Differential Diagnosis of Diffuse Ground Glass

Opacifications Made Easy

Award: Magna Cum Laude

Poster No.: C-2055
Congress: ECR 2019
Type: Educational Exhibit
Authors: S. Röhrich, F. Prayer, H. Prosch; Vienna/AT
Keywords: Lung, Thorax, CT, Education, Structured reporting, Education and
training
DOI: 10.26044/ecr2019/C-2055

Any information contained in this pdf file is automatically generated from digital material
submitted to EPOS by third parties in the form of scientific presentations. References
to any names, marks, products, or services of third parties or hypertext links to third-
party sites or information are provided solely as a convenience to you and do not in
any way constitute or imply ECR's endorsement, sponsorship or recommendation of the
third party, information, product or service. ECR is not responsible for the content of
these pages and does not make any representations regarding the content or accuracy
of material in this file.
As per copyright regulations, any unauthorised use of the material or parts thereof as
well as commercial reproduction or multiple distribution by any traditional or electronically
based reproduction/publication method ist strictly prohibited.
You agree to defend, indemnify, and hold ECR harmless from and against any and all
claims, damages, costs, and expenses, including attorneys' fees, arising from or related
to your use of these pages.
Please note: Links to movies, ppt slideshows and any other multimedia files are not
available in the pdf version of presentations.
www.myESR.org

Page 1 of 42
Learning objectives

To learn a step-by-step approach for narrowing the differential diagnosis of diffuse ground
glass opacification (GGO).

To identify differentiating clinical and radiologic features that point to the most probable
differential diagnosis.

Page 2 of 42
Background

Diffuse GGO is a commonly encountered pattern in CT scans of the lung and can prove
to be a very time-consuming finding, as there are many possible differential diagnoses
(1). Following a step-by-step approach can help to narrow down the differentials, as we
will show in this exhibit.

Page 3 of 42
Findings and procedure details

Pathophysiology of GGO on CT scans

Ground glass opacifications are one of the most commonly encountered pulmonary
patterns in chest CTs. The underlying mechanism is an increase in density caused by a
partial filling or collapse of the alveoli or the thickening of the interstitial tissue (Fig. 1).

Alveoli may fill with:

• Transudate (pulmonary edema, inflammatory reaction)

• Aspirated material
• Hyaline (ARDS)
• Mucins (mucinous adenocarcinoma of the lung, pulmonary alveolar
proteinosis)
• Pus
• Blood
• Cells (adenocarcinoma, lymphoma)

A collapse of alveoli may be triggered by:

• Longstanding obstruction of bronchi with consecutive absorption of remaining

air

An increase of surrounding interstitial structure occurs in:

• Sarcoidosis
• Organizing pneumonia
• Fibrotic lung disease

Three questions that guide the differential diagnosis:

1.) Is it a pathology? (mind the inspiration depth and the overall quality of the scan)

One of the most common findings simulating GGO is insufficient inspiration depth and
dependent atelectasis (Fig. 2 & 3). A look at the posterior membranous tracheal wall can
help to make sure that the patient has inhaled sufficiently (Fig. 2). The typical distribution
of dependent atelectasis in the posterior parts and adjacent to vertebral bodies further
helps to distinguish them from GGO.

Page 4 of 42
A second scan in deep inspiration or in a prone position can help to ventilate previously
less aerated lung regions (Fig. 3).

Another pitfall is the misclassification of normal lung tissue as GGO in mosaic perfusion
or next to air trapping. In this situation, scans both during inspiration and expiration are
mandatory:

Pathology: air trapping and mosaic perfusion (= reduced blood flow, Fig. 4)

• Hypodense = pathological
• Hyperdense = normal lung
• The difference will increase in expiration (i.e., normal lung becomes denser).

