thickening of the interstitium, or a
combination of the two.

Pneumocystis or viral pneumonia,

Acute Drug/Hypersensitivity Reactions,
Pulmonary Edema, Hemorrhage, Acute Aspiration , AIP,
NSIP, DIP
Mucinous adenocarcinoma
 The combination of ground-glass opacity and
interlobular septal thickening is termed “crazy
paving”
 This appearance is nonspecific and may be seen
with a variety of acute lung diseases such as
Pneumocystis or viral pneumonia, edema,
hemorrhage, and ARDS.
 Among patients with chronic lung disease, it
often is the result of alveolar proteinosis
 Mosaic pattern
- refers to regional attenuation differences
demonstrated on HRCT.
- depends on the amount of blood, parenchymal
tissue and air in that area.
- small airways disease(bronchiolitis obliterans),
occlusive vascular disease(chronic pulmonary
embolism) and infiltrative lung disease.
Mosaic pattern due to air trapping/altered perfusion
• Sarcoidosis is a systemic disorder of unknown
origin. It is characterized by non-caseating
granulomas in multiple organs, that may resolve
spontaneously or progress to fibrosis.
• Pulmonary manifestations are present in 90% of
patients.
• Less than 5% of patients die from sarcoidosis
usually as a result of pulmonary fibrosis.
Stages: Chest films in sarcoidosis have been
classified into four stages:
 I. Bilateral hilar lymphadenopathy

 II. Bilateral hilar lymphadenopathy +

pulmonary disease
 III. Only pulmonary disease

 IV. Irreversible fibrosis.

These stages do not indicate disease chronicity or

correlate with changes in pulmonary function
 Patient with stage I disease. There is hilar and
paratracheal adenopathy and no sign of
pulmonary involvement
• Common findings:
– Small nodules in a perilymphatic distribution (i.e. along subpleural
surface and fissures, along interlobular septa and the
peribronchovascular bundle).
– Upper and middle zone predominance.
– Lymphadenopathy in left hilus, right hilus and paratracheal (1-2- 3
sign). Often with calcifications.

• Uncommon findings:
– Conglomerate masses in a perihilar location.
– Larger nodules (> 1cm in diameter, in < 20%)
– Grouped nodules or coalescent nodules surrounded by multiple
satellite nodules (Galaxi sign)
– Nodules so small and dense that they appear as ground glass or
even as consolidations (alveolar sarcoidosis)
Sarcoidosis: typical presentation with nodules along the
bronchovascular bundle and the fissures Notice the partially calcified
node in the left hilum.
A detailed view with the typical HRCT-presentation with nodules
along bronchovascular bundle (red arrow) and fissures (yellow
arrow). This is the typical perilymphatic distribution of the noduless.
Another typical presentation of sarcoidosis with mediastinal
lymphadenopathy and small nodules in a perilymphatic distribution
along bronchovascular bundles and along fissures (yellow arrows).
Always look for small nodules along the fissures, because this is a very
specific and typical sign of sarcoidosis.
• Progressive fibrosis in sarcoidosis may lead to
peribronchovascular (perihilar) conglomerate masses of
fibrous tissue.
The typical location is posteriorly in the upper lobes,
leading to volume loss of the upper lobes with
displacement of the interlobar fissure.
Other diseases that commonly result in this appearance
are:
• Silicosis
• Tuberculosis
• Talcosis
Sarcoidosis with conglomerate masses of fibrous tissue
 A typical chest film of long
standing sarcoidosis (stage
IV) with fibrosis in the upper
zones and volume loss of the
upper lobes resulting in hilar
elevation. Fibrosis results in
obliteration of pulmonary
vessels, which can lead to
pulmonary hypertension

Sarcoidosis with fibrosis in the upper

lobes.
 Alveolar Sarcoidosis

In this case the appearance resembles a ground glass attenuation, but

with a close look you may appreciate that the increased attenuation is
the result of many tiny grouped nodules. Also notice the hilar
lymphadenopathy
A case of fibrosing sarcoidosis, showing fibrosis, traction
bronchiectases and crowding of the involved bronchi, predominantly
in the perihilar region and upper lobes. Nodular abnormalities are
absent, but the appearance and the location of the fibrosis are very
suggestive of the diagnosis of sarcoidosis
Differential diagnosis of Sarcoidosis
• Lymphadenopathy:
– Primary TB: asymmetrical adenopathy
– Histoplasmosis
– Lymphoma
– Small cell lung cancer with nodal metastases

• Nodular pattern:
– Silicosis / Pneumoconiosis: predominantly centrilobular and
subpleural nodules.
– Miliary TB: random nodules.

