See discussions, stats, and author profiles for this publication at: https://www.researchgate.

net/publication/11330147

Organizing pneumonia: The many morphological faces

Article  in  European Radiology · July 2002

DOI: 10.1007/s00330-001-1211-3 · Source: PubMed

CITATIONS READS

89 947

2 authors, including:

Anastasia Oikonomou
University of Toronto, Sunnybrook Health Sciences Centre
63 PUBLICATIONS   918 CITATIONS   

SEE PROFILE

All content following this page was uploaded by Anastasia Oikonomou on 04 June 2014.

The user has requested enhancement of the downloaded file.

Eur Radiol (2002) 12:1486–1496
DOI 10.1007/s00330-001-1211-3 CHEST

Anastasia Oikonomou Organizing pneumonia:

David M. Hansell
the many morphological faces

Received: 18 July 2001 / Accepted:
25 September 2001 / Published online:
13 November 2001
© Springer-Verlag 2001
A. Oikonomou · D.M. Hansell (✉)
Department of Radiology, Royal Brompton
Hospital, Sydney Street, London SW3
6NP, England
e-mail: d.hansell@rbh.nthames.nhs.uk
Tel.: +44-20-73518034
Fax: +44-20-73518098
Abstract Organizing pneumonia is
a non-specific response to various
forms of lung injury and is the
pathological hallmark of the distinct
clinical entity termed cryptogenic
organizing pneumonia. The typical
imaging features of this syndrome
have been widely documented and
consist of patchy air-space consoli-
dation, often subpleural, with or
without ground-glass opacities. The
purpose of this article is to highlight
the less familiar imaging patterns
of organizing pneumonia which in-
clude focal organizing pneumonia, a
variety of nodular patterns, a bron-
chocentric distribution, band-like
opacities, a perilobular pattern and a
progressive fibrotic form of organiz-
ing pneumonia.
Keywords Organizing pneumonia ·
Computed tomography · Patterns

Introduction coined as a term by Epler et al. [6] to emphasise to the

Organizing pneumonia is one of the main reparative re-
actions to acute injury by the lung and reflects the in-
complete resolution of inflammation within the alveoli,
and to a lesser extent the distal bronchioles [1, 2, 3]. Al-
though this pathological pattern is non-specific, given
that it can be incited by many different types of “injury”,
it is the particular hallmark of a more or less distinct
clinicopathological syndrome which has been given the
name cryptogenic organizing pneumonia (COP) [4].
Since the first description of COP in 1983 by Davison
et al. [5], and the later report on bronchiolitis obliterans
organizing pneumonia (BOOP) by Epler et al. [6], much
has been written about the terminology. There have also
been numerous reports about the typical radiographic
findings that characterize this entity. The purpose of this
article is to highlight the variable and sometimes idio-
syncratic imaging appearances of organizing pneumonia.
Terminology
The competing terms, i.e. COP vs BOOP, have generated
much discussion over the years. “BOOP” was first
pathological distribution of the pneumonic process in
both alveoli and terminal bronchioles; however, the use
of bronchiolitis obliterans in this term was a major
source of confusion because of the semantic similarity
that “BOOP” shared with bronchiolitis obliterans (oblit-
erative bronchiolitis) which is a completely different
entity [2, 3, 4, 7, 8]: obliterative bronchiolitis is an ob-
structive small airways disease with poor response to
treatment, without intraluminal exudate, in which bron-
chioles are cicatrized and replaced by scanty fibrotic
remnants. BOOP, on the other hand, is predominantly an
air-space process in which terminal bronchioles may be
filled with granulation tissue; but the airways are not
obliterated in the true sense of the word. The cardinal
component of “BOOP” is the organizing pneumonia, and
this is reflected by a restrictive, not obstructive, func-
tional deficit [3, 4, 8, 9, 10]. To overcome this confusion
“COP” has been suggested as the preferred term for the
clinicopathological syndrome as it conveys the essential
features of the entity [2, 3, 4, 9, 10].
Although it seems likely that some authors will per-
sist with the usage of BOOP, a working group sponsored
by the American Thoracic Society and the European
Respiratory Society has abandoned the term BOOP alto-
 1487