Pathology: GGO

• Hypodense = normal lung

• Hyperdense = pathological
• The difference will decrease in expiration (i.e., normal lung becomes denser
and harder to differentiate from GGO)

If all three patterns (normal, GGO, air trapping) are present, the distinction between the
respective patterns becomes difficult. However, this combination by itself is specific for
hypersensitivity pneumonitis and is called head-cheese-sign (Fig. 5).

2.) Is the GGO acute or chronic? (Fig. 5)

Acute: less than a few weeks

• Most imaging findings are of little help because they are unspecific in the acute
stage. Clinical symptoms and the patient's history are more important.

Chronic: more than 6 weeks

• In the chronic stage, there are important imaging findings that may guide the
diagnosis (see down below).

Pitfalls:

• Recurring acute GGO might be misinterpreted as chronic (e.g. pulmonary

hemorrhages in pulmonary-renal syndromes)
• Bronchoalveolar lavage can lead to sudden changes in the image in both
directions: either decreased attenuation (e.g., improvement in pulmonary
alveolar proteinosis) or increased attenuation (residuary fluid).

Page 5 of 42
3.) What is the patient's medical history?

Table 1 lists clinical features that are associated with pathologies that commonly produce
GGO.

Review of imaging findings:

1.) Spatial distribution of GGO

All causes of acute GGO may lead to similar patterns, rendering the distribution less
important in acute situations.
Generally, the following distributions can be distinguished: Mid to lower vs. upper lung
zones (Fig. 7 & 8), and peripheral vs. central lung zones (Fig. 9 & 10).

2.) Ancillary imaging findings

See table 2 for abbreviations

Fibrotic changes (NSIP, late stages of other diseases such as HP, DIP, LIP,
Sarcoidosis):
A first look should assess if there are fibrotic changes, including irregular reticulation,
traction bronchiectasis, honeycombing and decreased lung volume (Fig. 11).

Whereas there is more GGO and less honeycombing in non-specific interstitial

pneumonia, GGO is less common in usual interstitial pneumonia.

Airway wall thickening, inflammatory bronchiectasis, air trapping, and tree-in-bud:

These findings are all common in large and small airways disease. If there is a region of
distinct tree-in-bud, infection is very likely (Fig. 12).

Bronchiectasis is often irreversible (particularly if there is cystic bronchiectasis as this

resembles long-standing pathology). However, cylindrical bronchiectasis in regions of
GGO may resolve during convalescence (Fig. 13).

Distinct mosaic perfusion and air trapping (HP):

In combination with GGO, this pattern is typical for hypersensitivity pneumonitis (Fig. 4).

Cysts (DIP and LIP): (Fig. 14)

Page 6 of 42
GGO is less common in other cystic diseases, therefore the differential diagnosis of acute
GGO with cysts should include Pneumocystis jirovecii infection (cysts occur in 30% of
cases (2)), and in a chronic setting desquamative and lymphocytic interstitial pneumonia.

Emphysema (DIP & RB): (Fig. 15)

Emphysema, GGO, a history of smoking, and cysts are enough for the diagnosis of DIP
without a biopsy. However, due to the high prevalence of emphysema, this finding should
not be over-interpreted as it may merely coexist with a different disease.

Crazy Paving (PAP):

In chronic GGO additional interlobular septal thickening should lead to an inclusion of
pulmonary alveolar proteinosis as a differential diagnosis (Fig. 16).
Interlobular septal thickening does not change the differentials of acute GGO. The
ancillary finding of pronounced smooth interlobular septal thickening together with an
effusion, however, is suspicious for hydrostatic edema.

Nodules (infection, aspiration, HP, RB, FB, invasive mucinous adenocarcinoma of the
lung, sarcoidosis):
Centrilobular nodules: this pattern shows a sparing of the immediate subpleural space,
an even distance between the nodules and resembles peribronchiolar inflammation,
fibrosis or lymphatic infiltration. Together with GGO, it is commonly encountered in
hypersensitivity pneumonitis, atypical infections, respiratory bronchiolitis and follicular
bronchiolitis (when the nodules are of GGO density - Fig. 17) or endobronchial spread of
infections, tumor and aspiration (when the nodules are solid - Fig. 18).

