2013 July Chest Section PDF

An Approach to Diffuse Lung Disease
Jeffrey R. Galvin, MD
Describing Diffuse Lung Disease Lung Volumes [Figures 3 & 4]

• The alveolar versus interstitial problem • Reduced [Figure 3]
 Pathology distal to the airway
Alveolar or Interstitial? [Figure 1]  Fibrosis
 Idiopathic pulmonary fibrosis (IPF),
asbestosis, sarcoidosis, chronic
hypersensitivity pneumonitis
• Increased [Figure 4]
 Pathology of the airway
 Emphysema, asthma, bronchitis,
constrictive bronchiolitis,
lymphangleiomyomatosis (LAM)
Figure 1 A & B Figure 3
Most diffuse lung disease involves both the alveolar Fibrosis

spaces and the alveolar walls as seen in this case of results in
desquamative interstitial pneumonia. reduced
lung
volumes.
Radiologic-Pathology Continuum
[Figure 2]
Figure 2 A, B & C
Radiology and pathology are complimentary

disciplines, and radiologic studies function as the “in
vivo gross lung examination” for pathologists.
Figure 4
Airways
An Approach to Diffuse Lung Disease disease
• Radiography results in
 Lung volumes increased
 Opacity lung
volumes.
 Distribution
 Ancillary findings
• Computed tomography (CT)
 Opacity
 Distribution
Chest Radiology 13 An Approach to Diffuse Lung Disease

Distribution: Upper versus Lower Silicosis [Figure 7]
[Figure 5]
Figure 7 A & B
Figure 5 A & B
The nodules in silicosis are well-formed and are most
A lower lobe predominance of abnormality is commonly common in the upper lung zones.
seen in hematogenous spread of disease as in the
patient with metastasis (left image). On the other
hand, chronic inhalational lung disease such as silicosis
(right image) has an upper lobe predominance.
Plain Film and CT Opacities [Figure 8]
• Nodules
• Reticulation and Lines
 Fibrosis
Physiologic Gradients: Lymphatic Flow IPF: lower, subpleural
Asbestosis: lower, subpleural
[Figure 6]
Sarcoidosis: peribronchovascular
Chronic hypersensitivity
pneumonitis: mid and upper lung
zone
• Ground glass
• Consolidation
• Cystic airspaces
Figure 6
Lymphatic flow is driven by hydrostatic vascular

pressure and is best in the dependent lung.
Plain Film and CT Opacities

• Nodules
 Silicosis
 Sarcoidosis
 Hypersensitivity pneumonitis
 Metastasis
• Reticulation and lines
• Ground glass
• Consolidation Figure 8
• Cystic airspaces Reticulation is associated with fibrosis.
An Approach to Diffuse Lung Disease 14 Chest Radiology

Idiopathic pulmonary fibrosis [Figure 9] Plain Film and CT Opacities
• Nodules
• Ground glass
• Consolidation
 Infection
 Organizing pneumonia – bronchiolitis
obliterans organizing pneumonia
(BOOP)
 Bronchioloalveolar cell carcinoma
 Hemorrhage
 Chronic eosinophiic pneumonia
 Lymphoma
Organization [Figure 11]
Figure 9 A & B
The reticulation in idiopathic pulmonary fibrosis is a

peripheral process.
Plain Film and CT Opacities

• Nodules
• Ground glass
 Nonspecific
Airspace, interstitial, combined
−− Desquamative interstitial
pneumonia (DIP), nonspecific
interstitial pneumonia (NSIP),
acute interstitial pneumonia
(AIP), diffuse alveolar damage
Figure 11 A & B
(DAD) (32%)
Infection (32%) Organizing pneumonia demonstrates peripheral
Drug toxicity (11%) consolidation with sparing of the absolute periphery as
demonstrated on these coronal and axial CT images.
Hemorrhage (3%)
Ground glass with reticulation
−− Fibrosis
• Consolidation Plain Film and CT Opacities
• Cystic airspaces • Nodules
Cigarette Smoke Injury [Figure 10]
• Ground glass
• Consolidation
 Mimics reticulation on plain
radiographs
IPF: lower, subpleural
LAM: diffuse
Langerhans cell histiocytosis
(LCH): upper
Sardcoidosis: upper/
peribronchiolar
Lymphocytic interstitial pneumonia
(LIP): lower
Figure 10 A & B
The ground-glass opacity demonstrated on the

axial CT (right image) is the result of alveolar wall
thickening and filling of the alveolar spaces with
macrophages.
Idiopathic pulmonary fibrosis [Figure 12]
Figure 12
The cysts in idiopathic pulmonary fibrosis are strikingly

Figure 14 A & B
peripheral and lower lobe.
Thickened interlobular septa identified on the axial CT of
the left upper lobe (left image) and accompanying gross
Anatomy: Secondary Lobule [Figure 13] (right image).
• Core structures
 Axial interstitium Abnormal Patterns
 Bronchiole • Bronchovascular
 Pulmonary artery  Bronchus
 Lymphatics Asthma, cystic fibrosis (CF),
• Septal structures bronchitis
 Peripheral interstitium  Lymphatic
 Pulmonary veins Carcinoma (CA), lymphoma,
 Lymphatics sarcoidosis
• Parenchyma Edema
 Alveolar interstitium • Centrilobular
 Alveoli  Airway-related
 Pulmonary capillary bed • Panlobular
 Nonspecific
• Septal
 Lymphatic
CA, lymphoma, sarcoidosis
• Random
 Hematogenous spread of tumor
 Tuberculosis (TB)
Diffuse Panbronchiolitis [Figure 15]
Figure 13
Normal anatomy of the secondary lobule with central

bronchiole and arteriole. The pulmonary veins are
identified within the interlobular septa.
Figure 15 A & B
Bronchioloectasis demonstrated on the CT (left image)

The Secondary Lobule [Figure 14] with accompanying schematic of the secondary lobule
(right image).

Abnormal Patterns
• Bronchovascular
• Centrilobular
 Airway-related
• Panlobular
 Nonspecific
• Septal
 Lymphatic
CA, lymphoma, sarcoidosis
• Random
Secondary Lobule [Figure 16]
Figure 17 A & B
Prominent septal lines and thickening of the central

bronchovascular bundle in a patient with lymphangitic
carcinomatosis. CT (left image) with accompanying
schematic of the secondary lobule (right image).
Miliary Tuberculosis [Figure 18]
Figure 16 A & B
Centrilobular nodules in a patient with transbronchial

spread of tuberculosis (left image) with accompanying
schematic of the secondary lobule (right image).
Abnormal Patterns
• Bronchovascular
• Centrilobular
 Airway-related
• Panlobular
 Nonspecific
• Septal
 Lymphatic Figure 18 A & B
CA, lymphoma, sarcoidosis Random small nodules with involvement of the pleural
• Random surface in a patient with hematogenous spread of
tuberculosis (left image) with accompanying schematic
Lymphagitic Carcinomatosis [Figure 17] (right image).
Abnormal Patterns
• Bronchovascular
• Centrilobular
Sarcoidosis
• Panlobular
• Skin nodules
• Septal
 Resembles sarcoma
• Random
• “Benign sarcoid of skin”
 Hematogenous spread of tumor
 TB Boeck, C. J Cutan Genitourin Dis. 1899.
Sarcoidosis [Figure 19]

• Multisystem disorder
• Unknown etiology
• Non-necrotizing granulomas
ATS statement on sarcoidosis. 1999.

Sarcoidosis: Risk Factors/
Hypersensitivity Reaction
• Occupational exposures:
 Insecticides
 Agricultural employment
 Firefighting
 Moldy environment
 Bioaerosol exposure
 Bird handling
Figure 19 • Mycobacterial infection
• Genetic features
The diagnosis
of sarcoidosis  Monozygotic twins
is difficult and  Familial association (5x’s)
often delayed  Gene-specific associations
because • Negative association
multiple
 Cigarette smoke
organ
systems can
be involved Sarcoidosis in 9/11 First Responders:
and the Respiratory System
presentation • 70,000 first responders
is variable.
• Cough, wheezing, and asthma
• Interstitial lung disease
 Sarcoidosis
Granuloma formation:
Immunopathogenesis
• Protective
 Confines pathogens
 Restricts inflammation
 Protects tissue
Sarcoidosis: Epidemiology • Variety of antigens
• Worldwide • Antigen presenting cells
 High incidence: Northern Europe • CD4 T-cells
 Low incidence: Asia • Granuloma formation
• Predilection for young adults • “Paradoxical anergy”
 Third decade • Resolution (2/3)
 Prior to age 50 • Progressive fibrosis (1/3)
Pietinalho. Sarcoidosis 1995. Iannuzzi. NEJM. 2007.
Sarcoidosis: Clinical Features Sarcoidosis: Respiratory System
• Lungs (95%) [Figure 20]
• Skin (16%) • 100% lung involvement
• Eye (12%) • Portal of entry
• Spleen (5%)  Airways
• Liver (5%)  Macrophages
• Neuro (4%)  Lymphatics
• Cardiac (2%)  Local lymph nodes
• Renal (1%)  Distant organs
• Musculoskeletal (1%) • Lung involvement
Baughman. Am J Respir Crit Care Med. 2001.  Alveolar walls
 Lymphatics/lymph nodes
Sarcoidosis: Biopsy/Autopsy  Airways
• Lungs (95%)  Pulmonary vessels
• Skin (16%–25%)
• Eye (12%–25%)
• Spleen (15%)
• Liver (5%)
• Neuro (4%–25%)
• Cardiac (2%–25%)
• Renal (1%)
• Musculoskeletal (1%)
Iannuzzi. NEJM. 2007.

Figure 22
The
abnormalities
Figure 20 in sarcoidosis
are usually
In both bilateral and
tuberculosis and symmetrical
silicosis, we know with the
that the etiologic majority
agent is inhaled of small
and deposited opacities,
at the alveolar masses,
level where it and ground
is engulfed by glass in the
macrophages and mid and
transported via upper lung.
the lymphatics In patients
to the regional with fibrosis,
lymph nodes and the hila retract in a cephalad direction. The areas
from the lymph of conglomerate fibrosis are often associated with
nodes disseminated hematogenously to distant organs. emphysema, traction bronchiectasis, and bulla
This same process occurs in sarcoidosis. formation.
Sarcoidosis: Adenopathy [Figure 23]
Sarcoidosis and the Secondary Lobule Node Group Chest X-ray CT

[Figure 21] • Hilar 84 88
• Right paratracheal 76 100
• Aorto-pumonary window 72 92
• Subcarinal 12 64
• Anterior mediastinal 12 48
• Posterior mediastinal 0 16
Figure 23
The lymph
nodes in
sarcoidosis
are well-
Figure 21 A & B defined,
rubbery,
Bronchovascular distribution of granulomas in and hard.
sarcoidosis.
Sarcoid and the Lung: Radiography

[Figure 22]
• Bilateral Sarcoidosis: Staging based on
• Symmetrical Adenopathy and Parenchyma
• Nodules
• Reticulonodular
• Masses
• Ground glass
• Hilar retraction
• Bulla
• Honeycombing

Sarcoidosis Stages I–IV Bronchovascular Bundle Distortion
[Figure 26]
Sarcoidosis and the Parenchyma: CT
• Thickened bronchovascular bundles
• Nodules
 Peribronchovascular
 Pleural, subpleural and septal
• Consolidation and large nodules
• Ground-glass opacities
Figure 26
• Fibrosis
Peribronchovascular
Thickened Bronchovascular Bundles opacities and
[Figure 24] architectural
distortion are
typical changes in
sarcoidosis.
Conglomerate Mass [Figure 27]
Figure 24 A & B
Peribronchovascular opacities in sarcoidosis.
The tight associate between the bronchovascular
bundle and the granuloma is represented on the
right image which shows granulomas adhering to the
pulmonary vessel. This is nicely mirrored in the CT
(left image) showing thickening and nodular distortion
following the bronchovascular bundle.
Figure 27 A & B
Typical Sarcoidosis [Figure 25] Conglomerate masses of fibrous tissue resemble a

similar process in patients with silicosis.
Cyst Formation and Distribution

[Figure 28]
Figure 28
Areas of fibrosis
may progress
to cytsic and
bullous spaces
most typically
along the
bronchovascular
bundles.
Figure 25 A & B
Typical upper lobe predominance of nodules (right

image) and associated hilar adenopathy (left image) in
sarcoidosis.

Sarcoidosis and Pulmonary Vessels Cor Pulmonale [Figure 30]
[Figure 29]
• Common
• All pulmonary vascular levels
 Elastic arteries – pulmonary veins
 Veins most common
• Pulmonary hypertension
• Lymphatic involvement first
Figure 30 A & B
Cor pulmonale is the most common cause of death

in patients with sarcoidosis and is associated
with pulmonary fibrosis demonstrated along
bronchovascular bundles in the gross (right image).
Sarcoidosis: Mycetoma
• Present in 40%–50% of cystic lesions
Figure 29 A & B
 Bullae, cavities, or bronchiectasis
Gross exam (left image) demonstrates multiple • Hemorrhage
pulmonary veins filled with tan tissue that on • Steroids may convert to invasive process
histology showed a fibrotic granulomatous reaction
(occlusive granulomatous venulitis). CT (right image) Mycetoma and Sarcoidosis [Figures 31 & 32]
demonstrates multiple occluded pulmonary veins.
Sarcoidosis: Diagnosis
• Typical clinical and radiologic
manifestations
• Löfgren syndrome
• Noncaseating granulomas
• Transbronchial biopsy
• Endobronchial biopsy
• Kveim-Siltzbach test
• Angiotensin-converting enzyme
Sarcoidosis: Differential Diagnosis

• Infection
Figure 31 A & B
 Tuberculosis, fungal (histoplasmosis)
• Pneumoconiosis Mycetoma in a cystic space caused by sarcoidosis
 Silica, beryllium with axial CT (left image) and gross pathology (right
• Hypersensitivity pneumonitis image).
• Malignancy
 Lymphoma
Figure 32
Sarcoidosis: Mortality
• Mortality range 5%–10%
Mycetomas
• Cor pulmonale related to fibrosis may be
• Cardiac arrhythmia multiple and
• Pulmonary hemorrhage bilateral
 Aspergilloma as in this
axial CT of a
patient with
bulla from
sarcoidosis.

Sarcoidosis: response to inhaled Sarcoidosis: Cyst Formation [Figure 36]
antigen [Figure 33]
Figure 36
Figure 33 The fibrotic

process results
Sarcoidosis in cephalad
most likely migration of the
represents hilum and is
the body’s associated with
response to the formation of
an inhaled bulla.
antigen.
Sarcoidosis: adenopathy and nodules

[Figure 34]
Figure 34
The most
common
appearance
involves
small and
large nodules
along the
bronchovascular
bundles and in
the subpleural
area.
Sarcoidosis: conglomeration [Figure 35]
Figure 35
As the disease
progresses
there is
fibrosis and
conglomeration
of nodules in
the hilar area
with associated
fibrosis.

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Pathways to Fibrosis: The Idiopathic Interstitial
Pneumonias
The Idiopathic Interstitial Pneumonias
Chronic Diffuse Lung Disease
[Figure 1]
• Alveolar involvement
Figure 2
 Surrounding airways
 Fibrosis and/or cells The interstitium
Alveolar wall depicted in
Alveolar space yellow provides
• Restrictive physiology support for the
type 1 cells
• Decreased lung volumes (green), the
• Increased attenuation type 2 cells
• Subacute or chronic (purple), and
 Weeks to months the capillaries
(red).
Alveolar Wall Thickening/Volume Loss

[Figure 3]
Figure 1
The idiopathic
interstitial
pneumonias
are a diverse
collection of
pathologic
processes that
involve the
alveolar walls
and spaces.
Figure 3 A & B
The Idiopathic Interstitial Pneumonias The idiopathic interstitial pneumonias result in alveolar
[Figure 2]
wall thickening and volume loss. The alveolar wall
thickening can be the result of multiple processes.
• Liebow 1969
• Supporting lung structures
 Inflammation
 Fibrosis The Idiopathic Interstitial Pneumonias:
• Initiated in airspaces
Consensus Classification and Legacy
• Pathologic processes
 Not diseases
Terminology
• Idiopathic pulmonary fibrosis (IPF)
 Multiple etiologies
 Usual interstitial pneumonia (UIP)
• Diagnosis
• Respiratory bronchiolitis-interstitial lung
 Collaborative process
disease (RB-ILD)
Liebow. Frontiers of Pulm Radiology. 1969. • Desquamative interstitial pneumonia
(DIP)
• Acute interstitial pneumonia (AIP)
 Diffuse alveolar damage (DAD)
• Cryptogenic organizing pneumonia (COP)
• Nonspecific interstitial pneumonia (NSIP)
• Lymphocytic interstitial pneumonia (LIP)
ATS/ERS. Am J Resp Crit Care Med. 2002.
Chest Radiology 25 The Idiopathic Interstitial Pneumonias

Pathways to Fibrosis
[Figure 4]
Figure 4 A to E
There are 3 main mechanisms

that result in alveolar wall
thickening: (1) alveolar
collapse; (2) incorporation
of organized debris into the
alveolar wall (organization
incorporation); and (3) true
collagen deposition which
is associated with cigarette
smoke. Some of the patients
with alveolar wall thickening
and volume loss will have
a combination of histologic,
radiographic, and physiologic
features that place them into
the so-called center of the
target for idiopathic pulmonary
fibrosis, acute interstitial
pneumonia, or organizing
pneumonia.
Idiopathic Pulmonary Fibrosis Alveolus Injury [Figure 6]

• Usual interstitial pneumonia (UIP)
histology
• Presentation
Figure 6
 66% >60 years
 Cigarette smokers
Idiopathic
 Gastroesophageal (GE) reflux pulmonary
 Insidious onset of dyspnea fibrosis is
• Median survival 2.5–3.5 years the result of
• Histology an unknown
 Temporal heterogeneity injury to
the type 1
 Geographic heterogeneity cell shown
• Honeycombing here in
 Basal predominance fragments.
Selman. Ann Intern Med. 2001.
Alveolus [Figure 5] Migration [Figure 7]
Figure 5 Figure 7
The normal alveolar wall is depicted with the
Serum and fibroblasts migrate into the alveolar space.
interstitium as a dark purple core that supports the
type 1 cells, type 2 cells, and capillaries.
The Idiopathic Interstitial Pneumonias 26 Chest Radiology

Incorporation [Figure 8] Idiopathic Pulmonary Fibrosis: Imaging
[Figure 12]
• Radiograph abnormal (95%)
Figure 8  Volume loss
 Reticulonodular opacities
There is  Lower lobe
incorporation  Honeycombing
of the • Computed tomography (CT)
fibroblast  Peripheral and lower lobe
and serum
components  Reticulation and ground glass
into the Progress to honeycombing
alveolar wall.  Ground glass in areas of traction
bronchiectasis
Hartman. Chest. 1996.
Fibroblast Focus [Figure 9]
Figure 9
Resulting in Figure 12
a fibroblast
focus which The
is one of the abnomalities
histologic are
features of predominantly
idiopathic peripheral and
pulmonary lower lung
fibrosis. field. There is
progressive
volume loss.
Geographic Heterogeneity [Figure 10]
Idiopathic Pulmonary Fibrosis

Figure 10
[Figure 13]
Geographic
heterogeneity
is another
key histologic
feature of
idiopathic
pulmonary
fibrosis with
relatively
normal alveoli right next to dense areas of fibrosis.
Honeycombing is collapse, Not fibrosis

[Figure 11]
Figure 13 A & B
The region of lung affected in idiopathic pulmonary

fibrosis follows the gradient of alveolar size.
Figure 11
Honeycombing is primarily the result of numerous

small alveoli collapsing around larger alveolar ducts.

Utility of Biopsy for Diagnosis of
Idiopathic pulmonary fibrosis
• Prospective multi-center study
 91 patients suspected of IPF
• Clinical diagnosis
 Positive predictive value with a
confident diagnosis (87%) Figure 15
• Imaging diagnosis Acute
 Positive predictive value with a interstitial
confident diagnosis (96%) pneumonia
 CT always abnormal in patients with involves all 5
proven IPF lobes.
• Histologic diagnosis
 Agreement regarding the presence or
absence of IPF (85%)
 Agreement in patients without IPF
(48%) Organizing diffuse alveolar damage
Relevance to NSIP [Figure 16]
Hunninghake. Am J Respir Crit Care Med. 2001.
Acute Interstitial Pneumonia

• Legacy categories
 Hamman-rich, AIP, acute respiratory
distress syndrome (ARDS)
• Presentation
 Acute/subacute
 Antecedent flu-like syndrome
 High mortality
• Histologic spectrum of diffuse alveolar
damage (DAD)
Figure 16
 Injury to fibrosis and honeycombing
Type I cell injury
Collapse The acute phase of diffuse alveolar damage is followed
by an organizing phase of diffuse alveolar damage with
Organization fibroblasts invading the alveolar walls.
Katzenstein. Am J Pathol. 1986.
Acute diffuse alveolar damage [Figure 14]
alveolar Collapse [Figure 17]

Figure 14
Hyaline
membranes
and
alveolar
wall
edema are
indicative
of the
acute
phase of
diffuse
alveolar
damage.
Acute Interstitial Pneumonia:

Radiography [Figure 15] Figure 17
• Diffuse
Alveolar collapse is often overlooked in the patho-
• Airspace opacification physiology of this injury and can be the dominant
• Costal sparing pathophysiologic process in some cases.
• Mechanical ventilation
• Resembles ARDS

Acute Interstitial Pneumonia: Organizing Pneumonia [Figure 20]
Organizing and Acute [Figures 18 & 19]
Figure 20
Organizing
pneumonia
is defined
histologically
by the
presence
of intra-
alveolar
plugs of
organizing
fibroblastic
tissue.
Cryptogenic Organizing Pneumonia:

Radiography [Figure 21]
Figure 18 A & B • Consolidation
 Unilateral or bilateral
Traction bronchiectasis differentiates the organizing
phase of acute interstitial pneumonia from the acute  Focal or diffuse
phase.  Peribronchiolar
 Spares the periphery
 Lower lobe
• Small nodules
 10%–50%
• Lung volumes
 Normal in 75%
Figure 21
Cryptogenic
organizing
pneumonia is
characterized
by focal areas
of consolidation
more common
in the lower
lung fields.
Figure 19 A & B
Volume loss is prominent in the organizing phase of
acute interstitial pneumonia. Organizing Pneumonia [Figures 22 to 24]
Organization
• Legacy categories
 Bronchiolitis obliterans organizing
pneumonia (BOOP)
 Cryptogenic organizing pneumonia
(COP)
• Clinical presentation
 Subacute
 Cough, fever, dyspnea, weight loss
 Connective tissue disease, organ
transplant, drug reaction
 Steroid responsive
• Postinfectious
• May evolve to NSIP Figure 22 A & B
 Mural incorporation
The typical distribution of organizing pneumonia is
Davison, et al. QJ Med. 1983. peribronchiolar and peripheral with sparing of the
absolute periphery.

Organizing Pneumonia and Organizing
Pneumonia/Fibrosis [Figure 26]
Figure 23 A & B
Organizing pneumonia may be focal.
Figure 26 A & B
Organizing pneumonia leading to fibrosis with traction

bronchiectasis and a distorted major fissure.
Cigarette Smoke-Related Lung Injury

• Smoking results in inflammation
 Respiratory bronchiolitis (RB)
 Respiratory bronchiolitis interstitial
lung disease (RB-ILD)
 Desquamative interstitial pneumonia
(DIP)
• Cigarette smoke-related interstitial lung
disease (ILD)
• Strong association with fibrosis
 Thickened alveolar walls (ground-glass
Figure 24 A & B
opacity)
In some patients, organization leads to interstitial  Thickened emphysematous spaces
fibrosis instead of normal alveolar walls. The initial  May be labeled NSIP
step of clearing intraalveolar material is the ingrowth
of fibroblasts which form these intraalveolar plugs. Niewoehner. NEJM. 1974.
Respiratory bronchiolitis [Figure 27]
Organizing Pneumonia: Fibrosis

[Figure 25]
Figure 27
Figure 25 A & B
Respiratory bronchiolitis represented by “smoker’s
Fibroblastic tissue incorporated into the alveolar wall macrophages” in and around small airways.
may result in dense irreversible fibrosis.

Smoking-Related interstitial lung Smoking-Related interstitial lung
disease: Respiratory bronchiolitis disease (Inflammation) [Figure 30]
interstitial lung disease [Figure 28]
• Clinical
• Pathology
• Imaging
 Centrilobular nodules
Poorly defined 2–3 mm
Upper lobe predominance
• Ground-glass opacity
• Bronchial wall thickening
• Decreased attenuation
• Emphysema
• Air trapping
• Reticulation
Park. J Comput Assist Tomogr. 2002.
Figure 30
Smoking-related lung injury with upper lobe ground-

glass nodules and more diffuse areas of ground glass
at the lung bases.
Cigarette Smoke and Fibrosis: Divergent

responses to a common injury
• Fibrosis commonly associated with
emphysema
• No evidence of collapse
• No incorporation/fibroblast foci
• Cysts: size and distribution of emphysema
Figure 28 A & B
Typical respiratory bronchiolitis with ground-glass

Smoking-Related interstitial lung
nodules primarily in the upper lobes. disease [Figure 31]
Smoking-Related interstitial lung

disease: Desquamative interstitial
pneumonia [Figure 29]
• Clinical
• Pathology
 Pigmented macrophages
 Interstitial infiltrate
Plasma cells and eosinophils
 Fibrosis
• Imaging
Carrington. NEJM. 1978.
Figure 29
Figure 31 A & B
Respiratory
bronchiolitis and These well-outlined holes of emphysema resemble
desquamative honeycombing but follow the typical distribution of
interstitial cigarette smoke-related emphysema. The histology on
pneumonia the right demonstrates relatively uniform fibrosis of
represent a the alveolar walls, emphysema, and macrophages of
spectrum of respiratory bronchiolitis.
smoking-related
lung injury.

Smoking and Idiopathic Pulmonary Nonspecific Interstitial Pneumonia
Fibrosis [Figure 32] [Figure 34]

Smoking-related injury (left image) with upper lobe
Typical findings of idiopathic nonspecific interstitial
emphysematous holes surrounded by fibrotic walls.
pneumonia with lower lobe opacity and traction
The differentiation from idiopathic pulmonary fibrosis
bronchiectasis.
(right image) is striking with its basilar peripheral
distribution and traction bronchiectasis.
Pathways to Fibrosis
Nonspecific Interstitial Pneumonia: • Idiopathic pulmonary fibrosis (IPF)
Imaging  Usual interstitial pneumonia (UIP)
• Few reports on chest radiography • Acute interstitial pneumonia (AIP)
• Wide variety of CT patterns  Diffuse alveolar damage (DAD)
 Ground glass, consolidation, reticular, Acute or chronic
and honeycombing • Cryptogenic organizing pneumonia (COP)
• Traction bronchiectasis = fibrosis  Organizing pneumonia (OP)
• CT pattern indistinguishable • Smoking-related ILD
 UIP (32%)  Respiratory bronchiolitis (RB)
 Hypersensitivity (20%)  Respiratory bronchiolitis – ILD
 Organizing pneumonia (14%)  Desquamative interstitial pneumonia
 Other (12%) (DIP)
 Fibrosis
Hartman. Radiology. 2000.
Idiopathic pulmonary fibrosis [Figure 35]
Nonspecific Interstitial Pneumonia
Current View [Figure 33]
Figure 33
Nonspecific interstitial pneumonia is a nonspecific

pattern of fibrosis that can be seen in idiopathic
pulmonary fibrosis, smoking-related interstitial lung Figure 35
disease, hypersensitivity pneumonitis, and collagen
vascular disease. From Nicholson MD personal Idiopathic pulmonary fibrosis is strikingly peripheral
communication. and lower lobe and must demonstrate honeycombing
for a definite diagnosis.

Acute Diffuse alveolar damage Organizing Pneumonia: Incorporation
[Figure 36] [Figure 39]
Figure 39
Figure 36 Organizing
pneumonia
may lead
Diffuse to fibrosis
alveolar with
damage traction
involves bronch-
all 5 lobes iectasis.
with focal Again
areas of note the
sparing. peripheral
sparing.
Organizing Diffuse alveolar damage Respiratory Bronchiolitis [Figure 40]

[Figure 37]
Figure 40
Figure 37 Respiratory bronchiolitis is characterized by upper

lobe ground-glass nodules.
The organizing phase of diffuse alveolar damage is
characterized by volume loss, reticulation, and traction
bronchiectasis.
Respiratory Bronchiolitis/
Desquamative interstitial pneumonia
Organizing Pneumonia [Figure 38] [Figure 41]
Figure 38 Figure 41
Organizing pneumonia is characterized by Respiratory bronchiolitis and desquamative
peribronchiolar distribution of consolidation with interstitial pneumonia represent a spectrum of lung
peripheral sparing. inflammation related to cigarette smoke.

Respiratory Bronchiolitis/Desquamative Idiopathic Interstitial Pneumonia:
interstitial pneumonia/Fibrosis Multidisciplinary information [Figure 43]
[Figure 42]
Figure 42
Fibrosis
related to
cigarette
smoke will
result in
unusually
well-defined
emphy- Figure 43
sematous
spaces. An accurate diagnosis of the idiopathic interstitial
pneumonias requires collaboration between the
radiologist, pathologist, and clinician.
References
General
1. American Thoracic Society/European Respiratory Society International Multidisciplinary Consensus
Classification of the Idiopathic Interstitial pneumonias. This joint statement of the American Thoracic
Society (ATS), and the European Respiratory Society (ERS) was adopted by the ATS board of directors,
June 2001 and by the ERS Executive Committee, June 2001. Am J Respir Crit Care Med 2002;165:277-
304.
IPF/UIP
2. Wittram C, Mark EJ, McLoud TC. CT-histologic correlation of the ATS/ERS 2002 classification of idiopathic
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3. Hansell DM, Wells AU. CT evaluation of fibrosing alveolitis—applications and insights. J Thorac Imaging
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4. Katzenstein AL, Myers JL. Idiopathic pulmonary fibrosis: clinical relevance of pathologic classification. Am
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12.
6. Liebow AA. Definition and classification of interstitial pneumonias in human pathology. Prog Resp Res
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8. Schurawitzki H, Stiglbauer R, Graninger W, Herold C, Polzleitner D, Burghuber OC, Tscholakoff D.
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203.
DIP
12. Gaensler EA, Goff AM, Prowse CM. Desquamative interstitial pneumonia. N Engl J Med 1966; 274(3)113-
28.

13. Ryu JH, Myers JL, Capizzi SA, Douglas WW, Vassallo R, Decker PA. Desquamative interstitial pneumonia
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DAD/AIP
14. Bone RC. The ARDS lung. New insights from computed tomography [editorial; comment]. JAMA 1993;
269(16):21 34-5.
15. Desai SR, Wells AU, Rubens MB, Evans TW, Hansell DM. Acute respiratory distress syndrome: CT
abnormalities at long-term follow-up. Radiology 1999;210(1):29-35.
16. Greene R. Adult respiratory distress syndrome: acute alveolar damage. Radiology 1987;163(1):57-66.
17. Ichikado K, Johkoh T, Ikezoe U, Takeuchi N, Kohno N, Arisawa U, Nakamura H, Nagareda T, Itoh H,
Ando M. Acute interstitial pneumonia: high-resolution CT findings correlated with pathology. AUR Am J
Roentgenol 1997;168(2):333-8.
18. Johkoh T, Muller NL, Taniguchi H, Kondoh Y, Akira M, Ichikado K, Ando M, Honda 0, Tomiyama
N, Nakamura H. Acute interstitial pneumonia: thin-section CT findings in 36 patients. Radiology
1999;211(3):859-63.
19. Katzenstein AL, Myers UL, Mazur MT. Acute interstitial pneumonia. A clinicopathologic, ultrastructural, and
cell kinetic study. Am J Surg Pathol 1986;10(4):256-67.
20. Olson U, Colby TV, Elliott CG. Hamman-Rich syndrome revisited. Mayo Clin Proc 1990;65(12):1538-48.
21. Primack SL, Hartman TE, Ikezoe U, Akira M, Sakatani M, Muller NL. Acute interstitial pneumonia:
radiographic and CT findings in nine patients. Radiology 1993;188(3):817-20.
22. Cottin V, Donsbeck AV, Revel D, Loire R, Cordier JR Nonspecific interstitial pneumonia. Individualization of
NSIP
a clinicopathologic entity in a series of 12 patients. Am J Respir Crit Care Med 1998;158(4):1286-93.

23. Katzenstein AL, Fiorelli RF. Nonspecific interstitial pneumonia/fibrosis. Histologic features and clinical
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BOOP/Organizing Pneumonia
25. Akira M, Yamamoto S, Sakatani M. Bronchiolitis obliterans organizing pneumonia manifesting as multiple
large nodules or masses. AJR Am J Roentgenol 1998;170(2):291-5.
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bronchiolitis. Mayo Clin Proc 1993;68(3):307-8.
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bronchiolitis obliterans with organizing pneumonia vs usual interstitial pneumonia. AJR Am J Roentgenol
1986;147(5):899-906.
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pneumonia. N Engl J Med 1985;312(3):152-8.
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Roentgenol Radium Ther Nucl Med 1973;117(4):816-32.
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1992;65(776):674-80.
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interstitial pneumonia. A comparative clinicopathologic study. Am J Surg Pathol 1986;10(6):373-81.
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8.
33. Lee KS, Kullnig P, Hartman TE, Muller NL. Cryptogenic organizing pneumonia: CT findings in 43 patients.
AJR Am J Roentgenol 1994; 162(3):543-6.
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Organizing pneumonia. Features and prognosis of cryptogenic, secondary, and focal variants. Arch Intern
Med 1997;157(12):1323-9.
35. McLoud TC, Epler GR, Colby TV, Gaensler EA, Carrington CB. Bronchiolitis obliterans. Radiology
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patients. AJR Am J Roentgenol 1990;154(5):983-7.