Table 1 Causes of organizing pneumonia and associations with

other conditions

Infection
Bacterial
– Streptococcus pneumonia [15]
– Legionella pneumophila [16]
– Mycoplasma pneumonia [17]
– Coxiella burnetti [18]
– Nocardia asteroides [19]
– Chlamydia pneumonia [20]
Viral
– Adenovirus [21]
– Cytomegalovirus [14]
– Influenza [22] and parainfluenza [3, 23]
– Human immunodeficiency virus [24]
Fig. 1 An open-lung biopsy specimen showing polypoidal masses Drugs
of organized granulation tissue (Masson bodies) within the alveoli. Antibiotics
The intervening alveolar walls show mild thickening by an inflam- – Amphotericin B [14]
matory infiltrate, but the lung architecture is otherwise preserved. – Cephalosporins [25]
There are no features of established fibrosis. (Courtesy of A.G. – Minocycline [26]
Nicholson) – Nitrofurantoin [27]
Others
– Sulfasalazine [28]
gether and has put its authority behind the terms organiz- – Bleomycin [29]
ing pneumonia and COP to describe the pathological and – Amiodarone [30]
clinical entities, respectively [11]. – Acebutolol [31]
– Busulfan [32]
– Barbiturates [33]
– Paraquat [34]
Histology – Cocaine [35]
– Gold [36]
Histologically, organizing pneumonia is characterized – Phenytoin [37]
by the presence of buds of granulation tissue in the distal Connective tissue disorders
air spaces comprising fibrin exudates and collagen- – Systemic lupus erythematosus [38]
containing fibroblasts. The fibroblasts are embedded in a – Rheumatoid arthritis [39]
myxoid matrix with a variable infiltrate of lymphocytes, – Sjogren syndrome [40]
macrophages, plasma cells, neutrophils and eosinophils – Polymyositis [40]
forming characteristic elongated polypoidal masses – Dermatomyositis [41]
– Polymyalgia rheumatica [42]
(Masson bodies or bourgeons conjonctifs; Fig. 1); these
are located predominantly in the alveolar spaces but of- Immunological disorders
ten extend into bronchiolar lumens. The buds of connec- – Common variable immunodeficiency syndrome [43]
tive tissue frequently extend directly from one alveolus – Essential mixed cryoglobulinaemia [44]
to the next, through the pores of Kohn, producing a char- Organ transplantation
acteristic “butterfly” pattern. There is no disturbance of – Bone marrow [45]
the lung architecture. Other histological features include – Lung [46]
chronic inflammation in the walls of the surrounding – Renal [47]
alveoli with minor infiltration of the interstitium by Miscellaneous
mononuclear cells [1, 4, 6, 9, 10]. In a few cases the in- – Inflammatory bowel disease [48]
flammatory infiltrate is more intense with the incorpora- – Primary biliary cirrhosis [49]
tion of fibrosis in the alveolar walls [2, 10, 12]. – Polyarteritis nodosa [50]
– Haematological malignancies
– Myelodysplastic syndrome [51]
– T-cell leukaemia [52]
Association of OP with other conditions – Lymphoma [53]
– Seasonal syndrome with cholestasis [54]
It is worth emphasizing that there can be overlap be- – Radiotherapy [55, 56]
– Environmental exposure (textile printing dye) [57]
tween organizing pneumonia and other pneumonic enti- – Penicillium mould dust [58]
ties such as chronic eosinophilic pneumonia and extrin-
sic allergic alveolitis. In these conditions the presence of
clusters of eosinophils or occasional granulomas, in what
1488
would otherwise be regarded as organizing pneumonia,
suggest the diagnosis of eosinophilic pneumonia or ex-
trinsic allergic alveolitis, respectively [12]. Similarly,
diffuse alveolar damage in the organizing phase is simi-
lar to OP in that there is extensive cellular fibroblastic
proliferation associated with a myxoid-appearing matrix.
Diffuse alveolar damage differs in that the changes tend
to be more diffuse and uniform, with the characteristic
formation of hyaline membranes [9]. An organizing
pneumonia-like reaction can also be a major histological
feature in Wegener’s or bronchocentric granulomatosis
and other inflammatory lesions including lung abscesses,
pulmonary infarcts and lung cancer [12, 13, 14]. Indeed,
a component of organizing pneumonia is identifiable in