• Fibrotic pattern:
– Usual Interstitial Pneumonia (UIP): basal and peripheral fibrosis,
honeycombing.
– Chronic Hypersensitivity Pneumonitis: mid zone fibrosis with
mosaic pattern.
– Tuberculosis (more unilateral).
• Lymphangitic Carcinomatosis results from
hematogenous spread to the lung, with
subsequent invasion of interstitium and
lymphatics.

• Lymphangitic Carcinomatosis is seen in

carcinoma of the lung, breast, stomach, pancreas,
prostate, cervix, thyroid and metastatic
adenocarcinoma from an unknown primary.
• Interlobular septal thickening, thickening of fissures and
thickening of the peribronchovascular interstitium
(bronchial cuffing).
• Depending on filling with fluid or with tumor cells,
septal thickening is irregular or smooth.
• Focal or unilateral abnormalities in 50% of patients.
• Hilar lymphadenopathy in 50% of patients.
• Pleural effusion due to pleuritic carcinomatosis ( > 50%
of patients).
A patient with Lymphangitic Carcinomatosis. Notice the focal
distribution. This finding is helpful in distinguishing Lymphangitic
Carcinomatosis from other causes of interlobular septal thickening like
pulmonary edema or sarcoid. There is also lymphadenopathy.
Cardiogenic pulmonary edema:
bilateral abnormalities, filling of
alveoli, enlarged heart, rapid
response to diuretics, ground-glass
opacity due to filling of alveoli
with fluid, gravitational
distribution of the alveolar fluid

Alveolar proteinosis: sharply

demarcated secondary lobules
with ground glass attenuation as
opposed to secondary lobules
with normal aeration,
superimposed inter and
intralobular septal thickening
(crazy paving).
 Patients with pulmonary edema are not
imaged with HRCT as their diagnosis is
usually based on a combination of clinical and
chest radiographic findings.

 However sometimes the diagnosis is not that

straightforward and knowledge of the HRCT
appearance of pulmonary edema can be
helpful in avoiding misdiagnosis
• Bilateral septal thickening and ground-glass
opacity.
• Perihilar and gravitational distribution
predominatly in the dependent lung.
• Cardiomegaly and pleural fluid.
 There is smooth septal
thickening and some
ground glass opacity in the
dependent part of the
lungs. In addition there is
bilateral pleural fluid.

 In a patient with a known

malignancy lymphangitic
carcinomatosis would be
high in the differential
diagnostic list
 • Lymphangitic carcinomatosis

 • Interstitial pneumonia (viral, mycoplasma)

 • ARDS

 • Pulmonary hemorrhage
• The idiopathic interstitial pneumonias (IIPs) comprise a
heterogeneous group of disorders.

• They represent fundamental responses of the lung to injury

and do not represent 'diseases' per se.

• Idiopathic indicates unknown cause and interstitial

pneumonia refers to involvement of the lung parenchyma by
varying combinations of fibrosis and inflammation.

• IIPs include seven entities listed in the table in order of

relative frequency.

• These diseases have specific patterns of morphologic findings

on HRCT and histology.
 • UIP is a histological diagnosis. UIP has distinctive HRCT findings and
is usually shown at lung biopsy, when honeycombing is visible.

 • If the UIP pattern is of unknown cause (i.e. idiopathic), the disease is

called Idiopathic pulmonary fibrosis (IPF). IPF accounts for more than
60% of the cases of UIP.

 • In the presence of a surgical biopsy showing a UIP pattern the

diagnosis of IPF requires exclusion of other known causes of UIP
including drug toxicities, environmental exposures (asbestos), and
collagen vascular diseases like RA, SLE, polyarteritis nodosa and
scleroderma.

 • A long list of drugs have been implicated, but this pattern is most
commonly the result of cytotoxic chemotherapeutic agents such as
bleomycin, busulfan, vincristine, methotrexate, adriamycin, and
carmustine (BCNU).
 • The findings on the chest film comprise volume loss and fibrotic
changes in the basal lung area. The radiographic appearance of
honeycombing comprises reticular densities caused by the thick walls of
the cysts. Whenever you see a chest film with long standing reticulation
with a lower lobe and peripheral preference also think 'UIP'. Chest film in
a patient with UIP demonstrating the reticular pattern in basal and
subpleural distribution due to honeycombing.
 . • Honeycombing consisting of multilayered thick-walled
cysts.
 • Architectural distortion with traction bronchiectasis due to
fibrosis.
 • Predominance in basal and subpleural region.
 • Mild mediastinal lymphadenopathy
 • NSIP representing cases of idiopathic interstitial
pneumonia that cannot be classified as UIP, DIP, or OP.