Airways Disease: The Movement from Anatomic to Physiologic
Assessment
Assessment of Dyspnea: A Common
Clinical Problem
• 55 million adult smokers
• 15 million meet criteria for bronchitis
• 5 million with airway obstruction
• 10 million with asthma
Gordon Snyder.
Differential Diagnosis of Airways

Obstruction
• Common
 Emphysema, bronchitis,
bronchiectasis, asthma
• Uncommon
 LAM, BO, panbronchiolitis, sarcoid,
alpha-1 deficiency, ABPA Figure 2 A & B
Diseases with Obstructive Physiology Left Image: Small airway without cartilage partially
[Figure 1]
collapsed. Right Image: Small airway tethered to the
pleural surface by alveolar walls.
Figure 1
From the view

of the clinician,
those who
present with
obstructive
physiology most
commonly present with emphysema, asthma or
bronchitis.
The Changing Role of Imaging

• Diagnosis
• Functional assessment
Pulmonary Functions are Insensitive

• PFT’s based on wide range of normal
 80%–120% predicted
• Diseases with opposing physiologic Figure 3 A & B
processes Mosaic attenuation on an expiratory CT in patient with
• The “silent zone” of the lungs constrictive bronchiolitis.
The “silent zone” of the lungs

“Small Airways” [Figures 2 & 3]
• Peter Macklem
 1970’s
• No cartilage
 <2 mm physiologists Figure 3
 1 mm pathologists
Airways
• Tethered
involvement
 Fiber skeleton at the level of
 Pleura the secondary
Weibel. lobule.
Diffuse Lung Disease: Airways [Figure 3]

• Airways involvement
• Obstructive physiology
• Increased lung volumes
Chest Radiology 37 Airways Disease
Airways Disease: Direct Signs [Figure 4] Emphysema: Classification
• Changes • Proximal acinar
 Airway wall  Centrilobular
 Airway lumen  Resp bronchiole
• Opacities  Cigarette smoke
 Tubular  Upper lobes
 Nodular • Panacinar
 Branching  Entire acinus
 Alpha-1 deficiency
 Lower lobes
• Distal acinar
 Paraseptal
 Distal acinus
 Subpleura
 Pneumothorax
Emphysema: Proximal Acinar [Figure 5]
Figure 4
“Tree-in-
bud” in a
patient
with a
respiratory
infection.
Airways Disease Figure 5 A & B

• COPD
Typical upper lobe smoking-related emphysema.
 Emphysema
 Bronchitis
• Emphysema and fibrosis
• Alpha-1 deficiency
• Langherhans cell histiocytosis
• Bronchiectasis
• Asthma Emphysema: Clinical Presentation
• Allergic bronchopulmonary aspergillosis • Cough, dyspnea and sputum production
• Sarcoidosis • Hemoptysis rare
• Diffuse panbronchiolitis  Rule out cancer
• Bronchiolitis obliterans • Symptomatic air flow obstruction
• Lymphangioleiomyomatosis  After age 50, 20–30 years of smoking
• Cor Pulmonale (late) related to hypoxemia
Emphysema: ATS Definition and loss of capillary bed
• Permanent enlargement of airspaces
distal to the terminal bronchiole, Emphysema and Cor Pulmonale
accompanied by destruction of the walls
without obvious fibrosis Emphysema: Pulmonary Functions
• Important to identify patients at risk
Emphysema: Classification • Reduction in Fev1
• Proximal acinar  Most reproducible
• Panacinar • RV increases followed by TLC
• Distal acinar • Volumes and flows
 Insensitive to early changes
• Diffusing capacity
 Sensitive but non-specific
• Small airways tests
Airways Disease 38 Chest Radiology

Emphysema: Radiographic Feature Physiologic assessment: parenchyma
• Hyperinflation [Figure 8]
 Concave diaphragm
 Increased A-P diameter
 Retrosternal airspace
• Arterial deficiency pattern
• Bulla
 Cystic airspaces >1 cm
• Radiography is insensitive
 41% of moderate disease
 66% of severe disease
Saber Trachea [Figure 6]
Figure 8 Eric Hoffman.

Lower lobe predominance in Alpha-1 antitrypsin.
Physiologic assessment: airways

[Figure 9]
Figure 6 A & B
Saber trachea.
Emphysema and Computed Tomography

[Figure 7]
Figure 9 Eric Hoffman.

Lower lobe predominance in Alpha-1 antitrypsin.
Figure 7 A & B
Typical low attenuation lesions of emphysema.

Bronchitis
• Cough and sputum
 3 months
 2 consecutive years
• Airways obstruction
 Secretions
 Thickening
 Cells

Bronchitis [Figure 10] Relationship of RB and Emphysema
• Prospective study
• 111 subjects
 Followed for 5 years
Imaged at inception T0 and 5
years T1
 Smokers, nonsmokers and quitters
• Micronodules at T0 predisposes to the
development of emphysema at T1
• Micronodules and emphysema at T0
predicts more rapid decline in lung
function
Remy-Jardin. Radiology 2001.
Emphysema and Fibrosis

• Normal lung volumes and
• Normal flow rates
Figure 10 A & B • Reduced diffusing capacity
 Severe
Mosaic attenuation from bronchitis. • Minimal pulmonary reserve
Emphysema and Fibrosis [Figure 12]

• TLC (119%)
• VC (126%)
Respiratory Bronchiolitis: “Smoker’s • RV (109%)
Bronchiolitis” [Figure 11] • FEV1/FVC (88%)
• Common change • D/Va (28%)
 All smokers
• Pigmented macrophages
 In respiratory bronchioles
 Surrounding alveoli
• Upper lobe predominance
• Usually asymptomatic Figure 12
 May cause symptoms
Figure 11 A & B
Left image: Smoker’s macrophages. Right image:

Respiratory bronchiolitis.
Figure 13 A & B
Emphysema and fibrosis.

Idiopathic Pulmonary Fibrosis [Figure 14]
Figure 16 A & B
Figure 14 A & B Typical nodules in Langerhans cell histiocytosis.

Idiopathic pulmonary fibrosis.
Langerhans Cell Histiocytosis: Clinical

Presentation
• Cigarette smokers
• Cough and dyspnea
• Often asymptomatic
• Combined with other smoking-related
injury
 RB, DIP, emphysema and fibrosis
Langerhans Cell Histiocytosis: Histology

• Nodular
 Interstitial lesions
 Located near bronchioles
• Histiocytes, eosinophils, plasma cells and
lymphocytes Figure 17 A & B
• Diagnosis requires Langerhans cells
 Large histiocytes Cystic lesions in Langerhans cell histiocytosis.
 Folded nuclei
 Eosinophilic cytoplasm
• Path differential diagnosis
 Eos pneumonia, DIP, UIP Langerhans Cell Histiocytosis:
Radiographic Features
Langerhans Cell Histiocytosis
• Varies over time
[Figures 15 to 17]
• Upper lobe
 Predominance
• Nodules
 0.5–1.0 cm in upper lobes
 Early
• Cysts replace nodules
 Later
Figure 15 • Honeycomb lung
• Pneumothorax 15%
The range of
findings in
• Adenopathy and effusion are unusual
Langerhans
cell
histiocytosis.

Langerhans Cell Histiocytosis Pulmonary Langerhans cell
[Figures 18 & 19] histiocytosis [Figure 20]
Figure 18 A & B Figure 20 A & B

Nodules alone in pulmonary Langerhans cell Late stage pulmonary Langerhans cell histiocytosis.
histiocytosis.
Alpha-1 Antitrypsin Deficiency:

Pathophysiology
• 1%–2% of emphysema in the US
• Alpha-1 antitrypsin inactivates neutrophil
elastase
Figure 19 • Production controlled by 2 genes
• Level of antitrypsin dependent on allele
Pulmonary • ZZ homozygotes most severe
Langerhans • Smoking accelerates the destruction
cell
histiocytosis Alpha-1 Antitrypsin Deficiency: Imaging
with cysts,
nodules and Features
emphysema. • Radiograph may be normal
• Lower lobe predominance
• Panacinar emphysema
• CT
 Upper lobe involvement
 Bronchiectasis
Langerhans Cell Histiocytosis: EM and  Airway thickening common
Immunohistochemistry • CT more sensitive
• Immunoperoxidase staining
 CD1a, S-100 protein Alpha-1 Antitrypsin Deficiency [Figure 21]
• Cells in clusters in interstitium
• EM
 X-bodies
 Langerhans cell granules
 Birbeck granules
Langerhans Cell Histiocytosis - Clinical

Course
• Clinical resolution
 Common
• Radiographic abnormalities
 Persist
• Occasional progression
 Fibrosis and honeycombing
• May be fatal
 Rapid progression
Figure 21 A & B
Alpha-1 antitrypsin deficiency versus smoker’s
emphysema.
Alpha-1 Antitrypsin Deficiency Mounier-Kuhn Syndrome [Figure 24]
[Figure 22]
Figure 22 A & B
Alpha-1 antitrypsin deficiency.
Figure 24 A & B
Mounier-Kuhn.
Bronchiectasis: Pathophysiology
• Dilatation of bronchi
• Reversible form Bronchiectasis - Postinflammatory
 Infection • Primary ciliary dyskinesia
 Atelectasis  Kartagener’s
• Congenital • Immunodeficiency
 Tracheobronchomalacia • Post-infectious
• Post-inflammatory  TB, measles, pertussis, viral
• Post-obstructive • Post-toxic bronchitis
• Fibrotic  Gastric acid aspiration
 IPF • Immunologic
 Sarcoid  ABPA
Williams-Campbell [Figure 23] Post Obstructive Bronchiectasis
• Neoplasm
• Foreign body
• Broncholith
• Lymph node enlargement
Post Obstructive Bronchiectasis

[Figure 25]
Figure 23
Williams-Campbell.
Figure 25 A & B
Post obstructive bronchiectasis in a patient with

mucoepidermoid carcinoma.

Bronchiectasis – Clinical Presentation Respiratory bronchiolitis/Respiratory
• Cough bronchiolitis-associated interstitial
• Purulent sputum lung disease [Figure 28]
• Hemoptysis (50%)
• Dyspnea
• Rare
 Clubbing, brain abscess, amyloidosis
Bronchiectasis – CT Features
• Bronchi in the periphery
• “Signet rings”
• “Tram tracks”
• Sensitivity
 Collimation
Emphysema [Figure 26]
Figure 28 A & B
Respiratory bronchiolitis.
Figure 26 A & B
Upper lobe smoking-related emphysema.
Emphysema versus Bronchitis [Figure 27] Figure 29 A & B

Emphysema and fibrosis.
Langerhans Cell Histiocytosis

[Figures 30 to 32]
Figure 27 A & B
Emphysema and bronchitis.
Figure 30 A & B
Early Langerhans cell histiocytosis nodules.

Langerhans Cell Histiocytosis Bronchiectasis [Figure 34]
[Figures 30 to 32]

Late Langerhans cell histiocytosis cysts and nodules Bronchiectasis.
Diffuse Lung Disease – Airways

• Obstructive physiology
• Increased lung volumes
Asthma – American Thoracic Society

Definition
• Reversible airway disease
• Increased airway responsiveness
• Persistent airflow obstruction occurs in
chronic asthmatic
Figure 32 A & B  Why?
End-stage Langerhans cell histiocytosis. • 6% in the American population
 Rate has doubled in 20 years
 Higher incidence in large cities
Asthma – Extrinsic
Alpha-1 Antitrypsin Deficiency [Figure 33] • Family history atopy
• Early onset <30 years
• Seasonal symptoms
• Increased IGE
• Positive skin tests
• Often remits
Asthma – Intrinsic
• No atopy
 Absence of external triggers
• Older age group
• Increased blood eosinophils
• Increased sputum eosinophils
• Fixed airway obstruction
 Progressive
Figure 33 A & B
Lower lobe predominance in alpha-1 antitrypsin.

Asthma – Pathology Asthma – Hyperinflation [Figure 37]
• Airway smooth muscle
 Hypertrophy
• Airway wall
 Inflammation
 Edema
• Airway plugging Figure 37
 Mucus
 Inflammatory exudate Severe
hyperinflation
in which you
Asthma – Radiographic Features can see the
[Figures 35 & 36] slips of the
• Chest roentgenogram diaphragm as
 Often normal it inverts.
• Airway thickening
 Chronic disease
• Rapid attenuation of vessels
 Hypoxemia Asthma – CT Features [Figure 38]
• Pneumomediastinum • More sensitive than CXR
 Pneumothorax • Reversible
• Hyperinflation  Consolidation
 Adaptive  Atelectasis
 Later air trapping  Mucoid impaction
 Airway narrowing
 Air trapping
• Permanent
 Bronchial wall thickening
 Bronchiectasis
 Emphysema
Figure 35
Asthma with
mediastinal
emphysema.
Figure 38
Asthma
and mild
bronchiectasis.
Allergic Bronchopulmonary Aspergillosis

– Primary Criteria
• Asthma
• Eosinophilia
• Immediate skin test reactivity
• Precipitating antibodies (IgG)
Figure 36 • Elevated serum (IgE)
• Pulmonary infiltrates
Severe asthma with mediastinal emphysema and right • Central bronchiectasis
lower lobe collapse from secretions.

Allergic Bronchopulmonary Aspergillosis Sarcoidosis and the Airways [Figure 40]
– Presentation and Pathology
• Atopic individuals
 Most common
• Cystic fibrosis
• Airways filled
 Fungus
 Inspissated mucous
• Presentation with
 Cough, fever
 Hemoptysis
 Worsening asthma
• Seen in stable asthmatics
• Good response to steroids

– Imaging
• Bifurcating opacities
Figure 40 A & B
 “Gloved-finger”
 Mucous filled airways Sarcoidosis with airways involvement and mosaic
• Central bronchiectasis attenuation.
• Fleeting infiltrates
• Pleural disease
 Uncommon
Diffuse Panbronchiolitis
Allergic Bronchopulmonary Aspergillosis • Japan most common
[Figure 39]  Rarely: Korea, China, Europe and
North America
 HLA BW54
 Male:female = 2:1
• Presentation
 Dyspnea
 Cough
• Obstructive PFT’s
• Slowly progressive
 15-year mean survival
• Erythromycin
 May not be an antibacterial effect
Diffuse Panbronchiolitis – Pathology

• Discrete nodules
• Early infiltration
 Interstitium
 Respiratory bronchioles
Figure 39 A & B  Alveolar ducts
Allergic bronchopulmonary aspergillosis and mucoid  Foamy histiocyte, lymphocyte and
impaction. plasma cells
• Late secondary ectasia
 Proximal terminal bronchioles
Sarcoidosis and the Airways – Diffuse Panbronchiolitis – Imaging Early

Computed Tomography • Radiography
• Functional evidence of airways obstruction  Nodules 5 mm
 Obstructive PFT’s are common  Hyperinflation
• Endobronchial biopsies find granulomas • Computed tomography
• Obstructive physiology correlates with  Centrilobular nodules
 Decreased attenuation on expiratory  Branching opacities
scans (small airways)  Mosaic attenuation
 Reticular pattern and advanced fibrotic
disease (large airways)
Hansell, et al. Radiology. 1998.

Diffuse Panbronchiolitis – Imaging Early Constrictive Bronchiolitis – Clinical
[Figures 41] Presentation
• Cough, dyspnea and malaise
• History
 Prior infection
 Exposure
• Hypoxemia
• Airway obstruction
Figure 41 Constrictive Bronchiolitis –
Bronchioloectasis Classification
in diffuse • Infection
panbronchiolitis  RSV, adenovirus and mycoplasma
• Toxic inhalation
 Ammonia, acid and NO
• Aspiration: gastric acid
• Collagen vascular: RA
• Organ transplantation
• Unknown
Diffuse Panbronchiolitis – Imaging Late Constrictive Bronchiolitis – Histology
[Figure 42]
[Figure 43]
• Radiography
• Obstruction
 Nodules
 Terminal bronchiole
 Cysts and bulla
 Respiratory bronchioles
 Hyperinflation
• Polyps of fibrosis
• Computed tomography
• Cellular infiltration
 Centrilobular nodules
 Lymphs
 Bronchiolectasis
 Plasma cells
 Bronchiectasis
 Histiocytes
Figure 42
Figure 43
Severe airway Constrictive

involvement in Bronchiolitis.
panbronchiolitis.
Constrictive Bronchiolitis – Introduction

• Confusing terminology Constrictive Bronchiolitis – Imaging
 Obliterative bronchiolitis • Hyperinflation
 Bronchiolitis obliterans  Localized
 Bronchiolitis obliterans organizing  Diffuse
Pneumonia • Discrete nodules
Different disease  Airway associated
Cryptogenic organizing pneumonia • Mosaic pattern
• Small airways • Airway thickening
 Fibrosis • Bronchiectasis
 Inflammation • Air trapping
• Response to
 Inflammatory disorders
 Infectious disorders

Constrictive Bronchiolitis [Figure 44]
Figure 47 A & B
Figure 44 A & B
Swyer-James syndrome.
Constrictive bronchiolitis.
Lymphangioleiomyomatosis – Clinical
Presentation
• Exclusively women
• Reproductive years
• Progressive dyspnea
• Chylous pleural effusions
• Hemoptysis
• Massive hemorrhage
Lymphangioleiomyomatosis – Function
• Obstructive defect
Figure 45
• FEV1 is decreased
Central • TLC and RV increased
bronchiectasis • DLCO reduced
and mosaic • Hypoxemia
attenuation • Hypocapnia
in constrictive
bronchiolitis.
Lymphangioleiomyomatosis – Histology
• Smooth muscle proliferation
 Disorderly
 Bronchioles, alveolar septa, arteries,
veins and lymphatics
• Small air filled cysts
 Air trapping
Lymphangioleiomyomatosis – Gross
Swyer-James Syndrome [Figures 46 & 47] Features [Figure 48]
• Cysts
 0.2–2 cm
• Diffuse involvement
• Enlarged thoracic duct
• Enlarged lymph nodes
Figure 46
Unilateral
hyperlucent
lung in a
patient with
Swyer-
James.

Figure 50
Thin-walled
cysts and a
pneumothorax
in patient with
lymphangioleio-
myomatosis
Figure 48 A & B
Left image: Typical thin-walled cyst in lymphangioleio-

myomatosis. Right image: The upper and lower lobes
are equally involved in lymphangioleiomyomatosis.
Lymphangioleiomyomatosis – Therapy
Lymphangioleiomyomatosis – and Prognosis
Radiographic Features [Figure 49] • Slowly progressive course
• Reticulonodular opacities  Variable
 Basilar • Progression
• Lung volume  Cor pulmonale
 Normal  Respiratory insufficiency
 Increased • 50%–80% 5-year survival
• Pleural effusion  Average survival = 10 years
 60%–75% • Hormonal therapy
• Pneumothorax  Oophorectomy, progesterone
• Honeycombing late
Tuberous Sclerosis [Figure 51]
Figure 49
Lymphangioleiomyomatosis with right effusion and Figure 51 A & B

pneumothorax.
Cystic lung disease in tuberous sclerosis.
Lymphangioleiomyomatosis – CT
Features [Figure 50] Respiratory bronchiolitis/Respiratory
• Thin-walled cysts bronchiolitis-associated interstitial
 More sensitive than plain film lung disease
• Diffuse
• Bilateral involvement Emphysema
• Adenopathy

Emphysema and Fibrosis
Emphysema versus Bronchitis
Langherhans Cell Histiocytosis
Alpha-1 Antitrypsin Deficiency
Asthma
allergic bronchopulmonary aspergillosis
Sarcoidosis
Diffuse Panbronchiolitis
Figure 52 A & B
Mosaic attenuation in constrictive bronchiolitis.
Swyer-James Syndrome
lymphangioleiomyomatosis
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The Pneumoconioses
Pneumonokoniosis Particle Deposition: Inertial impaction,
• “It will then be necessary to embrace sedimentation, and diffusion
under a single title all essentially identical [Figures 3 & 4]
forms of disease • 10,000–20,000 liters/day
• …the pneumonokoniosis (from Konis, • Deposition related to particle size
dust) recommends itself” • >10 microns deposit in nasopharynx and
Zenker. 1866. Hematite Mining. large airways (100%)
• 1–5 micron particles deposit in lung
Inorganic Dusts parenchyma (20%)
• Silica
• Asbestos
• Coal
• Iron
• Beryllium Figure 3
Particles less that

Pneumoconiosis: The accumulation 5 microns can be
of dust in the lungs and the tissue deposited beyond
reaction to its presence [Figure 1] the conducting
airways in the
• Dust macules
alveolar spaces.
• Diffuse interstitial fibrosis
• Diffuse alveolar damage
• Alveolar proteinosis
• Giant cell (GIP)
• Granulomatous inflammation Figure 4
Small particles
tend to deposit
in close
proximity to
the respiratory
bronchioles.
Figure 1
Dust
macules are Particle Clearance: Cough,
common tracheobronchial, and alveolar
in urban transport [Figure 5]
dwellers.
• Most important
 Deposition less critical
• Mucociliary escalator
 Outer gel, inner liquid sol
• 90% of particles removed within 2 hours
• Alveolar transport
 Engulfed by macrophages
 Transported to lymphatics
Types and Sizes of Common Aerosols  Route?
[Figure 2]
Figure 5
Macrophages
remove small
particles to
regional lymph
nodes and also
transport material
to the mucociliary
escalator.
Chest Radiology 55 The Pneumonokoniosis

Particle Clearance: Entry into The Physiologic Gradients: Airflow total
interstitium/lymphatics lung capacity [Figure 8]
• Surfactant lines the alveoli
 Reabsorbed: type II cells/
macrophages
Figure 8
 Flows in the airways
 Flows into the interstitium The smaller
• Macrophages and particles alveoli in
 Follow surfactant flow the bases
enlarge to
 Exit via the airways and interstitium
a greater
5 million/hour degree than
 “Sumps”: entrance to the interstitium those in
Near respiratory bronchioles the apex.
Therefore
Macklin. Acta Anat. 1955. most airflow
is directed
Basal Deposition (lymphatic towards the
distribution) [Figure 6] bases.
Physiologic Gradients: Blood Flow

[Figure 9]
Figure 6
In this early case of siica inhalation that there
are thickened airways and prominent septal lines
suggesting lymphatic clearance.
Figure 9
Physiologic Gradients: Airflow
functional residual capacity [Figure 7] There is increased blood flow and hydrostatic pressure
in the dependent vessels.
Physiologic Gradients: Lymphatic Flow

[Figure 10]
Figure 7 Figure 10
Alveoli in the bases are smaller than those in the apex. The lymphatics are driven by hydrostatic pressure.
Therefore lymphatic flow is best in the dependent lung.
The Pneumonokoniosis 56 Chest Radiology

Removal to Lymph Nodes [Figure 11] Silicosis: Clinical manifestations
[Figures 12 & 13]
• Diagnosis
 Typical imaging pattern of adenopathy
and nodules
 Exposure to high concentration of
silica
 10–20 years of exposure
• Simple silicosis
 Asymptomatic
• Symptoms with progressive massive
fibrosis (PMF)
• Intense exposure
 Silicoproteinosis
• Tuberculosis (TB) and cancer
Figure 11
This explains the tendency for chronic diseases to be
upper lobe.
Silicosis: Mineralogy
• Silicon
 Element
Figure 12 A & B
• Silica (SiO2)
 Mineral Left image: Adenopathy with peripheral calcification is
• Silicone a hallmark of silicosis. Right image: Nodules with an
 Synthetic polymer upper lobe predominance is typical.
Silicosis: Epidemiology
• Occupational exposure predominates
 3 million workers
• Mining, stonecutting, engraving, and
foundry work
• Males more commonly affected
• Degree of exposure underestimated
• Increased risk of neoplasia and
scleroderma
Silicosis: Pathogenesis
• 5 million particles/cubic foot-lower
threshold
• 100 million particles/cubic foot – 100%
affected Figure 13 A & B
• 80% of particles removed in hours to days
 >5 micron particle removed in nares Left image: Silicoproteinosis is an acute lower lobe
process. Right image: Silicosis predisposes a patient to
and upper airways having active tuberculosis.
 Retained particles consistently 0.5–0.7
microns
• Macrophage/silica interaction
 Oxygen-free radicals Simple Silicosis: Pathology [Figure 14]
 Fibrogenic proteins • Progress to mature nodules: 3 zones
 Immune related tissue damage: anti-  Central dense fibrosis
nuclear antibody (ANA), rheumatoid  Mid-zone concentric collagen
factor, gamma globulin  Peripheral dust-laden cells

Figure 14 Figure 16
The silicotic Silicotic

nodule nodules
is typical are more
response to prevalent in
inhaled silica. the upper
lung zones.
Simple Silicosis [Figure 17]

Simple Silicosis: Imaging manifestations
[Figure 15]
• Adenopathy common
• Calcification 10%–20%
• Calcification 5%–10%
 Eggshell pattern
Figure 15
Eggshell
calcification
of lymph
nodes Figure 17 A & B
suggests the
diagnosis Peripheral silicotic nodules can give the appearance of
of silicosis. pleural plaques.
This
appearance
is also
seen in
sarcoidosis
and Progressive Massive Fibrosis: Pathology
berylliosis.
[Figure 18]
• Conglomeration of nodular lesions
• Pathology definition
 2 cm
• Radiology definition
Simple Silicosis: Imaging manifestations  1 cm
[Figure 16]
• Upper lung zones
• Well-circumscribed nodules  Posterior
 1–10 mm
• Upper lobe and posterior
 Lymphatic gradient
 CT more sensitive
• Pleural lesions
 Candle-wax or pseudoplaques

Coal Workers’ Pneumoconiosis: Simple
[Figure 20]
Figure 18 A & B
Progressive massive fibrosis is the result of coalescing

silicotic nodules. Figure 20 A & B
Simple coal workers pneumoconiosis demonstrating

anthracotic nodules.
Progressive Massive Fibrosis: Imaging
manifestations [Figure 19]
• Progression after exposure
• May fill entire upper lobe Coal Workers’ Pneumoconiosis:
 Posterior Complicated/Rapidly progressive
• Usually bilateral • Symptomatic <5 years
• Carcinoma mimic • Related to geography
 Solitary • Possible higher dust load
 Lower lobe • Mixed with quartz/silica
• Associated emphysema
 Not always smoking related Progressive Massive Fibrosis Mixed Dust
 Scar emphysema (Coal Workers/Silicosis) [Figure 21]
Figure 19 A & B
The bucket-handle motion of the ribs results in a

posterior predominance of lung disease.
Figure 21 A & B
Coal Workers’ Pneumoconiosis: Progressive massive fibrosis suggests the presence of

silica in a coal worker.
Pathology
• Coal dust macule
 Uniformly distributed
 3–6 per secondary lobule
 Black pigment
 Adjacent to respiratory bronchiole
• Associated focal emphysema
 Macrophage activation
Churg. Pathology of Occupational Lung Disease.

Silicosis and Tuberculosis [Figure 22] Asbestos: Introduction
• Group of naturally occurring mineral fibers
 Hydrated fibrous silicate
• Flexible and strong
• Corrosion, thermal, and electrical
resistance
• 500 tons – 3 million tons
 60 years
• 9 million people exposed
 Primary (mining)
 Secondary (industrial)
 Nonoccupational (air)
Asbestos Bodies [Figure 24]

• Indicates exposure
• Transparent fiber core
• Iron and mucopolysaccharide coat
Figure 22 A & B • Predominantly amphiboles
• Longer fibers are coated
There is an increased incidence of tuberculosis in a  <20 microns not coated
patients with silicosis.
 Uncoated fibers are pathogenic
 7–5,000x’s more uncoated fibers
• Fibers cannot be removed
Silicotic Alveolar Proteinosis: Pathology • Lower posterior disease
• High concentration of particulate silica
• Acute onset
 Weeks-months
• Alveoli filled with PAS+ material
• Similar to surfactant
• Type II cell hyperplasia
Silicosis Alveolar Proteinosis [Figure 23]
Figure 23
Silicotic
alveolar
proteinosis has
a more nodular
appearance
than idiopathic
pulmonary
Figure 24 A & B
alveolar
proteinosis.
Left image: Asbestos bodies are commonly found in
urban dwellers. Right image: Asbestos fibers are much
larger than macrophages and therefore cannot be
Silicosis: Computed tomographic removed to regional lymph nodes.
technique
• Thick sections of value in nodular diseases
 Small nodules easier to differentiate Asbestos: Serpentine: chrysotile
from vessels • 95% of commercial use
• Thin sections 1–2 mm collimation at 10 • Curly and pliable
mm intervals or 3–5 selected images with • Textile manufacture
prior thick section CT • Fragments easily
• High spatial frequency algorithm • Chemically unstable
• Supine  Dissolves easily
• No contrast • Less pathogenic
Silica and Lung Disease
• Adenopathy
• Nodules
• PMF
• Silicoproteinosis
• Tuberculosis
• Cancer
Asbestos Related Chest Disease
[Figures 25 & 26]
• Pleural effusions
• Pleural plaques
• Round atelectasis
• Pleural thickening
 Diffuse Figure 27
• Mesothelioma
• Asbestosis Parietal
• Lung cancer pleural
plaques
occur at a
relatively
low-level
exposure to
asbestos.
Pleural Plaques
Figure 25 A & B
• Postero-lateral parietal pleura
• Central diaphragm
Left image: Pleural effusions are the most common • Absent
early complication of asbestos exposure. Right image:  Apices and costophrenic angles
Rounded atelectasis is usually preceded by a pleural
effusion. • Almost always bilateral
• Sharply demarcated
• Millimeters to 10 cm
• May calcify extensively
• Highly suggestive of asbestos exposure
Roberts. AJCP. 1971.
Pleural Anatomy [Figure 28]
Figure 26 A & B
Left image: Asbestosis is lower lobe subpleural

process. Right image: Lung cancer has a markedly
increased incidence in cigarette smokers with asbestos
exposure.
Pleural Plaques: Pathology [Figure 27]

• Common autopsy finding
 (5%–10%) Figure 28 A & B
• Dense bands of collagen The visceral pleural stripe is best seen between the
 “Basket weave” ribs.
• Asbestos bodies absent
• Uncoated fibers in dissolved lung tissue
• Dose response
Pleural Plaques: Imaging
• Radiography insensitive
 Between parenchymal asbestos bodies
 (8%–40% of autopsy cases)
and presence of plaques
• Companion shadows
• Pathogenesis uncertain
 Fat and muscle
• High-resolution computed tomography
(HRCT)
 Best sensitivity and specificity

Pleural Plaques [Figure 29]
Figure 31
Parenchymal bands, round atelectasis, and pleural
thickening are all associated statistically.
Figure 29 A & B
Calcified parietal pleural plaques. Pleural Effusion: Definition
• History of exposure to asbestos
• Confirmation of effusion
Pleural Plaques: Imaging  Imaging or thoracentesis
• Radiography insensitive • Absence of other disease related to
 (8%–40% of autopsy cases) effusion
• Companion shadows • Absence of malignant tumor for 3 years
 Fat and muscle Epler. JAMA. 1982.
• HRCT
 Best sensitivity and specificity Pleural Effusion: Clinical presentation
• Most common abnormality
Pleural Fat [Figure 30]
 First 20 years
• 3% prevalence
 Asbestos exposed
• Small <500 ml
• Serosanguinous
• Persist for weeks to 6 months
• 66% asymptomatic
• 28% recur
Pleural Effusion: Differential diagnosis

• Lung cancer
• Tuberculosis
• Benign asbestos effusion
• Mesothelioma
Round Atelectasis
• Described 1928 Loeschke
Figure 30 A & B • Usually asymptomatic
• Folded lung versus inflammatory reaction
Pleural thickening can be the result of fat deposition.
• Associated conditions
 Asbestos exposure, congestive heart
failure (CHF), infarct, tuberculosis (TB)
Diffuse Pleural Thickening [Figure 31]
and histoplasmosis
• Smooth pleural density
• Preceded by effusion
 Chest x-ray: >25% of the length of
the chest wall Round Atelectasis: Histology
 CT: 3 mm thick, 8 cm wide, 5 cm [Figure 32]
craniocaudal • Irregular fibrous thickening of the visceral
• Posteromedial lower lobes pleura
• Involves costophrenic angle • Extensive pleural folding beneath the
• Mediastinal pleural involvement fibrosis
 Rare • Layers of invaginated pleura bound by
 Suggests mesothelioma fibrous adhesions
• Visceral and parietal pleura • Surrounding lung collapsed or fibrotic
 Adhesions
• Sequela of prior effusion? Menzies. AJSP. 1987.