a huge variety of different contexts, including resolving
infection, as a drug reaction, in association with connec-
tive tissue disorders, and many other conditions. A sam-
ple of the many causes and association of organizing
pneumonia are given in Table 1.
Classical COP: clinical and imaging presentation
The “typical” COP syndrome is characterized by an in-
dolent onset of a flu-like illness accompanied with fever,
non-productive cough, malaise, anorexia and weight
loss. Dyspnoea is common but usually mild and evident
only on exertion. Less common symptoms are bronch-
orrhoea, haemoptysis (but severe haemoptysis is exceed-
ingly rare), chest pain, arthralgia and night sweats. It
affects men and women equally and occurs in middle-
aged adults with a peak incidence in the sixth decade. No
cause has been identified, although there is the suspicion
that infection, viral or otherwise, may be the trigger in
some cases; in particular, COP is not related to smoking.
The mean duration of symptoms at presentation varies,
but in most cases it is less than 3 months. Patients are
often prescribed antibiotics (without obvious effect) in
the belief that the clinical picture is of a community-
acquired pneumonia. Pulmonary function tests show a
mild to moderate restrictive defect and the total gas
transfer (Dlco) is reduced, although the Kco (gas transfer
adjusted for alveolar volume) is preserved. Arterial
hypoxaemia is occasionally severe and probably reflects
right-to-left shunting through consolidated lung. Airflow
obstruction is not a feature [4, 5, 6, 10, 59, 60].
The imaging in classical COP has been thoroughly
described [4, 5, 6, 10, 59, 61, 62, 63, 64, 65, 66, 67, 68].
The most usual radiographic appearance is of bilateral
patchy areas of air-space consolidation with a tendency
to progress and change location over time. Spontaneous
regression of some focal areas of consolidation is a strik-
ing feature. The CT findings mirror the radiographic ap-
pearances, but there is often associated ground-glass
opacification, and the distribution of disease is predomi-
nantly peripheral and lower zone (Fig. 2). An air bron-
Fig. 2 A 58-year-old woman from Kuwait with a 6-month history
of lethargy, night sweats and increasing breathlessness on exer-
tion. A standard CT shows the typical CT features of cryptogenic
organizing pneumonia. There are several basal and peripheral ar-
eas of air-space consolidation. A lung biopsy confirmed the diag-
nosis of organizing pneumonia
chogram and bronchial dilatation may be present in con-
solidated areas. Response to corticosteroid treatment is
prompt in most cases and relapse does not occur if suffi-
cient therapy is given.
Serial radiographic and clinical features are regarded
as sufficiently characteristic in some cases, as to obviate
the need for biopsy confirmation. Nevertheless, there is
increasing awareness that imaging patterns of OP may
deviate from this typical picture. What follows is a de-
scription of the less commonly encountered and atypical
CT manifestations of organizing pneumonia.
CT variants of organizing pneumonia
Focal lesion
Focal organizing pneumonia can closely resemble lung
cancer on a chest radiograph and the exclusion of malig-
nancy cannot be made on the basis of the radiographic
appearances alone. In most cases resection or biopsy is
mandatory.
In a study by Cordier et al., COP was stratified into
one of three clinical profiles with “focal COP” being
one of them (Fig. 3) [69]. This category accounted for
one-third of the study group and is noteworthy that the lo-
cation in 4 of 5 patients was in the upper lobes, the com-
monest site for lung cancer. The patient’s symptoms may
also suggest the diagnosis of lung cancer as focal orga-
nizing pneumonia may present with haemoptysis [70, 71,
72]. Occasional cavitation of focal organizing pneumonia
raises the question of whether such lesions are in fact
sterile post-infective or post-infarctive abscesses. The CT
characteristics of 18 cases of focal solitary OP were eval-