 • NSIP is histologically characterized by a homogeneous,

uniform pattern of cellular interstitial inflammation
associated with variable degrees of fibrosis.

 • In contrast, UIP is associated with extensive fibrosis which

is temporally inhomogeneous (i.e. various lesions are of
different ages).

 • NSIP ranges from type I which is a cellular pattern seen as

ground glass opacity on HRCT to type IV with a fibrotic
pattern, which may be indistinguishable from UIP
 • Cryptogenic organizing pneumonia (COP) used to be described
as bronchiolitis obliterans with organizing pneumonia (BOOP) in
an earlier version of the classification of idiopathic interstitial
pneumonias.

 • It is a inflammatory process in which the healing process is

characterized by organization of the exudates rather than by
resorption ('unresolved pneumonia').

 • Organizing pneumonia is mostly idiopathic and then called

cryptogenic, but is also seen in patients with pulmonary infection,
drug reactions, collagen vascular disease, Wegener's
granulomatosis and after toxic-fume inhalation.

 • OP presents with a several-month history of nonproductive

cough, low- grade fever, malaise and shortness of breath. There is
a good response to corticosteroid therapy and a good prognosis.
• Bilateral peripheral consolidations, sharply demarcated.

• Consolidations may be migratory.

• Lesions may show pleural tags or spiculae and give the

impression of volume loss and slight retraction of the
surrounding parenchyma (DD bronchogenic carcinoma).

• Bronchial wall thickening and dilatation are seen in most

patients and are usually restricted to areas of consolidation or
ground glass opacifications.

• Additional findings are pleural thickening, small pleural

effusions and parenchymal ba
a patient with the typical bilateral peripheral
consolidations of OP.
bilateral peripheral consolidations as a result of organizing pneumonia.
 • Chronic eosinophilic pneumonia

 • Bronchoalveolar cell carcinoma

 • Aspiration pneumonia

 • Pulmonary infarction

 • Lymphoma
Chronic eosinophilic pneumonia (left) versus Organizing
pneumonia (right)

The images show the similarities between chronic eosinophilic pneumonia and
organizing pneumonia. Differentiation has to be made on the basis of clinical
and laboratory findings
• Respiratory bronchiolitis (RB), respiratory bronchiolitis-associated
interstitial lung disease (RB-ILD), and desquamative interstitial
pneumonia (DIP) represent different degrees of severity of small
airway and parenchymal

• All smokers have various degrees of respiratory bronchiolitis, but it

is usually asymptomatic.

• The term RB-ILD was proposed to describe the bronchocentric (or

centrilobular) lung disease in these patients and the term DIP was
used to describe the more diffuse disorder.

• Radiologically however these diseases cannot be clearly separated

because of the overlap of CT findings.reaction to cigarette smoke
• Centrilobular nodules of ground glass opacity
with upper lobe predominance

• Bronchial wall thickening

• Secondary lobuli with decreased attenuation

(air trapping)
 A patient with RB-ILD.
The dominant feature is ground glass opacification and there are some
thickened interlobular septa (arrow).
Usually these patients will also have smoking induced centrilobular
emphysema and there is some evidence that respiratory bronchiolitis is the
precursor of emphysema.
 LEFT: RB-ILD in smoker RIGHT: Hypersensitivity
pneumonitis in non- smoker
Note the difference in severity of ground glass opacities and the well defined
areas of air trapping in HP. If a patient is a smoker, think RB-ILD and look for
additional smoking related features.
If a patient is a non-smoker, think HP, and look at the expiratory CT scans.
Somehow smoking seems to protect against HP.
This is not a 100% specific criterion but is quite helpful for differential diagnosis.
• AIP, earlier named Hamman Rich Pneumonitis is a
rare idiopathic lung disease characterized by diffuse
alveolar damage with subsequent fibrosis.

It has a fatal outcome in many cases.

The histologic pattern as well as the HRCT findings in

AIP are indistinguishable from acute respiratory
distress syndrome (ARDS).

HRCT characteristics of AIP : Diffuse or patchy

consolidation, often with a crazy paving.
there are areas of consolidation and extensive areas of ground-glass density
with a crazy-paving appearance.
These abnormalities developed in several days and this rapid progression of
disease combined with these imaging findings are very suggestive of the
diagnosis AIP.
LIP is uncommon, being seen mainly in patients with autoimmune
disease, particularly Sjögren's syndrome, and in patients with AIDS.
Symptoms are nonspecific and often those of the patient's underlying
disease.