Consolidations (aspiration, OP, EP, invasive mucinous adenocarcinoma of the lung):

Whereas the spectrum from GGO to consolidations is continuous, some pathologies
commonly occur with consolidations next to GGO (Fig. 19).

Lymphadenopathy (sarcoidosis, hydrostatic edema, infection):

Bihilar and mediastinal lymphadenopathy is common in sarcoidosis. Additionally, lymph
nodes are often enlarged in hydrostatic edema and infection.

Pathologies with GGO as one of the predominant patterns:

1.) Acute:

Atypical infections:

Page 7 of 42
The most common atypical pathogens causing infections include viruses, Pneumocystis
jirovecii (Fig. 20), and bacteria such as Legionella pneumophila, Chlamydia pneumoniae,
and Mycoplasma pneumoniae. Compared to common pulmonary infections, atypical
infections may cause more subtle respiratory symptoms, present without marked
leukocytosis, and frequently do not respond to empirically administered antibiotics.

Distribution:

• Patchy, diffuse, or centrilobular GGO (often found in viral and Pneumocystis

jirovecii infections)

Ancillary imaging findings:

• Cysts (Pneumocystis jirovecii)

• Airway wall thickening
• Centrilobular nodules
• Mosaic perfusion and air trapping

Pulmonary edema:

Pulmonary edema is caused by hydrostatic or oncotic pressure changes, and/

or increased capillary permeability. In cases of increased pulmonary hypertension,
pulmonary edema progresses from vascular congestion to interstitial edema and finally,
alveolar edema.

Increased capillary permeability is commonly observed in cases of diffuse alveolar

damage (DAD, see further down for details).

Distribution:

• Depending on patient position, lung architecture, cardiac disease, and

neurogenic effects (Fig. 21)

Ancillary imaging findings:

• Pulmonary edema is the most common cause for GGO combined with
pronounced smooth interlobular thickening, however, this is still a very
unspecific finding on its own.

Pulmonary hemorrhage: (Fig. 22)

Pulmonary hemorrhage may be focal or diffuse.

Page 8 of 42
Causes of focal pulmonary hemorrhage may be identified on HRCT and include
bronchiectasis, malignancy, trauma, mycetoma, and thromboembolic disease.

Diffuse pulmonary hemorrhage is a manifestation of a systemic disorder such as

vasculitis, pulmonary-renal syndromes or decreased coagulation.

Distribution:

• Unspecific - focal or diffuse, symmetric or asymmetric GGO

Ancillary imaging findings:

• Consolidations
• Centrilobular GGO nodules
• Interlobular septal thickening in the subacute stage when the hemorrhage is
removed over the interstitially located lymphatic vessels.

Diffuse alveolar damage (DAD):

DAD is the pathological correlate of the adult respiratory distress syndrome (ARDS) which
may occur secondarily to a multitude of causes (e.g., trauma, inhalation injury, infection,
multi-organ dysfunction, …) or idiopathically (= acute interstitial pneumonia).

Distribution:

• Starts in the periphery followed by a diffuse distribution.

Ancillary imaging findings:

• Patchy consolidations = hyaline organization in the alveoli (Fig. 23).

• Fibrotic features can be seen in anterior lung parts in patients who survive -
this represents ventilator-associated lung damage.

Aspiration:

Aspiration shows an acute onset and occurs in a variety of disorders, such as

gastroesophageal reflux disease or dysphagia (neurogenic disorders).

Distribution:

• Depending on patient position. In the recumbent patient, GGO or

consolidation is frequently seen in the posterior segments of the upper

Page 9 of 42
 lobes or apical segments of the lower lobes. In the standing patient, GGO or
consolidation is usually localized in the basal lower lobes, predominantly on
the right side.