Fig. 3a, b Two examples of focal organizing pneumonia. a The
mass-like lesion in the lingula was thought, at radiographic pre-
sentation, to represent a lung cancer. Note ground-glass opacity in
the contralateral right lower lobe. b Patient with ulcerative colitis
and focal cavitating lesion in the right upper lobe, shown to be a
focus of organizing pneumonia on surgical resection
Fig. 4 A 59-year-old man with ulcerative colitis and insulin-de-
pendent diabetes mellitus. The CT shows multiple focal mass-like
lesions, some of which contain an air bronchogram. On biopsy
these lesions proved to be areas of organizing pneumonia
uated and a trend towards location of the lesion in the
lung periphery (outer third of the lung parenchyma) was
reported [73]. Helpful, but not definitive, differentiating
CT features from lung cancer include:
1. Location of the lesion in contact with the pleura (i.e.
relatively broad pleural-based lesion) or along the
bronchovascular bundle with some contraction and
convergence of vessels
2. The presence of flat, oval or trapezoidal-shaped mass-
es instead of a rounded lesion
3. The presence of satellite lesions [73]
1489
Focal OP can also present as multiple mass-like opacities
(Fig. 4) [74, 75, 76]. This was the most frequent finding
in one study in which the majority of cases were periph-
erally located and demonstrated a pulmonary vessel
leading to a nodular opacity or a small bronchus entering
the centre of the nodular opacity [77]. In a series of
Akira et al., in which COP manifested as focal multiple
large nodules or masses, the most prominent feature was
the irregular and spiculated margin [78]. It is noteworthy
that bleomycin-induced lung organizing pneumonia can
present as pseudometastatic pulmonary nodules, occa-
sionally with cavitation [29].
Nodular pattern
Organizing pneumonia can present as one of two nodular
patterns:
1. A well-defined “acinar” pattern with nodules of ap-
proximately 8 mm in diameter (Fig. 5)
2. A more subtle poorly defined (micro)nodular pattern
(Fig. 6).
In two early CT series describing COP, nodules were re-
ported to be one of the more prevalent features. In
Müller et al.’s study, well-defined nodules of up to 5 mm
diameter and situated predominantly along the broncho-
vascular bundles were described [65]. The authors also
noted the presence of nodules up to 10 mm in diameter
(“acinar” nodules). Pathological correlation showed that
these represented focal areas of organizing pneumonia
around plugged bronchioles. This type of lesion was sep-
arated from others by a zone of relatively normal aerated
lung, which explained the nodular appearance. In the
study by Lee et al., nodules were present in one-third of
patients [66]. They were the sole finding in 9% of pa-
1490
Fig. 5 A CT of the right upper lobe of a patient with a 10-day his-
tory of dyspnoea and suspected community acquired pneumonia.
Combined pattern of peripheral “acinar” nodules and smaller nod-
ules, some of which resemble a tree-in-bud pattern. Biopsy-proven
organizing pneumonia. (Courtesy of S. Diederich, Muenster)
tients and part of a mixed pattern in the remaining cases.
Most of the nodules had well-defined margins and were
randomly distributed. Nishimura and Itoh reported a
nodular pattern (nodules of approximately 1 cm in diam-
eter) superimposed on an overall increase in lung density
or ground-glass opacification [67]. In a recent study the
presence of parenchymal nodules with ill-defined mar-
gins and a predominantly peripheral distribution was the
most important discriminating CT feature between orga-
nizing pneumonia and chronic eosinophilic pneumonia
[79].
A micronodular pattern (nodules ≤4 mm) in which the
micronodules are poorly defined and of relatively low
attenuation is an uncommon CT appearance of organiz-
ing pneumonia (Fig. 6) [64, 80] and is more frequently
encountered in subacute extrinisic allergic alveolitis. In
a study of the CT and histopathological characteristics
of bronchiolar diseases, the authors mention that in
occasional cases of organizing pneumonia the CT ap-
pearances resemble an infectious bronchiolitis with a
tree-in-bud pattern [81].
Cordier describes in a recent review article, a distinct
bronchiolocentric distribution in which organizing pneu-
monia is limited to the alveoli immediately adjacent to
the involved bronchioles, thus giving a miliary pattern
[4]. Although organizing pneumonia is not mentioned as
a differential diagnosis in a survey of cases characterized
by tree-in-bud appearance [82], it is reasonable to assume
that in order to have any kind of “nodular” pattern the af-
fected bronchioles and adjacent alveoli occupied by OP
must be surrounded by normally aerated parenchyma.
Fig. 6 a A 23-year-old bodybuilder gradually became severely
dyspnoeic and ultimately required mechanical ventilation. The
diagnosis of organizing pneumonia was confirmed on lung biopsy
and he responded slowly to prolonged treatment with steroids (no
specific cause was found). On CT there is a micronodular pattern
characterized by small ill-defined centrilobular nodules of less
than 5 mm. b Lung biopsy specimen showing discrete small foci
of organizing pneumonia, surrounded by normal aerated lung
Bronchocentric pattern
The bronchocentric pattern was first identified in the
first two CT series by Müller et al. [65] and Lee et al.
[66] (Figs. 7, 8). In Müller et al.’s study one-third of pa-
tients showed a combination of subpleural and peribron-
chovascular consolidation [65]. In Lee et al.’s study, ap-
proximately one-third of cases also had a predominantly
peribronchovascular pattern [66].
There have been subsequent reports about pulmonary
disease associated with polymyositis and dermatomyosi-
tis that have emphasized the association with predomi-
nantly bronchocentric organizing pneumonia. In a study
of patients with poly- or dermatomyositis the consolida-
tion on CT had a predominantly peribronchovascular
distribution which corresponded pathologically to OP
[83]. The authors concluded that although air-space con-
solidation is a nonspecific finding, in the context of