Asbestosis: American Thoracic Society
criteria 1986
• Reliable history of exposure
• Latency of at least 10 years
• Restrictive pulmonary functions
 Carbon monoxide diffusing capacity
(DLco) and vital capacity (VC) <80%
• Appropriate physical findings
 Inspiratory crackles, clubbing
• Chest radiographic abnormalities
 International Labor Organization (ILO)
perfusion >1/0 (s, t, or u)
Asbestosis: Histology
• Early
 Fibrosis of respiratory bronchioles
• Progression
Figure 32 A & B
 Terminal bronchioles, alveolar ducts,
Round atelectasis with folding of the visceral pleura and alveolar septa
into the lung parenchyma. • Minimum 2 asbestos bodies in area of
fibrosis
Craighead. Arch Pathol Lab Med. 1982.
Round Atelectasis: Imaging criteria Asbestosis [Figure 34]

[Figure 33]
• Well-circumscribed
• Round or oval opacity
• “Comet tail” sign
• Pleural thickening
• Volume loss
Figure 33
Figure 34 A & B
Round
atelectasis. Early asbestosis starts in close proximity to the
respiratory bronchiole.
Asbestosis: Chest radiography

• Lower lobe
 Irregular opacities
 Nonspecific
 Associated pleural disease
Asbestosis: Pathologic definition • Large inter-observer variation
• Interstitial fibrosis  Low perfusion
 Associated with asbestos bodies • Normal in 26% of path proven cases
• Biopsy
 Not the standard of practice Asbestosis: High-resolution CT
• Lower lobe and posterior
Asbestosis  Reticulonodular opacities
• Dose-response relationship  Curvilinear subpleural line
• Probable exposure threshold  Honeycombing
• Latency period inversely proportional to • High sensitivity
exposure level • Nonspecific
• Latency is several decades • Specificity increases with number of
• Cigarette smoke may act synergistically abnormalities
• Prone imaging is key!
Reticulonodular Opacities [Figure 35] Asbestosis versus usual interstitial
pneumonia
• Asbestos exposure in the last 30 years is
low
• Clinical asbestosis requires substantial
exposure
• Asbestos exposed individuals can have
other interstitial lung diseases
• Band-like opacities merging with the
pleura are rare in usual interstitial
pneumonia (UIP)
• Upper zone fibrosis and ground glass are
rare in asbestosis
Gaensler. ARRD. 1991.
Al-Jarad. Thorax. 1992.
Asbestosis: High-resolution CT
Figure 35 A & B • Strong association with diffuse pleural
disease
Peripheral reticulation in a patient with asbestosis. • Multifocal
• HRCT finds asbestosis in exposed
individuals with normal radiographs and
PFT’s
Honeycombing [Figure 36]
• Obstructive PFTs correlate with
emphysema
Aberle. Radiology. 1988.
Aberle. AJR. 1988.
Staples. ARRD. 1989.
Asbestosis: Dependent density

• Posterior blood flow
 5x’s greater
• Posterior alveoli
 Smaller or collapsed
 Less steep ventilatory gradient
 Closing volumes (10%–40% of VC)
Asbestosis: Computed tomographic

technique
Figure 36
• 1.5–2 mm collimation
• 10 mm interval
Asbestosis with associated pleural disease and • High spatial frequency algorithm
honeycombing.
• Prone
• Thick section supine: CA screen?
Asbestos Related Chest Disease

Asbestosis and Cigarette Smoking
Small irregular opacities Silicosis
• Small opacities are related to
 Dust exposure, cigarette smoke, age, Asbestosis
radiographic technique, and obesity
• Cigarette smoke causes Particle Deposition and Clearance:
 Interstitial fibrosis Cough, tracheobronchial, and alveolar
 Emphysema transport
 Bronchiolar thickening
• Asbestos causes
 Interstitial fibrosis
• Asbestos workers who smoke
 Have more opacities
 Related to dust exposure and
cigarettes

Pulmonary Lymphoid Disorders
The Pulmonary Lymphoid System
• Lymphatics
• Lymph nodes
• Bronchus associated lymphoid tissue
(BALT)
Figure 2
• Lymphoid aggregates
• Lymphocytes The majority of
• Dendritic cells intrapulmonary
• Langerhans cells lymph
nodes are
The Pulmonary Lymphoid System probably not
visible radio-
[Figures 1 & 2] graphically.
• Lymphatics [Figure 1] Almost all of
 Originate in the pleura these lymph
 Valves nodes are
subpleural and
 Drain towards hilum inferior to the
 Follow interlobular septa carina.
 Accompany blood vessels
• Lymph nodes [Figure 2]
 Encapsulated lymph nodes
Proximal bronchi
Bifurcations
 Reactive lymph nodes
Peripheral and septal Reactive Lymph Nodes [Figure 3]
Cigarettes or dust
• BALT
• Lymphocytes
• Dendritic cells
• Langerhans cells
Figure 3 A & B
Intrapulmonary lymph nodes.
The Pulmonary Lymphoid System

• Lymphatics
• Lymph nodes
• BALT
 Bronchus associated lymphoid tissue
Figure 1
• Lymphocytes
Lymphatics of the lung. • Dendritic cells
• Langerhans cells
Chest Radiology 65 Pulmonary Lymphoid Disorders

BALT – The organizing principle Follicular Hyperplasias of BALT –
[Figure 4] Hyperplasia of BALT [Figure 6]
• Lymphoid collections • Follicular bronchitis and bronchiolitis
 Bronchial epithelium • Pathologic features
 Bifurcations  Antigenic stimulation of BALT
• Absent in the normal adult  Lymphoid aggregates
 Absent at birth  Peribronchial
 Common in young children  Reactive follicles
• Reappears with antigenic stimulation  Minimal alveolar extension
 Cigarette smoke • Clinical
 Connective tissue disease
 AIDS
• Basis of pulmonary lymphoid disorders Figure 6
Follicular
bronchitis is
characterized
Figure 4 by hyperplastic
lymphoid
Bronchus follicles with
associated reactive
lymphoid tissue germinal
or BALT is centers
found along distributed
the bronchiole, along
interlobular septa bronchioles
and pleura. It is and to a lesser
normally found extent bronchi.
only in young
children.
Pulmonary Lymphoid Disorders – Follicular Hyperplasias of BALT –

Derivations of BALT [Figure 5]
Hyperplasia of BALT
• Pathologic features
• Hyperplasias of BALT
• Clinical
 Follicular hyperplasia
 Young adults (44 years)
Follicular bronchitis
 Cough and dyspnea
 Diffuse hyperplasia
Fever and weight loss
Lymphoid interstitial pneumonia
 Immune deficiencies
 Nodular lymphoid hyperplasia
AIDS
Pseudolymphoma
Congenital
• Non-Hodgkin’s lymphomas
 Collagen vascular diseases
 Low-grade B-cell lymphomas
Sjogren’s
 Lymphomatoid granulomatois
Rheumatoid arthritis
• Immune impairment
 Uncertain etiology
 PTLD, AIDS and other
Hypersensitivity reactions?
Koss. Sem Diag Pathol. 1995.
Follicular Hyperplasias of BALT –
Hyperplasia of BALT: Imaging
• Imaging
 Radiography
Diffuse
Reticulonodular
 CT
Figure 5 Nodules 3–12 mm
−− Centrilobular
Bronchus −− Peribronchial
associated
lymphoid Ground glass
tissue. Air trapping
Pulmonary Lymphoid Disorders 66 Chest Radiology

Follicular Hyperplasia [Figure 7] Follicular Hyperplasia – Mosaic [Figure 9]

Mosaic attenuation in follicular bronchitis.
Almost all patients with follicular bronchiolitis have
centrilobular nodes that are less than 3 mm. These
nodules correlate with the peribronchiolar distribution
of hyperplastic lymphoid follicles shown on the
histology section to your left.
Diffuse Hyperplasias of BALT –
Hyperplasia of BALT [Figure 10]
• Lymphocytic interstitial pneumonia
Follicular Hyperplasia – Differential • Pathologic features
diagnosis  Alveolar septal infiltration
• Respiratory bronchiolits Lymphocytes (T-cells)
• Hypersensitivity pneumonitis Diffuse
 Lymphoid follicles (B-cells)
Follicular Hyperplasia – Diffuse Germinal centers
[Figure 8] Peribronchial distribution
Spectrum with follicular
hyperplasia of BALT (follicular
bronchitis)
• Clinical
Figure 8
Follicular bronchitis.
Figure 10
Lymphocytic interstitial pneumonia is characterized by

diffuse infiltration of the alveolar septa.

Diffuse Hyperplasia of BALT –
Hyperplasia of BALT
• Clinical
 Women > men
 Fourth–sixth decade
 Collagen vascular disease
Sjogrens, RA, and SLE
 Bone marrow transplantation
 AIDS rare in adults
Common in children
 Dysproteinemia
 Restrictive lung functions
Diffuse Hyperplasia of BALT – Figure 12 A & B
Lymphocytic interstitial pneumonia with cysts and
Hyperplasia of BALT nodules.
• Imaging
 Radiography
Lower lung zone
Reticulonodular Lymphocytic interstitial pneumonia
 CT – Consolidation and Septal Lines
Ground glass [Figure 13]
Nodules
−− Centrilobular
−− Poorly defined
Cystic air spaces
Thickened BVBs
Adenopathy
Lymphocytic interstitial pneumonia –

Nodules to Cysts [Figures 11 & 12]
Figure 13 A & B
Consolidation and septal lines.

verus Lymphoma
LIP Lymphoma
Figure 11 A & B • Cysts 82% 2%
• Consolidation 18% 66%
Thin walled cysts are often found deep within the lung • Large nodules 6% 41%
parenchyma. Previous reports have suggested that • Effusions 0% 25%
airway narrowing or obliteration results in these cystic
lesions.

Nodular Lymphoid Hyperplasia - Nodular Lymphoid Hyperplasia
Hyperplasia of Bronchus associated Hyperplasia of BALT [Figures 15 & 16]
lymphoid tissue [Figure 14] • Imaging
• Pseudolymphoma  Radiography
• Pathologic features Solitary nodule
 Solitary, subpleural mass Focal consolidation
 Lymphoid proliferation  CT
Interstitial Air bronchograms
Perivascular −− 100%
B and T-cells Indistinct margins
Polyclonal pattern Occasionally multiple
−− Benign Adenopathy and/or effusion
 Reactive germinal centers suggests lymphoma
 Difficult to separate from lymphoma
• Clinical
Figure 14
Nodular
lymphoid
hyperplasia.
Figure 15 A & B
The CT demonstrates the typical subpleural, solitary
lesion with indistinct margins.
Nodular Lymphoid Hyperplasia -

Hyperplasia of Bronchus associated
lymphoid tissue
• Pseudolymphoma
• Clinical
 Rare entity
 Most cases were lymphomas
Monoclonal B-cell proliferation
 Middle age
Asymptomatic
 Autoimmune diseases 15% Figure 16 A & B
Sjogren
Air bronchograms are universally present and the
SLE lymphoid infiltration gradually diminishes resulting in
Transverse myelitis the classical indistinct margin.
 Surgical excision curative
Pulmonary Lymphoid Disorders –

Derivations of BALT
• Non-Hodgkin lymphomas
 Low-grade B-cell lymphomas
 Lymphomatoid granulomatosis
• Immune impairment

Low-Grade B-Cell Lymphoma Lymphomatoid Granulomatosis
• Pathologic features [Figure 18]
 Lymphocytic infiltration • Pathologic features
 Small lymphocytes  Majority of cases are B-cell
Alveolar wall lymphomas
Peribronchiolar  Reactive small T-cells
Perivascular  Malignant B-cells
 Immunologic evidence of malignancy Majority of infiltrate
Monoclonality  Epstein-Barr virus
B-cell marker CD20  Angiocentric infiltration
 Germinal centers  Necrosis
• Clinical Peribronchovascular
Peripheral
Low-Grade B-Cell Lymphoma • Clinical
• Clinical
 Similar presentation to nodular
lymphoid hyperplasia
 Fifth–sixth decade Figure 18
 Male = female
 Asymptomatic 50% Lymphomatoid
 5-year survival 85%–95% granulomatosis
 Surgical resection is an
angiocentric
Rare recurrence B-cell
lymphoma
Low-Grade B-Cell Lymphoma [Figure 17] which often
• Imaging demonstrates
 Radiography areas of
necrosis.
Solitary nodule/mass
−− Multiple
Consolidation
Air bronchogram
−− 50%
Slow growth
 CT
Consolidation Lymphomatoid Granulomatosis
Air bronchograms • Pathologic features
Airway narrowing or “stretching” • Clinical
 7–85 years (mean 48 years)
 Male:female (2:1)
 Malaise and weight loss
 Lung involvement 100%
 Skin 39%–53%
Nodules, ulcers and rash
 CNS 37%–53%
 Renal 32%–40%
 High mortality rate 53%–90%
 Most proceed to lymphoma
Lymphomatoid Granulomatosis:
Etiology and demographics
• Majority of cases are B-cell lymphomas
• Epstein-Barr virus
• Reactive small T-cells
Figure 17 A & B
 Majority of infiltrate
Grossly low-grade B-cell lymphoma usually presents • Malignant B-cells
as a single white tan lesion that can be either well • Age range
circumscribed or indistinct.  7–85 years
• Mean age of onset
 48 years
• Male:female (2:1)

Pathology [Figure 19]
• Angiocentric infiltration
 Mixed cell population
Atypical lymphocytes, plasma cells,
histiocytes
• Vascular invasion
• Vascular destruction
• Necrosis
 Peripheral
Figure 20 A & B
Figure 19 Nodular areas of infarction in lymphomatoid
granulomatosis.
Lymphomatoid
granulomatosis
is an
angiocentric
B-cell Treatment and prognosis
lymphoma • Mortality rate
which often  53%–90%
demonstrates • Long term remissions reported
areas of
necrosis.  Cyclophosphamide and steroids
• All who fail therapy proceed to develop
lymphoma
 12%–47%
Pulmonary Lymphoid Disorders –

Derivations of BALT
Clinical presentation • Non-Hodgkin lymphomas
• Lung involvement • Immune impairment
 100%  Posttransplantation
 Cough and dyspnea Lymphoproliferative disease (PTLD)
• Skin  AIDS
 39%–53%  Other forms of prolonged immune
 Nodules, ulcers and rash suppression
• CNS
 37%–53% Lymphoma and Immune Impairment
• Renal [Figure 21]
 32%–40% • Pathologic features
• Malaise and weight loss  B-cell Non-Hodgkin lymphoma
 35% Driven by Epstein-Barr virus
infection
Diffuse polyclonal expansion
Imaging [Figure 20]
−− Reduced T-cell control
 Nodules Malignant transformation
80% • Clinical
Multiple
Bilateral (80%)
 Mid and lower lobes
 Cavitation
20%
 Large masses
Correspond to infarcts
 Diffuse reticulonodular opacities
 Hilar adenopathy
25%

Post-transplant lymphoproliferative
disorder [Figure 22]
Figure 21
Post-transplant
lymphomas
are driven by
Epstein-Barr,
reduced T-cell
surveillance
and malignant
transformation.
Figure 22 A & B
A 58-year-old man with alpha-1 antitrypsin deficiency

who underwent a double lung transplant 7 years prior
to presenting with shortness of breath, cough, fever,
and chills for two months. The CT reveals multiple
indistinct nodules in a characteristic distribution along
Lymphoma and Immune Impairment the bronchovascular bundles.
• Pathological features
• Clinical
 Spectrum of benign to malignant
Infectious mono-like Pulmonary Lymphoid Disorders –
PTLD polymorphic Derivations of Bronchus associated
PTLD monomorphic lymphoid tissue
 Cyclosporin shortens induction • Hyperplasias of BALT
(<1 year) • Non-Hodgkin lymphomas
 May respond to reduction in • Immune impairment
immunosuppression, anti-virals and  PTLD
surgery  AIDS
 Chemotherapy should be avoided  Other
 Heart-lung up 20%
Follicular Hyperplasia [Figure 23]
Lymphoma and Immune Impairment
• Imaging
 Nodules
May cavitate
Halo
Along bronchovascular bundles
 Lymph node
 Ground glass
 Septa thickening
 Consolidation
 Effusion
Figure 23 A & B
Follicular bronchitis.

Diffuse Hyperplasia of Bronchus Low-Grade B-Cell Lymphoma
associated lymphoid tissue – [Figure 26]
[Figure 24]
Figure 26 A & B
Low-grade B-cell lymphoma.

Figure 24 A & B
Lymphocytic interstitial pneumonia.
Lymphomatoid granulomatosis
[Figure 27]
Nodular Lymphoid Hyperplasia
[Figure 25]
Figure 27 A & B
Lymphomatoid granulomatosis.
Figure 25 A & B
Nodular lymphoid hyperplasia which was formerly

known as pseudolymphoma.
73
Immune Impairment –
Posttransplantation lymphoproliferative
disorder [Figure 28]
Figure 28 A & B
Posttransplantation lymphoproliferative disorder.
Bronchus associated lymphoid tissue –

The organizing principle
• Lymphoid collections
• Basis of pulmonary lymphoid disorders
References
1. Koss MN. Pulmonary lymphoid disorders. Semin Diagn Pathol. 1995;12:158–171.

2. Travis WD, Galvin JR. Non-neoplastic pulmonary lymphoid lesions. Thorax. 2001;56:964–971.

Angiitis and Granulomatosis
Angiitis and Granulomatosis
• First characterized by Averill Liebow 1973
• Unknown etiology
• Angiitis
 Cellular infiltration of blood vessel
• Granulomatosis
 Necrosis of lung parenchyma not
related to blood vessel occlusion
Figure 1
Angiitis and Granulomatosis: Current

Blood
list vessel
• Wegener granulomatosis associated
• Churg-Strauss syndrome nodules.
 Allergic granulomatosis
• Necrotizing sarcoid granulomatosis
• Bronchocentric granulomatosis
• Lymphomatoid granulomatosis
Vasculitis Classification:
Chapel Hill Consensus Conference
• Large vessel
 Takayasu arteritis Antineutrophil cytoplasmic antibody
 Behçet disease Laboratory [Figure 2]
• Small vessel • ANCA
 ANCA-associated vasculitis  Serum antineutrophil cytoplasmic
Wegener granulomatosis autoantibody
Churg-Strauss syndrome (CSS) • c-ANCA cytoplasmic pattern
Microscopic polyangiitis  Proteinase 3
 Collagen vascular associated  99% specificity and 96% sensitivity in
SLE, RA active disease
 Goodpasture syndrome  Wegener granulomatosis
 Positivity drops to 30% in remission
Angiitis and Granulomatosis:
Differential Multiple vessel associated
nodules [Figure 1]
• Metastatic disease
 Squamous
• Multifocal infection
 Fungus, tuberculosis (TB), bacteria
• Septic emboli
• Vasculitis
Vasculitis: General concepts

• Clinical and laboratory findings key to Figure 2
diagnosis
• Adequate tissue samples are important SC-
• Must rule out infection: mycobacterial or antineutrophil
cytoplasmic
fungal antibody
• Must rule out malignancy positive
• Pathogenesis pattern.
 Antineutrophil cytoplasmic antibody
(ANCA)
Cytoplasmic (Wegener)
Perinuclear (Churg-Strauss,
microscopic polyangiitis)
Chest Radiology 75 Angiitis and Granulomatosis

Antineutrophil cytoplasmic antibody Pathogenesis of Vasculitis [Figure 4]
Laboratory [Figure 3]
• ANCA Vasculitis Classification:
 Serum antineutrophil cytoplasmic Chapel Hill Consensus Conference
antibody • Large vessel
• p-ANCA perinuclear pattern  Takayasu arteritis
 Reacts with myeloperoxidase  Behçet disease
 Positive: • Small vessel
Collagen vascular disease  ANCA-associated vasculitis
Churg-Strauss Wegener granulomatosis
Microscopic polyangiitis Churg-Strauss syndrome (CSS)
Microscopic polyangiitis
 Collagen vascular associated
SLE, RA
 Goodpasture syndrome
Behçet Disease [Figure 5]

• Chronic systemic vasculitis
Figure 3 • Male predominance
• “Old silk route”
p-anti-  Japan, China to the Mediterranean
neutrophil
cytoplasmic (Turkey and Iran)
antibody • Thoracic involvement 8%
positive  Pulmonary vasculitis
pattern. PA aneurysms (30% mortality)
Thrombosis
Infarction
Hemorrhage
A–V shunts
Vasculitis: General concepts
• Clinical and laboratory findings key to
diagnosis
• Adequate tissue samples are important
• Must rule out infection: mycobacterial or
fungal
• Must rule out malignancy
• Pathogenesis
 Antineutrophil cytoplasmic antibody
(ANCA)
Cytoplasmic (Wegener)
Perinuclear (Churg-Strauss,
microscopic polyangiitis)
 Type II: specific antibody deposition
(Goodpastures)
 Type III: antigen/antibody complexes
(SLE) Figure 5 A & B
 Typer IV: T-cell hypersensitivity
Behçet disease with aneurysm pulmonary artery and
contained rupture with bleeding.
Wegener Granulomatosis: Classic

pathology triad
• Vasculitis described 1852
 Von Rokitansky
• Wegener described 1936
Figure 4
 Wegener
• Focal vasculitis of
 Arteries and veins
• Necrotizing granulomas
 Upper and lower airways
• Necrotizing glomerulitis
 Focal
Angiitis and Granulomatosis 76 Chest Radiology

Wegener Granulomatosis: Gross Wegener Granulomatosis: Limited
pathology [Figures 6 & 7] • Involvement of lungs alone
• Necrotic nodules • Clinical sparing
 With and without cavitation  Kidneys
• Parenchymal consolidation  Upper respiratory tract
• Massive hemorrhage • Biopsy positive
• Airway narrowing  When clinically normal
• Better prognosis
Wegener Granulomatosis: Clinical

presentation
• Classic triad
 Sinusitis
 Pulmonary symptoms
Figure 6  Renal insufficiency
• Variable onset and course
Solid and
cavitary
• Chronic URI symptoms
nodules  May persist for years before
often pulmonary disease
coexist in • Overwhelming vasculitis
patients with  Diffuse
Wegener
granulo-
matosis. Upper Airway
• Chronic nasal obstruction
 Chronic discharge
• Destruction of cartilaginous nasal septum
• “Saddle nose deformity”
• Laryngeal involvement
 Subglottic stricture
• Eustachian tube obstruction
• Otitis media
• Cochlear nerve vasculitis
Pulmonary
• Most commonly affected (94%)
• Multiple bilateral nodules or masses
• Cavitation common (30%–50%)
• Occasionally solitary mass or nodule
 Diagnosis difficult
Figure 7
 All patients progress
• Less common
 Diffuse alveolar hemorrhage
Airway
narrowing is • Pleural lesion and effusions are rare
a common
complication. Renal
• Tempo: insidious to explosive
• Segmental necrotizing glomerulonephritis
• UA: erythrocyte casts and proteinuria
• Large vessel vasculitis
Wegener Granulomatosis: Other organ

involvement
• Skin (50%)
 Symmetric papulonecrotic lesion of
Wegener Granulomatosis: extremities
Demographics • Eye and orbit (30%)
• Rare  Scleritis, conjunctivitis, optic nerve
 3/100,000 in US and retro-orbital mass
• Second–eight decades of life • Nervous system (30%)
• Average age – 50 years  Mononeuritis multiplex
• Male = female • Joints
 Slight male predominance (4:3)  Acute arthritis follows activity of
• May occur in children disease (+RA latex)

Wegener Granulomatosis: Airway Wegener Granulomatosis:
involvement [Figures 8 to 10] Radiography
• Endobronchial abnormalities • Earliest lesions
 59% bronchoscopy  Bilateral reticulo-nodular opacities
• Subglottic stenosis • Multifocal nodules
• Tracheobronchitis  Bilateral
 Ulcerating  5 mm–10 cm
• Tracheal or bronchial stenosis • Sharply marginated
• Often multifocal • Cavitation 20%–50%
 Variable length of involvement • Evolution
• CT key for evaluation  Thick walls to thin walled cysts with
 Chest x-ray often normal treatment
• Airspace consolidation
Necrosis and Hemorrhage [Figure 11]
Figure 8
Typical
subglottic
involvement
in Wegener.
Figure 11 A & B
Massive necrosis and hemorrhage in Wegener’s.
Figure 9
Diffuse Evolution with Treatment [Figure 12]

airway
involvement
in Wegener
granulo-
matosis
Figure 10
Focal airway
involvement
in Wegener
granulo-
matosis
Figure 12 A & B
Air-fluid levels imply infection in patients with

Wegener granulomatosis.

Superinfection: fungal [Figure 13]
Figure 15
Nodules
with feeding
vessels are
common in
vasculitis.
Figure 13 A & B Wegener Granulomatosis: Treatment

Air-fluid levels imply infection in patients with and prognosis
Wegener granulomatosis. • Universally fatal without treatment
• Trimethoprim/sulfa effective in localized
disease
• Steroids and cyclophosphamide
Wegener Granulomatosis: Computed  Remission in 93%
tomography [Figures 14 & 15] • 5-year survival 90%–95%
• Feeding vessels • Infectious complications
 88%  Relapse and drug toxicity require close
• Cavitation monitoring and follow-up imaging
 Nodules greater than 2 cm • Relapse has different manifestations from
• Subpleural location presentation
 Predominant
• CT “halo” sign Diffuse Pulmonary Hemorrhage
• Pleural based lesions Capillaritis [Figure 16]
 Mimic infarcts • Common
• Reveals more nodules  Microscopic polyangiitis
 Wegener granulomatosis
 SLE
• Uncommon
 Goodpastures
Anti-GBM
 Collagen vascular
 Idiopathic pulmonary hemorrhage
 Churg-Strauss syndrome
 Behcet syndrome
 IgA nephropathy
Figure 14
Blood
vessel
with
associated
infarct. Figure 16
Pulmonary
hemorrhage
in
capillaritis.

Diffuse Pulmonary Hemorrhage Churg-Strauss Syndrome: Pathology
Capillaritis [Figure 17] • Necrotizing vasculitis
• Common • Eosinophilic tissue infiltration
 Microscopic polyangiitis • “Allergic granulomas”
 Wegener granulomatosis  Extravascular
 SLE  Eosinophils
• Uncommon  Multinucleated giant cells
 Goodpastures
Anti-GBM Churg-Strauss Syndrome:
 Collagen vascular Demographics
 Idiopathic pulmonary hemorrhage • Second–fourth decades
 Churg-Strauss syndrome • 28 years mean age of onset
 Behcet syndrome • Male = female
 IgA nephropathy • Excellent response to steroids
Churg-Strauss Syndrome: Background

• Late onset asthma
 100%
• Precedes CSS by weeks to years (30)
• Severe rhinitis and sinusitis
 70%
Churg-Strauss Syndrome: Prodromal

stage
• Infiltration of tissues with eosinophils
• Blood eosinophilia
• Elevated IgE
• + Rheumatoid factor
• Progressive asthma, sinus pain,
myocardial involvement
• Loffler’s like fleeting infiltrates
Figure 17 • Abdominal pain
Diffuse pulmonary hemorrhage with ground glass,  Diarrhea and eosinophilic peritonitis
consolidation and septal lines. • Myalgias and neuritis
Churg-Strauss Syndrome: Vasculitic

stage
Microscopic Polyangiitis • Increasingly severe and widespread
• No longer considered microscopic symptoms
polyarteritis nodosa • Lung
• Most common cause of pulmonary-renal  Eosinophilic consolidation, miliary to
syndrome 2 cm nodules (without cavitation), and
• Necrotizing vasculitis diffuse hemorrhage
 P-ANCA positive • Cardiac
 No granulomatous change  Coronary vasculitis and eosinophilic
• 5th decade myocarditis (50% of mortality)
• Male > female • GI
• Renal, musculoskeletal, pulmonary, GI  Ulcerations, perforations and
and cutaneous peritonitis
• Diffuse ground glass
Churg-Strauss Syndrome: Computed
Churg-Strauss Syndrome: Allergic tomography
Angiitis and Granulomatosis • Parenchymal opacification
• Described by Churg and Strauss  Predominantly peripheral 59%
 1951  Effusions
• True systemic vasculitis • Nodules
• Associated  12%
 Asthma • Bronchial thickening
 Allergic rhinitis • Dilatation
 Blood eosinophilia  12%
• Hypersensitivity response to inhaled • Interlobular septal thickening
antigen?  6%
Worthy. AJR. 1998.

Churg-Strauss Syndrome [Figures 18 to 20] Churg-Strauss Syndrome: Comparison
with Wegener
• CSS
 High incidence of asthma
 High incidence of cardiac involvement
(47%)
 Less severe renal and sinus disease
 Associated with p-ANCA
Churg-Strauss Syndrome: Therapy and

prognosis
• Prognosis relates to early diagnosis and
therapy
• High dose steroids usually effective
• Cyclophosphamide in resistant cases
Figure 18
• Therapy stopped after 6–12 months of
Peripheral consolidation in Churg-Strauss. remission
Necrotizing Sarcoid Granulomatosis –

How is this related to sarcoidosis?
• A distinct entity?
 Katzenstein
• Some reported cases are undiagnosed
infections
• Those with extrapulmonary involvement
 Sarcoidosis
Necrotizing Sarcoid Granulomatosis:

Demographics
• Third–seventh decades
• Mean age 49 years
• Female:male
Figure 19  2.2:1
Vasculitic stage in patient with Churg-Strauss.
Pathology
• Noncaseating granulomas
 Similar to sarcoidosis
• Vasculitis
 Pulmonary arteries
 Pulmonary veins
 Found in areas away from
parenchymal granulomas
• Coagulative necrosis
 Widespread
 Main distinction from sarcoidosis

Clinical presentation
• 100% lung involvement
• Cough most common symptom
• Chest pain, fever and dyspnea
• Weight loss and fatigue
• May be asymptomatic
 15%–40%
• Rare extrapulmonary involvement
 13%
• Aspergillus antigens in some patients
Koss, et al. Human Pathology. 1980.
Figure 20
Septal pattern in Churg-Strauss.

Imaging [Figure 21]
• Hilar adenopathy
 Variable
 Up to 79%
• Nodules
 Cavitation is common
 Subpleural
 Perivascular
• Parenchymal opacities
 Same distribution
Figure 22
Large B-cells staining for Epstein–Barr virus.
Lymphomatoid Granulomatosis: Clinical

presentation
• Lung involvement
 100%
• Skin
 39%–53%
 Nodules, ulcers and rash
Figure 21 A & B
• CNS
Typical nodules in necrotizing sarcoid granulomatosis.  37%–53%
• Renal
 32%–40%
Necrotizing Sarcoid Granulomatosis: • Malaise and weight loss
 35%
Prognosis and therapy
• May require no therapy Lymphomatoid Granulomatosis:
• Prompt response to steroids
Imaging
• No reported deaths
• Nodules
Lymphomatoid Granulomatosis: Etiology  80%
 Multiple
and demographics [Figure 22]
 Bilateral (80%)
• Majority of cases are B-cell lymphomas
• Mid and lower lobes
• Epstein-Barr virus
• Cavitation
• Reactive small T-cells
 20%
 Majority of infiltrate
• Large masses
• Malignant B-cells
 Correspond to infarcts
• Age range
• Diffuse reticulonodular opacities
 7–85 years
• Hilar adenopathy
• Mean age of onset
 25%
 48 years
• Male:female (2:1)
Pathology
• Angiocentric infiltration
 Mixed cell population
Atypical lymphocytes, plasma cells,
histiocytes
• Vascular invasion
• Vascular destruction
• Necrosis
 Peripheral

Lymphomatoid Granulomatosis Bronchocentric Granulomatosis: Clinical
[Figures 23 & 24] and demographics – Non-Asthmatics
• Average age 50 years
• Males = females
• Fungal infections
 Histo, Bastomyces, Aspergillus
• Mycobacterial infections
• Rheumatoid arthritis
• Wegener granulomatosis
• Idiopathic
Bronchocentric Granulomatosis:
Pathology
• Nonspecific reaction
• Early invasion of mucosa
 Histiocytes
 Eosinophils
Asthmatics
 Neutrophils
Figure 23 A & B
 Non-asthmatics
Nodular areas of infarcted lung with feeding vessels in • Secondary involvement of adjacent
patient with lymphomatoid granulomatosis. arteries
• Granulomatous destruction
 Bronchial walls
• Bronchopneumonia
 Distal to affected airways
Bronchocentric Granulomatosis:
Imaging [Figure 25]
• Most often unilateral
 75%
• Multiple or solitary nodules
• Parenchymal consolidation
 Upper lobe predominance
• Associated findings of ABPA
 Bronchiectasis
Figure 24  Mucoid impaction
Lymphomatoid granulomatosis is highly destructive
and a close mimic of Wegener granulomatosis.
Treatment and prognosis
• Mortality rate
 53%–90%
• Long term remissions reported
 Cyclophosphamide and steroids
• All who fail therapy proceed to develop
lymphoma
 12%–47%
Bronchocentric Granulomatosis: Clinical

and demographics – Asthmatics
• Average age 22 years
• Tissue manifestation of ABPA
• Dyspnea, cough, fever, malaise and
hemoptysis
Figure 25
• Peripheral and tissue eosinophilia
• No extrapulmonary findings Mucoid impaction in patients with bronchocentric
granulomatosis.

Bronchocentric Granulomatosis and Angiitis and Granulomatosis: Conclusion
Tuberculosis [Figure 26] • Wegener granulomatosis
• Churg-Strauss syndrome
 Allergic granulomatosis
• Necrotizing sarcoid granulomatosis
• Bronchocentric granulomatosis
• Lymphomatoid granulomatosis
Vasculitis Classification
Chapel Hill Consensus Conference
• Large vessel
 Takayasu arteritis
 Behçet disease
• Small vessel
 ANCA-associated vasculitis
Wegener granulomatosis
Churg-Strauss syndrome (CSS)
Microscopic polyangiitis
 Collagen vascular associated
Figure 26 A & B
SLE, RA
Older woman with known tuberculosis and  Goodpasture syndrome
bronchocentric granulomatous reaction.
Angiitis and Granulomatosis:
Differential Multiple vessel associated
nodules
Bronchocentric Granulomatosis: • Metastatic disease
Treatment and prognosis  Squamous
• Asthmatics respond to steroids • Multifocal infection
• Some cases remit without treatment  Fungus, TB, bacteria
• Must rule out treatable infection and • Septic emboli
Wegener granulomatosis • Vasculitis
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Tuberculosis
Tuberculosis Tuberculosis: United States [Figure 2]
• Leading cause of death from infectious • 2002: 15,075 cases
disease  5.2/100,000
• 8–10 million new cases/year  43% decrease from 1992
• 2–3 million deaths/year  4%–6% of population infected
• 1/3 of world population infected 15 million people
• >90% of new cases in developing • 51% foreign-born
countries  Mexico, the Philippines, Vietnam, India
• 80% 15–59 years of age and China
• Highest incidence • US-born
 Southeast Asia: 247/100,000  African Americans 25% of all cases
 Sub-Saharan Africa: 191/100,000  Homeless, immunocompromised,
HIV co-infection: 60% of children, elderly
70% of adults • Urban areas, coastal states, states
bordering Mexico
Tuberculosis: History
MMWR. 2003;March 21, Vol 52.
• Ancient disease
• 1882: Robert Koch
 Isolation of M. tuberculosis
• 1944: streptomycin
• 1952: INH
Tuberculosis Pre-Antibiotic Era
Tuberculosis: United States [Figure 1]

• 1953: 84,304 cases
 19,707 deaths
• 1985: 22,201 cases
 1,752 deaths
• 1986-1992: 20% increase in reported
cases
 HIV
 Immigration
 Congregate settings Figure 2
 Deteriorating TB services
 MDR-TB
 Decreasing TB research Mycobacteria
• Tuberculosis complex
 M. tuberculosis, M. bovis, M.
africanum, M. microti
• M. tuberculosis and M. bovis
• ≥95% of pulmonary mycobacterioses
• Slow growth
• Person-to-person transmission
M. tuberculosis: Pathologic features

[Figure 3]
• Gram-positive pleomorphic rod
• Acid fast:
 Resists decolorization with acid alcohol
• Virulence related to cell wall
Figure 1
 No endotoxin or enzymes
• Caseous necrosis
• Caseating granuloma
 Central caseous necrosis
 Rim of histiocytes, giant cells
Chest Radiology 87 Tuberculosis

Figure 5
Figure 3
Even though
we tend
to think of
Tuberculosis has a tuberculosis
thick waxy envelope as an upper
requiring type 4 lobe disease,
immune mechanisms we inhale
and delayed most bacteria
hypersensitivity to into the mid
contain. and lower
lung zones.
Tuberculosis: Pathogenesis
Caseous Necrosis [Figure 4]
• Inhaled bacteria
 Mid to lower lung zones
 Ghon focus
• Regional lymph node spread [Figure 6]
 Ranke complex
• Lymphatic/hematogenous dissemination
• Cell-mediated immunity
• Delayed hypersensitivity
 Caseous necrosis
 2–10 weeks
• Healing
Figure 4
A&B
The Figure 6
caseating
granuloma
is the In primary
hallmark of tuberculosis
tuberculosis. the ineffective
The actively macrophages
growing carry bacteria
bacilli reside to regional
in the lymph nodes
macrophages where they
in the proliferate
periphery. and
disseminate.
• Latent TB infection
 +PPD
 No active signs of infection
• Survival of organisms [Figure 7]
 Apical/posterior upper lobe
Tuberculosis: Pathogenesis  Superior segment lower lobe
• Inhaled bacteria [Figure 5] Oxygen gradient
 Mid to lower lung zones Lymphatic gradient
 Ghon focus Bucket handle rib motion
• Active tuberculosis (TB) infection
Tuberculosis 88 Chest Radiology

Figure 7
The lymphatic
gradient helps
explain the
upper lobe
distribution of
reactivation
tuberculosis.
Figure 8 A & B
Left image: lymphadenopathy is hallmark of primary

tuberculosis and is more common in children. Right
image: the lymph nodes which surround airways may
cause narrowing that results in atelectasis.
• Latent TB infection
• Survival of organisms Postprimary Tuberculosis: Clinical
• Active TB infection Features
 5% within 2 years • Reactivation
 5%–10% lifetime risk  Fever, malaise, anorexia, weight loss,
 HIV: 50% within 2 years night sweats
 Pulmonary fibrotic lesions,  Dyspnea, cough, chest pain,
underweight, silicosis, DM, renal hemoptysis
failure, gastrectomy, jejunoileal • Active TB infection
bypass, transplantation, head  5% within 2 years
and neck cancer, prolonged  5%–10% lifetime risk
immunosuppressive therapy  HIV: 50% within 2 years
 Pulmonary fibrotic lesions,
Tuberculosis: Clinical features underweight, silicosis, DM, renal
• Primary TB failure, gastrectomy, jejunoileal
• Postprimary TB bypass, transplantation, head
• Disseminated TB and neck cancer, prolonged
immunosuppressive therapy
Primary Tuberculosis: Clinical features
• Asymptomatic 65% Postprimary Tuberculosis: Pathogenesis
 Nonspecific symptoms when present [Figures 9 & 10]
• Progressive primary complex • Delayed hypersensitivity
 Fever, cough, hemoptysis, weight loss • Liquifaction
• Cavitation
Primary Tuberculosis: Radiologic  Airway
features  Vessel
• Lymphadenopathy [Figure 8 left]  Pleura
 Children 95%, young adults 43%,
elderly 10%
 Right paratracheal, hilar
 Peripheral enhancement, central low- Figure 9
attenuation
• Atelectasis, overinflation [Figure 8 right] Postprimary
tuberculosis
 Children implies
 Anterior segments upper lobes reactivation
 Medial segment middle lobe of dormant
• Consolidation bacilli.
 Homogeneous, patchy, linear, nodular It is
characterized
• Pleural effusion by tissue
 Adults 38%, children 11% destruction.

