Download Acute Lung Injury: HRCT and Histopathologic Spectrum

Acute Lung Injury: HRCT and Histopathologic Spectrum
Obadina ET , Kanne JP , Torrealba JR , Meyer CA
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1. University of Wisconsin Department of Radiology, Madison, WI; 2. University of Wisconsin Department of Pathology, Madison, WI
INTRODUCTION
ACUTE FIBRINOUS AND ORGANIZING PNEUMONIA
ORGANIZING PNEUMONIA
Acute lung injury (ALI) and acute respiratory distress syndrome
(ARDS) are major pulmonary causes of morbidity and mortality.
Acute pulmonary injury often results in acute hypoxemic
respiratory failure. Patients with acute pulmonary injury typically
present clinically with ARDS. ARDS was formally defined in 1994
by the American–European Consensus Conference on ARDS as
acute hypoxemia with a ratio of partial pressure of arterial oxygen
to the fraction of inspired oxygen (i.e., PaO2:FIO2) of 200 mm Hg
or less, bilateral infiltrates with a radiographic appearance that is
consistent with pulmonary edema, and no evidence of cardiac
failure clinically. ALI is less severe than ARDS and has similar
diagnostic criteria with the exception of PaO2:FIO2 of 300 mm Hg.
Acute fibrinous and organizing pneumonia (AFOP) is
a recently described histologic pattern associated with
ALI. Most patients present with severe respiratory failure
similar to ARDS. However, a small subset of patients
may have a subacute clinical course not requiring
ventilatory support. AFOP can be idiopathic or related
to insults such as drug reaction.
Organizing pneumonia (OP) most often presents with a subacute
clinical course without fulminant respiratory failure. Although it
is not associated with clinical ALI or ARDS, OP is discussed in
this exhibit because it is frequently included in the pathologic
differential diagnosis of ALI. The underlying causes of OP include
infection, collagen vascular disease and drug reaction. It can
also be idiopathic, which is clinically referred to as cryptogenic
organizing pneumonia (COP).
When examined pathologically, most patients with clinical ARDS
and ALI will show histologic evidence of diffuse alveolar damage
(DAD). However, it should be emphasized that these terms are
not synonymous. Other histologic patterns have been described
in association with ALI/ARDS. These include acute eosinophilic
pneumonia (AEP), acute fibrinous and organizing pneumonia
(AFOP), and diffuse alveolar hemorrhage (DAH). Organizing
pneumonia (OP) is also included in the differential diagnosis of
ALI. This exhibit will illustrate the HRCT findings in the spectrum
of acute lung injury with histopathologic correlation.
DIFFUSE ALVEOLAR DAMAGE
Diffuse alveolar damage (DAD) is the most common histologic
manifestation of ARDS and ALI. Patients present with severe
hypoxemia and almost always require mechanical ventilation.
While the precise mechanism of injury is unclear, capillary
endothelial and alveolar epithelial damage result in exudation of
fluid and products of cellular breakdown. With time, pneumocyte
hyperplasia and fibroblast proliferation ensue.
The histologic appearance of DAD is divided into three phases:
the acute or exudative phase, the organizing or proliferative
phase, and the chronic or fibrotic phase. The acute phase occurs
during the first week after the initial insult, and findings may
include intra–alveolar edema, interstitial widening, and hyaline
membranes (composed of cellular and proteinaceous debris).
Thrombi may also be seen as a result of localized alterations
in the coagulation pathway. The organizing phase follows
with features of interstitial fibrosis and type 2 pneumocyte
hyperplasia. Squamous metaplasia, residual hyaline membranes,
and organizing fibroblastic tissue within air spaces may also
be present. The fibrotic phase is characterized by features of
interstitial lung fibrosis.
AFOP
HRCT image of a patient with drug–induced AFOP
demonstrating extensive peribronchial, subpleural,
and perilobular consolidation and ground–
glass opacity, similar to but more extensive than
organizing pneumonia.
The dominant histopathologic finding in AFOP is
fresh intra–alveolar fibrin or so–called “fibrin balls.”