Fig. 7 Bronchocentric pattern of organizing pneumonia: areas of
consolidation surround the bronchovascular bundles in a patient
admitted to intensive care
Fig. 8 Bronchocentric pattern of organizing pneumonia: a strik-
ingly peribronchovascular distribution in a diabetic patient with bi-
opsy proven organizing pneumonia. (Courtesy of A. Vathi, Bolatti,
Milan)
known polymyositis/dermatomyositis, dense broncho-
centric opacification on CT is likely to represent organiz-
ing pneumonia.
In a study that assessed the diagnostic accuracy of
thin-section CT in patients with idiopathic interstitial
pneumonias, although a peripheral distribution was
found in the majority of OP cases, 17% had a predomi-
nantly peribronchovascular pattern [80]. Furthermore, a
bronchocentric location of air-space and ground-glass
consolidation was found to be a more frequent feature
in organizing pneumonia when compared with chronic
eosinophilic pneumonia [79].
1491
Linear and band-like pattern
A linear or band-like pattern of OP is unusual and strik-
ing and has been described in isolation or in combination
with other patterns. It is seen on CT as lines or bands
longer than 2 cm, smooth or irregular sometimes forming
arcades and/or containing air bronchograms. These lines
or bands are usually at least 8 mm in width (Fig. 9) [85].
Murphy et al. reported two distinct types of linear opac-
ity [86]: (a) those extending in a radial manner along the
line of the bronchi towards the pleura, usually intimately
related to bronchi; and (b) those occurring in a peripheral
location bearing no relationship to the bronchi [86]
These linear opacities are usually associated with
multifocal areas of consolidation, but in 2 of 11 patients
they were the sole HRCT abnormality. Organizing pneu-
monia may present on CT with extraordinary crescentic
and ring-shaped opacities surrounding areas of ground-
glass opacification (Fig. 10) [87]. These features may be
accompanied by a more typical nodular or a consolida-
tion pattern. The CT pathological correlation has shown
that the central areas of ground-glass opacification in CT
reflect alveolar septal inflammation and cellular debris.
In an HRCT study of patients with polymyositis or der-
matomyositis, subpleural band-like opacities have been
described which lie in the lung periphery parallel to the
chest wall [83]. This may be regarded as bronchocentric
distribution of organizing pneumonia around adjacent
subpleural bronchi that gives the impression of a band as
bronchi are “joined” together by intervening organizing
pneumonia (Fig. 11).
Perilobular pattern
A “perilobular” distribution was a term first coined by
Murata et al. in their description of the localization of
parenchymal disease at the level of the secondary pulmo-
nary lobule [88]. They reserved this term for lesions that
mainly involved the structures bordering the lobule, no-
tably the interlobular septa and the pleura. In a more re-
cent study the authors added in the definition of the peri-
lobular region the peribronchovascular interstitium of
the larger bronchi and accompanying pulmonary arteries
which are too large to be located within the centre of the
secondary lobules and therefore are located in the pe-
riphery of the lobule [89]. In this context, interstitial and
air-space disease involving these perilobular (paraseptal)
alveoli may mimic abnormalities of the interlobular sep-
ta on HRCT. Accumulation of organizing exudate (i.e.
organizing pneumonia) or the infiltration of the alveolar
walls, even if they are not associated with thickening of
the interlobular septa histologically, may be seen as “ap-
parent” septal thickening contributing to a coarse reticu-
lar pattern on HRCT. In terms of anatomical distribution
there is some congruence between the perilobular pattern
1492