Figure 12
Endobronchial
spread leads
to airways
nodules.
Figure 10
Cavitation and necrosis enable spread via the airway,

blood stream or pleura. Postprimary Tuberculosis – Nodules
[Figures 13 & 14]
Postprimary Tuberculosis: Radiologic

features
• Consolidation 50%–70%
 Heterogeneous, nodular, linear
 Apical, posterior 85%, superior
segments 14%
• Cavitation 40%–45% [Figure 9]
 Thin or thick walls, air-fluid levels 20%
• Nodules
 Tuberculoma
 Endobronchial spread [Figures 10 to 12]
 Hematogenous spread
Miliary 1–3 mm, random
Figure 13 A & B
Postprimary Tuberculosis – Cavitation Endobronchial spread leads to airways nodules.
[Figures 11 & 12]
Figure 11 A & B
Cavitation implies large numbers of bacilli and

Figure 14 A & B
connection to an airway.
Endobronchial spread leads to airways nodules.

Thoracoplasty [Figure 15] Postprimary Tuberculosis: Radiologic
Features
• Consolidation
• Cavitation 40%–45%
• Nodules
 Tuberculoma
 Endobronchial spread
 Hematogenous spread
Figure 15 Miliary 1–3 mm, random
Thoracoplasty.
Postprimary Tuberculosis – Nodules
[Figures 18 & 19]
Oleothorax [Figure 16]
Figure 16
Figure 18 A & B
Oleothorax.
Random nodules in miliary spread of tuberculosis.
Plumbage [Figure 17]
Figure 17
Figure 19 A & B
Plumbage.
Miliary tuberculosis with pleural involvement and
random nodules.

Postprimary Tuberculosis: Assessment Hemoptysis – Mycetoma [Figure 21]
of Activity
• Cannot discern activity from a single film
• Inactive disease
 Radiographic stability
 6 months
• Negative cultures
• Suggestive of active disease
 Cavitation
 Consolidation
 Ground glass
 Centrilobular opacities
Lee, et al. Chest 1996.
Tuberculosis: Complications
• End-stage disease
• Hemoptysis
 Bronchial arteries in chronic cavities
Figure 21 A & B
 Mycetoma
 Rassmussen (pulmonary artery) Mycetoma in old tuberculous cavity.
aneurysm
• Chest wall involvement
• Pericardial involvement
• Empyema
 BPF, empyema necessitatis
Pulmonary Artery Aneurysm [Figure 22]
Hemoptysis – Bronchial Artery
[Figure 20]
Figure 22 A & B
Rasmussen aneurysm.
Figure 20 A & B
Endobronchial spread leads to airways nodules.
Tuberculosis: HIV/AIDS
• CD4 > 200
 Well formed granulomas
 Upper lobe cavities, consolidation and
nodules
• CD4 < 200
 Poorly formed granulomas
 Adenopathy, consolidation and miliary
disease
• CD4 < 60
 No hypersensitivity reaction
 Organisms spread from GI tract
 Miliary disease

Tuberculosis and AIDS – Low CD4
[Figure 23]
Figure 23 A & B
Miliary tuberculosis in acquired immune deficiency
syndrome patient with low CD4 count.
Tuberculosis: Diagnosis
• Conventional methods
 Acid-fast smear: 1 day
 Culture: 1–2 weeks
 Identification: 2–3 weeks
 Drug susceptibility testing: 3–4 weeks
• Radiometric methods
• Polymerase chain reaction (PCR)
• HPLC
Summary
• Primary TB
 Consolidation
 Ipsilateral lymphadenopathy
 Pleural effusion
• Postprimary TB
 Consolidation
 Cavitation
 Apical/posterior upper lobe nodules
 Tracheobronchial spread
Reference
1. Leung AN. Pulmonary tuberculosis: the essentials. Radiology. 1999;210:307–322.

Lung Cancer
Histological Classification of Tumors Clinical Presentation [Figure 1]
• World Health Organization • Central tumors
• Lung tumor editions  Cough
 1967  Wheezing
 1981  Hemoptysis
 1999  Pneumonia
 2004 • Extrapulmonary invasion
• Improve communication  Pain
• Consistent treatment  Pancoast syndrome
• Basis for comparative studies  Superior vena cava (SVC) syndrome
• Prognosis • Metastases
• Paraneoplastic syndromes
Changes in the 1999/2004 World Health • Asymptomatic (10%)
Organization
• Subclasses of adenomas
• Preinvasive lesions
• Adenocarcinoma
• Definition of bronchioloalveolar
carcinoma (BAC)
• Neuroendocrine tumors
• Biphasic and pleomorphic tumors
Incidence of Lung Cancer

Gazdar, Semin Oncol 1988.
Lung Cancer Demographics

• Most common cancer in male gender
world-wide
• Leading cause of cancer mortality in
women and men (United States)
• Mortality rates in women began increasing
in 1935 and surpassed breast cancer in
1987
Age-Adjusted Cancer Death Rates: Male

versus Female Genders
Cancer 49:1999. Figure 1
Lung Cancer Etiology: Cigarette Approximately 25% of lung cancer patients present
smoking with symptoms that are attributable to the primary
• 85%–90% of lung cancer deaths tumor. Cough, wheezing, hemoptysis, and pneumonia
are common as in this central tumor involving the
• 25% of lung cancer in nonsmokers right mainstem bronchus and extending into the right
attributed to passive smoke upper lobe.
• Risk related to:
 Number of cigarettes smoked
 Depth of inhalation
 Age at which smoking began Paraneoplastic Syndromes [Figure 2]
• Persistent oxygen free radicals • Cachexia, malaise, and fever

• Air pollution <2.5 micron particles • Ectopic hormone production
 Adrenocorticotropic hormone (ACTH)
 Antidiuretic hormone (ADH)
 Hypercalcemia
• Clubbing and hypertrophic pulmonary
osteoarthropathy (HPO)
• Thrombotic endocarditis
 Nonbacterial
• Migratory thrombophlebitis
Chest Radiology 95 Lung Cancer

Squamous Cell Carcinoma:
Gross features [Figure 3]
• Central lesion
 Polypoid, endobronchial, exophytic
growth
• Central necrosis common
• Bronchial wall invasion
 Common
 Positive cytology
• Proximal growth
 Along bronchial mucosa
Figure 3
Squamous
cell
carcinomas
tend to
be central
lesions.
Figure 2 A & B
Hypertrophic pulmonary osteroarthropathy causes

formation of new subperiosteal cancellous bone at the
distal ends of the long bones. In occurs most often in
the radius/ulna (80%) and the tibia/fibula (74%).
Squamous Cell Carcinoma:
Radiographic features
• Hilar or perihilar mass
Squamous Cell Carcinoma • Bronchial wall thickening
• Terminology  Often focal
 Squamous • Consolidation
Flattened cells  Must clear completely
 Epidermoid • Atelectasis
Mimics differentiation of the • Peripheral nodule or mass (30%)
epidermis • Cavitation
• Rapid local growth
• Distant metastases later
• Strong association
 Cigarette smoking
Preinvasive Lesions: Squamous

dysplasia
• Similar to cervical cancer
• Squamous metaplasia
• Progression
 Dysplastic epithelium
• Carcinoma in situ
 Full thickness dysplasia
• Precursor
 Invasive squamous cell carcinoma
Lung Cancer 96 Chest Radiology

Atelectasis [Figures 4 to 6] Cavitation [Figure 7]
Figure 7 A & B
Figure 4
Cavitation is most common in squamous cell cancer.
Volume loss in an adult should raise suspicion of lung
cancer.
Small Cell Lung Cancer

• Rapid growth
• Considered metastatic at presentation
• Poorest survival
• Strongest association with cigarette
smoking
Small Cell Lung Cancer: Microscopic

features
• Small uniform cells
• Scant cytoplasm
• Necrosis is common
 Often extensive
• >10 mitosis per 10 high-power fields
(HPF)
Figure 5 A & B  Average 60–70
Central squamous cell carcinoma in the apical-posterior
• Neuroendocrine morphology
segment of the left upper lobe with mucus-filled distal • Neuroendocrine markers (75%)
airways due to obstruction. • Light microscopy diagnosis
World Health Organization. 2004.
Small Cell Lung Cancer: Gross features

• Large
• Central mass (90%)
• Bronchial compression
• No endobronchial lesion
• Proximal growth
 Along submucosa
• Extensive necrosis
• Hemorrhage
Figure 6 A & B
Golden’s “S” sign.

Small Cell Lung Cancer [Figure 8] Adenocarcinoma: 1999/2004 World
Health Organization
• Acinar
• Papillary
• Bronchioloalveolar
 Nonmucinous
 Mucinous
 Mixed nonmucinous and mucinous or
indeterminate
• Solid with mucin production
• Adenocarcinoma, mixed subtype (90%)
• Atypical adenomatous hyperplasia (AAH)
bronchioloalveolar carcinoma versus

Adenocarcinoma [Figure 10]
Figure 8 A & B
Small cell carcinoma tends to spread along the
peribronchovascular lymphatics. Note tumor following
a lymphatic distribution along the airways (left image)
and the associated right hilar mass on the (right
image).
Large Cell Carcinoma

• Rapid growth
• Location
 Segmental
 Subsegmental
• Early metastases
• Poor prognosis Figure 10 A & B
• Strong association with cigarette smoking The histologic definition of bronchioloalveolar
carcinoma is now quite strict and the majority
Large Cell Carcinoma: of cases that were previously called mucinous
Microscopic features bronchioloalveolar carcinoma are now called invasive
mucinous adenocarinoma.
• Large cells
• Prominent nucleoli
• Poorly differentiated
• Diagnosis of exclusion Adenocarcinoma: Etiology
• Neuroendocrine features [Figures 11 & 12]
• Cigarette smoke causally linked to lung
Large Cell Carcinoma [Figure 9]
cancer
 1950
 Squamous cell 18x adenocarcinoma
 Squamous cell: central
• Adenocarcinoma most common
 Peripheral
• Filtered low-yield cigarettes
 Smaller particles
 Reduced nicotine
 Greater depth and number of puffs
 N-nitrosamines
• Other factors (10%)
 Passive smoke
 Radon
 Cooking practices
 Persistent free radicals (PFR)
Figure 9 A & B
Large cell cancers are commonly necrotic but rarely

cavitate.

Adenocarcinoma: Microscopic features
• Glands
• Papillary structures
• Mucin
 Intracellular
 Extracellular
Figure 11 • Prominent nucleoli
• Moderate cytoplasm
Fifty years • Desmoplastic reaction
ago the most • “Scar carcinoma”
common lung
cancer was  Rare
squamous cell
carcinoma Adenocarcinoma: Radiographic features
and was a • Peripheral (75%)
predominantly • Solitary mass or nodule
central tumor.
• Upper lobes 3:2
• Right lung 3:2
• Lobulated
• Borders
 Ill-defined
 Well-defined
• Spiculated
Figure 12
• Obstructive pneumonitis (25%)
Spiculation and Retraction [Figure 13]

Filtered cigarettes
and a change in
the composition
of tobacco during
the last 4 decades
now favor
the induction
of peripheral
adenocarinomas.
Filters remove
large particles
that tended to
be deposited in
central airway
where squamous
cell cancer
preferentially
develops.
Figure 13 A & B
Adenocarcinoma: Epidemiology
• 10% central airways Adenocarinomas are commonly spiculated peripheral
nodules. Pleural retraction indicates a fibrotic reaction.
 Solid architecture
 No precursor
• 90% terminal respiratory unit (TRU)
 Precursors
Atypical adenomatous hyperplasia
(AAH)
Bronchioloalveolar carcinoma
(BAC)
Sun. Nature Reviews. 2007.

Scar Carcinoma [Figure 14] Necrosis [Figure 16]
Figure 14 A & B
Figure 16 A & B
In scar carcinomas, the scar is usually a reaction to
the malignancy. A localized scar is rarely the cause of Foci of necrosis are common in larger lung
malignancy. adenocarcinomas, but cavitation is rare.
Diffuse Pulmonary Fibrosis [Figure 15) Air Bronchogram [Figure 17]
Figure 17 A & B
Air bronchograms are commonly seen in

Figure 15 A & B adenocarcinomas.
Diffuse pulmonary fibrosis is associated with an
increased risk of adenocarcinoma.

Slow Growth-Convergence [Figure 18] Atypical Adenomatous Hyperplasia
[Figure 19]
• Alveoli/respiratory bronchioles
 Mild to moderate atypia
 Lepidic growth
• Atypia falls short of BAC
• Precursor/transition to BAC
• Commonly found in resection specimens
• Independent lesion
Kitamura. AJCP. 1999.
Figure 18 A & B
Vessels converge as there is a fibrotic response to the Figure 19

tumor.
Atypical
adenomatous
hyperplasia is
characterized
Adenocarcinoma in “Never Smokers”: by lepidic
Epidemiology growth of
premalignant
• Global Statistics
cells.
 15% of men
 53% of women
 300,000 deaths/year
• Distinct pathogenesis
 Location
 Genetics
Sun, Nature Reviews, 2007
Adenocarcinoma in “Never Smokers”: Atypical Adenomatous Hyperplasia
Etiology • Peripheral, often upper lobe
• Small, usually less than 5 mm
• Risk factors
• Ground-glass opacity
 Environmental tobacco smoke
 Spherical (76%)
 Cooking practices
• Slow growth
 Radon
 Doubling time >800 days
 Persistent free radicals (PFR)
Motor vehicle density Travis, et al. J Thoracic Oncology. 2011.
• Air pollution (<2.5 microns)
 Genetics
Atypical Adenomatous Hyperplasia
 15%–27% increase 10 mcg/m3
– adenocarcinoma in situ –
Adenocarinoma: Continuous
Adenocarcinoma: Changing terminology developmental spectrum of
• Atypical adenomatous hyperplasia (AAH) bronchioloalveolar neoplasia
• Adenocarcinoma in situ (AIS) • “Well-defined criteria are lacking for
 Former bronchioloalveolar carinoma differentiating purely lepidic BAC (AIS)
(BAC) from AAH….
• Minimally invasive adenocarcinoma (MIA) • …There are few hard data to indicate
• Adenocarcinoma exactly how much invasive growth is
• Invasive mucinous adenocinoma allowed… before the lesion should simply
 Former mucinous BAC be termed adenocarcinoma”
Travis, et al. J of Thoracic Oncology. 2011. Kitamura. Am J Clin Path. 1999.
Ritter. Am J Clin Path. 1999.

Adenocarcinoma In Situ: Adenocarcinoma
Radiographic Features [Figure 20] • Controversy
• Irregular shape  Minimally invasive adenoca
• Variable • Tumors with:
 Ground-glass and solid elements  Predominant nonmucinous BAC
 Central scar  Localized fibrosis less than 5 mm,
• Internal air space regardless of invasion
 Dilated airways (fibrosis)  100% 5-year survival similar to BAC
• Slow growth  5–10 mm 70% 5-year survival
 >10 mm 60% 5-year survival
Shimosato. Am J Surg Path. 1980.
Suzuki. Ann Thorac Surg. 2000.
Adenocarcinoma
• Requires exclusion of invasion
• Small biopsies
Figure 20 • Requires complete lesion for accurate
classification
As we move Kerr. Histopathology. 2009.
along the
spectrum Atypical Adenomatous Hyperplasia
from atypical
adenomatous Versus Respiratory Bronchiolitis
hyperplasia to and Pulmonary Langerhans Cell
adenocarcinoma histiocytosis [Figure 22]
in situ there is
often increased
density and
distortion.
Adenocarcinoma [Figure 21]
Figure 22 A & B
Inflammatory and malignant changes in the lung can
have a similar appearance.
Invasive mucinous adenocarinoma:

former mucinous bronchioloalveolar
carinoma
• Alveolar spaces distended with mucin
• Aerogenous spread is common
Figure 21 A & B • Multifocal consolidation
Adenocarcinomas of the lung may get smaller related • KRAS genetic mutation (75%)
to fibrosis and alveolar collapse. • 20%–25% of BACs
• May form
 Localized masses
 Consolidation
• Lack hemorrhage and necrosis
• No architectural distortion
• Aerogenous spread common
 Satellite tumors
 Lobar consolidation

Invasive Mucinous Adenocarinoma Adenocarcinoma [Figure 24]
[Figure 23]
Figure 23
Mucinous bronchioloalveolar carinoma is now called

invasive mucinous adenocarinoma. It is commonly
Figure 24 A & B
multifocal and spreads via the airways.
Ten percent of lung adenocarcinomas arise from
the airway epithelium and typically have a solid
architecture.
Invasive Mucinous Adenocarinoma:
Radiographic features
• Solitary nodule Atypical Adenomatous Hyperplasia,
 Excellent prognosis
Atypical Adenomatous Hyperplasia –
Resection
• Consolidation adenocarcinoma in situ – Minimally
 May be multifocal invasive Adenocarcinoma –
• Ground glass Adenocarcinoma Continuous spectrum
• Multiple nodules of neoplasia and invasion [Figure 25]
• May cavitate?
National Lung Screening Trial
Adenocarcinoma: • 53,000 current or former smokers
Changing Terminology  55–74 years old
• Atypical adenomatous hyperplasia  Heavy smokers (48 pack/years, mean
• Adenocarcinoma in situ exposure)
 Bronchioloalveolar carinoma • Screened with low-dose helical CT
• Minimally invasive adenocarcinoma • 20% fewer lung cancer deaths
 Adenocarcinoma
Figure 25 A to I
Ninety percent
of lung
adenocarcinomas
arise from
the terminal
respiratory unit
and may grow
quite slowly.
Increase in density
and/or distortion
are signs of
malignancy.

References
1. Cagle PT, Allen TC, Dacic S, Beasley MB, Borczuk AC, Chirieac LR, Laucirica R, Ro JY, Kerr KM. Revolution
in lung cancer: new challenges for the surgical pathologist. Arch Pathol Lab Med. 2011;135:110–116.
2. Shimosato Y, Suzuki A, Hashimoto T, et al. Prognostic implications of fibrotic focus (scar) in small
peripheral lung cancers. Am J Surg Pathol. 1980;4:365–373.
3. Lindell RM, Hartman TE, Swensen SJ, et al. 5-year lung cancer screening experience: growth curves
of 18 lung cancers compared to histologic type, CT attenuation, stage, survival, and size. Chest
2009;136:1586–1595.
4. Travis WD, Brambilla E, Noguchi M, et al. International association for the study of lung cancer/american
thoracic society/european respiratory society international multidisciplinary classification of lung
adenocarcinoma. J Thorac Oncol. 2011;6:244–285.
5. Sun S, Schiller JH, Gazdar AF. Lung cancer in never smokers – a different disease. Nat Rev Cancer.
2007;7:778–790.
6. Lindell RM, Hartman TE, Swensen SJ, et al. Five-year lung cancer screening experience: CT appearance,
growth rate, location, and histologic features of 61 lung cancers. Radiology. 2007 Feb;242(2):555–562.
7. Godoy MC, Naidich DP. Subsolid pulmonary nodules and the spectrum of peripheral adenocarcinomas of
the lung: recommended interim guidelines for assessment and management. Radiology. 2009;253:606–
622.
8. de Hoop B, Gietema H, van de Vorst S, et al. Pulmonary ground-glass nodules: increase in mass as an
early indicator of growth. Radiology. 2010;255:199–206.

Chest Seminar 1
Case 1 [Figures 1 to 4]
• This 57-year-old man presents with a long
history of smoking cigarettes
• He now complains of malaise and a
chronic cough
Figure 1
Figure 4 A & B
Case 2 [Figures 5 & 6]

• This 20-year-old white female presented
7 years prior to the current admission
with sudden onset of shortness of breath.
The original chest radiograph revealed a
pneumothorax.
• The patient now presents with increasing
shortness of breath
Figure 2 A & B
Figure 5
Figure 3
Chest Radiology Chest Seminar 1

105
Case 4 [Figures 9 to 11]
• This 72-year-old white woman presented
with cough and occasional fever
• She was treated intermittently with
antibiotics for 6 months
• Open biopsy was obtained because of
progressive symptoms
Figure 6
Figure 9 A & B
Case 3 [Figures 7 & 8]

• This 58-year-old white woman presented
with a one month history of hemoptysis
Figure 10 A & B
Figure 7
Figure 11 A & B
Figure 8 A & B
Chest Seminar 1 Chest Radiology

106
Case 5 [Figures 12 to 14] Case 6 [Figures 15 to 17]
• A 46-year-old white man with long • A 61-year-old white woman worked as a
standing year history of shortness of hospital storage room manager
breath. He presents with a 3 months of • She presented to the ER complaining of
worsening dyspnea. fatigue, increasing shortness of breath,
• He demonstrated a mild leukocytosis and chest pain, and cough productive of blood
an increase in serum LDH tinged sputum
Figure 15
Figure 12
Chest Radiology Chest Seminar 1

107
Pulmonary Hypertension
Aletta Ann Frazier, MD

Pulmonary arterial hypertension: Pulmonary arterial hypertension:
The clinical essentials A spectrum of disease [Figure 1]
• Mean pulmonary artery pressure >25 mm • Left-sided cardiac disease
Hg  Myocardial failure
 Pulmonary capillary wedge pressure  Valvular disorder (mitral, aortic)
normal or decreased  Atrial or ventricular mass/thrombus
• Hemodynamic consequence of vascular
injury
 Initiating factors plus genetic
susceptibility
 Insidious clinical onset, variable
severity and tempo Figure 1
• Right ventricular hypertrophy (cor
Medical
pulmonale)
illustration
 Late in disease course showing
 Key prognostic indicator enlargement
• Fourth World Symposium (2008) of central
• Revised classification based upon pulmonary
arteries and
emerging clinical understanding and right heart
therapeutic approaches chambers.
Pulmonary arterial hypertension:

A spectrum of disease [Figure 1]
• Idiopathic pulmonary hypertension (IPH)
 Severe expression of disease
 Relentless rapid clinical course
 Heritable form now distinct from Pulmonary arterial hypertension:
idiopathic pulmonary arterial
A spectrum of disease [Figure 2]
hypertension (IPAH)
• Pulmonary capillary hemangiomatosis
• Congenital S-to-P shunt
• Pulmonary veno-occlusive disease
 Eisenmenger syndrome
 Atrial septal defect (ASD), ventricular
septal defect (VSD), patent ductus
arteriosus (PDA), APVR
 Corrected or uncorrected
• Vaso-occlusion/constriction
 Chronic hemolytic anemias
 Intravenous talcosis
 Schistosomiasis
 Tumor thromboembolism
 Chronic thromboembolism
 Mediastinal fibrosis Figure 2 A & B
• Comorbid conditions
Medical illustration diagramming the features of
 Chronic obstructive pulmonary disease pulmonary capillary hemangiomatosis (A) and
 Connective tissue disorders pulmonary veno-occlusive disease (B).
 Human immunodeficiency virus (HIV)
infection
 Interstitial lung disease
Idiopathic pulmonary fibrosis The Pulmonary Circulation: Vascular
(IPF)/usual interstitial pneumonia remodeling [Figure 3]
(UIP) • Hypoxia
Nonspecific interstitial pneumonia • Inflammation
(NSIP) • Vasoconstriction
Acute interstitial pneumonia (AIP) • Dysregulation of endothelial and smooth
Organizing pneumonia (OP) muscle cell growth
 Sarcoidosis • Resistance to apoptosis
 Obstructive sleep apnea • Misguided angiogenesis
Chest Radiology 109 Pulmonary Hypertension

Dilatation of Central Pulmonary Arteries
[Figures 5 & 6]
Figure 3
Schematic
illustration of
pulmonary
arterial
anatomy with
emphasis on
typical site
of pulmonary
arterial
hypertension
patho-
physiology. Figure 5
Chest x-ray in pulmonary arterial hypertension shows

central pulmonary artery dilatation, enlarged cardiac
silhouette, and peripheral oligemia.
Histopathology: Muscular Arteries
[Figure 4]
• Intimal proliferation
• Medial hypertrophy
• In situ thrombosis Figure 6
If
transverse
diameter
of the main
pulmonary
artery
measures
>3 cm,
there is
greater
than 85%
Figure 4
sensitivity and specificity for pulmonary arterial
hypertension.
Histopathology
of pulmonary
arterial Central Pulmonary Artery Calcifications
hypertension.
[Figure 7]
Figure 7
Central
Histopathology: Plexiform Lesions pulmonary
• IPH arterial
• Eisenmenger syndrome calcifications
• HIV-associated in explant
specimen
• Schistosomiasis radiograph.
Pulmonary Hypertension 110 Chest Radiology

Constrictive Mediastinal Calcifications Nodular Ground-Glass Opacities
[Figure 8] [Figure 11]
Figure 8
Figure 11
CT of
mediastinal
fibrosis CT of
constricting nodular
central ground-
pulmonary glass
arteries. opacities in
pulmonary
capillary
heman-
giomatosis.
Bronchial Arterial Collaterals [Figure 9]
Ground-Glass Opacities and Septal Lines

[Figure 12]
Figure 9
Maximum
intensity
projection
(MIP) coronal
reconstruction
shows
bronchial Figure 12
arterial
collateral
vessels. CT of
ground-
glass
opacities
and septal
lines in
pulmonary
Vascular Pruning and Mosaic veno-
Attenuation [Figure 10] occlusive
disease.
Cor Pulmonale: Right ventricular strain

and hypertrophy
Figure 10 • Anterior free wall right ventricle (RV) >6
mm
CT of • Dilatation of RV chamber: RV/LV >1
vascular • Septal flattening or curve reversal
pruning
and mosaic • Regurgitant flow: pulmonary and tricuspid
perfusion. valves
• Increased glycolytic activity on
fluorodeoxyglucose-positron emission
tomography (FDG-PET CT)

Pulmonary Arterial Hypertension:
Review of Imaging Manifestations
• Central pulmonary artery dilatation
• Pulmonary artery calcifications
• Bronchial collaterals
• Vascular pruning
• Mosaic attenuation
• Ground-glass nodules
• Cor pulmonale
• Septal lines
 Disorder arises in pulmonary veins or
left heart

Clues to Etiology
• Intravascular filling defects
• Emphysema
• Interstitial fibrosis
• Mediastinal calcifications
• Dense perihilar masses
• Cardiac septal defect
• Valvular calcifications

Final Points
• Spectrum of disorders
 IPH, pulmonary capillary
hemangiomatosis, pulmonary veno-
occlusive disease
 Vaso-occlusion
 Comorbidities and chronic hypoxia
 Left-sided cardiac disease
• Severity, tempo widely variable
 Cor pulmonale = advanced PAH
• Vascular remodeling mimics cancer
biology
• Imaging may detect PAH and suggest
underlying etiology
• Radiologists must partner with clinicians
 In the recognition of PAH
 In the discernment of etiology
 In surveillance during therapy
Pulmonary Hypertension 112 Chest Radiology

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Pulmonary Metastases
Aletta Ann Frazier, MD

Key Points Principle: “Generalizing Sites”
• The pathogenesis of pulmonary • Venous drainage via liver
metastases is complex  Colon
• The spectrum of radiological  Pancreas
manifestations reflects pathways of  Stomach
spread • Venous drainage via bone
• Many extrathoracic malignancies produce  Prostate
characteristic radiologic patterns of • Dual venous drainage (simultaneous
pulmonary metastases seeding)
 Kidney, bladder, ureters
Metastatic Disease to the Lung  Uterus, cervix
• Most common lung neoplasm  Anus, rectum
• Incidence: 20%–55% of patients dying • Complex venous (and lymphatic) drainage
from extrathoracic malignancy  Breast
• Lung is the ONLY site of metastatic
disease in 15%–25% of these patients Pathogenesis of Hematogenous
Metastases [Figure 1]
Metastatic Disease to the Lung: Routes • Tumor cells penetrate draining venules
of Spread • Enter systemic venous circulation
• Pulmonary and bronchial arteries • Filtered by pulmonary arterial circulation
• Pulmonary and pleural lymphatics
• Thoracic duct
• Airways
• Transdiaphragmatic lymphatics
What are the most likely primary

extrathoracic malignancies?
• Breast
• Colon
• Uterus
• Kidney
• Prostate
• Oropharynx
• Stomach
• Pancreas
Which malignancies are the most highly

predisposed?
• Choriocarcinoma
• Osteosarcoma
• Testicular tumors
• Melanoma Figure 1
• Ewing sarcoma
• Thyroid carcinoma Hematogenous metastases arise from tumor cells
which penetrate vessels and lymphatics at the primary
• Kaposi sarcoma site and are transported to the right heart via the
systemic venous circulation.
Principle: “Generalizing Sites”
• Certain tumors seed the lung directly,
others first drain via another filtration
organ (bone or liver)
• Systemic venous drainage directly to lung
 Melanoma
 Sarcomas
 Choriocarcinoma
 Thyroid
 Kidney, testes, adrenal gland
 Oropharynx
Chest Radiology 115 Pulmonary Metastases

Pathogenesis of Hematogenous Parenchymal Nodular Metastases:
Metastases [Figure 2] HRCT-Pathologic Correlation: Nodules
• Adherence, extravasation in distal <1 cm [Figure 3]
arterioles • Peribronchovascular (12%)
• Expansile growth in interstitium and • Periseptal (28%)
alveoli • Intermediate (68%)
• Vascularization • Angiocentric (76%)
 Pulmonary arteries  Directly centered on feeding vessel
 Bronchial circulation (18%)
 Transpleural collaterals  Eccentric to feeding vessel (58%)
Hirakata, et al. AJR. 1993;161:37-43.
Figure 3
Secondary
pulmonary lobule.
Hematogenous
metastases may
be angiocentric
but are random
with respect to
the secondary
pulmonary lobular
architecture.
Figure 2
Blood-borne tumor cells arrest in distal arterioles
Parenchymal Nodules: Imaging
of the pulmonary circulation, extravasate into the Features: Chest CT [Figure 4]
interstitium, and establish nodules by expansile • Multiple
growth. • Peripheral, basilar
• Variable size
• “Random” – eccentrically located between
Parenchymal Nodules: Histology BVB and interlobular septa
• Well-defined • Occasionally – angiocentric
• Homogeneous cell population • Less commonly – “cannonball” or miliary
• Adjacent to arteries and arterioles • Rarely
• Alveolar septa compressed or obliterated  Cavitary
 Calcified
Nodular Metastases  Solitary
• Rounded, coalescent, or multilobulated  Ground-glass halo (hemorrhagic)
• Multiple Angiosarcoma
• Peripheral, basilar Choriocarcinoma
• Variable size Posttherapy
• Mixed areas of viability, necrosis,
hemorrhage
Parenchymal Nodules: Multidetector

Chest CT
• High sensitivity
 95% for nodules >1 cm
 91% for nodules .5–1 cm
• Low specificity (60% in 40–65-year-old
adults)
 Intrapulmonary lymph nodes
 Granulomatous diseases
Figure 4
Sarcoidosis
Silicosis Metastatic colon carcinoma in middle-aged man:
 Amyloidosis Variable-sized nodules are random, peripheral,
 Infection occasionally angiocentric in location.
Pulmonary Metastases 116 Chest Radiology

“Cannonball” Metastases [Figures 5 to 7] Figure 7
• Colorectal carcinoma
Cannonball
• Renal cell carcinoma metastases in
• Sarcomas a young adult
• Melanoma male with a
soft tissue
sarcoma
(scout; axial
lung and
mediastinal
CT images).
Micronodular (Miliary) Metastases

Figure 5 [Figure 8]
• Malignancies
Cannonball  Thyroid CA (papillary)
metastases
(gross
 Choriocarcinoma
lung) in • Opacities may persist posttreatment
young male (“sterile”)
adult with • Differential diagnosis
soft tissue  Miliary tuberculosis
sarcoma.
 Viral pneumonia
 Sarcoidosis
Pulmonary Metastases: Unusual

Manifestations
• Cavitary, calcified, or solitary pulmonary
nodules
• Lymphangitic carcinomatosis
• Tumor thromboembolism
• Endobronchial metastases
• Pleural-based metastases
Figure 6 Figure 8
Micronodular metastases in middle-aged woman with
Cannonball thyroid cancer.
metastases in
a young male
adult with a
soft tissue
sarcoma
(scout; axial
lung and
mediastinal
CT images).