Hyaline membranes should not be present, in contrast
to DAD. Other histologic findings that can be seen with
AFOP include mild interstitial widening, lymphocytic
infiltrates, and organizing fibroblastic tissue.
HRCT findings of AFOP are not well described
but include peripheral and peribronchial foci of
consolidation and ground–glass opacity, similar to
organizing pneumonia, but greater in extent with
superimposed features more typical of DAD.
AFOP, 200X
Lung tissue demonstrates alveolar parenchyma
with predominantly intra–alveolar fibrin
aggregates (“fibrin balls”) within airspaces.
Associated mild interstitial mononuclear
infiltrate is also noted.
AEP is characterized by fever, hypoxemia, peripheral eosinophilia
and fulminant respiratory failure. AEP may be idiopathic or
result from infection (especially parasites), toxic inhalation, drug
reaction, and recent onset of heavy smoking. At BAL, eosinophils
are generally greater than 25%. In contrast to other forms of
ALI, patients with AEP usually have a dramatic response to
corticosteroids.
Diffuse alveolar hemorrhage (DAH) is characterized by
hemorrhage into the alveolar spaces, and is due to injury to the
alveolar microcirculation. Patients with DAH typically present
with hypoxemia and occasionally present with fulminant
respiratory failure. When there is significant alveolar hemorrhage,
patients will often present clinically with hemoptysis. Although
DAH can occur with or without capillaritis, it is the cases of
DAH with capillaritis that may present with clinical findings of
ALI. Causes of DAH include immune–mediated disorders such as
collagen vascular diseases, microscopic polyangiitis, Goodpasture
syndrome, Wegener granulomatosis, drug reactions, and
infections.
Histopathologic findings of AEP include intra–alveolar fibrin,
macrophages, hyaline membranes (similar to the acute phase of
DAD), and numerous eosinophils. Eosinophils may be present in
the interstitium, may infiltrate blood vessel walls, and may form
eosinophilic microabscesses.
HRCT findings of acute eosinophilic pneumonia are nonspecific,
and include consolidation and ground–glass opacities in a random
(2/3) or peripheral (1/3) distribution. Smooth interlobular septal
thickening and small pleural effusions are frequently present and,
in the absence of cardiomegaly, are helpful clues to the diagnosis.
Figure 5
Acute
Eosinophilic
Pneumonia
HRCT image of a
young female patient
with recent onset of
smoking shows diffuse
septal thickening and
multiple peripheral foci
of lung consolidation.
Figure 6
Eosinophilic
Pneumonia (200X)
This section of lung shows
interstitial widening
accompanied by mixed
infiltrates of lymphocytes,
macrophages and
eosinophils. Focal alveolar
fibroblastic proliferation is
also present (arrow).
Figure 10
HRCT image of
a patient with
cryptogenic
organizing pneumonia
demonstrates ground–
glass attenuation
nodules with
faint peripheral
consolidation (“reverse
halo”) in addition to
nodular foci of lung
consolidation.
Organizing Pneumonia
10a. 40X
Lung section shows
diffuse filling of the
alveolar spaces with
fibroblastic plugs
(Masson bodies),
involving the
respiratory bronchioles,
alveolar sacs and
alveoli.
10b. 200X
HRCT findings of DAH consist of extensive bilateral ground–glass
opacities, which may be diffuse or patchy, often in an “acinar”
distribution. Subpleural sparing is often a useful diagnostic feature.
With subacute DAH, small poorly defined centrilobular nodules
and interlobular septal thickening can develop, presumably
related to lymphatic resorption of the blood.
Alveolar spaces are diffusely
occupied by proliferation
of fibroblasts and myxoid
connective tissue (Masson
bodies) plugging the
terminal bronchioles,
alveolar sacs and alveoli.
There is associated vascular
congestion and minimal
focal lymphocytic infiltrate.
Figure 7
Diffuse Alveolar
Hemorrhage
HRCT image shows
bilateral ground–
glass acinar nodules,
predominantly affecting
the right lung, with
relative sparing of
the peripheral lung
parenchyma.
Diffuse Alveolar
Hemorrhage
CONCLUSION
The patterns of acute lung injury and acute respiratory distress
syndrome have different HRCT and histopathologic features.