Fig. 9 A 41-year-old man developed cryptogenic organizing

pneumonia concurrent with an episode of pericarditis. On CT
there are bilateral band-like opacities, both of which contain an
air-bronchogram. Biopsy of one of these lesions confirmed orga-
nizing pneumonia
Fig. 10a, b A CT scan of a 14-year-old boy not responding to
treatment for suspected tuberculosis (later excluded). A striking
pattern of ring-like opacities surrounding areas of ground-glass
opacification is seen in the a upper and b lower lobes. Open-lung
biopsy revealed organizing pneumonia
Fig. 11 A bronchocentric distribution of organizing pneumonia
around adjacent bronchi resembling a band as bronchi are “joined
together” by the intervening organizing pneumonia

and the grosser distribution of “typical” OP: a subpleural

distribution is the dominant feature in COP and, at a
much smaller or microscopic level, a perilobular disposi-
tion of OP can also be regarded as “subpleural”
(Fig. 12). One of the secondary changes that accompa- Fig. 12 A perilobular pattern of organizing pneumonia. There is
nies OP is a mild inflammatory infiltrate [9] which prob- opacification around the periphery of individual secondary lobules
ably contributes to the perilobular disease. It can be resembling poorly defined thickened interlobular septa
speculated that this pattern of OP is responsible for the
reported resolution of an apparently irreversible (fibrot-
 1493

ic) pattern in nitrofurantoin-induced lung disease, in

which there is an OP-like reaction [27, 90].
In some CT studies of OP, thickening of the interlobu-
lar septa is described and is usually associated with areas
of consolidation or near nodules and masses [65, 78, 86,
91]; however, it remains uncertain how often this is
“real” thickening of the interlobular septa, as opposed to
“apparent” thickening caused by perilobular disease, as
described above.