Cavitation in Metastases [Figure 9] Solitary Metastasis versus Lung Primary
• Incidence 4% (versus 9% of lung • “The likelihood of a primary lung
primaries) cancer versus a metastasis depends
• Malignancies on the histologic characteristics of the
 Squamous cell CA (head and neck; extrapulmonary neoplasm and the
cervix) – 69% patient’s smoking history.”
 Adeno CA (colon, breast) – 31% Quint, et al. Radiology. 2000;217:257-61.
 Sarcomas (bone) – spontaneous ptx
• Wall thickness NOT indicative of benignity Solitary Metastasis versus Lung Primary
• Differential diagnosis • A SPN is more likely to be bronchogenic
 Septic emboli CA than a solitary met if the patient has
 Vasculitis carcinoma of:
 Collagen vascular disease  Head and neck
 Bladder
 Esophagus
Figure 9  Breast
 Cervix
Cavitary
 Bile ducts
metastases
in elderly  Ovary
man with  Prostate
oropharyngeal  Stomach
cancer. • The incidence is fairly equal in patients
with carcinoma of:
 Kidney
Calcification in Metastases [Figure 10]
 Colon
• Malignancies
 Adrenal gland
 Osteo-, chondro- and synovial
 Uterus
sarcomas
 Salivary or parotid gland
 Papillary/mucinous adenocarcinomas
 Thyroid gland
(ovary, thyroid, GI)
• SPN is more likely solitary metastasis in:
• Postchemotherapy or postradiation
 Melanoma
• Variable content
 Sarcoma (soft tissue, bone)
 Osteoid matrix
 Testicular carcinoma
 Dystrophic calcification
 Psammoma body formation Parenchymal Nodules: Assessing
Therapeutic Response
Figure 10 • Tumor doubling time
 25% increase in tumor diameter
Calcified separated by time (Tdt)
metastases  Nodule growth rates vary widely
in middle- Histologic tumor cell type
aged woman Within the same patient
with ovarian
cancer. Each nodule a different monoclonal
population with variable response
to chemo
• Document changes in several nodules in
the same patient
Solitary Metastasis
• Impacts treatment strategy and
• Unusual: 1%–28% of all metastatic
participation in clinical trials
lesions
• 3%–10% of all SPNs are solitary Chojniak, et al. Am J Clin Oncol. 2003;26:374–
metastases 77.
• Variable margins
 Well-defined
 Multilobulated
 Spiculated
• Solitary metastasis versus lung primary
• “In patients with known primary
malignancies and single parenchymal
nodules, the overall incidence of second
primary lung carcinoma is greater than
that of solitary metastases.”
Coppage, et al. J Thorac Imaging. 1987;2:24-37.

Parenchymal Nodules: Indications for Lymphangitic Carcinomatosis
Metastasectomy • Cords of tumor in lymphatics of the
• To cure, but only if interlobular septa and peribronchovascular
 Complete resection possible interstitium
 No extrathoracic metastases (except • Edema and desmoplastic reaction
colon CA and liver mets) accentuate interstitial expansion,
 Chemotherapy-insensitive tumors thickening
 Multiple nodules not a contraindication
• Prolongs 5-year survival Lymphangitic Carcinomatosis: Imaging
 Colorectal cancer: 20%-50% Features – Chest radiograph
 Osteogenic and soft tissue sarcomas: • Normal (50%)
40% • Kerley B lines
 Melanoma, renal cell, head & neck, • Reticulonodular opacities
female GU: 30% • Subpleural edema
 Thyroid, parathyroid: 61% • Pleural effusion (30%–50%)
• Hilar, mediastinal lymphadenopathy
Yoneda, et al. Curr Opin Pulm Med. 2000;6:356-
(20%–40%)
363.
• Bilateral or unilateral findings
Lymphangitic Carcinomatosis
Lymphangitic Carcinomatosis: Imaging
[Figure 11]
• Blood-borne tumor cells extravasate and
Features – Chest CT [Figure 12]
• Smooth or nodular thickening of
invade lymphatic channels
 Bronchovascular bundles
• Tumor also enters lymphatics “retrograde”
 Interlobular septa (Kerley lines;
via mediastinal, hilar lymph nodes (25%)
polygonal arcades)
• Lymphatics expand with tumorlets and
 Lobar fissures (subpleural edema)
edema
• Ground-glass opacities
• Focal or unilateral distribution (50%)
 Lung or breast CA
• Pleural effusion (30%)
• Lymphadenopathy (up to 50%)
Figure 11
Figure 12
Secondary
pulmonary lobule. Lymphangitic
Lymphangitic carcinomatosis
carcinomatosis in a middle-
produces smooth aged woman
and nodular with breast
expansion of cancer.
bronchovascular
bundles sheaths
and interlobular
septa.
Tumor Embolism
• Lodges in distal arterioles (100–200
micron diameter)
• 26% cancer patients (at autopsy)
• < 1% clinically significant
Lymphangitic Carcinomatosis • Complications
• Adenocarcinomas in 80%:  Cor pulmonale (PAH)
 Lung  Lung infarction
 Breast  Lung hemorrhage
 Stomach • Parenchymal or lymphatic mets if
 Pancreas extravasation
 Prostate
 Colon
• Incidence 6%–55%
• Symptoms: gradual onset dyspnea, cough
• PFT’s: reduced lung compliance and
diffusing capacity
• Diagnosis: bronchial lavage or TBB

Tumor Embolism Endobronchial Metastases
• Malignancies • Tumor arrives via bronchial arteries and
 Stomach peribronchial lymphatics
 Lung (especially adenocarcinoma) • Rarely, via airways (BAC)
 Breast • 2%–5% incidence in patients dying from
 Choriocarcinoma metastases
 Ovary • Malignancies
 Prostate  Kidney
 Liver  Colon, rectum
 Kidney  Breast
 Lymphoma  Melanoma
 Right atrial myxoma  Pancreas
• Mean interval from diagnosis of primary:
Tumor Embolism [Figure 13] 65 months
• C x-ray • Mean survival after discovery: 15.5
 Typically normal months
 If widespread: nodules, airspace • Treatment options
opacities  Radiation
• CT  Chemotherapy
 “Beading” of peripheral pulmonary  Surgery
arteries  Interventional bronchoscopy (stenting;
 Mosaic perfusion laser or mechanical resection;
 Wedge-shaped peripheral opacities brachytherapy; photodynamic
 If extravasation: nodules, therapy)
lymphangitic carcinomatosis
Chan, et al. Curr Opin Pulm Med. 2003;9:301–
308.
Endobronchial Metastases: Imaging

Features [Figure 14]
• Intraluminal soft tissue mass
• Atelectasis or postobstructive pneumonia
Figure 13 • Serpentine or nodular opacities (distal
mucoid impaction)
Tumor thrombo- • Hilar mass (if adjacent mediastinal
embolism may invasion)
produce beading • Differential diagnosis: bronchogenic
along peripheral carcinoma
bronchovascular
bundles, as well
as pulmonary
infarction
(courtesy Marc V
Gosselin, MD).
Figure 14 A & B
Endobronchial metastases with left upper lobe collapse

(renal cell carcinoma).

Pleural Metastases [Figures 15 & 16]
• Malignancies
 Lung
 Breast (50% of patients)
 Ovary Figure 16
 Stomach
 Lymphoma Pleural
• Via lymphangitic or vascular invasion rind-like
• Typically manifest as exudative pleural metastases
effusion in elderly
woman with
 Pleural nodules less common non-small cell
• Scattered nodules on pleural surface lung cancer
• Visceral and parietal pleura typically both (NSCLC).
involved
• Rind-like or sheet-like pattern
• Differential diagnosis of gross and rads
 Mesothelioma
 Postinflammatory fibrothorax Patterns of Metastatic Disease to the
Lung: Overview
• Parenchymal nodules
 Well-circumscribed, random or
angiocentric, basilar > apical
Figure 15
 Unusual: cavitary, calcified, solitary
Large • Lymphangitic carcinomatosis
pleural  Septal lines, nodular/thickened
effusion fissures, GGO
and pleural-
based  Pleural effusion
nodule in  Lymphadenopathy
patient • Tumor thromboembolism
with breast  Beading of peripheral arteries
cancer.
 Mosaic perfusion
 Pleural-based opacity (infarction)
• Endobronchial nodule
 Rounded defect in airway, or cutoff of
airway lumen
 Postobstructive atelectasis,
pneumonia, mucoid impaction
• Pleural-based metastases
 Nodules on pleural surface
 Variation: plaque-like pattern mimics
mesothelioma

References
1. Chan AL, Yoneda KY, Allen RP, Albertson TE. Advances in the management of endobronchial lung
malignancies. Curr Opin Pulm Med. 2003;9:301–308.
2. Chojniak R, Younes RN. Pulmonary metastases doubling time: Assessment by computed tomography. Am
J Clin Oncol. 2003;26(4):374–377.
3. Coppage L, Shaw C, Curtis A. Metastatic disease to the chest in patients with extrathoracic malignancy. J
Thorac Imag. 1987;2(4):24–37.
4. David SD, Westcott J, Fleishonet al. Screening for pulmonary metastases. American College of Radiology.
ACR Appropriateness Criteria. Radiology. 2000;215 Suppl:655–662.
5. Davis S. CT evaluation for pulmonary metastases in patients with extrathoracic malignancy. Radiology.
1991;180:1–12.
6. Heffner JE, Milam MG. Sarcoid-like hilar and mediastinal lymphadenopathy in a patient with metastatic
testicular cancer. Cancer. 1987; Oct 1;60(7):1545–1547.
7. Hirakata K, Nakata H, Haratake J. Appearance of pulmonary metastases on high-resolution CT scans:
comparison with histopathologic findings on autopsy specimens. Am J Roentgenol. 1993;161:37–43.
8. Jungraithmayr W, Hasse J, Stoelben E. Completion pneumonectomy for lung metastases. Eur J Surg
Oncol. 2004;30:1113–1117.
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multi-detector row CT scans of 5-mm nominal section thickness: Autopsy lung study. Radiology.
2003;226:231–234.
10. Libshitz HI, North LB. Pulmonary metastases. Radiol Clin North Am. 1982;20:437–451.
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statement from the Fleischner Society. Radiology. 2005;237:395–400.
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sites. J Thorac Imag. 1987;2(4):38–43.
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14. Murata K, Takahashi M, Mori M, Kawaguchi N et al. Pulmonary metastatic nodules: CT-pathologic
correlation. Radiology. 1992;182:331–335.
15. Parra ER et al. Pulmonary and mediastinal “sarcoidosis” following surgical resection of cancer. Pathol Res
Pract. 2004;200(10);701–705.
16. Poste G, Fidler I. The pathogenesis of cancer metastasis. Nature. 1980; 283:139–145.
17. Pugatch RD. Radiologic Evaluation in Chest Malignancies. Chest. 1995; 107:294S–297S.
18. Quint L, Park C, Iannettoni M. Solitary pulmonary nodules in patients with extrapulmonary neoplasms.
Radiology. 2000;217:257–261.
19. Seo JB, Im J, Goo JM, Chung MJ, Kim M. Atypical pulmonary metastases: spectrum of radiologic findings.
RadioGraphics. 2001;21:403–417.
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1998;8(1):29–48.
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Oncology. 1998;12(3):441–444.
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measurement–initial experience. Radiology. 2005;234:934–939.

Differential Diagnosis of Mediastinal Masses
Melissa L. Rosado-de-Christenson, MD, FACR

Learning Objectives
• To define the mediastinum and the
mediastinal compartments Figure 2
• To describe a practical approach to the A&B
imaging diagnosis of mediastinal masses
Anatomic
• To list clinical and cross-sectional imaging and surgical
features that allow a focused differential mediastinal
diagnosis of mediastinal masses compart-
• To describe lesions with pathognomonic ments.
imaging features
• To differentiate neoplastic from non-
neoplastic conditions with emphasis on
management (surgical versus nonsurgical)
Mediastinal Compartments [Figure 1]

• Mediastinum – space between pleural
surfaces and lungs
• Bound by sternum and vertebrae
• From thoracic inlet to diaphragm
• Thymus, lymph nodes, heart, great
vessels, trachea, esophagus, nerves, and
other soft tissues
• Arbitrary division into compartments – No
anatomic boundaries
Figure 3 A & B
Radiographic mediastinal compartments.
Figure 1
Felson/Fraser and Paré.
The
mediastinum.
The space
between
the pleural Mediastinal Masses – Mayo Clinic (N =
surfaces and 1,064)
lungs. • Thymoma (20%)
• Cyst (20%)
• Neurogenic (20%)
• Lymphoma (30%)
Mediastinal Compartments [Figures 2 & 3] • Teratoma
• Anatomic – superior, anterior, middle, • Granuloma
posterior • Mediastinal goiter
 Excludes paravertebral areas
Wychulis, et al. J Thorac Cardiovasc Surg. 1971.
• Surgical – superior, anterior, middle,
posterior Approach to Mediastinal Masses
 Includes paravertebral areas • Clinical
• Radiographic (Felson) – anterior, middle,  Demographics (age, gender)/
posterior symptoms
• Radiographic (Fraser, Müller, Colman, • Radiography
Paré) – anterior, middle-posterior,  Mediastinal compartment
paravertebral  Diffuse mediastinal enlargement
versus focal mass
Mediastinal Masses
 Contours/associated findings
• Patients are often asymptomatic
• Cross-sectional imaging
• 83% of asymptomatic masses are benign
 Specific location/relationship to normal
• 57% of symptomatic masses are
structures
malignant
 Morphology/attenuation-signal/
• Approximately 1/3 are malignant
associated findings
• Approximately 1/10 are vascular
Chest Radiology 123 Differential Diagnosis of Mediastinal Masses

Mediastinal Masses Lymphoma
• Neoplasia • Non-Hodgkin lymphoma – 75% of all
 Malignant (secondary/diffuse) cases
 Benign and malignant (primary/focal) • 50%–70% of mediastinal lymphoma is
• Congenital cysts Hodgkin disease
• Glandular enlargement (thymus, thyroid)  15%–21% is non-Hodgkin lymphoma
• Vascular lesions • Hodgkin: 66% intrathoracic at
• Herniations/esophageal abnormalities presentation
• Miscellaneous conditions  Non-Hodgkin: 37% intrathoracic at
presentation
Malignant Neoplasia – Lung Cancer • Treatment: radiotherapy, chemotherapy
• Small cell/poorly differentiated lung
cancer Lymphoma: Clinical Features
• Elderly smokers; males and females • Hodgkin disease
• Cough, dyspnea, SVC syndrome, weight  Males = females (NSHD, 2x as
loss common in females)
• Mediastinal mass, lymphadenopathy, local  Bimodal distribution: second and third
invasion and > fifth decades
• Primary neoplasm may not be evident  Lymphadenopathy: cervical,
• Nonsurgical lesion supraclavicular
 20%–30%; fever, night sweats,
Malignant Neoplasia – Metastases weight loss
[Figure 4] • Non-Hodgkin lymphoma
• Known malignancy  Systemic disease with constitutional
• Cell types sx: lymphadenopathy, local invasion
 Renal cell carcinoma  Lymphoblastic – male children/
 Testicular carcinoma adolescents
 Head and neck cancer  Diffuse large B-cell – young female
 Breast carcinoma adults
 Melanoma
 Thyroid Lymphoma: Pathologic Features
[Figures 5 & 6]
• Hodgkin disease
 Nodal cellular infiltrate, collagenous
connective tissue (NS) Reed-Sternberg
cell
Figure 4  Lymphadenopathy, nodal coalescence,
primary thymic involvement, cystic
Metastatic renal
cell carcinoma. change, hemorrhage, necrosis
Diffuse bilateral  Local invasion
mediastinal • Non-Hodgkin lymphoma
enlargement.  Lymphoblastic (precursor
T-lymphoblastic) – lymphoblasts
 Diffuse large B-cell (primary
mediastinal [thymic] large B-cell);
large cells, vesicular nuclei, prominent
nucleoli
Malignant Neoplasia – Lymphoma  Large mass, infiltrative, locally
• Hodgkin disease/Non-Hodgkin lymphoma invasive, necrosis
• All age groups (young patients); males
and females
• Palpable lymphadenopathy, constitutional
symptoms
• Lobular/diffuse mediastinal enlargement Figure 5
• Prevascular, paratracheal
lymphadenopathy Hodgkin
 Nodal coalescence, local invasion disease.
Reed-
• Primary mediastinal lymphoma
Sternberg
• Nonsurgical lesion cell.
Differential Diagnosis of Mediastinal Masses 124 Chest Radiology

Figure 9
Non-Hodgkin
lymphoma.
Nodal
coalescence
with focal low
attenuation
corresponding
Figure 6 to necrosis.
Hodgkin
disease.
Nodal
coalescence. Non-Neoplastic Lymphadenopathy
• Infection
 Fungal: mediastinal fibrosis;
calcification
 Other granulomatous infections/
fibrosing disorders
• Sarcoidosis
 Bilateral symmetric hilar
Lymphoma: Imaging Features lymphadenopathy
[Figures 7 to 9]  Typical pulmonary involvement
• Lobular diffuse bilateral mediastinal • Castleman disease
enlargement  Enhancement/calcification (10%)
 Hodgkin disease: intrathoracic
involvement in 85% Mediastinal Fibrosis
Lymphadenopathy; prevascular, • Granulomatous lymphadenopathy
paratracheal • Young patients with signs and symptoms
Nodal coalescence (homogeneous/ of obstruction
heterogeneous)  Trachea, bronchi, esophagus, vessels
Cystic change • Mediastinal mass, circumscribed or locally
Ca++; 1% – 1 year posttherapy, invasive, calcification
rare pretherapy • Systemic antifungal agents, excision,
 Non-Hodgkin: Prevascular, dilatation, bypass graft
paratracheal lymphadenopathy • 30% mortality
Isolated involvement of other
mediastinal lymph nodes Castleman Disease
• Local invasion • Angiofollicular or giant lymph node
• Primary mediastinal lymphoma hyperplasia
• Hyaline vascular type (>90%) versus
plasma cell variant
• Localized versus systemic
Figure 7 • Adult females (female:male = 4:1) may
be asymptomatic
Hodkin • Middle mediastinal/hilar mass
disease.
Bilateral  Solitary mass
lobular  Dominant mass with lymphadenopathy
mediastinal  Multiple enlarged lymph nodes
enlargement.  Enhancement, calcification (10%)
Secondary Neoplasia: Pearls

• Malignant
 Diffuse bilateral mediastinal
enlargement
Figure 8  Lymphadenopathy (nodal coalescence)
Hodgkin  Local invasion
disease. • Differential diagnosis
Prevascular/  Advanced lung cancer – elderly
paratracheal smokers
lymphade-
nopathy and  Metastases – known malignancy (GU)
left pleural  Lymphoma – young adult (wide age
effusion. range)

Primary Neoplasia
• Thymus
 Thymoma
 Thymic malignancy
 Thymolipoma
 Germ cell neoplasm
• Neurogenic neoplasms
Thymoma Figure 11
• Epithelial neoplasm, most common
Thymoma.
primary thymic neoplasm Fibrous
• Slow growth, “benign” behavior capsule,
• M=F; 70% in the fifth and sixth decades tumor lobules
• Most patients asymptomatic compart-
• 25%–30% with symptoms of mentalized by
fibrous bands.
compression/invasion
• Associated parathymic syndromes:
 Myasthenia gravis
 Pure red cell aplasia
 Hypogammaglobulinemia
Thymoma and Myasthenia Gravis

• Myasthenia gravis (MG) – autoimmune
neurological disorder
• 85% of patients with MG have follicular
thymic hyperplasia
• 15% of patients with MG have thymoma
• Of all patients with thymoma, 30%–50%
have MG
Figure 12
Thymoma: Pathologic Features

Thymoma.
[Figures 10 to 13]
Central
• Lymphocytes and epithelial cells in hemorrhage
varying proportions and necrosis.
• WHO 1999 classification (morphology and
lymphocyte-to-epithelial cell ratios)
 Types A, AB, B1, B2, B3
 Poor reproducibility or prediction of
prognosis
• Tumor lobules compartmentalized by
fibrous septa
• Encapsulated versus invasive
• Spherical mass, variable size, lobular
contours, typically encapsulated
• Hemorrhage, necrosis, cystic change
(mural nodules)
• Invasive thymoma: microscopic
documentation of capsular invasion
 Local invasion, tumor implants,
metastases
Figure 13
Cystic lesion
with lobular
Figure 10
mural nodules.
Thymoma.
Tumor
lobules
compart-
mentalized
by fibrous
bands.

Thymoma: Imaging Features Figure 17
[Figures 14 to 18]
• Anterior mediastinal mass; lobular, Cystic
unilateral, variable size thymoma.
• Normal radiographs in 25% (occult Spherical right
thymic cystic
thymoma) mass with
• Focal, spherical, homogeneous, or peripheral
heterogeneous curvilinear
 Necrosis, cystic (mural nodules), calcification
calcification (typically curvilinear and and mural
nodules.
peripheral)
• No lymphadenopathy
• Exclude local invasion of fat,
cardiovascular structures, lung
• Pleural implants (may cause diffuse Figure 18
pleural thickening)
Invasive
thymoma.
Direct invasion
of left brachio-
cephalic vein.
Thymoma: Staging (Masaoka-Koga

Staging)
I Encapsulated/no microscopic capsular in-
vasion
Figure 14 A & B
IIa Microscopic capsular invasion
IIb Macroscopic invasion of surrounding fat,
Thymoma. Unilateral, lobular, left anterior mediastinal
mass. adherence to but no invasion of pleura or
pericardium
III Macroscopic invasion of adjacent organs;
pericardium, great vessels, lung
IVa Pleural/pericardial dissemination
IVb Lymphatic/hematogenous dissemination
Figure 15
Thymoma: Therapy
Thymoma. • Role of imaging is identification of patients
Spherical with advanced disease. Familiarity with
soft tissue reporting recommendations
mass in left
thymic lobe.  Stage I – surgery
 Stage II – post operative radiation for
incomplete resections
 Stages III–IVa – neoadjuvant
chemotherapy followed by surgery and
post operative radiotherapy
 Stage IVb – chemotherapy
Figure 16
Thymoma: Imaging Follow-up
Thymoma. • Annual chest CT for five years after
Well-defined
large right surgery
cardiophrenic • Alternate annual chest radiograph and CT
angle mass for up to 11 years
with extensive • After 11 years, annual chest radiography
low attenuation only
corresponding
to necrosis. • Chest CT every six months for three years
in
 Stage III or IVa thymoma
 Incomplete resection of thymoma
 Thymic carcinoma

Thymic Malignancy: Carcinoid/ Thymolipoma: Pathologic Features
Carcinoma [Figures 20 & 21]
• Rare malignant epithelial neoplasms • Encapsulated, soft, lobular, yellow
• Symptomatic patients • Mature adipose tissue and thymic tissue
• Poor prognosis in variable proportions
Thymic Carcinoid
• Neuroendocrine neoplasm; atypical
carcinoid (necrosis, mitoses, invasion)
• Males > females; 3:1; wide age range (43
years)
• 50% functionally active
 ACTH: cushing syndrome (33%–40%)
• MEN type 1: (Wermer syndrome) (19%– Figure 20
25%)
 Hyperparathyroidism (90%), islet cell Thymolipoma.
Thymic tissue
tumor of pancreas (80%), pituitary admixed
adenoma (65%) with mature
adipose
Thymic Carcinoma tissue.
• Male > female; wide age range (mean:
fifth decade)
• Several cell types identical to primary
lung cancer
 Rule out metastases
• WHO type C thymoma
Thymic Carcinoid/Carcinoma Imaging

Features [Figure 19] Figure 21
• Large anterior mediastinal mass
(rule out thymoma) Thymolipoma.
Anterior
• Rule out metastatic lung malignancy mediastinal
(histology) mass with
• Crosses midline anatomic
• Lymphadenopathy connection to
the thymus
• Local invasion, pleural or pericardial
and mixture
effusion/implantation, metastases of fat and
• Carcinoid soft tissue
 Octreotide imaging for occult lesions elements.
(nonspecific – metastases and other
thymic neoplasms)
Thymolipoma: Imaging Features
• Well-defined anterior/inferior mediastinal
Figure 19
mass
Thymic  Unilateral or bilateral, slow growth
carcinoid. • May conform to shape of structures
Mediastinal  Rule out cardiac enlargement/
mass with
adjacent diaphragmatic elevation
lymphaden-  Positional change in shape
opathy  Anatomic connection to the thymus
associated (pedicle)
with ACTH  Mixed fat and soft tissue attenuation/
production
and MEN 1. signal
Thymolipoma
• Rare benign thymic neoplasm
• Male=female; wide age range (28 years)
• Asymptomatic patients: 50%
 Symptoms with large tumors

Germ Cell Neoplasms
• Most common in the gonad
• Extragonadal germ cell neoplasms;
midline locations, most commonly the
mediastinum
• Postulated origin in multipotential Figure 23
primitive germ cells “misplaced” during
embryogenenesis Mature
• Cell types: teratoma.
Multilocular
 Teratoma (mature, immature cystic tumor
[immature neuroectoderm], with lipid-rich
“malignant” [mixed malignant germ cyst content.
cell neoplasm])
 Seminoma
 Nonseminomatous germ cell
neoplasms
Mature Teratoma
• 60%–75% of mediastinal germ cell Mature Teratoma: Imaging Features
neoplasms
[Figure 24]
• Males = females
• Unilateral anterior mediastinal mass
• Children and young adults (<40 years)
• Spherical, lobular contours, well-defined
• Often asymptomatic
• Multilocular cystic – 85%
• Symptoms of compression or rupture
• Attenuation: fluid 89%, fat 76%, Ca++
Mature Teratoma: Pathologic Features 53%
 Fat-fluid level 11%
[Figures 22 & 23]
 ST/FL/FAT/Ca++ 39%
• More than one embryonic germ cell layer
 ST/FL/FAT 24%
 Ectoderm: skin, dermal appendages
 ST/FL 15%
 Mesoderm: bone, cartilage, muscle
 Endoderm: GI, respiratory, tissue,
mucus glands Figure 24
• Spherical, encapsulated, lobular borders
• Multilocular or unilocular cystic mass Mature
teratoma.
 Oily, sebaceous, gelatinous material Unilateral,
(lipid) anterior
 Focal solid areas: hair, teeth, bone mediastinal,
multilocular
cystic mass
with intrinsic
fluid, soft
tissue, fat,
and calcium.
Figure 22 Mature Teratoma: Therapy/Prognosis

• Complete excision is curative
Mature
teratoma.
• Excellent prognosis
Cystic  Near 100% 5-year survival
neoplasm
with Seminoma
ectodermal, • 40% of malignant germ cell neoplasms of
mesodermal, a single histology
and
endodermal • Caucasian males, 3rd to 4th decades
components. • Most patients are symptomatic
• Round cells with sharp borders, clear
cytoplasm, fibrous bands, lymphocytes,
plasma cells, noncaseating epithelioid
granulomas
• Homogeneous soft tissue mass
• Radiation therapy/Cisplatin-based
chemotherapy
 60%–80% long-term survival

Seminoma: Imaging Features [Figure 25] Neurogenic Neoplasms [Figure 27]
• Anterior mediastinal mass (bilateral • 20% of primary mediastinal neoplasms
growth) (35% in children)
 Large, bulky, well-defined, lobulated, • 70%–80% benign
locally invasive • Peripheral nerves
• CT:  Schwannoma
 Homogeneous soft tissue mass  Neurofibroma
 Mimics nodal coalescence  Malignant peripheral
 Slight homogeneous contrast  Nerve sheath tumor
enhancement • Sympathetic ganglia
 Rarely necrosis/cystic change (8%)  Ganglioneuroma
Ganglioneuroblastoma
Figure 25  Neuroblastoma
Seminoma.
Diffuse
homogeneous
anterior Figure 27
mediastinal
mass with Neurogenic
mass effect. neoplasms
may arise from
peripheral
nerves or
Non-Seminomatous Malignant Germ Cell sympathetic
Neoplasms [Figure 26] ganglia.
• Yolk sack (endodermal sinus) tumor
• Embryonal carcinoma
• Choriocarcinoma
• Mixed germ cell neoplasm Schwannoma/Neurofibroma [Figure 28]
• Males, 90% symptomatic • Schwannoma – most common mediastinal
 Klinefelter syndrome (20%); neurogenic neoplasm
hematologic malignancy  Spherical, encapsulated
• Serology  Cellular and less cellular areas (Antoni
 Alpha-fetoprotein (EST, EC) A/B)
 ß-human chorionic gonadotropin – ß • Neurofibroma – second most common
HCG (choriocarcinoma) mediastinal neurogenic neoplasm
 LDH (60%) tumor burden  Spherical/fusiform, unencapsulated
• Large, unencapsulated • Calcification, cystic change, hemorrhage
• Hemorrhage, necrosis, “cyst” formation • Young adults; third and fourth decade
• Cisplatin-based chemotherapy, excision of • Most (65%) asymptomatic
residual tumor • Symptoms and signs of compression
Figure 26
Non-
seminomatous
malignant germ
cell neoplasm.
Large locally
invasive
heterogeneous
anterior
mediastinal
mass with Figure 28
central
necrosis. Schwannoma.
Heterogeneous
spherical mass.
Non-Seminomatous Germ Cell
Neoplasms: Imaging Features
• Large, well- or poorly-defined anterior
mediastinal mass
 Extends to both sides of midline
• Heterogeneous
 Large areas of central low attenuation
 Frond-like peripheral soft tissue
• Loss of tissue planes
 Local invasion, lymphadenopathy

Schwannoma/Neurofibroma: Imaging Neurofibromatosis (NF1)
Features [Figures 29 & 30] • Multiple neoplasms (including
• Spherical, smooth/lobular, well-defined ganglioneuroma)
paravertebral mass • Plexiform neurofibroma
• Osseous findings (50%); pressure • Vagus nerve, sympathetic chain, phrenic
erosion/deformity of ribs or vertebrae; nerve
expanded neuroforamen • Diffuse enlargement of peripheral nerve
• Homogeneous/heterogeneous; • Multiple masses along a nerve
 Heterogeneous enhancement; Ca++ in
10% Ganglioneuroma [Figure 31]
 Intraspinal growth – 10% • Children, adolescents, young adults
• MR Imaging – rule out spinal involvement  Asymptomatic patients
 T1 – Low-to-intermediate signal • De novo; maturation of neuroblastoma
 T2 – Foci of high signal • Benign paravertebral neoplasm
• Mature ganglion cells, Schwann cells,
nerve fibers
• Encapsulated, elongate mass
 Gray/yellow with lobular surface
Schwannoma. Unilateral paravertebral spherical mass

Ganglioneuroma.
with benign pressure erosion on posterior third rib.
Elongate
paravertebral
mass.
Ganglioneuroma: Imaging Features

[Figures 32 & 33]
Figure 30 A & B • Well-defined, oblong paravertebral mass
Schwannoma. Neuroforaminal and intraspinal growth.
• Osseous erosion/displacement
• Homogeneous or heterogeneous
 Calcification in 25%
• MR: Homogeneous intermediate signal on
T1/T2
Malignant Peripheral Nerve Sheath  Rule out intraspinal growth
Tumor
• Most frequent in the paravertebral region
• Rare among neurogenic neoplasms
• Large (>5 cm) spherical mass
 Central low attenuation – necrosis
 Calcification
 May exhibit local invasion Figure 32
Ganglioneuroma.
Peripheral Nerve Neoplasms: Therapy Elongate
and Prognosis paravertebral
• Excision mass with benign
pressure erosion
• Schwannoma/neurofibroma
on right posterior
 Excellent prognosis fifth rib.
• Malignant peripheral nerve sheath tumor
 Solitary – 75% 5-year survival
 Neurofibromatosis – 30% 5-year
survival

Sympathetic Ganglia Tumors
• Ganglioneuroma
 Excision is curative
• Ganglioneuroblastoma
 5-year survival near 90%
Figure 33
• Neuroblastoma
Ganglioneuroma.  5-year survival – 30%
Elongate  More favorable course with: age <2
paravertebral
mass with benign
years, mediastinal
pressure erosion  Spontaneous maturation to
on right posterior ganglioneuroma
fifth rib.
Paraganglioma
• Middle mediastinum: AP paraganglia
 Paravertebral: Aortico sympathetic
paraganglia
 Heart
Ganglioneuroblastoma/Neuroblastoma
• Adults (average age 30–40 years)
• Infants and young children
 Males > females; 2:1
• Asymptomatic; chest wall pain, paraplegia,
 Asymptomatic; excess catecholamines
Horner syndrome, diarrhea, hemothorax
• Well-defined spherical mass
• Elevation of urine catecholamines
 Homogeneous/heterogeneous
 Elevation of urine/serum VMA
• Marked contrast enhancement
(screening)
 90% uptake of I-131 or I-123 MIBG
• Neuroblastoma
 50% <2 years Thoracic Meningocele
 90% <5 years • Intrathoracic extrusion of meninges and
 May be congenital their fluid content
• Associated with neurofibromatosis in 75%
Ganglioneuroblastoma/Neuroblastoma
of cases
Pathologic Features • Well-defined spherical paravertebral mass
• Adrenal – most common location • Enlarged neuroforamen, pressure erosion,
 Paravertebral – second most common sclerosis
location • Homogeneous fluid attenuation/signal
• Ganglioneuroblastoma: neuroblasts and
ganglion cells Primary Neoplasia – Pearls
 Well/poorly-differentiated • Benign
• Neuroblastoma: neuroblasts, Homer-  Focal, unilateral mass
Wright pseudorosettes  No lymphadenopathy
 Well/poorly-differentiated  No local invasion
• Malignant
Neuroblastoma: Imaging Features  Focal/diffuse, unilateral/bilateral mass
[Figure 34]  Lymphadenopathy
• Well-defined large elongated paravertebral  Local invasion
mass
• Radiographic evidence of Ca++ in 10% Bronchogenic Cyst [Figure 35]
• Osseous erosion • Most common congenital cyst of the
• Rule out intraspinal growth mediastinum
• Local soft tissue invasion • Abnormal ventral foregut bud
• Failure to induce mesenchymal
development to lung parenchyma
• Mediastinum (85%), pericardium,
diaphragm, pleura, lung
Bronchogenic Cyst: Clinical Features

• Rare in infants, infrequent in children
• Young adults
• Asymptomatic – incidental finding
• Symptomatic – chest pain, mass effect,
Figure 34 A & B
obstruction, infection
Neuroblastoma. Unilateral calcified paravertebral mass • Excision, observation, drainage, sterile
with intraspinal extension in a neonate. alcohol ablation

Bronchogenic Cyst: Imaging Features
[Figures 38 & 39]
• Well-defined spherical middle-posterior
mediastinal mass
• Near trachea, carina, stem bronchi
• CT:
Figure 35
 Thin smooth wall (enhancement)
Bronchogenic  Water (40%) or soft tissue (43%)
cyst. Typical attenuation
subcarinal  Homogeneous/heterogeneous, non-
location.
enhancing content
• MR:
 T1 – variable (slightly hyperintense to
muscle)
 T2 – isointense or hyperintense to CSF
• Thin-walled pulmonary cyst; air, fluid, air-
Bronchogenic Cyst: Pathologic Features fluid level
[Figures 36 & 37]
• Respiratory epithelium
• Wall: Bronchial glands, cartilage, smooth
muscle
• Closed foregut connection
• Spherical, ovoid, unilocular
• Thin wall
• Fluid variable: clear, turbid, hemorrhagic,
serous, viscous
Figure 38 A & B
Bronchogenic cyst. Subcarinal spherical mass with
extension to the right and mass effect on bronchus
intermedius.
Figure 36
Bronchogenic
cyst.
Lined by
respiratory
epithelium
with cartilage
Figure 39 A & B
and smooth
muscle in Bronchogenic cyst. Spherical subcarinal mass with
wall. water or soft tissue attenuation.
Other Congenital Cysts