Ancillary imaging findings:

• Tree in bud
• Consolidations

Acute hypersensitivity pneumonitis (HP):

An acute presentation of HP is rare and is similar in appearance to the subacute stage

of HP (see further down).

Acute eosinophilic pneumonia (AEP): (Fig. 24)

AEP is characterized by an acute onset of respiratory symptoms and commonly occurs

in smokers. While bronchoalveolar lavage and pathology show eosinophilic infiltration,
peripheral eosinophilia is often missing in AEP. While Corticosteroids may achieve rapid
amelioration within days, AEP may also progress towards fatal ARDS.

Distribution:

• Diffuse or extensive GGO

Ancillary imaging findings:

• Consolidations
• Unspecific smooth interlobular septal thickening
• Nodules

2.) Chronic:

Non-specific interstitial pneumonia (NSIP): (Fig. 25)

NSIP may be cellular (with more inflammation and possibly reversible) or fibrotic
(irreversible). Its commonest association is connective tissue disease and when there is
an NSIP-pattern in such a patient this is enough for diagnosis even without a biopsy.

Distribution:

Page 10 of 42
 • Lower and subpleural with a sparing of the immediate subpleural parts of the
lung (in 50% of NSIP-cases)
• Involves the costophrenic angle

Ancillary imaging findings:

• Cellular: Fine reticulation and traction bronchiectasis are possible (these can
be quite extensive but are still reversible)
• Fibrotic: Irregular reticulation and traction bronchiectasis; honeycombing is
rare and only minor compared to usual interstitial pneumonia (UIP) pattern

Desquamative interstitial pneumonia (DIP) and Respiratory bronchiolitis (RB): (Fig.

26)

An inflammatory reaction in smokers from alveolar macrophages surrounding the

bronchioles; there is a strong overlap of RB and DIP. They often coexist as they resemble
different manifestations of the same pathological spectrum.
A history of smoking, GGO, emphysema, and cysts are enough for the diagnosis of DIP
without a biopsy.

Distribution:

• Centrilobular GGO (RB)

• Lower and peripheral GGO (DIP)

Ancillary imaging findings:

• Cysts (not as many as in other cystic lung diseases)

• Emphysema
• Mosaic perfusion and air trapping (not as much as in hypersensitivity
pneumonitis)

Lymphocytic interstitial pneumonia (LIP) and follicular bronchiolitis (FB): (Fig. 27)

An infiltration with lymphoid follicles in the interstitium (LIP) and around bronchioles (FB);
there is a strong overlap of LIP and FB. They often coexist as they resemble different
manifestations of the same pathological spectrum.
The diagnosis of LIP or FB is more likely in patients with a history of immunosuppression
or connective tissue disease (especially Sjögren's disease).

Distribution:

Page 11 of 42
 • Centrilobular GGO (FB)
• Patchy GGO (LIP)

Ancillary imaging findings:

• Cysts make LIP more likely and may be the only finding in LIP, especially in
association with Sjögren's disease.
• Sometimes perilymphatic nodules and consolidations (LIP)
• Rarely slight mosaic perfusion and air trapping

Organizing pneumonia (OP): (Fig. 28)

50% of OPs are idiopathic (= cryptogenic OP; COP) and 50% are in association with
other diseases (especially infections and hypersensitivity pneumonitis). OP responds to
steroids but can recur after the treatment has finished.

Distribution:

• Lower lobes
• Curvilinear bands in a subpleural or peribronchovascular location

Ancillary imaging findings:

• Mass-like or focal consolidations

• Reversed-halo or atoll sign = surrounding consolidations with central GGO

Subacute/chronic hypersensitivity pneumonitis (HP): (Fig. 5)

Overshooting immune reaction to organic antigen exposure (e.g., bird droppings, hay,
…) leads to symptoms over the course of weeks to months. An acute progression after
exposure to large amounts of antigen is rare.