Knowledge of the characteristics and features of the different
patterns in the spectrum of ALI and ARDS is important and helpful
for guiding appropriate diagnosis and treatment of affected
patients.
8a. 100X
Lung tissue shows
alveolar parenchyma with
patchy, intra–alveolar cell
infiltrates predominantly
consisting of hemosiderin–
laden macrophages.
Figure 2
8b. 400X
HRCT of the same patient (from Figure 1a),
obtained three months later, demonstrates
interstitial fibrosis characterized by reticulation,
traction bronchiectasis, and ground–glass
opacity with a basal predominance.
HRCT findings of OP are airspace consolidation in a subpleural
or peribronchial distribution. Ground–glass opacities may also be
present, often with a bilateral asymmetric distribution. The reverse
halo sign may be present in almost 20% of cases.
Histopathologic findings seen in DAH include diffuse intra–
alveolar blood admixed with hemosiderin–laden macrophages.
Organizing fibroblastic tissue may also be present. In capillaritis,
neutrophils are seen within alveolar septa with resultant vascular
necrosis. Hyaline membranes may also be present.
Figure 8
Diffuse Alveolar Damage
1b. Fibrotic Phase
Histopathologic findings seen in OP include patchy accumulation
of loose plugs of granulation tissue (Masson bodies) in the
alveoli and respiratory bronchioles. Mild alveolar septal chronic
inflammation is often present.
Figure 9
Organizing
Pneumonia
DIFFUSE ALVEOLAR
HEMORRHAGE
1a. Acute Phase
HRCT image of a patient with acute DAD shows
patchy consolidation and ground–glass opacities.
Figure 4
ACUTE EOSINOPHILIC
PNEUMONIA
Initially, HRCT usually shows heterogeneous foci of consolidation
and ground–glass opacity with a posterior and basal
predominance. In the healing phase, findings of fibrosis such as
reticulation, architectural distortion and traction bronchiectasis
may be present.
A recent study evaluating the predictive value of CT for survival
in patients with ARDS demonstrated higher mortality in those
patients with
Figure 1
greater than 80%
lung involvement,
Diffuse Alveolar Damage
RA/LA ratio
greater than 1, and
varicoid traction
bronchiectasis.
Figure 3
2a. Acute Phase, 400X
2b. Organizing Phase, 200X
Lung section shows alveolar lung parenchyma
with hyaline membranes (arrows), intra–
alveolar red cells and interstitial mononuclear
inflammatory infiltrates.
After the acute phase, hyaline membranes
become incorporated in alveolar septa with
fibroblast proliferation and septal widening.
Interstitial inflammatory infiltrates may persist
at this stage.
In this lung section,
the alveolar spaces are
filled with pigmented
macrophages. The
cytoplasms of these
macrophages show
coarse, thick granules,
corresponding
to hemosiderin.
Rare interstitial
polymorphonuclear cells
and plasma cells are also
seen in this case.
REFERENCES
1. Beasley MB. The Pathologist’s Approach to Acute Lung Injury. Arch Pathol Lab Med
2010; 134: 719-727.
2. Bernard GR, Artigas A, Brigham KL, et al. The American-European Consensus
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coordination. Am J Respir Crit Care Med 1994; 149(3): 818-824.
3. Muller NL, Silva CI. Imaging of the Chest. Philadelphia: Saunders, 2008.
4. The Armed Forces Institute of Pathology Website: www.afip.org
5. Chung JH, Kradin RL, Greene RE, et al. CT Predictors of mortality in pathology
confirmed ARDS. Eur Radiol 2010. Epub DOI 10.1007/s00330-010-1979-0.
6. Daiman T et al. Acute eosinophilic pneumonia: Thin-section CT findings in 29 patients.
Eur J Radiol 2008; 65: 462-465.
7. Kim SJ, Lee KS, Ryu YH, et al. Reversed halo sign on high resolution CT of cryptogenic
organizing pneumonia: diagnostic implications. Am J Roentgenol 2003; 180: 1251e4.
Corresponding Author:
Eniola Obadina, MD
University of Wisconsin Department of Radiology
E3/312 CSC
Madison, WI 53792–3252
[email protected]