• Foregut cysts
• Esophageal – within esophageal wall;
ectopic gastric mucosa
• Neuroenteric – associated spinal anomaly
• Pericardial – cardiophrenic angle,
imperceptible wall, fluid attenuation;
asymptomatic patients
Figure 37
Bronchogenic Thymic Cyst [Figures 40 & 41]

cyst. Thin- • Uncommon (3% of mediastinal masses)
walled ovoid • Acquired versus congenital
unilocular • Children/young adults
cyst.
• Association with neoplasia, AIDS
• Diffuse infiltrative lymphocytosis
syndrome (DILS)
• Epithelial lining and thymus in cyst wall
• Multilocular/unilocular
• Rule out cystic neoplasm

Mediastinal Goiter [Figure 42]
• 20% of cervical goiters
• Asymptomatic females: incidental finding
 May produce symptoms by mass effect
• Adenomatous goiter; rarely malignancy or
thyroiditis
• Fibrous capsule; nodules composed of
thyroid follicles
Figure 40
• Hemorrhage, calcification, cystic change
Thymic cyst.
Multilocular
cyst.
Figure 41
Thymic cyst. Figure 42 A & B

Multilocular Mediastinal goiter. Thyroid follicles with iodine content
anterior (left), well-defined lobular encapsulated mass (right).
mediastinal
cyst with
enhancing
tissue septa.
Mediastinal Goiter: Imaging Features
[Figures 43 & 44]
• Unilateral anterior mediastinal mass
Mediastinal Cysts – Pearls (80%)
• Focal, spherical, or ovoid  Other compartments also affected,
• Unilocular (multilocular thymic) R>L
• Thin-walled • Well-defined lobular borders
• No mural nodules • Continuity with cervical thyroid
• No lymphadenopathy • Calcification – punctate, coarse,
• Foregut cysts along foregut-derived curvilinear
structures • Cystic change
• Signal drop on chemical shift MRI • High attenuation
 Intense, sustained contrast
Thymic Hyperplasia enhancement
• Lymphoid hyperplasia (lymphofollicular/
autoimmune thymitis) – secondary
follicles with germinal centers; may not
produce thymus enlargement
• Myasthenia gravis, hyperthyroidism,
lupus, scleroderma, rheumatoid arthritis, Figure 43
cirrhosis
• True hyperplasia – global increase in the Mediastinal
goiter. Large
size and weight of the thymus calcified
• Rebound hyperplasia – following unilateral
chemotherapy (2 weeks–14 months), mass with
steroids or severe insult extension into
the neck and
• Anterior mediastinal widening
mass effect on
• Homogeneous soft tissue on CT suprasternal
• Maximal thickness trachea.
 Under 20 years – 1.8 cm
 Over 20 years – 1.3 cm
• Follicular thymic hyperplasia – normal or
mildly enlarged thymus
• Signal drop on chemical shift MRI
Figure 44 Figure 45
A&B
Lymphangioma.
Mediastinal Interconnecting
goiter. endothelial
Continuity lined vascular
between channels
cervical and containing
mediastinal lymphatic fluid.
components,
high
attenuation
and
calcification.
Parathyroid Adenoma
• Ectopic parathyroid glands: superior pole
of thymus (39%), mediastinum (2%), Figure 46
intrathyroid (0.2%–3.5%)
• Primary hyperparathyroidism postsurgical Lymphangioma.
parathyroidectomy Multilocular
cystic
• MEN I appearance
• Imaging: due to
 Tc99m/Tl201 traction imaging, distention and
T123/Tl201 Tc99m – Sestamibi enlargement
(mitochondria) of vascular
channels.
 Single radionuclide/dual radionuclide
• CT/MRI correlation of mediastinal uptake
Glandular Enlargement – Pearls

• Anatomically related to normal gland Lymphangioma: Imaging Features
• Continuity with normal gland [Figures 47 & 48]
• Morphology and function similar to that of • Anterosuperior mediastinum; other
normal gland compartments affected
• Cervical/axillary/chest wall mass;
Lymphangioma mediastinal extension
• Benign mesenchymal mediastinal tumor • Spherical, lobular, well-defined borders
• Proliferation of lymphatic vessels without • Circumscribed mass/infiltrative mass
communication with lymphatic tree • Multilocular, cystic, heterogeneous
• Developmental versus neoplasm versus  Solid components, tissue septa
hamartoma
• Asymptomatic/symptoms of compression
• Mediastinal extension of cystic hygroma
(10%), soft palpable mass; 90%
diagnosed in infancy
• Mediastinal mass in asymptomatic child/
adult
Lymphangioma: Pathologic Features

[Figures 45 & 46]
• Spaces of variable size lined by
endothelial cells
• Soft, cystic mass
Figure 47 A & B
• Cystic hygroma – large vascular spaces
• Cavernous lymphangioma – small Lymphangioma. Multilocular cystic mediastinal mass
with extension into the right axilla.
vascular spaces
Vascular Lesion – Aneurysm
• Abnormal mediastinal contour contiguous
with vascular structures
• Saccular aneurysms may resemble other
primary mediastinal masses
• Curvilinear peripheral calcification
• Contrast enhancement
• Continuity with vascular lumen
Figure 48 A & B
Vascular Lesion – Varices
Lymphangioma. Infiltrative (left) or localized (right) • Esophageal/paraesophageal
multilocular cystic mediastinal mass.
• Severe liver disease and portal
hypertension; left gastric – portosystemic
collaterals
Hemangioma [Figures 49 & 50] • Visible on radiography in 10%
• Rare vascular mediastinal tumor • Middle-posterior-paravertebral cluster
 Neoplasm versus developmental of serpiginous vessels with intense
• Young patients; 75% <35 years old enhancement
• Asymptomatic; 1/3–1/2 with symptoms of
compression Vascular Lesions – Pearls
 Rendu-Osler-Weber syndrome • Focal versus infiltrative
• Communicating vascular spaces • Lymphatic
 Endothelial lining, organized thrombi,  Multilocular cystic
Ca++, phleboliths  Extramediastinal involvement
• Anterior mediastinal mass (also in other • Blood vessels
compartments)  Intense, heterogeneous/serpiginous
• Spherical, well-defined, Ca++ 28%, enhancement
punctate, phleboliths Pleboliths in hemangiomas
• Heterogeneous intense enhancement • Aneurysms
 Focal vascular enlargement
Herniations – Hiatus Hernia [Figure 51]

• Gastric herniation through enlarged
esophageal hiatus
• Increased intra-abdominal pressure/
Increased prevalence with increasing age
• Asymptomatic; reflux/bleeding
• Retrocardiac mass, homogeneous, air-
filled, air-fluid
• Identification of abdominal contents in
hernia sac
Figure 49
Hemangioma. Anterior mediastinal mass with intrinsic Figure 51

phleboliths.
Hiatus hernia.
Herniation of
abdominal
contents
through
esophageal
hiatus.
Figure 50
Hemangioma.
Intense Herniation – Morgagni
heterogeneous • Developmental defect in right
enhancement. anteromedial hemidiaphragm
• Asymptomatic/abdominal pain
• Right cardiophrenic angle mass
• Demonstration of internal fat (omentum),
bowel loops or abdominal organs (liver)

Herniations – Pearls Mediastinal Masses – Summary: Cystic
• Intrathoracic extension of abdominal • Thymoma (mural nodules)
contents • Bronchogenic cyst (unilocular, middle/
 Bowel posterior mediastinum - carinal)
 Omental fat • Pericardial cyst – right cardiophrenic
• Esophageal hiatus angle, water attenuation content,
• Morgagni hernias imperceptible wall
• Thymic cyst (multilocular, anterior
Miscellaneous – Achalasia mediastinum)
• Absent peristalsis with incomplete • Neurogenic neoplasm (paravertebral,
relaxation of lower esophageal sphincter heterogeneous, osseous erosion)
• Primary – deficiency of ganglion cells in  Meningocele (NF1, continuity with
myenteric plexus spinal canal, homogeneous water
• Secondary – (pseudo achalasia) Chagas attenuation/signal)
disease and primary or secondary • Mature teratoma (multilocular cystic
malignancy at the GE junction lesion with fat content)
• Esophageal dilatation with air-fluid level • Lymphoma (lymphadenopathy with cystic
 Esophageal displacement to the right, change)
mass effect on mediastinum (posterior • Lymphangioma (multilocular cysts with
trachea), pulmonary consolidation extrathoracic extension)
(aspiration) • Achalasia (enlarged esophagus with
internal debris, imperceptible gastric
Miscellaneous – Extramedullary bubble)
hematopoiesis • Mediastinal goiter (high attenuation,
• Extramedullary hematopoiesis continuity with thyroid)
• Compensatory formation of blood
elements outside osseous medulla Mediastinal Masses – Summary: FAT
• Hemolytic anemia • Lipomatosis (diffuse, no mass effect)
• Unilateral or bilateral paravertebral mass; • Lipoma
may exhibit internal fat attenuation • Thymolipoma (fat/soft tissue, connection
• Adjacent medullary expansion to thymus)
• Mature teratoma (cystic lesion with fat
Miscellaneous – Acute Mediastinitis content)
• Surgery, instrumentation with esophageal • Morgagni hernia (right cardiophrenic
perforation angle, continuous with abdominal fat)
• Ill patients with fever, chills, and chest
pain Mediastinal Masses – Summary: Intense
• Focal or diffuse mediastinal widening, Enhancement
pneumomediastinum, pleural effusion, • Mediastinal goiter (continuity with cervical
pneumothorax thyroid)
• Abscess, abnormal mediastinal air, • Hemangioma (phleboliths, follows
extraluminal ingested contrast, vascular enhancement)
obliteration of tissue planes • Castleman disease (enhancing
lymphadenopathy)
Mediastinal Masses – Summary: • Paraganglioma (hypertension,
Pathognomonic catecholamine production)
• Lateral thoracic meningocele • Aneurysm/varices (enhancement of
• Extramedullary hematopoiesis vascular lumen)
• Aneurysm
• Paraesophageal varices Mediastinal Masses – Summary: Non-
• Teratoma surgical Lesions
• Lipomatosis • Advanced lung cancer
• Congenital cyst (bronchogenic, • Metastatic lymphadenopathy
pericardial) • Lymphoma
• Mediastinal goiter • Malignant germ cell neoplasm
• Mediastinal fibrosis
• Castleman disease
• Paraesophageal varices
• Morgagni hernia (if asymptomatic)

Mediastinal Masses – Summary:
Surgical Lesions
• Thymoma/thymolipoma
• Thymic carcinoma/carcinoid (if resectable)
• Mature teratoma
• Neurogenic neoplasm
• Congenital cyst (if symptomatic)
• Mediastinal goiter (if airway compromise)
• Lymphangioma/hemangioma
• Aneurysm (if large, symptomatic, or
complicated)
Approach to Mediastinal Masses

• Clinical
 Demographics (age, gender)/
symptoms
• Radiography
 Mediastinal compartment
 Diffuse mediastinal enlargement
versus focal mass
 Contours/associated findings
• Cross-sectional imaging
 Specific location/relationship to normal
structures
 Morphology/attenuation-signal/
associated findings
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19. Strollo DC, Rosado-de-Christenson ML. Primary mediastinal malignant germ cell neoplasms: imaging
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24. Rossi SE, McAdams HP, Rosado-de-Christenson ML, Franks TJ, Galvin JR. Fibrosing mediastinitis.
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45. Fraser RS, Müller NL, Colman N, Paré PD. The diaphragm. In: Fraser RS, Müller NL, Colman N, Paré
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Chest Seminar 2: Where is the Lesion?
Melissa L. Rosado-de-Christenson, MD, FACR
Learning Objectives Solitary Lung Mass [Figure 3]
• To review the radiographic features of • Lung cancer
thoracic radiologic abnormalities based on  Size/frequency
location  Stage ?
• To enumerate the radiologic • Carcinoid
characteristics that allow lesion  Borders/associated bronchus
localization and the formulation of a • Solitary metastasis
focused differential diagnosis  Lower lobe location/shape
• Hamartoma/Infection
Case 1: A 38-year-Old woman with  Borders
cough [Figures 1 & 2]
• Location
• Differential diagnosis
• Next best study
• Diagnosis:
Figure 3
Solitary Lung Mass

• Young, relatively asymptomatic woman
• Mass with well-defined lobular borders
Figure 1
• Lower lobe location
• Abutting bronchus
Case 2: A 16-year-Old girl with cough

[Figures 4 to 6]
• Location
• Next best study
• Diagnosis:
Figure 4
Figure 2
Chest Radiology 141 Chest Seminar 2: Where is the Lesion

Figure 7
Figure 5
Figure 6
Figure 8
Anterior Mediastinal Mass

• Young girl, relatively asymptomatic
• Well-defined, unilateral mass with
peripheral calcification and lobular borders
• No lymphadenopathy
• Central water attenuation
• Heterogeneous mural nodule
Anterior Mediastinal Mass

• Mature teratoma
 Fluid/fat/Ca++
• Thymic cyst
 Fluid/Ca++ but mural nodule
• Lymphoma
 Correct age group… but no
lymphadenopathy Figure 9
• Thymoma
 Fluid, calcium, mural nodule but fat
attenuation
Case 3: A 58-year-Old Man with chest

pain and hemoptysis
• Location
• Next best study Lung/Chest Wall Mass with Cavitation
• Diagnosis: • Bronchogenic carcinoma
 Chest wall invasion
Lung Mass with Cavitation and Chest  Stage?
Wall Involvement [Figures 7 to 9] • Infection
• Symptomatic older man  Actinomycosis, tuberculosis, fungus
• Chest wall involvement (rib destruction) • Primary chest wall tumor/metastasis –
• Upper lobe location rarely produces cavitation
• Cavitation; thick nodular cavity wall • Other
Chest Seminar 2: Where is the Lesion 142 Chest Radiology

Case 4: Asymptomatic 40-year-Old Man;
Preoperative radiograph [Figures 10 to 13]
• Location
• Next best study
• Diagnosis:
Figure 13
Multifocal Pleural Nodules

• Asymptomatic patient
Figure 10
• No known malignancy
• Well-defined peripheral pleural nodules
• Associated findings - abdominal
abnormalities?
Multifocal Pleural Nodules

• Splenosis
 Where is the spleen?
• Pleural metastases – may be unilateral
• Malignant pleural mesothelioma –
typically with circumferential nodular
pleural thickening
• Other
Splenosis
• Auto-transplantation of splenic tissue
following splenic rupture
• Most common manifestation: Multiple
Figure 11 peritoneal nodules
• Thoracic splenosis:
 Splenic rupture with diaphragmatic
disruption
 Multiple pleural-based nodules
 May be missed on radiography
 99mTC-tagged heated RBC
scintigraphy
 Liver-spleen scan
Case 5: A 34-year-Old Man with left

chest pain for many years [Figures 14 & 15]
• Location
• Next best study
• Diagnosis:
Figure 12
Figure 14
Chest Radiology 143 Chest Seminar 2: Where is the Lesion

Figure 14
Multifocal Chest Wall and Mediastinal

Masses
• Chronic minimal symptoms
• Is involvement unilateral or bilateral?
• Benign pressure erosion
• Pulmonary involvement
• Other chest wall/mediastinal involvement
Multifocal Chest Wall and Mediastinal

Masses [Figure 14]
• Neurofibromatosis
 Malignant potential
• Vascular lesions
 Arteriovenous malformations
 Collateral vessels
• Metastases
• Other
Figure 14
Chest Seminar 2: Where is the Lesion 144 Chest Radiology

Pulmonary Infections
Rosita M. Shah, MD
Objectives
• Illustrate the usual imaging patterns of
typical and emerging pulmonary infections
and discuss the responsible pathology
• Discuss epidemiologic trends in Figure 1
pulmonary infections Novel H1N1
swine
Pneumonia: Impact influenza.
• Most common cause of death from A 45-year-
infection old woman
with asthma.
• Most common cause of death Chest x-ray
 Human immunodeficiency virus (HIV) demonstrates
 Other immune-suppressed diffuse dense
 Children <5 (worldwide) alveolar
• Second most common reason for hospital consolidation.
admission after childbirth
Respiratory pathogens Timeline of Novel H1N1 Epidemic

• Typical bacteria and mycobacteria • 2009
responsible for most deaths  April 14 Center for Disease Control
• Emerging infections and changing (CDC) identifies H1N1 in first US
epidemiology patient
 Drug resistance  April 17 second infection documented
 Immune-suppressed hosts 100 miles away
 Zoonoses  April 21 CDC alerts physicians to novel
• Zoonotic infections pose pandemic risk H1N1
 Severe acute respiratory syndrome  April 24 complete genome becomes
(SARS) available
 Influenza A/swine flu (H1N1)  April 25 World Health Organization
(WHO) public health emergency
Progressive pandemic risk: lessons  June 11 global pandemic
from Three viral zoonoses 17,000 deaths, 0.02%
• Hantavirus >90% hospitalizations <65 years
 Bunyavirus – rodent pathogen old
 No human-human transmission  August 10 end of pandemic
 Isolated human infection
 Controlled with removal of animal H1N1 [Figure 2]
source • Mammalian influenza A derived from
• SARS avian influenza (normal reservoir)
 Coronavirus – small mammal  Human
pathogen  Swine
 Effective human-human transmission  Equine
 Rapid identification, removal of • Occasional human infection with non-
animal source and patient quarantine human strain
prevented pandemic • Host tropism prevents human-human
transmission
H1N1 [Figure 1]  Altered by recombination
• Triple recombination of avian, human, and  Antigenic drift/shift
swine influenza in infected pig • Influenza strain determined by two
• Effective human-human transmission surface glycoproteins
• Fourth pandemic in recorded history  HA hemagglutinin
• 0.02% mortality compared with Binding/entry host cells
 0.2% mortality 1918 Spanish influenza  NA neuraminidase
 0.1% mortality seasonal influenza Budding
 60% mortality H5N1 avian influenza • Genomic changes result in new strains
 Antigenic drift – minor
 Antigenic shift – major
Chest Radiology Pulmonary Infections

145
Influenza A [Figures 4 & 5]
Figure 4
Influenza
pneumonia/
bronchiolitis
in a 33-year-
Figure 2 old patient
with chronic
myelogenous
leukemia,
24 months
status post
allogeneic
bone marrow
Pathogenicity of Respiratory Virus trans-
plantation.
• Determined by Imaging
 Concentration in respiratory secretions features consist of centrilobular nodules, ground-glass
 Affinity for, and ability to, replicate in opacity and peribronchial infiltration.
lower respiratory tract epithelium
 Greater involvement of alveolar
epithelium associated with DAD and
ARDS presentation
• Pathogenicity of H1N1
 Intermediate severity
 Between seasonal influenza and
H5N1(avian influenza)
Pathology of viral pneumonia [Figure 3]

• Epithelial cell infection
 Necrosis bronchial epithelium and type
1 alveolar pneumocytes
 Proliferation type 2 pneumocytes
• Mononuclear cell infiltration
 Interstitium Figure 5 A & B
 Bronchiolar lumen
 Centrilobular acini Influenza A in a 49-year-old patient with end stage
renal disease. Axial and coronal CT demonstrate
• Resulting centrilobular ground glass opacity. Centrilobular
 Interstitial pneumonia nodules in this case are larger and more indistinct.
 Bronchiolitis
 Diffuse alveolar damage
 Alveolar hemorrhage
Other viral bronchiolitides [Figure 6]
• Respiratory syncytial virus (RSV)
 25% hospitalizations <5 years old
 80% hospitalized patients <6 months
Figure 3 old
Pathology
• Human metapneumovirus
of viral • Rhinovirus
pneumonia. • Para-influenza/influenza
• Adenovirus
Figure 6
Imaging of seasonal influenza and Respiratory

other respiratory viruses producing syncitial virus
in a 12-week-
bronchiolitis old premature
• Centri lobular nodule (CLN) – hallmark of infant. Chest
bronchiolitis x-ray reveals
• Increasing inflammation, edema central
peribronchial
and hemorrhage involving adjacent thickening
centrilobular acini associated with larger and right
and more indistinct CLN/peribronchial upper lobe
nodules atelectasis.
Pulmonary Infections Chest Radiology

146
Human metapneumovirus [Figure 11]
Figure 7
Manifestations
of airway
disease
secondary to
viral infection.
Swyer-James Syndrome [Figures 8 & 9] Figure 11 A & B

Human metapneumovirus in 42-year-old patient with
multiple myeloma. Axial CT images demonstrate
extensive peribronchovascular ground glass
opacification and consolidation.
Varicella Pneumonia [Figure 12]

• Complication of adult chickenpox
• Acinar opacities
 5–10mm nodules
 Coalescent
Figure 8 A & B  Patchy GGO
Swyer-James syndrome following childhood viral • May heal with miliary calcification
pneumonia, with long-standing left lung bronchiolitis
obliterans and associated bronchiectasis. Chest X-ray
and coronal CT reconstruction demonstrate reduced
left lung volume and advanced bronchiectasis. Figure 12
Varicella
Figure 9 pneumonia
in patient
Bronchiolitis presenting to
obliterans and emergency
organizing room with
pneumonia rash and
diagnosis by shortness
lung biopsy in a of breath.
78-year-old man Chest X-ray
with progressive demonstrates
dyspnea after a a prominent
respiratory viral acinar
illness. Coronal nodular
CT demonstrates pattern.
peribronchial
consolidation.
Cytomegalovirus Pneumonia [Figure 13]
• Most common viral pneumonia in
Adenovirus [Figure 10]
suppressed patients
• Frequent alveolar hemorrhage may
 HIV CD4<100
contribute to consolidative component
 Bone, lung or solid organ treatment
• In lung transplant pts, associated with
1–6 months
primary graft failure, accelerated rejection
Figure 10
Adenovirus
pneumonia in a
48-year-old man
following left
lung transplant.
Coronal CT image
demonstrates
left lower lobe
peribronchial Figure 13
consolidation
and surrounding Cytomeglovirus pneumonia 6 months post renal
ground glass transplant. CT reveals widespread centrilobular
opacification. ground-glass opacification.

147
Viral and bacterial Co-infection Centrilobular nodules
• Secondary bacterial pneumonias • The centrilobular nodule is a major finding
confirmed in 25% of fatal viral pneumonia in bronchiolitis and bronchopneumonia
 Mucosal disruption • Centrilobular = distribution
 Inflammatory cycle  Involvement of core structures of the
• Up to 1/3 of community-acquired secondary pulmonary lobule
pneumonia (CAP) occur with concurrent • Centrilobular nodules may manifest as
viral pneumonia  ‘Tree-in-bud’ opacities
 Acinar nodules
Health Care-acquired Pneumonia  Peribronchial nodules
[Figure 14]
• HCAP – distinct form of pneumonia ATS/ Bronchiolitis and bronchopneumonia
IDSA 2005 represent a continuum of findings
• HC = health care • Greater degrees of airspace involvement
• Epidemiologic features HAP > CAP manifest as progressively indistinct
 Pathogen: methicillin-resistant centrilobular/peribronchial nodules
Staphylococcus aureus (MRSA),
Pseudomonas aeruginosa, other gram- Streptococcus pneumoniae [Figure 16]
negative) • Most common CAP
 Susceptiblity • Most common CAP resulting in
 Mortality hospitalization
• Most common cause of lobar pattern
• Common cause of HAP in patients
admitted <3 days
Figure 14 • <50% present as focal lobar pattern; Can
be multifocal or bronchopneumonic
 Noncavitary
Health Care-acquired Pneumonia  Preserved volume
• Nosocomial pneumonia is most common  Homogeneous
COD from health-care related infection  Nonsegmental – ‘round’
• Rising incidence attributed to use of broad
spectrum antibiotics
• Antibiotic therapy replaces normal flora
with gram negative organisms
Pathophysiology Figure 16
• 45% incidence of ‘normal’ micro-
aspiration Streptococcus
• Aspiration accounts for up to 15% of CAP pneumoniae
• Microaspiration producing
 Normal flora lobar pattern
consolidation
 Gram negative on chest x-ray.
• Inhalation Nonsegmental
 Viruses distribution can
 Mycoplasma produce ‘round’
or mass-like
 Legionella
opacities.
 Tuberculosis, fungi
• Vascular
 Co-infection
Pathology of bacterial pneumonia

[Figure 15]
Mycoplasma pneumoniae [Figure 17]
• Most common summer CAP
• Transmission via aerosolized secretions
• Acute cellular bronchiolitis
 + Bronchopneumonia
 + Interstitial infiltrates
• GGO
• CLN
Figure 15 A & B
• Air-trapping
Patterns of air-space filling in bacterial pneumonia. A =
lobar pattern, B = bronchopneumonia.

148
Pseudomonas aeruginosa
[Figures 19 & 20]
• Most common in ICU setting
• Frequent colonizer in chronic lung/airway
diagnosis
• Up to 80% mortality
 Greatest severity in bacteremic and
neutropenic patients
• Prominent alveolar hemorrhage
component
Figure 19
Figure 17 A & B P. aeruginosa

Mycoplasma pneumoniae in patient presenting with in a patient
dyspnea. CT images demonstrate ground-glass with cystic
opacity, centrilobular nodularity, and sublobular fibrosis.
opacification. Axial CT
demonstrates
nodular
Legionella opacities in the
• Epidemic outbreaks associated with lingula and left
lower lobe.
contaminated water sources
• Prominent extra-pulmonary
manifestations
 ‘Atypical pneumonia’ – GI, GU, CNS
• May produce lobar or bronchopneumonia
patterns
• Cavitation associated with immune- Figure 20 A & B
suppression
Necrotizing
bronchopneumonia
Klebsiella pneumoniae [Figure 18]
due to S. aureus in
a 66-year-old with
history of asthma
and diabetes. Axial
CT demonstrates
cavitary
peribronchial
consolidations.
Staphylococcus aureus
Figure 18 A, B & C • Most common HCAP
• Second most common HAP, VAP
Klebsiella
pneumoniae • Associated with IVDA history, HIV, post-
resulting in surgical or nursing home settings, and
progressive viral pneumonia (CAP)
necrotic
pneumonia (A and Prognosis of hospital acquired
B) with pulmonary
gangrene (C). pneumonia associated with duration
CT demonstrates of hospitalization prior to onset of
air-fluid level pneumonia
replacing right
• Early <3–5 days
upper lobe.
 Normal flora
• Late >5 days
 MRSA
 P. aeruginosa
 Enterobacteriaceae
 Acinetobacter spp.
 Stenotrophomonas maltophilia

149
Acinetobacter baumannii [Figure 21]

Late onset nosocomial pneumonia due to Aspiration pneumonia, culture positive for
Acinetobacter. Chest x-ray (A) and CT (B) demonstrate Staphylococcus aureus (A), complicated by acute
a multifocal cavitary pneumonia. respiratory distress syndrome 1 week later (B).
Nodules in acute airspace disease

Lemierre Syndrome [Figure 22] support infectious Diagnosis
• Head and neck thrombophlebitis resulting • Centrilobular nodules
in pneumonia • Mass-like consolidations
 Fusobacterium • Macro and micro interstitial nodules
 Streptococcus • Granulomatous infection
 MRSA  Mycobacterium tuberculosis
 Bacteroides  Non-tuberculous mycobacterial (NTB)
• Fulminant pneumonia  Fungi
 Actinomycosis
 Nocardia
 Some parasites
Tuberculosis [Figure 24]

• Tuberculosis (TB) resurgence
 Human immunodeficiency virus (HIV)
 Other immune-suppressed
• 1993 World Health Organization (WHO)
emergency
 Subsaharan Africa – epicentre HIVTB
Figure 22 A & B epidemic
Lemierre syndrome in a 20-year-old patient with • 2003 peak incidence
streptococcal pharyngitis. Left jugular vein thrombosis • More than 8 million new infections 2010
(arrow) confirmed on neck CT (A). Coronal CT  Multi-drug-resistant tuberculosis
(B) demonstrates widespread pneumonia due to (MDR-TB)
streptococcus. • 2/6 billion infected
• 10% cases industrialized countries
Nosocomial Pneumonia and Aspiration Figure 24

[Figure 23]
• Pneumonitis (Mendelson syndrome) Immune status.
 pH < 2.5, >0.3 ml/kg
 Biphasic inflammatory response
1–2 hours permeability edema
4–6 hours acute inflammation
 Followed by
Rapid clearing or DAD with 30% Tuberculosis
mortality if ARDS develops • Primary infection contained by cellular
immunity
 Two weeks post exposure
• Lymphatic and hematogenous
dissemination
 5% normal hosts and up to 40%
immune-suppressed hosts
 Classic primary and post-primary
patterns less common in suppressed
hosts

150
Primary infection [Figures 25 & 26] caseating Tuberculosis Granuloma
• Peribronchovascular, noncavitary [Figures 28 & 29]
consolidation
• Adenopathy
 Incidence decreases with age
 Necrosis more common in normal
hosts Figure 28
• Effusions
Caseating
 Sterile tuberculosis
granuloma.
Figure 29
Figure 25 A, B & C
Mycobacterium tuberculosis infection with primary
pattern in a 28-year-old immune-competent man.
At time of presentation, imaging reveals noncavitary
consolidation (A), mediastinal adenopathy (B), and Post-primary disease [Figures 30 to 32]
moderate pleural effusion (C).
• Delayed type 4 hypersensitivity reaction
• Caseous necrosis
• Tissue destruction
 Lung most common site
Figure 26  Apical distribution associated with
reduced lymphatic clearance and
Pott’s disease higher oxygen tension
(same as
previous Figure 30
patient).
Severe spinal Miliary
osteomyelitis tuberculosis
and in a 58-year-
paravertebral old patient
abscess with AIDS,
secondary to CD4 count
post-primary of 500. Axial
Mycobacterium thin-section
tuberculosis CT reveals
seen three innumerable
years after randomly
presentation. distributed
interstitail in
micronodules throughout both lungs.
Non-caseating Tuberculosis Granuloma

[Figure 27]
Figure 27
Figure 31 A & B
Non-
caseating Post-primary tuberculosis pattern with bronchogenic
tuberculosis spread in a 32-year-old woman presenting with cough
granuloma. and weakness. Extensive cavitary necrosis of the right
upper lobe (A) is associated with additional sites of
consolidation and centrilobular nodularity (B).

151
Figure 34
Non-classical
pattern of
mycobacterium
avium complex
in immune-
competent host.
High-resolution
computed
Figure 32 A & B tomography
Mycobacterium tuberculosis following immune demonstrates
reconstitution with anti-retroviral therapy. Anterior anteriorly
mediastinal contour abnormality on chest x-ray (A) distributed
with corresponding necrotic adenopathy on contrast- bronchiectasis and multifocal bronchiolitis.
enhanced CT (B). Left pleural effusion is also present.
Non-tuberculous mycobacteria
• Frequent colonizer, possible pathogen
• Pre-existing lung disease
 Chronic obstructive pulmonary disease
(COPD)
 Bronchiectasis
• Other infections
• Immune-suppression
• Ubiquitous distribution
• Endemic infection
• Biofilms
Non-tuberculous mycobacteria
[Figures 33 to 35]
• Should be considered in any case with
cavitary consolidation, chronic bronchiolitis Figure 35 A & B
and/or bronchiectasis Diffuse M. avium-intracellulare infection in a 39-year-
 Mimics mycobacterium tuberculosis old man with HIV, confirmed by abdominal lymph
(M.TB) and fungal infection node biopsy. Chest x-ray (A) and axial CT (B, C,
• Mycobacterium avium-intracellulare and D) demonstrate moderate left supra-aortic,
complex (MAC) retrocrurual and retroperitoneal adenopathy.
 Most common pulmonary pathogen
• Mycobacterium kansasii Mycobacterium abscessus [Figure 36]
 Most pathogenic
Figure 36 A & B
Mycobacterium abscessus in patient with esophageal
achalasia. Widespread bronchiolitis and multifocal
consolidation are demonstrated in CT. Arrow (B)
denotes fluid-filled esophageal lumen.
Figure 33 A & B
Classical pattern Mycobacterium avium-intracellulare

complex in a 79-year-old man with severe chronic
obstructive pulmonary disease. Chest x-ray (A) and CT
(B) demonstrate cavitary left upper lobe pneumonia
mimicking Mycobacterium tuberculosis infection.

152
Mycobacterium kansasii [Figure 37]
Figure 37
M. Kansasii
infection in a 30
year old man
with AIDS and
CD4 count of
20. Axial CT
reveals a right
upper lobe
cavitary nodular
consolidation
and surrounding
centrilobular
nodularity.
Changing epidemiology of fungal Figure 38 A & B

pneumonia Aspergillus fumigatus pneumonia in a 38-year-old
• Increasing immune-suppression patient with acute myelogenous leukemia. Initial
CT (A), with corresponding white blood cell count of
 ICU population 800, demonstrates a mass-like consolidation with
 Chronic infection surrounding ground-glass opacity. Follow-up CT 1
 Drug resistance month later, with corresponding white blood cell count
• Candida species most common of 2,100 demonstrates crescentic cavitation within the
fungal pathogens in ICU, solid-organ mass-like consolidation.
transplantation, and bone marrow
transplant (BMT)
• 2/3 invasive Aspergillus have
hematological diseases or BMT
• P. jiroveci, C. neoformans most common
fungal infections in HIV
White Blood Cells – necessary defense

against Tissue-invasive hyphael form
[Figures 38 &39]
Figure 39 A & B
• Aspergillus and candida become prevalent
Chronic necrotizing aspergillosis in a 44-year-old
>2 weeks neutropenia
receiving intermittent high dose steroids. Sequential
 Acute leukemia axial CT reveals enlarging irregular pulmonary
 Induction chemotherapy nodules.
 Graft versus host
• Chronic immune-suppression associated
with progressive invasion Chronic Granulomatous Disease
 Vascular [Figure 40]
 Airway • Phagocytic defect
 Soft tissue  Recurrent catalase + infections
including Staphylococcus aureus,
Nocardia, and Aspergillus
 Extensive granuloma formation
Figure 40 A & B
Aspergillus nidulans infection in a 30-year-old
patient with chronic granulomatous disease. CT (A)
demonstrates a necrotic right upper lobe mass with
mediastinitis (closed arrow), rib destruction (open
arrow), and left axillary extension (B).