Distribution:

• Patchy and bilateral

• Upper lung, but may involve mid to lower lung as well
• Spares the costophrenic angle

Ancillary imaging findings:

• Distinct mosaic perfusion and air trapping

Page 12 of 42
 • Centrilobular GGO-nodules representing peribronchiolar inflammation (HP
is the commonest cause of GGO-nodules and these are diagnostic together
with an antigen-exposure)
• Headcheese-sign
• Additional fibrotic alterations in chronic HP

Eosinophilic pneumonia (EP): (Fig. 24)

EP shows a peripheral eosinophilic infiltration of the lung and an increase in blood

eosinophiles. Chronic EP is the most common idiopathic eosinophilic disease.
There are several clinical associations depending on the subtype of EP, especially
asthma (chronic EP, and others), cardiac and nervous system (hypereosinophilic
syndrome), central nervous system and skin (eosinophilic vasculitis = Churg-Strauss-
Syndrome).

Distribution:

• Upper and peripheral

• Sometimes peribronchovascular (chronic eosinophilic pneumonia)
• Diffuse GGO (hypereosinophilic syndrome)

Ancillary imaging findings:

• Consolidation and reversed-halo-sign (chronic eosinophilic pneumonia)

• Centrilobular GGO-nodules (Churg-Strauss)

Sarcoidosis: (Fig. 29)

Normally, a perilymphatic distribution is the typical finding in pulmonary sarcoidosis.

However, in rare cases, GGO can be the predominant pattern.

Distribution:

• Peripheral patchy GGO (representing alveolar collapse due to multiple

micro-granulomas)

Ancillary imaging findings:

• Mediastinal and bihilar lymphadenopathy

• Other, more typical findings of sarcoidosis such as consolidations
surrounded by nodules (= galaxy-sign) and perilymphatic nodules.

Page 13 of 42
Mucinous adenocarcinoma of the lung: (Fig. 30)

Whereas the non-mucinous type of adenocarcinoma is more likely to result in a single

GGO-nodule, the mucinous type grows alongside the inner walls of the bronchioles (=
lepidic growth), secretes fluids and leads to a bronchopneumonia-like image.
Patients may produce large amounts of watery sputum (= bronchorrhea)

Distribution:

• Asymmetric, focal or diffuse, uni- or bilateral

Ancillary imaging findings:

• Centrilobular nodules are common

• Consolidations
• Crazy paving

Pulmonary alveolar proteinosis (PAP): (Fig. 16)

An autoimmune reaction leads to a decreased removal of lipoproteins in the alveoli.

Nearly 90% are idiopathic and symptoms are nonspecific.
CT can guide the bronchoalveolar lavage and monitor the treatment effect.

Distribution:

• Diffuse and geographical distribution

Ancillary imaging findings:

• Crazy paving is typical but nonspecific. After bronchoalveolar lavage, the

GGO decreases, whereas the septal thickening may remain.

Page 14 of 42
Images for this section:

Fig. 1: The pathomechanism of GGO is the partial collapse or filling of the alveoles, or
the compression by an increase in interstitial tissue.

© Department of Biomedical Imaging and Image-guided Therapy, Medical University of

Vienna - Vienna/AT

Page 15 of 42
Fig. 2: The same axial slice through the upper part of a lung with reticular abnormalities
and ground glass opacification. In expiration (left image), the membranous posterior part
of the trachea bulges anteriorly (black arrow) and the lung parenchyma shows a markedly
higher attenuation, decreasing the visibility of true pathological changes; deep inspiration
(right image).

© Department of Biomedical Imaging and Image-guided Therapy, Medical University of

Vienna - Vienna/AT

Fig. 3: On the left image, the GGO in the posterior lower lobes represents dependent
atelectasis. On the right image, after repeating the scan in a prone position, the GGO has

Page 16 of 42
vanished allowing the differentiation from pathological lung alterations (e.g., interstitial
lung abnormalities).