• Bilateral abnormalities ;diffuse or have a lower lung

predominance.
• ground-glass attenuation,(interstitial inflammation)
• thin-walled perivascular cysts.
• In contrast to the subpleural, lower lung cystic changes in UIP,
the cysts of LIP are usually within the lung parenchyma
throughout the mid lung zones and presumably result from air
trapping due to peribronchiolar cellular infiltration .
• In combination with groundglass opacities, these cysts are highly
suggestive of LIP.
• Occasionally, centrilobular nodules and septal thickening are seen
HRCT findings are usually nonspecific.
a patient with Sjogren's syndrome with LIP.
• Elastotic fibrosis of both pleura and
underlying subpleural parenchyma

• Upper lobe predominance

• Dense subpleural consolidations with traction

bronchiectasis
Idiopathic Pleuroparenchymal Fibroelastosis
• Rare disease, that occurs only in premenopausal
women

• Characterized by progressive proliferation of

atypical muscle cells along the bronchioles leading to
air trapping and the development of thin-walled
cysts, that replace normal lung parenchyma.

• Identical pulmonary changes seen in 1% of patients

with tuberous sclerosis (predominant involvement of
young men)
• Numerous thin-walled cysts, surrounded by normal parenchyma.

• Cysts range from 2mm to 5cm in diameter, are round in shape and
more or less uniform.

• Cysts are distributed diffusely throughout the lungs and upper and
lower lobes are involved to a similar degree.

• Wall thickness of the cysts ranges from barely perceptible to 4 mm.

• Mediastinal or hilar adenopathy and pleural effusions (40%).

• Recurrent pneumothorax (40%).

 A typical case of LAM with multiple evenly spread thin walled
cysts complicated by a pneumothorax.
• Langerhans cell histiocytosis is also known as
pulmonary histiocytosis X or eosinophilic granuloma.

• LCH is probably an allergic reaction to cigarette

smoke since more than 90% of patients are active
smokers.

• In the early nodular stage it is characterized by a

centrilobular granulomatous reaction by Langerhans
histiocytes.

• In the cystic stage bronchiolar obliteration causes

alveolar wall fibrosis and cyst formation.
• Early stage:
– Small irregular or stellate nodules in centrilobular location.

• Late stage (more commonly seen)

– Cystic airspaces < 10 mm in diameter with walls that range
from barely perceptible to several millimetres thick.

– Cysts have bizarre shapes, they may coalesce and than

become larger.

– Upper and mid lobe predominance.

– Recurrent pneumothorax.
Early stage Langerhans cell histiocytosis with small
nodules.

There are no cysts visible

 In a later stage the nodules start to cavitate and become
cysts.

 • These cysts start as round structures but finally coalesce

to become the typical bizarre shaped cysts of LCH.

 • In patients with LCH 95% have a smoking history.

Late stage Langerhans' cell histiocytosis. Cysts progress to
typical bizarre shaped cysts.
 Nodular LCH:
– Sarcoidosis: perilymphatic distribution.
– Metastases: random distribution.

 Cystic LCH:
– LAM: round cysts, evenly distribution in
women in the child-bearing age
– Cystic bronchiectasis: 'signet ring sign'.
– Centrilobular emphysema: no walls, central dot.
– LIP
• Alveolar proteinosis is a rare disease characterized
by filling of the alveolar spaces with PAS positive
material due to an abnormality in surfactant
metabolism. The diagnosis is based on the suggestive
HRCT pattern (crazy paving) and the characteristic
features of BAL fluid (Broncho Alveolar Lavage)

• Usually between 30 and 50 years old.

• Nonproductive cough, fever, and mild dyspnea.

• Prognosis has improved since the advent of

treatment using bronchoalveolar lavage.
 • Crazy paving pattern: reticular pattern
superimposed on ground glass opacification.

 • Opacifications range from ground glass to

consolidation.
.A typical case of alveolar proteinosis with extensive thickening of
interlobular and intra-lobular septa. This is caused by the fact that the
proteinacious material, which is removed from the alveolar space by
macrophages is transported to the interstitium and thus leads to
thickening of septa.
The crazy paving pattern is a rather non-specific finding. Many
other diseases may present with this finding and are listed in
the differential diagnosis.

• Non cardiogenic edema, ARDS, Acute Interstitial Pneumonia.

• Pneumonia:
– Infection (PCP and CMV).
– OP (organizing pneumonia).
– Chronic eosinophilic pneumonia.

• Haemorrhage.

• Bronchoalveolar ca.
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