153
Pneumocystis jiroveci [Figure 41]
• Opportunistic fungus
 Isolated in chronic lung disease
 Reduced incidence with prophylaxis/
highly active antiretroviral therapy
(HAART)
 Remains most common ‘opportunistic’
infection in HIV
 Increasing prevalence in non-HIV
Steroids, immune-suppressives
Figure 42 A, B & C
• Alveolar attachment associated with
capillary leak Fibrosing mediastinitis
secondary to
 GGO histoplasmosis in
• Chronicity associated with fibrosis/cysts a 20-year-old man
presenting with pulmonic
valvular mumur.
Open biopsy revealed
dense fibrosis, necrotic
granulomas, and positive fungal stains. CT (A) reveals
infiltrative mediastinal soft tissue mass encasing right
main pulmonary artery (arrow) and subcarinal nodal
calcification (B).
Figure 41 A & B
P. jiroveci infection in a 49-year-old woman 9 months

status post bone marrow transplantation for acute
lymphocytic leukemia. Axial (A) and coronal (B) CT
demonstrates geographic ground-glass opacity.
Endemic fungi [Figure 42 & 43]

• Histoplasmosis
• Coccidiomycosis
• Blastomycosis
• Primary infection usually asymptomatic Figure 43
• Nodular/cavitary consolidations and C. Immitis in a 29-year-old presenting with
adenopathy hemoptysis after travel. Chest x-ray reveals a left mid
• Extra-thoracic disease frequent lung cavity.
 Skin, musculoskeletal, central nervous
system (CNS)
• Disseminated disease associated with
immune-suppression, late pregnancy, age Fungal-like infections
 AIDS-defining • Actinomycosis
 Normal flora
 Associated with aspiration risk
• Nocardiosis
 Ubiquitous
 Associated with hematologic
malignancy, neutropenia, PAP
 Indolent pleuro-parenchymal infection
Mass-like consolidation
Cavitation
Chest wall/osseous involvement

154
Actinomycosis [Figures 44 & 45]
Figure 44 A & B
Actinomycosis infection in a 62-year-old man following Figure 46 A & B
bilateral lung transplantation. Chest X-ray reveals
a left pleural effusion. CT demonstrates bilateral E. multilocularis in a 48-year-old patient with
pulmonary nodules. left chest discomfort. Coronal and sagittal MRI
demonstrate a multilocular cystic mass.
Ascariasis lumbricoides/Strongyloides
stercoralis [Figure 47]
• Roundworm infections
• Complete lifecycle in human host
• Entry (small bowel or skin) – systemic
circulation – alveoli – trachea – small
bowel
Figure 45 A, B & C • Strongyloides – continuous auto-infection
results in hyperinfection syndrome (ARDS,
Actinomycosis in a hemorrhage)
20-year-old patient with
left chest wall pain. CT  HIV, steroids
(A) reveals a nectrotic left
lower lobe pneumonia.
Caudal CT images
demonstrate involvement
of the spleen (B) and left chest wall (C).
Parasitic Infection
• Pulmonary involvement due to
hypersensitivity or direct invasion
• Radiographic findings may overlap with
other infections
 Fleeting, patchy infiltrates
 Reticulonodular opacities
 Bronchopneumonia Figure 47 A & B
 Atelectasis Strongyloides hyperinfection in a 38-year-old woman
• Radiographic findings may be dominated 3 months post renal transplant, presenting with rash
by eosinophilic pneumonia and abdominal pain. Stool culture confirmed the
presence of Strongyloides. Coronal (A) and axial (B)
Echinococcus granulosus [Figure 46]
CT demonstrate extensive ground-glass opacity.
• Cestode/tapeworm
• Dog/wolf – definitive host
• Duodenum – portal venous system – liver Bacillus anthracis [Figure 48]
 45%–75% isolated liver involvement • Dormant endospores
 15%–35% pulmonary involvement  Livestock infection
• Three layers • Exotoxin production
 Pericyst – host inflammatory cells • Hemorrhagic mediastinitis
 Exocyst – acellular laminated • Edema
membrane
 Endocyst – fluid-filled germinal center Earls Radiology: 2001
containing daughter cysts

155
Figure 48 A, B & C
Bacillus anthracis producing pumonary lymphedema

(arrows in A) and hemorrhagic mediastinal adenopathy
(B). Bilateral pleural effusions are also present.
Always consider Clinical Setting
References
1. Blasi F. Atypical pathogens and respiratory tract infection. Eur Radiol. 2004;24:171–182.
2. Franquet T. Imaging of viral pneumonia. Radiology. 2011;260:18–39.
3. Herold CJ, Sailer JG. Community-acquired and nosocomial pneumonia. Eur Radiol. 2004;14:E2–E20.
4. Kanne JP, Godwin DJ, Franquet T, et al. Viral pneumonia after hematopoetic stem cell transplantation:
high-resolution CT findings. Journal Thorac Imaging. 2007;22:292–299.
5. Kim YJ, Boeckh M, Englund JA. Community respiratory virus infections in immuno-compromised patients:
hematopoietic stem cell and solid organ recipients and individiuals with HIV infection. Semin Respir Crit
Care Med. 2007;28:222-242.
6. Muller NL, Franquet T, Lee KS. Imaging of Pulmonary Infections. Lippincott Williams & Wilkins 2006.
7. Nambu A, Akitoshi S, Ozawa K. C. pnumoniae: comparison with findings of M. pneumoniae and S.
pneumoniae at thin section CT. 2006:238:330–338.

156
Uncommon Malignant Tumors of the Lung
Gerald F. Abbott, MD
Uncommon Malignant Tumors of the Neuroendocrine Cells and Tumors:
Lung: Electron microscopy
• Bronchial carcinoid (most common • Cytoplasmic neurosecretory granules
“uncommon”) • Central or eccentric dense core
• Adenoid cystic carcinoma (salivary gland • Thin lucent halo
tumors) • May contain biologically active peptides
• Mucoepidermoid carcinoma – (salivary
gland tumors) Neuroendocrine Markers:
• Carcinosarcoma (mixed tumors) Immunohistochemistry
• Pulmonary blastoma (mixed tumors) • Chromogranin
• Synaptophysin
Bronchial Adenoma: History Lesson • Neural cell adhesion molecules (NCAM)
• Term formerly referred to:
 Bronchial carcinoid Carcinoid: Relationship to Small Cell
 Adenoid cystic carcinoma Carcinoma
 Mucoepidermoid carcinoma • Similarities
• A misnomer  Neurosecretory granules
• These tumors are not benign  Rosette and trabecula formation
• Differences
Carcinoids  Fewer granules in small cell carcinoma
• Gastrointestinal tract (90%)  Carcinoid not associated with smoking
• Lung
• Thymus Tumors with neuroendocrine
• Biliary tract Morphology
• Ovarian teratomas A spectrum by light microscopy
Bronchial Carcinoid Low-grade: typical carcinoid

• Typical carcinoid Intermediate: atypical carcinoid
 Low-grade malignancy High-grade: small cell lung carcinoma
• Atypical carcinoid large cell neuroendocrine
 Moderate-grade malignancy carcinoma
Typical Carcinoid Neuroendocrine Tumors: World Health

• 0.6%–2.4% of all pulmonary neoplasms Organization criteria (1999)
• Low-grade malignancy • Typical carcinoid: <2 mitoses per 10 high
• Good prognosis power field (HPF)
 95% 5-year survival • Atypical carcinoid: 2–10 mitoses per 10
• Not associated with smoking HPF
• Large cell neuroendocrine carcinoma: 11
Typical Carcinoid: Demographics or more mitoses per 10 HPF (median 70)
• Male = female • Small cell carcinoma: 11 or more mitoses
• Wide age range; median age: 50 years per 10 HPF (median 80)
• Symptoms: cough, hemoptysis, dyspnea
Typical Carcinoid: Microscopy

• Uniform cells
• Forming nests, ribbons, rosettes,
trabeculae
• Stroma highly vascular
• May exhibit calcification or osseous
metaplasia
• Polygonal cells, pale cytoplasm, stippled
nuclear chromatin
• Rare mitoses
• Ultrastructure: neurosecretory granules
Chest Radiology 157 Uncommon Malignant Tumors

Atypical Carcinoid: Histopathologic Bronchial carcinoid: Central
criteria • Bronchiectasis
• Poor architectural organization • Mucoid impaction
• Cellular pleomorphism • Obstructive pneumonia
• Focal necrosis
• Increased mitotic activity Bronchial carcinoid: Peripheral
• Usually asymptomatic
Arrigoni J. Thorac Cardiovasc Surg. 1972.
• Late presentation
• Discovered incidentally
Atypical Carcinoid
• Morphology between typical carcinoid and
Bronchial Carcinoid: Radiographic
small cell carcinoma
Findings [Figures 2 & 3]
• Tend to be larger, more invasive,
• Central tumors in 80%
peripheral
• Lobar, segmental, subsegmental bronchi
• Age: decade older than typical
• Consolidation, atelectasis
• Symptoms: similar to typical
• Pleural effusion
• Imaging: similar to typical
Atypical Carcinoid
• 10% of bronchial carcinoid
• Peripheral
• Increased mitoses
• Aggressive behavior – early mets
• Osteoblastic bone metastases
• Pathology differential diagnosis: small cell
carcinoma
Bronchial Carcinoid: Gross Pathology

[Figure 1]
• Usually seen at bronchoscopy
• Soft, fleshy, endobronchial mass
• Sessile – may be pedunculated
• Often extend through wall
Figure 2
Bronchial carcinoid manifesting as a central well-

defined left perihilar mass.
Figure 1
Growth patterns of bronchial carcinoid tumors. Partially

endobronchial tumors (“iceberg” configuration) most
common.
Figure 3 A & B
Small endobronchial carcinoid tumor in distal left

mainstem bronchus.
Uncommon Malignant Tumors 158 Chest Radiology

Bronchial Carcinoid: CT Features
[Figures 4 to 6]
• Bronchial relationship in 83%
• Partially endobronchial
• Completely endobronchial
• Abutting a bronchus
• Sharply marginated, lobulated mass
• May enhance or demonstrate Ca++
• Atelectasis, consolidation, bronchiectasis,
mucoid impaction
• Lymphadenopathy
Precontrast Postcontrast
Figure 6 A & B
Bronchial carcinoid in a 34-year-old man with a

3-year history of cough and recurrent pneumonia.
Unenhanced CT (left image) demonstrates central
tumor and distal peripheral consolidation. Contrast-
enhanced CT (right image) shows diffuse contrast
enhancement.
Bronchial Gland Tumors

Figure 4 • Adenoid cystic carcinoma
Bronchial carcinoid. Partially endobronchial (“iceberg”)
• Mucoepidermoid carcinoma
tumor in left upper lobe. • Equivalent to salivary gland tumors of
same name
Adenoid Cystic Carcinoma [Figure 7]

• Synonym: cylindroma
• 80% of bronchial gland tumors
• 20%–35% of all tracheal tumors
• Second most common tracheal
malignancy (after squamous cell
carcinoma)
Figure 5
Bronchial carcinoid obstructing left upper lobe

Figure 7
bronchus with distal atelectasis, pneumonitis, and
associated left hilar lymphadenopathy. Adenoid cystic carcinoma partially occluding the
trachea and extending into the adjacent soft tissues of
the mediastinum.

Adenoid Cystic Carcinoma
• Guarded prognosis
• Common local recurrence
• Occasional metastases to regional nodes
• Rarely extrathoracic spread
Adenoid Cystic Carcinoma:

Demographics
• Male = female
• Wide age range (average 40–50 years)
• Symptomatic patients: cough, wheezing,
dyspnea, hemoptysis
Adenoid Cystic Carcinoma: Microscopy

• Mucin-containing cysts
• Varying in caliber
• Within larger tumor tubules
• Surrounds, invades nerves
• Encases vessels, infiltrates bronchi
• Few mitoses
Adenoid Cystic Carcinoma: Pathologists’

Pitfalls
• Misdiagnosis
 Adenocarcinoma
 Pleomorphic adenoma
 Small cell carcinoma
• Metastatic salivary gland tumor Figure 8 A & B
• Solid pattern on small biopsy Adenoid cystic carcinoma. Coronal (left image) and
sagittal (right image) surface-rendered CT images
Adenoid Cystic Carcinoma: Gross of the trachea demonstrate both nodular and
• Endobronchial mass circumferential deformity of the air-column in the
 Trachea and main bronchi lower trachea.
• Sessile, polypoid, annular growth
• Proximal and distal spread
• Extension into mediastinum
Mucoepidermoid Carcinoma [Figure 9]
Adenoid Cystic Carcinoma: Radiology
[Figure 8]
• Central: trachea and main bronchi
• Intraluminal nodule or mass
• Constriction of tracheal/bronchial lumen
• 10%–15% in lung periphery
• CT/MRI: length of involvement,
mediastinal involvement
Mucoepidermoid Carcinoma:
Demographics and Prognosis
• Male = female, wide age range
• Cough, fever, hemoptysis, pneumonia,
atelectasis
• Low-grade: excellent prognosis
• High-grade: better prognosis than
bronchogenic carcinoma Figure 9
Mucoepidermoid carcinoma arising in the right

mainstem bronchus at the origin of the right upper
lobe bronchus.

Mucoepidermoid Carcinoma: Microscopy
• Low-grade
 Mucinous cysts
 Solid collections of squamous cells
• High-grade
 Solid sheets of tumor
 Mitoses and necrosis
Mucoepidermoid Carcinoma: Gross

• Submucosal, smooth-surfaced
• Endobronchial, exophytic, polypoid
• High-grade may have ragged invasive
appearance
Mucoepidermoid Carcinoma: Radiologic

Findings [Figures 10 & 11]
• Solitary nodule or mass
• Most in main or lobar bronchi
• Few in trachea
• Distal effects
 Atelectasis, pneumonia
• Central lesions
• Atelectasis, pneumonia
Figure 11
Central mucoepidermoid carcinoma manifesting as

mild prominence of the superior aspect of the right
hilum with associated atelectasis of the right upper
lobe.
Mixed Tumors: Neoplasms with

malignant epithelial and mesenchymal
components
• Carcinosarcoma
• Pulmonary blastoma
Carcinosarcoma
• Rare (0.3% of all lung neoplasms)
• Middle-aged and elderly males
• Poor prognosis
• Aggressive: local invasion, widespread
metastases, rapid death
Carcinosarcoma: Microscopy
• Epithelial component
 Squamous cell carcinoma
Figure 10  Adenocarcinoma
 Undifferentiated carcinoma
Mucoepidermoid carcinoma manifesting as a solitary
pulmonary nodule on chest radiography. • Mesenchymal component
 Usually dominant
 Spindle cell (common)
 Chondrosarcoma
 Osteosarcoma
 Rhabdomyosarcoma

Carcinosarcoma: Gross Pulmonary Blastoma: Demographics
• Peripheral and Prognosis
 Large mass • Predominantly male gender
 Average diameter 6 cm • Biphasic age distribution: first and
 Frequent necrosis and hemorrhage seventh decades
• Central • Symptoms: cough, hemoptysis, dyspnea,
 Endobronchial growth chest pain
 May extend to adjacent parenchyma • Poor survival
 Tumor-distended bronchi may
resemble mucus plugs Pulmonary Blastoma: Microscopy
• Mixture:
Carcinosarcoma: Imaging [Figure 12]  Epithelial-lined tubules
• Peripheral  Primitive stroma
 Large • Resembles embryonal lung
 Well-circumscribed mass • Metastases: mesenchymal, epithelial, or
• Central mixed
 Atelectasis, pneumonia
 Tumor “mucus plugs” Pulmonary Blastoma: Gross
 Upper lobe predominance • Large mass
 Direct extension to pleura, chest wall, • Unencapsulated and soft
and mediastinum • Abundant central necrosis and
hemorrhage
Pulmonary Blastoma: Radiology

[Figure 13]
• Large peripheral mass
• Well-circumscribed
• May show pleural invasion
• May metastasize
Figure 13
Pulmonary
blastoma
manifesting
as a large
heterogeneous
mass in the
left lower lobe.
Figure 12
Carcinosarcoma. Contrast-enhanced CT demonstrates

a peripheral mass with irregular and lobulated borders
in the right upper lobe.
Endobronchial Tumors: Malignant

• Squamous cell carcinoma
Pulmonary Blastoma • Adenocarcinoma
• Primary lung tumor • Small cell carcinoma (rare)
• Mix of epithelial and mesenchymal • Carcinoid
components • Adenoid cystic carcinoma
• Both components blastomatous and • Mucoepidermoid carcinoma
immature • Carcinosarcoma
• Morphologic mimic of embryonal lung • Pulmonary blastoma
• ? A variant of carcinosarcoma • Sarcoma (10%)
• Endobronchial metastasis
• Lymphoid malignancies (non-Hodgkin
lymphoma > Hodgkin disease)

Benign Tumors of the Lung and Tumor-Like Lesions
Benign Tumors and Tumor-Like Lesions Hamartoma: Microscopic
• Hamartoma • Cartilage nests (lobules) in 95%
• Papilloma/papillomatosis • Surrounded by fibrous tissue
• Inflammatory pseudotumor • Mature fat cells
• Granuloma • Cleft-like invaginations of entrapped
respiratory epithelium
Hamartoma
• Albrecht, 1904 Hamartoma: Gross
• Tumor-like malformation • Solitary
• Tissues normal to location • 1–3 cm (rarely “giant”)
• In excess or disarray (disorganized) • Rounded, well-circumscribed, lobulated
• Adult, classic, and local hamartoma • Firm lesions, usually cartilaginous
• May see areas of fat
Hamartoma • Easily “shelled-out”
• Acquired lesion
• Disorganized growth of tissues normally Hamartoma: Radiographic
found in lung • Sharply defined, lobulated subpleural
• Benign neoplastic proliferation • Most <3 cm
• Probably derived from bronchial • Calcification on chest x-ray (10%–15%)
wall mesenchymal cell (“benign • Rarely see fat on chest x-ray
mesenchymoma”) • May enlarge on serial chest x-rays
• Up to 3–5 mm per year
Hamartoma
• Most common benign tumor of lung Hamartoma: Calcification
• 77% of benign lung tumors • Speckled or “popcorn” (10%–15%)
• 8% of solitary pulmonary nodules (SPN) • Popcorn less frequent than once thought
• 3% of all lung tumors • Diagnostic when present
 Nodular growths within lesion
Hamartoma: Evidence of Acquired  Protrude in different directions
Lesion
• Onset in adult life Hamartoma: CT
• Often adults with previously normal chest • Distinguishes fat and cartilage
x-ray • Most are 2.5 cm or less
• Almost never seen in infants • Smooth edge
• Histology: passive entrapment of • No fat/focal fat alone/fat with areas of
epithelium calcification
• Cytogenetics: chromosome 12, abnormal • Cavitation: rare
q13–q15 regions (as in other benign soft
tissue neoplasms) Hamartoma: CT [Figures 1 to 3]
• Thin sections (2 mm)
Hamartoma: Demographics • Smoothly contoured nodule
• Age range: 30–70 years • ≤2.5 cm diameter focal fat in 8 voxels or
• Peak incidence: sixth decade more or fat with calcification
• Male:female = 2:3 (1:1 for endobronchial
hamartoma)
• Asymptomatic in 90% Figure 1
• <8% obstructive symptoms
Hamartoma.
Hamartoma: Clinical Unenhanced
• Most are peripheral and asymptomatic chest CT
• If symptomatic: hemoptysis demonstrates
a peripheral
• If bronchial obstruction: pneumonitis solitary
• Fever, cough, expectoration, chest pain nodule with
focal fat
attenuation.
Chest Radiology 163 Benign Tumors of the Lung

Chondroma
• Rare
• Benign cartilaginous tissue
• Parenchymal or endobronchial
• Lack epithelial-lined clefts seen in
hamartomas
• In young women
• Search for Carney triad
Hamartoma: Endobronchial
• Morphologically identical to parenchymal
• Often polypoid – sessile or thin pedicle
• Manifest by airway obstruction
• Micro: more fat, lack clefts, cartilage
scant or absent
Hamartoma: Treatment and Prognosis

• Benign
Figure 2 • Surgical excision = cure
• Exceptional cases: additional hamartomas
Hamartoma. Unenhanced chest CT demonstrates a
central mass in the left lower lobe with a lobular area Papillomas
of popcorn calcification.
• Branching or coarsely lobulated tumor
• Arise from and project above an epithelial
surface
• Rare pulmonary tumors
• Solitary (rare) or multiple (papillomatosis)
• Proximal or peripheral
Solitary Papillomas
• Rare
• Usually in adults
• Papillary exophytic growth
• Trachea, main or lobar bronchi
• Men >40 years old
• Postobstructive pneumonia, bronchiectasis
Juvenile Laryngeal Papillomatosis

• Children 18 months to 3 years old
• Majority remain localized, disappear
Figure 3 spontaneously
• May spread distally and obstruct airways
Hamartoma. Unenhanced chest CT demonstrates
speckled calcification in a central endobronchial tumor
 5% spread remains limited to trachea
with associated loss of volume in the left lung.  1% develop lung disease; 10 years
after laryngeal disease (extension
to bronchi, bronchioles, alveolar
airspaces)
Hamartoma: CT
• No fat or calcification (36%)
Laryngeal Papillomatosis:
• Diffuse calcification (4%) Demographics and Etiology
• Areas of fat (38%) • Human papilloma virus (HPV) types 6 and
• Calcium and fat (21%) 11
• Occasionally: focal calcification, no fat • 0.1% of infants develop laryngeal
papillomatosis (LP); predilection for first-
Carney Triad born infants
• Gastric smooth muscle tumors • 50% of mothers have genital tract
• Extra-adrenal paragangliomas involvement
• Pulmonary chondromas • HPV spread transvaginally at birth
• Association unclear • Infects oropharyngeal secretions of child
• Young women <20 years old
• May have only 2/3 of the triad Papillomas: Microscopic
• Nonkeratinizing squamous cells
Carney JA. Cancer. 1979. • Fibrovascular core
• Form papillomatous projections
Benign Tumors of the Lung 164 Chest Radiology

Papillomatosis: Gross
• Cauliflower-like excrescences
• Protrude into bronchial lumens
• May extend into parcenchyma as nodules
or cavities
Laryngeal Papillomatosis
• Majority remain localized
• 5% spread to trachea and distal airways
Tracheobronchial Papillomatosis
• Many remain limited to trachea
• 1% develop lung disease
• Patients with lung disease may develop
squamous cell carcinoma
Tracheobronchial Papillomatosis:
Pathogenesis of lower respiratory
tract involvement
• Implantation of inhaled fragments from
larynx?
• Multifocal viral infection?
• Trauma-induced by tracheostomy?
• In children, papillomas in bronchi and Figure 5
lung associated with multiple papillomas
A 29-year-old woman with papillomatosis since age 3.
of trachea or larynx Papillomatosis and squamous cell carcinoma. Contrast-
enhanced chest CT demonstrates central squamous
Papillomatosis: Imaging cell carcinoma in the left lower lobe with distal
[Figures 4 & 5] pneumonitis.
• Multiple, well-defined nodules
• Perihilar, posterior thorax Papillomatosis: Squamous cell
• Grow to several centimeters Carcinoma
• Cavitate, 2–3-mm thick walls • Risk for squamous cell carcinoma 15
• Air-fluid levels may develop years after diagnosis
• Cavities may represent: • Risk factors
 Papillomatosis  Radiation
 Squamous cell carcinoma  Smoking
 Abscess (obstructive pneumonitis)  Other carcinogens
Papillomatosis: Treatment and

Prognosis
• Multiple recurrences
• Multiple excisions
• Tracheostomy
• 37.5% mortality if spread to lungs
• Worse if malignant degeneration occurs
Inflammatory Pseudotumor: Synonyms

• Plasma cell granuloma
• Histiocytoma
• Fibroxanthoma, xanthoma
• Myofibroblastic tumor
• Mast cell granuloma
Inflammatory Pseudotumor
• Uncommon; reactive or neoplastic
process?
• May begin as organizing pneumonia
Figure 4 • May have aggressive features:
Papillomatosis. Chest CT demonstrates nodular and
 Vascular invasion
cystic opacities that predominantly involve the dorsal  Vertebral destruction
aspects of both lungs.  Recurrence

Inflammatory Pseudotumor Inflammatory Pseudotumor: CT
• World Health Organization 1999: [Figure 6]
histologic spectrum of fibroblastic and • Solitary nodule or mass
myofibroblastic proliferations • Sharply circumscribed
• With varying infiltrate of inflammatory • Lobulated
cells • Heterogeneous or homogeneous
• Usually solitary, tumefactive lesion • Enhancement: calcification variable,
• Destroys underlying lung architecture nonspecific
• Reactive or neoplastic? • Calcification: variable
• Endobronchial lesions occur
Inflammatory Pseudotumor:
Demographics
• Males = females
• Wide age range of 1 to 77 years (average
29.5 years)
• 60% <40 years
 Children: peak 6–7 years
 Most common primary lung mass in
children
• 74% asymptomatic
• Many patients have history of respiratory
infection
Inflammatory Pseudotumor:
Microscopic
• Variable
• A continuum from plasma cell granuloma
to fibrohistiocystic
• Mixture of collagen, fibroblasts,
myofibroblasts, and chronic inflammatory Figure 6
cells Inflammatory pseudotumor. Contrast-enhanced chest
CT demonstrates an irregular heterogeneous mass in
Inflammatory Pseudotumor: Gross the left upper lobe.
• SPN or mass
• Well-defined, firm, lobulated
• Lack a capsule
• Cut surface: whorled, heterogeneous
Inflammatory Pseudotumor: Therapy
• 1–10 cm/4.4 cm mean
and Prognosis
Inflammatory Pseudotumor • Diagnosed and treated by surgical
• Solitary nodule or mass in 70% excision
• Well-defined • Excellent prognosis after resection
• May manifest as consolidation • Recurrence in 5%
• May mimic neoplasm  Especially if mediastinal or chest wall
• Endobronchial lesions occur in 10% involvement
• Differential diagnosis: fibrous
Inflammatory Pseudotumor: histiocytoma, sarcomatoid carcinoma
Radiographic
• Solitary, well-defined nodule or mass Granulomas
(70%) • Infectious
• Endobronchial lesions occur (10%) • Sarcoid (necrotizing granulomatosis)
• May extend into mediastinum (5%) • Hypersensitivity pneumonitis
• Parenchymal consolidation (6%)
Infectious Granulomas
• Calcification, cavitation infrequent
• Mycobacterial (64%)
• May mimic malignant neoplasm
• Fungal (30%)
• Usually no or slow growth, may regress
• Parasitic (6%)
Infectious Granulomas
• Tuberculoma or histoplasmoma
• Satellite lesions common
• Usually small, smooth
• Often calcified if healed
Benign Tumors of the Lung 166 Chest Radiology

Granuloma
• Well-defined pulmonary nodule
• Multiple ill-defined pulmonary nodules
• Tuberculosis
• Histoplasmosis
• Coccidioidomycosis
• Cryptococcosis
• Aspergillosis
Granuloma: Tiny Nodules

• <5 mm, micronodular, miliary
• Histoplasmosis
• Blastomycosis
• Coccidioidomycosis
• Cryptococcosis
Solitary Pulmonary Nodule (n = 955)

• Malignant (49%)
 Primary carcinoma (38%)
 Metastases (9%)
 Other primary malignancy (2%)
• Benign (51%)
 Non-neoplastic lesion (37%)
 Tumor (14%)
(Hamartoma 8%)
Toomes H. The coin lesion of the lung. Cancer.
1983.

Pleural Disease I
Pleural Disease I and II: Objectives Pleural Anatomy [Figure 2]
• Anatomy and physiology • Caudal limit of pleura lower than lung
• Non-neoplastic and neoplastic pleural • Costal and diaphragmatic pleura contact
disease to form costophrenic recess
• Chest wall disease
• Radiologic-pathologic correlation
Pleural Disease I
• Normal anatomy
 Standard fissures
 Accessory fissures
• Non-neoplastic pleural disease
 Effusions
 Fibrosis
 Pneumothoraces
Pleural Anatomy
• Parietal pleura
 Covers nonpulmonary surfaces
 Systemic supply/drainage
 Lymphatics communicate with
Pleural space
Pain fibers
 5–15 ml of pleural fluid
• Visceral pleura [Figure 1]
 Covers lung surface
 Dual supply/drainage Figure 2
 Vagus nerve/sympathetic trunks Pneumothorax in a supine patient manifesting as a
 Lymphatics do not communicate with “deep sulcus” and hyperlucency overlying the left
pleural space hemidiaphragm.
Pleural Anatomy
• Junction lines
• Apposition of layers of pleura
 Anterior
 Posterior
Pleural Anatomy: Fissures

• Visceral pleura
Figure 1
• Variable depth into parenchyma
Forms standard (solid lines) and accessory (dashed • Complete
lines) fissures. • Incomplete
Incomplete Fissures: CT
• More frequent on right
Pleural Imaging • Right upper lobe (RUL)/right lower lobe
• Radiography/CT (RLL) (70%)
 Inconspicuous • Right middle lobe (RML)/RLL (47%)
 Visceral + parietal = 0.2 mm • Left upper lobe (LUL)/left lower lobe (LLL)
• Thin-collimation (40%)
 1–2 mm thick line • Lingula/LLL (46%)
 Intercostal regions
Normal fluid
Endothoracic fascia
Innermost intercostal muscle
Chest Radiology 169 Pleural Disease I

Major Fissure: Radiography Incomplete Minor Fissure: High-
• Major (oblique) fissures Resolution CT
• Best seen on lateral chest x-ray • Curvilinear line or band
• Origin: T4 left, T5 right • Increased attenuation
• Right fissure more oblique • C-shaped
• LUL collapse • Fusion between RUL/RML (60%–90%)
Major Fissure: CT Accessory Fissures: Radiography

• 80%–90% on standard CT [Figure 4]
 Lucent band • 10% chest x-ray/20% CT (50% of
 Line anatomic specimens)
 Dense band  Azygos, superior, inferior, left minor
Major Fissure: CT-Propeller-like
morphology [Figure 3]
• Upper thorax
 Anterior concave
 Lateral-facing
• Inferior thorax
 Anterior convex Figure 4
 Medial-facing
Diagram
illustrates
position of
inferior (I),
superior (S),
and azygos
(AZ) accessory
fissures.
Accessory Fissures: Azygos

• Abnormal migration of posterior cardinal
vein
Figure 3 • 4 layers of pleura
• 1% population
Chest CT (lung window) demonstrates right upper lobe
loss-of-volume manifested by displacement of the right
• Male:female = 2:1
major fissure. An endobronchial carcinoid obstructs the
origin of the right upper lobe bronchus. Accessory Fissures: Azygos-CT
[Figure 5]
Standard Fissures: Radiography

• Minor fissure
 44%–80% normal chest x-rays
 Variable position
 Fourth intercostal space
Minor Fissures: Radiography

• “Lights up” in congestive heart failure
(CHF)
• Interstitial edema
(subpleural interstitium)
Minor Fissure: CT
• Lucent area
• Devoid of vasculature Figure 5
• Triangular (44%)
• Round/ovoid (8%) Chest CT demonstrates an azygos fissure forming the
• Ground-glass attenuation lateral margin of an azygos lobe.
Pleural Disease I 170 Chest Radiology

Accessory Fissures: Inferior accessory Indirect Signs of Atelectasis:
[Figures 6 & 7] Juxtaphrenic Peak
• Separates medial basal segment from • Common in RUL or LUL atelectasis
remaining basilar segments  Less common in RML
• Most common • Seen post upper lobectomy
 30%–45% anatomic specimens • Small triangular opacity
 Chest x-ray (5%–10%) • Projects upward from diaphragm
 80% right-sided • Related to inferior accessory fissure
 CT (15%)
Accessory Fissures: Superior accessory
• Separates superior segment from basilar
segments
• 6% anatomic specimens
• Right > left
• Horizontal course
 Inferior to minor fissure
Figure 6 Accessory Fissures: Left Minor Fissure

Coned-
• Separates lingula from remainder of upper
down view lobe
of right lung • 8%–18% anatomic specimens
demonstrates • Chest radiographs (1.5%)
an inferior • Oblique course
accessory
fissure • More cephalad
separating
the medial Pulmonary Ligament
basal • Formed by parietal and visceral pleura
segment • Courses inferiorly and posteriorly
from the
• Contains
remaining
basal  Bronchial veins
segments  Lymphatics
of the right  Nodes
lower lobe.
Pulmonary Ligament: Imaging
[Figure 8]
• Chest x-ray: not visualized
• CT (60%–70%)
Figure 8
Chest CT demonstrates inferior accessory fissure

(arrowhead) and right and left pulmonary ligaments
(arrows).
Figure 7
Chest CT demonstrates an inferior accessory fissure

(arrow).

Pleural Effusion: Cardiac Pleural Effusion: Empyema [Figure 11]
decompensation [Figure 9] • Lenticular shape
• Most common transudate • Obtuse margins
•  hydrostatic pressure • Compress lung
• Bilateral >80% • Split pleura sign
• Unilateral = right-sided
• Pseudotumor
Figure 11
Figure 9 Contrast-
enhanced
Lateral chest chest CT
radiograph demonstrates
demonstrates smoothly
lenticular thickened
opacity of fluid parietal and
accumulation in visceral
the minor fissure pleura
(pseudotumor). enclosing a
fluid collection
of empyema
(split pleura
sign).
Pleural Effusion: Bacterial Pneumonia

• Parapneumonic effusions (40%)
• Exudate Pleural Effusion: Lung abscess or
• 10% require drainage Empyema?
• Complications
 Loculation Pleural Effusion: Empyema
 Empyema • Lenticular shape
• Obtuse margins
Pleural Effusion: Empyema [Figure 10]
• Compress lung
• 3 phases • Split pleura sign
 Exudative • Disparity in length of air-fluid level
 Fibrinopurulent
 Organizing Pleural Effusion: Lung abscess
• Round shape
• Does not compress lung
• Equal length of air-fluid level
Pleural Effusion: Empyema

• Treatment
 Tube thoracostomy
 Fibrinolytics
 Decortication
Pleural Effusion: Empyema necessitatis

• Inadequate treatment
• Drainage into chest wall
• Tuberculosis (73%)
• Bacterial/fungal
• Malignancy
Figure 10
• Immunocompromised patients
Ultrasound demonstrates multiple septations within a
loculated fluid collection representing empyema. Pleural Effusion: Tuberculosis
• Exudate
 Increase lymphocyte count
 Decrease glucose level
• Unilateral
• Small to moderate

Pleural Effusion: Pulmonary Round Atelectasis: Chest X-Ray
Thromboembolic Disease • Peripheral mass
• Small • Abuts thickened pleura
• Unilateral • 3.5–7 cm
• 30%–50% patients • Posterior lower lobe most common
• Exudate (75%)  Other lobe, diaphragms
• Bloody effusion: infarction • Bronchovascular bundles converge,
forming “comet tail”
Pleural Effusion: Subpulmonic
• Fluid accumulates between lung base and Round Atelectasis: CT
diaphragm • Rounded subpleural mass
• Shifts apex of diaphragm laterally • Broadly abuts contiguous pleural
• Usually transudate thickening
 Cardiac decompensation • Air-bronchogram hilar aspect
 Renal failure • Bronchovascular “comet tail”
 Cirrhosis with ascites • Loss of volume in same lobe
Pleural Effusion: Subpulmonic Round Atelectasis: Required CT Findings

• Imaging [Figure 12]
 Apparent elevation diaphragm • Subpleural mass
 Ill-defined costophrenic angle • Thickened pleura
 Diaphragmatic spur • Loss of volume
 Mobile fluid • Comet tail
 Displace gastric bubble
 “Rock of Gibraltar” on lateral
Pleural Effusion and Ascites: CT

Features
• Effusion = outside hemidiaphragm
• Ascites = inside hemidiaphragm
Pleural Effusion: Connective Tissue

Disease
• Rheumatoid arthritis
• Most common thoracic manifestation
• Antedates clinical disease
• Exudate/chyliform/low glucose
• Imaging
 Unilateral
 Chronic
 Transient/relapse
 Fibrothorax/decortication Figure 12 A to E
Pleural Effusion: Asbestos Exposure Chest CT (mediastinal and lung windows) images
• Diagnosis of exclusion demonstrate the CT findings of round atelectasis.
• Occupational exposure
• No malignancy within 3 years
• 10 years postexposure
• Exudate Round Atelectasis: Pathogenesis
• 1/3 patients have chest pain • Asbestos exposure
• Recurrent (15%–30%) • Pleural effusion
• Small (<500 ml) • Atelectasis
• Pleural adherence
Pleural Effusion - Asbestos Exposure • Effusion subsides
• Associated with diffuse pleural thickening
• Lung re-expands
 Involves costophrenic (CP) angle
• Implicated in formation of rounded
atelectasis

Pleural fibrosis Pleural Plaques: Imaging [Figure 14]
• Contraction • Bilateral (80%)
• Pleural fibrosis • Lateral chest wall
• Second most common pleural abnormality • Fourth to eighth ribs
• Result of many primary diseases of the • Tendinous diaphragm
pleura • Spares apices and CPAs
• Complication of inflammatory disease • En face “holly leaf”
• Most localized to single area
• Less often diffuse
 May have functional abnormalities
Pleural Fibrosis: Focal Figure 14

• Healed pleuritis
• Bacterial pleuritis/trauma Chest
• Imaging radiograph
 Blunt posteriolateral CP sulci demonstrates
multiple
 Rule out small effusion bilateral
calcified pleural
Pleural Fibrosis: Focal [Figure 13] plaques.
• Pleural plaques
• Serpentine (chrysotile) asbestos
• Dense hyalinized collagen
• Parietal pleural surface
• Asbestos exposure
• Asymptomatic
Pleural Fibrosis: Diffuse Fibrothorax
[Figure 15]
• Fibrous obliteration of normal pleural
space
 Tuberculosis/bacterial empyema
 Hemothorax
 Asbestos-related pleural effusions
 Rheumatoid effusions
• Volume loss/restrictive disease
Figure 15
Pleural
fibrosis. Chest
radiograph
demonstrates
pleural
thickening and
calcification
Figure 13 in the right
hemithorax.
Chest CT (lung window) demonstrates multiple
bilateral pleural plaques.