© Department of Biomedical Imaging and Image-guided Therapy, Medical University of

Vienna - Vienna/AT

Fig. 4: If mosaic perfusion is present, the less attenuating parts (blue circles) are the
pathological lung and the higher attenuating parts are the normal lung. Healthy lung tissue
shows more and thicker vessels (black arrows).

© Department of Biomedical Imaging and Image-guided Therapy, Medical University of

Vienna - Vienna/AT

Page 17 of 42
Fig. 5: The head-cheese-sign consists of 3 different patterns: GGO (white arrow), normal
lung (black arrow), and mosaic perfusion / air trapping (blue circles). This is a case of
hypersensitivity pneumonitis, a typical example for a disease with this pattern.

© Department of Biomedical Imaging and Image-guided Therapy, Medical University of

Vienna - Vienna/AT

Page 18 of 42
Fig. 6: The diagnostic approach should be adjusted to whether GGO is acute (less than
a few weeks) or chronic (more than 6 weeks).

© Department of Biomedical Imaging and Image-guided Therapy, Medical University of

Vienna - Vienna/AT

Page 19 of 42
Table 1: Clinical features and their associated pathologies in cases with diffuse GGO

© Department of Biomedical Imaging and Image-guided Therapy, Medical University of

Vienna - Vienna/AT

Page 20 of 42
Fig. 7: Pathologies with GGO in a mid to lower distribution; the image is taken from a
case of NSIP. One of the most important locations to look at in a lower distribution of
chronic GGO is the costophrenic angle, which may be involved (NSIP, DIP) or spared
(HP). NSIP - non specific interstitial pneumonia DIP - desquamative interstitial pneumonia
HP - hypersensitivity pneumonitis

© Department of Biomedical Imaging and Image-guided Therapy, Medical University of

Vienna - Vienna/AT

Fig. 8: The upper lung zones also include the apical segments of the lower lobes, as
shown in this image from a mild case of HP. HP - hypersensitivity pneumonitis RB -
respiratory bronchiolitis

© Department of Biomedical Imaging and Image-guided Therapy, Medical University of

Vienna - Vienna/AT

Page 21 of 42
Fig. 9: A peripheral distribution (a) is commonly found in different interstitial pneumonias.
b) shows a case OP with peripheral GGO and consolidations (black arrows). NSIP - non
specific interstitial pneumonia DIP - desquamative interstitial pneumonia OP - organizing
pneumonia EP - eosinophilic pneumonia

© Department of Biomedical Imaging and Image-guided Therapy, Medical University of

Vienna - Vienna/AT

Fig. 10: The image in b) is taken from an acute case of GGO (pneumonia). HP -
hypersensitivity pneumonitis PAP - pulmonary alveolar proteinosis

Page 22 of 42
© Department of Biomedical Imaging and Image-guided Therapy, Medical University of
Vienna - Vienna/AT

Table 2

© Department of Biomedical Imaging and Image-guided Therapy, Medical University of

Vienna - Vienna/AT

Page 23 of 42
Fig. 11: GGO with fibrotic changes such as irregular reticulation (white arrow), traction
bronchiectasis (black arrow) and volume loss (arrow-heads) is a typical pattern of non-
specific interstitial pneumonia (NSIP). In this case, because there is only little GGO, a
probable usual interstitial pneumonia (UIP) pattern must be mentioned as a differential.

© Department of Biomedical Imaging and Image-guided Therapy, Medical University of

Vienna - Vienna/AT

Page 24 of 42
Fig. 12: The tree-in-bud-sign is quite specific for infections (with some rarer exceptions).
The pathomechanism is detritus inside of the bronchioles and alveoles, leading to an
increased attenuation in the typical shape of a budding twig. Tree-in-bud may be well
defined (black arrow) or coalesce with peribronchovascular GGO when the inflammation
starts to spread arround the bronchioles (white arrow).

© Department of Biomedical Imaging and Image-guided Therapy, Medical University of

Vienna - Vienna/AT

Page 25 of 42
Fig. 13: If GGO is found in conjunction with inflammatory bronchiectasis (black arrows)
and airway wall thickening (white arrows), the main differential diagnosis includes
infectious airways disease (e.g., exacerbation in cystic fibrosis).

© Department of Biomedical Imaging and Image-guided Therapy, Medical University of

Vienna - Vienna/AT

Page 26 of 42
Fig. 14: Diffuse GGO together with cysts (black arrows) may occur in pneumocystis
jirovecii infection (PCP), desquamative interstitial pneumonia (DIP) and lymphocytic
interstitial pneumonia (LIP).

© Department of Biomedical Imaging and Image-guided Therapy, Medical University of

Vienna - Vienna/AT

Page 27 of 42
Fig. 15: As smoking is a typical risk factor of desquamative interstitial pneumonia (DIP)
and respiratory bronchiolitis (RB), emphysema (black arrows) is often encountered as an
ancillary imaging finding, such as in this patient with DIP.

© Department of Biomedical Imaging and Image-guided Therapy, Medical University of

Vienna - Vienna/AT

Page 28 of 42
Fig. 16: Crazy paving is a typical pattern found in pulmonary alveolar proteinosis. In
an acute setting, however, the differential diagnoses are basically the same as in GGO
without the addition of interlobular septal thickening.

© Department of Biomedical Imaging and Image-guided Therapy, Medical University of

Vienna - Vienna/AT

Page 29 of 42
Fig. 17: Centrilobular GGO-nodules are evenly spaced and show a subpleural sparing.
They represent peribronchiolar infiltration with different kinds of cells, depending on their
aetiology (e.g., in hypersensitivity pneumonitis, respiratory- or follicular bronchiolitis).

© Department of Biomedical Imaging and Image-guided Therapy, Medical University of

Vienna - Vienna/AT

Fig. 18: Solid nodules may be present together with diffuse GGO in aspiration,
endobronchial spread of tumors or infection, and also, rarely, in diseases that would
normaly show GGO-nodules (e.g., hypersensitivity pneumonitis).

© Department of Biomedical Imaging and Image-guided Therapy, Medical University of

Vienna - Vienna/AT

Page 30 of 42
Fig. 19: In acute interstitial pneumonia (a), the consolidations (black arrows) typically
represent the complete filling of alveoli with hyaline material. Mucinous adenocarcinoma
of the lung (b) may show extensive regions of GGO (this is mucus produced by the tumor
cells which line the inner bronchial walls) and consolidations in regions with increased
risk of invasion.

© Department of Biomedical Imaging and Image-guided Therapy, Medical University of

Vienna - Vienna/AT

Page 31 of 42
Fig. 20: In this case of Pneumocystis jirovecii pneumonia, GGO is the predominant
pattern in a bilateral, diffuse distribution. Depending on whether inhalative medication
was administered, either the upper or the lower zones may be involved to a greater extent,
demonstrating the limited value of distribution patterns in acute cases of diffuse GGO.

© Department of Biomedical Imaging and Image-guided Therapy, Medical University of

Vienna - Vienna/AT

Fig. 21: In an acute setting, distribution of GGO is not suitable to guide the diagnosis.
Both a) and b) are pulmonary edemas in two different patients. Here, the correct diagnosis
can be made when taking together the acute GGO, a history of cardiac or renal disease,
and the effusion.

© Department of Biomedical Imaging and Image-guided Therapy, Medical University of

Vienna - Vienna/AT

Page 32 of 42
Fig. 22: Pulmonary hemorrhage (here in systemic lupus erythematodus) may show
centrilobular nodules of GGO (blue circle) that coalesce to focal (black arrows) or
ultimately diffuse GGO.

© Department of Biomedical Imaging and Image-guided Therapy, Medical University of

Vienna - Vienna/AT

Fig. 23: Acute interstitial pneumonia at a) baseline, b) after 6 weeks, and c) after 14
weeks. Diffuse GGO changes to focal consolidations (black arrow) which represent intra-
alveolar hyaline membranes.