• Radiographic definition
Pleural Fibrosis: Focal Smooth, uninterrupted
• Pleural plaques 25% or more of chest wall
• 50% of exposed individuals May obliterate CP suclus
• Visible plaques ≤2-cm thickness
 15 years noncalcified +/- calcification
 20 years calcified
• Imaging CT
 Extends >8 cm craniocaudal
 Pleura >3-mm thick
 Extrapleural fat hypertrophy
 +/- pleural calcification
 Mediastinal pleura spared

Pneumothorax Pneumothorax: Secondary Spontaneous
• Air within the pleural space • Lymphangioleiomyomatosis (LAM)
• Spontaneous • Women of child-bearing age
 Primary • Proliferation of smooth muscle
 Secondary • Bronchiolar obstruction
• Traumatic  Cysts  pneumothorax (PTX)
• Recurrence (~40%)
Pneumothorax: Primary Spontaneous
[Figure 16] Pneumothorax: Secondary Spontaneous
• Male:female = 5:1 • Langerhans cell histiocytosis
• Third to fourth decade • Smokers
• Right-side predominance • Cysts rupture
• Ipsilateral recurrence (30%) • Recurrent patients (25%)
• Contralateral recurrence (10%)
• Rupture of apical bleb/bulla
Figure 16
Chest CT demonstrates left pneumothorax and a bleb

along the visceral pleural surface of the collapsed lung.
Pneumothorax: Secondary Spontaneous

• Chronic obstructive pulmonary disease
(COPD)
• Most common concurrent condition
• 0.5% per year
• 45–65 years of age
• Peripheral emphysematous lung
• Mortality rate (~3%)

• Pneumocystis jiroveci pneumonia (PCP)
• Destruction of alveolar septa  bulla
• Subpleural necrosis  cystic
degeneration/bulla

• Pneumocystis jiroveci pneumonia (PCP)
• Complicates in 12%
• Refractory “air leaks”
• Poor prognosis
• Death in 8 weeks (<57%)

Pleural Disease II and Chest Wall
Malignant Pleural Effusion Localized Fibrous Tumor
• Most common manifestation of metastatic • Rare (<5% of pleural neoplasms)
involvement • Not related to asbestos
• Exudative effusion • Male = female
• Lung carcinoma (36%) • Mean age: 50 years
• Breast carcinoma (25%) • Symptoms in 54%
• Lymphoma (10%) • Cough, chest pain, dyspnea
• Ovarian (5%) • Hypertrophic pulmonary osteoarthropathy
• Gastric carcinoma (2%) (HPO) 0%–35%
• Hypoglycemia (4%)
Tumor Node Metastasis Staging of Lung
Cancer Localized Fibrous Tumor: Microscopic
• Malignant effusion = T4 • Variable patterns
• Disorderly arrangement
• Spindle cells and collagen
• High mitotic activity
 Suggests malignancy (20%)
Localized Fibrous Tumor: Gross

• 2–40 cm
• 80% visceral/20% parietal
• Lobular, encapsulated
• Pedicle: good prognosis
• Cut-surface: whorled, nodular, fibrous
hemorrhage, necrosis, cysts
Localized Fibrous Tumor: Chest X-Ray

[Figures 1 to 3]
• Incidental finding
Malignant Pleural Effusion:
• Solitary rounded, lobular mass
Diagnosis and Prognosis • Mid to inferior thorax
• Combined pleural cytology and pleural
• Obtuse or acute angles at interfaces
biopsy
• Pedunculated tumors
• Multiple thoracenteses/pleural biopsies
 Positional mobility
• Poor prognosis
 Pathognomonic
 Lung carcinoma: mean survival 2–3
months
 Breast carcinoma: mean survival 7–15
months
Pleural/Chest Wall Mass

• Discrepant margins on orthogonal views
• Elliptical shapes
• Obtuse angles
• Cross boundaries
Pleural Neoplasms
• Primary
 Localized fibrous tumor
 Malignant mesothelioma
• Secondary
 Pleural metastases
Bronchogenic carcinoma
Other carcinomas Figure 1
Lymphoma
Invasive thymoma Localized fibrous tumor. Posterior to anterior chest
radiograph demonstrates a pleural mass a peripheral
mass in the right lower hemithorax with incomplete
borders.
Chest Radiology 177 Pleural Disease II
Localized Fibrous Tumor: Therapy and
Prognosis
• Treatment of choice: complete surgical
Figure 2 excision
• 90% cure rate
Localized • Symptoms usually resolve postop
fibrous tumor. • Recur with tumor recurrence
Chest CT (lung
windows) • Recurrence in 10% of patients
demonstrates
a pleural mass Malignant Mesothelioma
that forms • Most common primary pleural neoplasm
obtuse angles • 2,000–3,000 cases/year in USA
at its interface
• 10% of exposed individuals
with the chest
wall. • Shipyards/asbestos plants
• Sixth–eighth decades
• Male: female = 3–6:1
• Amphiboles most tumorigenic
• Latency: 30–40 years
Figure 3 Malignant Mesothelioma: Clinical

• Insidious onset of symptoms
Localized fibrous
tumor. Posterior • 6–8 months prior to diagnosis
to anterior chest • Dyspnea, chest pain, cough, weight loss
radiograph • Rarely: superior vena cava (SVC)
demonstrates syndrome, Horner syndrome, dysphagia,
a large mass
that opacifies
vocal cord paralysis, HPO, clubbing,
most of the hypoglycemia
right hemithorax
and produces Malignant Mesothelioma: Microscopic
mass effect with • Epithelioid (50%)
contralateral • Sarcomatous (15%)
shift of the
mediastinum. • Biphasic (25%)
• Interobserver agreement (50%)
Malignant Mesothelioma: Gross

• Sheets, plaques, masses
Localized Fibrous Tumor: CT • Parietal > visceral
[Figure 4] • Bulk in inferior hemithorax
• Well-defined, smooth, lobular • Lung encasement
• Abutting pleural surface • Fissural growth
• Elongated, lenticular • Parenchymal involvement
• Heterogeneity: • Mediastinal, chest wall, diaphragmatic
 Hemorrhage, necrosis, cysts invasion
• Contrast enhancement
Malignant Mesothelioma: Radiographic
[Figure 5]
• Pleural masses
Figure 4 • Circumferential
• Mediastinal shift
Localized • Pleural plaques (25%)
fibrous tumor.
Contrast- Figure 5
enhanced
chest CT Malignant
demonstrates mesothelioma.
a large Posterior to
heterogeneous anterior chest
mass in the radiograph
right lower demonstrates
hemithorax circumferential,
with lobulated nodular, and
contours. contiguous
pleural masses
throughout the
left hemithorax.
Pleural Disease II 178 Chest Radiology

Malignant Mesothelioma: Radiographic Malignant Mesothelioma: Treatment and
• Malignant mesothelioma cannot be Prognosis
reliably differentiated from pleural • Median survival: 10 months
metastases. • Best prognosis:
 5-year survival (25%–30%)
Malignant Mesothelioma: CT  Negative margins
[Figure 6]  Epithelial cell type
• Pleural thickening (92%)  No metastases
• Fissural thickening (86%) • Extrapleural pneumonectomy
• Pleural effusion (74%)  High mortality/morbidity
• Ipsilateral  volume (42%)
• Pleural calcification (20%) Pleural Metastases: Most common
• Ipsilateral  volume (14%) pleural neoplasm
Kawashima. AJR. 1990. • Common
 Adenocarcinoma
Lung, breast, ovary, stomach
• Less common
 Lymphoma, invasive thymoma
• Imaging
 Pleural masses
 Or both
Pleural Metastases
• Hematogenous/lymphatic
• Direct extension
 Lung carcinoma, breast carcinoma
• Drop metastases
 Invasive thymoma
• May be bilateral
Malignant Pleural Thickening

[Figure 7]
• Circumferential
• Nodular
 >1 cm
Figure 6 • Mediastinal pleura
Leung, et al. AJR. 1990.
Chest CT demonstrates circumferential, nodular
pleural thickening in the left hemithorax that extends
into the major interlobar fissure. Calcified pleural
plaques are demonstrated bilaterally.
Malignant Mesothelioma: Diagnosis

• Video-assisted thoracoscopic surgery
(VATS): sensitivity 98%
 Complication: tumor seeding along
entry ports
• Open biopsy: when adhesions preclude
VATS
• Cytology and fine-needle asperiation
(FNA) biopsy of limited value
Malignant Mesothelioma: MR
• Staging
• Comparable/superior to CT
• Tumor enhancement Figure 7
• Increased signal intensity
Pleural metastases. Chest CT demonstrates
adenocarcinoma arising from a right upper lobe
bronchus and pleural metastases that are nodular,
circumferential, and involve the mediastinal pleura.

Chest Wall Chest Wall: Inflammatory/Infectious
• Congenital and developmental anomalies Diseases
• Inflammatory and infectious diseases • Hematogenous
• Non-neoplastic conditions • Direct extension
• Neoplasia: benign and malignant • Pyogenic infection: S aureus, P
aeruginosa
Chest Wall: Congenital/Developmental • Imaging
Anomalies [Figures 8 & 9]  Osseous destruction if advanced
• Pectus deformities  CT/MR for better delineation
• Anomalous ribs  CT for biopsy and/or drainage
• Cleidocranial dysostosis
• Poland syndrome Chest Wall: Tuberculosis [Figure 10]
• Uncommon
• Hematogenous spread
• Contiguous spread
• Abscess/sinus tract (25%)
• Imaging
 Bone/cartilage destruction
 Soft tissue mass
 Calcification
 Peripheral enhancement
Figure 8
Lateral chest radiograph demonstrates pectus

carinatum.
Figure 10
Tuberculosis. Contrast-enhanced chest CT

demonstrates an anterior chest wall abscess with
subtle peripheral enhancement and right pleural
effusion and pleural thickening.
Chest Wall: Inflammatory/Infectious

Diseases
Figure 9 Chest Wall: Actinomycosis
Poland syndrome. Chest CT demonstrates congenital [Figure 11]
absence of the right pectoralis muscles. • Actinomyces israelii
• Anaerobic gram-positive
• Lung → pleura → chest wall
• Proteolysis → fistulas
• Diagnosis: anaerobic cultures
• Imaging: soft-tissue mass, draining sinus,
periostitis

Chest Wall Neoplasms: Soft Tissue
Involvement [Figure 12]
• Adults
• Malignant
 Fibrosarcoma
 Malignant fibrous histiocytoma
Figure 11 Figure 12
Actinomycosis. Contrast-enhanced chest CT Fibrosarcoma. Chest CT demonstrates postsurgical

demonstrates peripheral consolidation in the left upper changes of right mastectomy and a soft tissue
lobe with contiguous soft-tissue density extending into mass in the left chest wall. The patient received
the adjacent mediastinum and anterior chest wall. radiation therapy through ports that included the left
posterolateral chest wall.
Chest Wall: Neoplasms – Adults

• Benign: Chest Wall Neoplasms: Osseous
 Lipoma Involvement [Figure 13]
 Other mesenchymal neoplasms • Rib expansion
• Malignant:  Fibrous dysplasia
 Fibrosarcoma  Enchondroma
 Malignant fibrous histiocytoma • Pressure erosion
 Other mesenchymal neoplasms  Neurogenic (slow growth)
 Lymphoma • Rib destruction
 Metastatic or primary
Chest Wall Neoplasms: Lipoma
 Inflammatory
• Common
• Subcutaneous
• Intrathoracic
• Both
• Diagnostic CT number
Chest Wall Neoplasms: Desmoid Figure 13

(Fibromatosis)
• Aggressive fibromatosis Fibrous
• Most: second to fourth decades dysplasia.
• Shoulder, chest wall Chest CT
• Soft tissue mass demonstrates
an expansile
• Frequent recurrence lesion with
intact cortical
margins
involving a
right rib.

Chest Wall Neoplasms: Osseous
Involvement
• Pressure erosion
 Slow growth
 Neurogenic
Chest Wall Neoplasms: Osseous

Destruction
• Adult
 Metastatic disease (lung, breast,
prostate, etc.)
 Multiple myeloma
 Chondrosarcoma
• Child
 Ewing sarcoma
 Neuroblastoma
 Lymphoma
 Askin tumor primitive neuroectodermal
tumor (PPNET)
Chest Wall Neoplasms: Myeloma

• Men > women
• Fifth to seventh decades
• Axial skeleton
• Multiple or solitary
• Imaging:
 Osseous destruction
 Soft tissue mass
Chest Wall Neoplasms: Chondrosarcoma

• Adults
• Painful, palpable mass
• Costochondral junction, rib, sternum
• Imaging:
 Expansile, destructive
 Chondroid calcification
 Soft-tissue mass
Askin Tumor: Primitive

Neuroectodermal Tumor
• Malignant small round cell tumor
• Children, adolescents
• Male:female = 1:3
• Unilateral
• Rib destruction 2/3
• Poor prognosis

Immune Mediated Lung Diseases
Seth J. Kligerman, MD
Type 1 Immediate Hypersensitivity Type II: Antibody Dependent
Initial Exposure • IgM and IgG bind to antigen on cell
• Antigen captured by naive B-cell and • Leads to cell death in two ways
engulfed  Membrane attack complex via
• Antigen peptides expressed on cell complement system
surface  Natural killer (NK) cells kill via
• Th2 helper T-cells activates B-cell antibody dependent cell toxicity
• B-cell secretes IgE which attaches to Fc • Examples
receptor on mast cell  Transfusion reactions
• Mast cell activated  Autoimmune hemolytic anemia
 Goodpasture
Type 1 Immediate: Re-exposure  Myasthenia gravis
• Crosslinking of antigen to IgE receptors
• Mast cell degranulation Type III: Immune Complex
• Mild symptoms to sudden death Hypersensitivity
• Examples • Soluble immune complexes (IC) form
 Allergic rhinitis • Deposit in tissues
 Asthma • Trigger complement activation
 Systemic anaphylaxis • Acute inflammation at sites of IC
deposition
Asthma • Examples
• Acute and chronic inflammation of large  Systemic lupus erythematosus (SLE)
and small airways  Serum sickness
• Decrease in airway radius  Post-streptococcal glomerulonephritis
 Resistance =(1/r4)  Polyarteritis nodosa
 Airway plugging
Mucus Hypersensitivity Pneumonitis: Early
Inflammatory cells Immune Response
 Submucosal thickness • Type III
Inflammation • Immune complexes form
Fibrosis • Activate MØ
Smooth muscle mass  Neutrophilic chemotactic factors
 Luminal narrowing Neutrophils invade alveoli
Loss of alveolar attachments  Proteases
• Most chest X-rays are normal  Reactive oxygen intermediates
 Hyperinflation
 Airway wall thickening T-cell Differentiation
• CT findings • Antigen presenting cell (APC) interacts
 Normal with naïve CD4+ T-cells (Th0)
 Bronchial wall thickening and mucus • Th0 differentiates depending on cytokine
plugging stimulation
Occasional bronchiectasis  IL-12  Th1 CD4+ T-cell
 Mosaicism  IL-6  Th17 CD4+ T-cell
Air trapping on expiration  IL-4  Th2 CD4+ T-cell
 Centrilobular nodules  TGF-ß  Treg CD4+ T-cell
Bronchiolar impaction
Type IV: Hypersensitivity Reaction
Initial Exposure
• APC interacts with Th0 cell
• Releases IL-12 and IL-6
• Promotes Th0 differentiation into
 Th1 CD4+ T-cells
 Th17 CD4+ T-cells
Chest Radiology Immune Mediated Lung Disease

183
Type IV: Hypersensitivity Reaction to Hypersensitivity pneumonitis Stages
Re-exposure • Stages
• Th1 CD4+ T-cells releases cytokines that  Acute
recruit  Subacute
 Monocytes (type IVa)  Chronic
 Eosinophils (type IVb) • No fixed case definitions
 CD8+ cytotoxic T cell (type IVc) • No data on outcomes at stage
• Th17 CD4+ T-cells recruit
 Neutrophils (type IVd) Acute Hypersensitivity pneumonitis
• Th2 CD4+ T-cell • Rapid inflammatory reaction to antigen
 Stimulate IgE production  Usually large dose of inhaled antigen
 Can occur as soon as 2 hours after
Evidence of Type IV reaction in exposure
Hypersensitivity pneumonitis Peak typically 6–24 hours post
• Up-regulation of Th1 pathway  increase exposure
likelihood of developing hypersensitivity  Symptoms include fever, chills,
pneumonitis (HP) malaise, cough, and shortness of
• Attenuated T-cell response  less severe breath
or no disease • Imaging
 Athymic mice resistant to developing  Acute lung injury with diffuse
HP alveolar damage (DAD), edema, or
 When T-cells repleted, they developed hemorrhage
HP lesions  Air space consolidation
• Increased IL-17 levels higher in HP mice
compared with non-HP mice A 40-year-Old woman with shortness
• T-cell activity evolves over course of of breath for Three months [Figures 1 & 2]
disease
 Inflammatory stage – Th1 pathway
 Fibrotic stage – Th2 pathway
Hypersensitivity pneumonitis
• Allergic reaction
 Exposure to organic antigen via
inhalation
Bacterial, fungal, plant, or animal
proteins
• Genetic predisposition
• Smoking considered protective
 Decreased delivery of antigen to
alveoli
 Decreased antibody response
 Immune modulation from nicotine
Figure 1 A & B
Antigen
CT images obtained at the apex and through the
• T-cell response is induced to antigen lower lobes shows extensive tree-in-bud, centrilobular
 Type III and IV hypersensitivity nodularity which is more severe in the upper lung
reaction zones.
• Antigen characteristics play important role
 Degree of antigen load
 Solubility, immunogenicity, and size of
the molecule
• Antigen must penetrate into distal
respiratory tree and alveoli for allow
immune response
 Usually antigens less than 3 microns
 Host characteristics also impact
immune response
Figure 2
Low-power micrograph shows marked airway-centric

inflammation (arrows) involving the bronchioles within
a secondary pulmonary lobule (black outline).
Immune Mediated Lung Disease Chest Radiology

184
Subacute Hypersensitivity pneumonitis: Hot Tub Lung
Clinical • Inhalation of aerosolized mycobacteria
• Gradual onset over several days to weeks  Indoor hot tub
• Symptoms can be mild or severe Poor maintenance
• Usually lasts 1–2 weeks Uninhibited micro bacterium avium
• Reversible in most instances complex (MAC) growth
 Aerosolization and inhalation of MAC
Subacute Hypersensitivity pneumonitis: • Hypersensitivity reaction versus infection
Radiology • Debate in treatment
• Upper lobe centrilobular nodules
• Mosaic attenuation Treatment [Figure 6]
• Ground-glass opacity • Removal of inciting antigen
• Headcheese sign • Steroids
• Outcomes
Subacute Hypersensitivity pneumonitis  Improvement
[Figure 3]  Progression
Figure 3
CT image
show ill-
defined,
hazy
upper lung
predominant
centrilobular
nodules.
Figure 6 A & B
Images obtained two months after removed of inciting
antigen shows complete resolution or centrilobular
nodules.
Hypersensitivity pneumonitis Air
Trapping [Figure 4]
Hypersensitivity pneumonitis
Progression [Figure 7]
Figure 4 A & B
Expiration images show diffuse well-defined areas

of air-trapping which is the cause of the mosaic
attenuation on inspiratory images. Figure 7 A & B
Coronal images in a patient with hypersensitivity
Airway Centered Inflammation [Figure 5] pneumonitis shows progression of disease from 2007
to 2009. The patient refused to get rid of her birds.
Chronic Hypersensitivity pneumonitis

Radiology
• Fibrosis
 Reticulation
 Traction bronchiectasis
 Honeycombing
• Superimposed findings of subacute HP
sometimes present
Figure 5 • Distribution different than idiopathic
pulmonary fibrosis (IPF)
High-power photomicrographs shows marked
inflammatory changes involving the respiratory  Patchy and perihiliar instead of lower
bronchiole in the center of a secondary pulmonary lobe and peripheral
lobule.

185
A 73-year-Old female bird owner A 45-year-Old male with chronic cough
with progressive Shortness of Breath and Shortness of Breath [Figure 11]
[Figure 8]
Figure 8 A & B
Images from CT show upper lung predominant fibrosis

with mosaic attenuation. Figure 11 A & B
Posterior anterior chest radiograph and associated
coronal CT image show perihilar predominant
usual interstitial pneumonia Pattern of bronchiectasis with areas of mucus plugging
Fibrosis? [Figure 9]
Pathogenesis
• Hypersensitivity reaction to Aspergillus
antigens (AH)
 Type I – Aspergillus-specific IgE-
mediated
 Type III – IgG-mediated Ag-Ab
complexes
 Type IVb – eosinophil rich delayed
reaction
• Inhaled A fumigatus conida germinate
• Hyphae release antigens
 Inhibit mucociliary clearance
 Breach airway epithelial barrier
 Activate innate lung immunity

Figure 9 Pathogenesis: Innate Lung Immunity
Low-power photomicrograph show temporally and • Th2 dominant response
spatially heterogeneous fibrosis which looks like usual  IgE synthesis
interstitial pneumonia.
 Mast cell degranulation
• Th1 response
Airway Fibrosis [Figure 10]
 Type IVb
 Eosinophilic response
Allergic Bronchopulmonary
Aspergillosis: Clinical
• Asthma
 28% have aspergillus hypersensitivity
(AH)
 12.9% in allergic bronchopulmonary
aspergillosis (ABPA)
• Diagnostic criteria include
 Asthma or cystic fibrosis (CF)
 Peripheral blood eosinophilia
 Positive skin test for Aspergillus
antigens
 Increased serum IgE levels
• Fungal hyphae seen without tissue
invasion
 Treatment is corticosteroids
Figure 10
High-power photomicrographs show airway centered

fibrosis.
Immune Mediated Lung Disease Chest Radiology

186
Allergic Bronchopulmonary Secondary Causes of Eosinophilic Lung
Aspergillosis: Radiology Disease
• Bronchiectasis • Infection
 Mid and upper lung  Parasitic/helminthic
 Mucoid impaction  Fungal (e.g., Coccidioides)
 Finger-in-glove  Other (Pneumocystis, mycobacteria)
Hyphal masses • Drugs
Distal mucoid impaction  Antibiotics
Impacted mucus high density or  Nonsteroidal anti-inflammatory drug
calcified (NSAIDs)
• Centrilobular nodules • Asthma/atopy
• Patchy ground-glass opacity  Allergic bronchopulmonary
aspergillosis
Eosinophils • Primary malignancy with eosinophilia
• Bone marrow derived  Leukemia
• Exposed tissues  Lymphoma
 Lung, GI, and lower GU  Graft versus host disease
• Specific granules  Myelodysplastic syndromes
 Cathepsins  Solid tumors (e.g., lung cancer)
Cleave proteins • Other
 Major basic protein  Systemic mastocytosis
Toxic to parasites  Sarcoidosis (rare)
Histamines and mast cell activation
−− Smooth muscle contraction Simple Pulmonary Eosinophilia: Clinical
−− Mucous secretion • Unknown cause
−− Vascular permeability • Increased peripheral blood eosinophils
• Minimal or no pulmonary symptoms
Eosinophils: Major Basic Protein • Spontaneous resolution <1 month
• Toxic to parasites • Recurrence rare
• Histamines and mast cell activation
 Smooth muscle contraction Simple Pulmonary Eosinophilia:
 Mucous secretion Radiology
 Vascular permeability • Migrating peripheral consolidation
• Neutrophil activation • Ill-defined airspace nodules
• Alveolar macrophage activation • Reverse halo sign
• Direct epithelial cell damage
Simple Pulmonary Eosinophilia:
Eosinophilic Lung Disease Pathology
• Primary disorders • Edema
• Secondary disorders • Accumulation of eosinophils in alveolar
 Much more common septa and interstitium
• Diagnosis of eosinophilic lung disease can
be made if A 28-year-Old solider in Iraq develops
 Pulmonary opacities with peripheral severe pneumonia requiring intubation
eosinophilia [Figure 12]
 Tissue eosinophilia at lung biopsy
 Increased eosinophils in
bronchoalveolar lavage (BAL) fluid
Primary Eosinophilic Lung Disease

• Lung limited
 Simple pulmonary eosinophilia
(Loeffler’s syndrome)
 Acute eosinophilic pneumonia
 Chronic eosinophilic pneumonia
• Systemic
 Churg-Strauss vasculitis (CSV)
 Hypereosinophilic syndromes (HES)
Figure 12
Portable radiograph in an intubated patient shows
diffuse perihilar predominant consolidation with pleural
effusions.

187
Undiagnosed Acute Pneumonia A 66-year-Old Man with worsening
• 19 cases of respiratory failure Shortness of Breath [Figure 14]
• 4/19 bacterial infections
• 10/19 Eosinophilia
 Blood 8
 Bronchoalveolar lavage (BAL) 3
 Pleural fluid 1
 Pulmonary tissue 1
• Recent-onset cigarette smokers
Acute Eosinophilic Pneumonia:

Radiology
• Effusions in 100%
 Bilateral 92% Figure 14 A & B
• Consolidation and ground-glass opacity Frontal radiograph and associated CT in a patient
• Septal thickening shows peripheral areas of consolidation and ground-
• Can look like glass opacity due to chronic eosinophilic pneumonia.
 Fluid overload
 Acute respiratory distress syndrome
(ARDS)
chronic eosinophilic pneumonia:
 Pneumonia
radiology
Acute Eosinophilic Pneumonia [Figure 13] • Photonegative of pulmonary edema
 Peripheral consolidation
 Seen <50% of cases
Figure 13 • Other findings
CT images in  Ground-glass opacity
same patient  Nodules
demonstrates  Reticulation
areas of
 Pleural effusion uncommon
consolidation,
ground-glass • Can lead to fibrosis in rare instances
opacity, and
pronounced chronic eosinophilic pneumonia:
septal Etiology and Pathology
thickening
• Unknown cause
consistent with
capillary leak • Lab findings
in a patient  Alveolar eosinophilia ≥40%
with normal  90% have peripheral blood
left ventricular eosinophilia
pressures.
  ESR
  Serum IgE levels
• Accumulation of eosinophils and
Acute Eosinophilic Pneumonia: lymphocytes in alveoli and interstitium
Pathology • Differentiation from acute eosinophilic
• BAL fluid pneumonia (AEP)
 Eosinophilia in BAL fluid (25%  Damage to basal lamina
eosinophils)  Areas of fibrosis
  Lymphocytes and neutrophils
Lung injury Chronic Eosinophilic pneumonia: Clinical
• Lung biopsy • 1/3 to 1/2 have asthma or other atopic
 Eosinophilic PNA with superimposed disease
diffuse alveolar damage (DAD) • Symptoms
 Fever, cough, dyspnea, exercise
Acute Eosinophilic Pneumonia: Clinical intolerance
• Acute febrile illness <1 month • Treatment
• Hypoxemia  Oral corticosteroids
• Lung eosinophilia  Frequently recurs
 >25% eosinophils on BAL
 Eosinophilic pneumonia on biopsy (Bx)
• Rapid response to steroids
 Relapses rare
• Numerous secondary causes
 Drugs
 Infections
188
Hypereosinophilic Syndome Summary
• 1° hypereosinophilia • Immune mediated lung diseases are a
• Multisystem complex group of disease based on
• Loeffler endocarditis  Antigen
 Subcategory of hypereosinophilic  Length of exposure
syndrome (HES) with cardiac  Patient characteristics
involvement  Type of Immune response
 Mechanism unknown • Many have known causes
 Fibrous thickening of endocardium  Asthma
Mural thrombi  HP
Subendocardial enhancement  ABPA
Restrictive cardiomyopathy (CM)  Secondary eosinophilic diseases
• Some have unknown cause
Loeffler’s Endocarditis [Figure 15]  SPE
 AEP
 CEP
 HES
Figure 15 A & B
4-chamber delayed
enhancement image
from a cardiac MRI
shows subendocardial
enhancement
(red arrow) and
an associated intracavitary thrombus (arrow).
Corresponding gross specimen demonstrates the
subendocardial fibrosis (yellow arrow).
References
1. Lacasse Y, Girard M, Cornier Y. Recent Advances in hypersensitivity pneumonitis. Chest. 2012; 142:208–
217.
2. Dhar S and Daroowalla F. Hypersensitivity pneumonitis. Clinical Pulmonary Medicine. 2011;169–174.
3. Murphy DM and O’Byrne PM. Recent advances in the pathophysiology of asthma. Chest. 2010;137:1417–
1426.
4. Cottin V and Cordier JF. Eosinoplilic lung disease. Immunol Allergy Clin North Am. 2012;32:557–586.
5. Daimon T, Johkon T, Sumakawa H, et al. Acute eosinophilic pneumonia: Thin-section CT findings in 29
patients. European Journal of Radiology. 2008;65:462–467.
6. Jeong YJ, Kim KI, Lee CH. Eosinophilic lung diseases: A clinical, radiologic, and pathologic overview.
RadioGraphics 2007;27:617–637.

189

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An Approach to Diffuse Lung Disease

Describing Diffuse Lung Disease Lung Volumes [Figures 3 & 4]

Figure 1 A & B Figure 3

Most diffuse lung disease involves both the alveolar Fibrosis

Radiology and pathology are complimentary

Chest Radiology 13 An Approach to Diffuse Lung Disease

Lymphatic flow is driven by hydrostatic vascular

Plain Film and CT Opacities

An Approach to Diffuse Lung Disease 14 Chest Radiology

Organization [Figure 11]

The reticulation in idiopathic pulmonary fibrosis is a

Plain Film and CT Opacities

The ground-glass opacity demonstrated on the

The cysts in idiopathic pulmonary fibrosis are strikingly

Diffuse Panbronchiolitis [Figure 15]

Normal anatomy of the secondary lobule with central

Bronchioloectasis demonstrated on the CT (left image)

An Approach to Diffuse Lung Disease 16 Chest Radiology

Secondary Lobule [Figure 16]

Prominent septal lines and thickening of the central

Miliary Tuberculosis [Figure 18]

Centrilobular nodules in a patient with transbronchial

Sarcoidosis [Figure 19]

Chest Radiology 17 An Approach to Diffuse Lung Disease

An Approach to Diffuse Lung Disease 18 Chest Radiology

Sarcoidosis: Adenopathy [Figure 23]

Sarcoidosis and the Secondary Lobule Node Group Chest X-ray CT

Sarcoid and the Lung: Radiography

Chest Radiology 19 An Approach to Diffuse Lung Disease

Conglomerate Mass [Figure 27]

Typical Sarcoidosis [Figure 25] Conglomerate masses of fibrous tissue resemble a

Cyst Formation and Distribution

Typical upper lobe predominance of nodules (right

An Approach to Diffuse Lung Disease 20 Chest Radiology

Cor pulmonale is the most common cause of death

Sarcoidosis: Differential Diagnosis

Chest Radiology 21 An Approach to Diffuse Lung Disease

Figure 33 The fibrotic

Sarcoidosis: adenopathy and nodules

Sarcoidosis: conglomeration [Figure 35]

An Approach to Diffuse Lung Disease 22 Chest Radiology

Chest Radiology 23 An Approach to Diffuse Lung Disease

An Approach to Diffuse Lung Disease 24 Chest Radiology

Alveolar Wall Thickening/Volume Loss

Chest Radiology 25 The Idiopathic Interstitial Pneumonias

There are 3 main mechanisms

Idiopathic Pulmonary Fibrosis Alveolus Injury [Figure 6]

Alveolus [Figure 5] Migration [Figure 7]

The Idiopathic Interstitial Pneumonias 26 Chest Radiology

Geographic Heterogeneity [Figure 10]

Idiopathic Pulmonary Fibrosis

Honeycombing is collapse, Not fibrosis

The region of lung affected in idiopathic pulmonary

Honeycombing is primarily the result of numerous

Chest Radiology 27 The Idiopathic Interstitial Pneumonias

Acute Interstitial Pneumonia

Acute diffuse alveolar damage [Figure 14]

alveolar Collapse [Figure 17]

Acute Interstitial Pneumonia:

The Idiopathic Interstitial Pneumonias 28 Chest Radiology

Cryptogenic Organizing Pneumonia:

Chest Radiology 29 The Idiopathic Interstitial Pneumonias