Page 33 of 42
© Department of Biomedical Imaging and Image-guided Therapy, Medical University of
Vienna - Vienna/AT

Fig. 24: Acute eosinophilic pneumonia shows diffuse lobar GGO with consolidations
(black arrow). An improvement after the administration of corticosteroids is another typical
finding.

© Department of Biomedical Imaging and Image-guided Therapy, Medical University of

Vienna - Vienna/AT

Page 34 of 42
Fig. 25: There are peripherally distributed regions of GGO (black arrows) in this case
of non specific interstitial pneumonia (NSIP). If present, a sparing of the immediate
subpleural lung is specific for NSIP.

© Department of Biomedical Imaging and Image-guided Therapy, Medical University of

Vienna - Vienna/AT

Page 35 of 42
Fig. 26: A smoking history, GGO in a lower distribution and cysts (white arrow) are key
findings in making the diagnosis of desquamative interstitial pneumonia (DIP).

© Department of Biomedical Imaging and Image-guided Therapy, Medical University of

Vienna - Vienna/AT

Page 36 of 42
Fig. 27: In patients with immunosuppression or connective tissue disease, and diffuse
GGO with cysts (black arrows), lymphocytic interstitial pneumonia (LIP) must be included
as a differential diagnosis. However, in patients with Sjögren's disease, cysts may be the
only imaging finding without any GGO.

© Department of Biomedical Imaging and Image-guided Therapy, Medical University of

Vienna - Vienna/AT

Page 37 of 42
Fig. 28: There are different patterns of organizing pneumonia (OP). a) a case of
peribronchovascular OP with an inversed-halo-sign (GGO in the center with a peripheral
rim of consolidation). b) the OP is located peripherally in the posterior lower lobes (black
arrow).

© Department of Biomedical Imaging and Image-guided Therapy, Medical University of

Vienna - Vienna/AT

Page 38 of 42
Fig. 29: The diffuse and bilateral GGO in this image is an uncommon manifestation
of pulmonary sarcoidosis. The impression of GGO is merely generated by the vast
amount of tiny nodules in the lung interstitium that lead to a collaps of adjacent alveoles.
(Pulmonary sarcoidosis typically shows multiple nodules in a perilymphatic distribution)

© Department of Biomedical Imaging and Image-guided Therapy, Medical University of

Vienna - Vienna/AT

Page 39 of 42
Fig. 30: In this case of mucinous alveolar adenocarcinoma of the lung, most of the GGO
is a representation of the mucus secreted by the tumor cells that line the insides of the
bronchioles. There are only smaller areas of consolidation (black arrows). If the solid
parts increase in size, this may be hinting at increased risk of invasion.

© Department of Biomedical Imaging and Image-guided Therapy, Medical University of

Vienna - Vienna/AT

Page 40 of 42
Conclusion

Three questions guide the differential diagnosis of diffuse GGO:

1. Is it a pathology?
2. Is the GGO acute or chronic?
3. What is the patient's medical history?

Followed by the review of imaging findings regarding:

• Spatial and temporal distribution of GGO

• Ancillary imaging findings

Page 41 of 42
References

(1) Collins J, Stern EJ. Ground-glass opacity at CT: the ABCs. AJR American journal of
roentgenology. 1997;169(2):355-67.

(2) Müller NL, Franquet T, Lee KS et-al. Imaging of pulmonary infections. Lippincott
Williams & Wilkins. (2007) ISBN:078177232X.

(3) Collins, Jannette, and Eric J. Stern. 2012. Chest Radiology: The Essentials. Lippincott
Williams & Wilkins.

(4) Elicker, Brett M., and W. Richard Webb. 2012. Fundamentals of High-Resolution Lung
CT: Common Findings, Common Patters, Common Diseases and Differential Diagnosis.
Lippincott Williams & Wilkins.

Page 42 of 42