Progressive fibrotic pattern

A less distinct pattern (unlike the previous relatively

well-defined morphological patterns) encompasses those
cases of “aggressive” OP in which there is supervening
irreversible fibrosis. This pattern, if it can be called that,
was initially described as a separate clinical–radiologic
profile of COP having an overlap with usual interstitial
pneumonia and consequently a worse prognosis than
typical COP [69]. In a recent study, 10 patients with an
initial histological diagnosis of OP had a fulminant
course leading to death. Post-mortem examination re-
vealed OP associated with alveolar septal inflammation,
established fibrosis and honeycombing [92]. The authors
suggested that OP can, on occasion, be the precursor of
interstitial fibrosis and end-stage honeycomb lung.
One of the main objectives of the defining series by
Epler et al. was the differentiation between UIP and OP,
particularly given the much better prognosis of OP [6].
As background to this apparent overlap, it may be useful
to consider the following histopathological concepts
[93, 94, 95, 96, 97, 98, 99]. Alveolar epithelial damage is
an early event in both UIP and OP. In OP the necrosis of
bronchiolar and alveolar epithelium is followed by
migration of fibroblasts from the interstitial compart-
ment into the airways and air-spaces through gaps in the
damaged basal membrane; organization begins with the
formation of fibro-inflammatory buds with deposition
of a loose connective tissue matrix (intraluminal organi-
zation) [4, 9, 10]. The alveolar architecture is remarkably
preserved and there is a variable inflammatory cellular
infiltration of the interstitium. On the other hand, when
organization is predominantly interstitial the epithelial
basal lamina is disrupted and fibrosis is incorporated
within the alveolar interstitium [61, 93]. In UIP small fi-
broblastic foci are usually restricted to interstitium, and
intraluminal fibrosis is much less extensive than in OP
[9]. After a seemingly similar initial alveolar injury, it is
not clear what determines whether organization will pro-
ceed intraluminally (OP) or in the interstitium (UIP) [61,
93, 94, 95]. One determinant may be that significant fi-
broblastic proliferation occurs where the continuity of
basal lamina is disrupted [96, 97], whereas the integrity
of the lung parenchyma can be restored after injury if
basal lamina remains relatively intact [98, 99].
Fig. 13a, b A 36-year-old woman presented with the presumptive
diagnosis of bronchopneumonia, with minor improvement on anti-
biotics; however, exertional dyspnoea and a restrictive ventilatory
defect remained. a The initial CT showed patchy areas of consoli-
dation concentrated in the lower lobes, but no obvious features
established interstitial fibrosis. b The same patient 15 months later
after prolonged steroid treatment. The areas of consolidation had
largely resolved, but an extensive coarse reticular pattern, indicat-
ing supervening fibrosis, had developed
The radiographic pattern of organizing pneumonia
admixed with interstitial fibrosis probably first appeared
in the literature in 1973 when Gosink et al. [100] report-
ed five patients with organizing pneumonia and linear/
reticular opacities on chest radiography; however, it was
not until 1989 that Cordier et al. formally suggested a
separate group, characterized by more interstitial in-
volvement [69]. On CT a bibasal reticular pattern may be
superimposed on a background of areas of frank consoli-
dation or acinar nodules (Fig. 13) [10]. It is the relative
paucity of consolidation and ground-glass opacification
together with the predominance of reticular elements
with architectural distortion that distinguishes this pat-
tern from typical or “simple” OP. Other features of inter-
stitial fibrosis, including traction bronchiectasis, honey-
combing, with or without patchy areas of ground glass,
may all be seen on CT in this “overlap” entity. This pat-
tern is most frequently encountered in organizing pneu-
1494

monia associated with connective tissue diseases, partic-
ularly polymyositis/dermatomyositis, and has a poorer
prognosis [84].
Conclusion
In the 20 years since cryptogenic organizing pneumonia
was first described, the terminology and pathological
concepts surrounding this entity have been clarified.
The basic imaging pattern of changing multifocal
air-space consolidation that characterizes cryptogenic
organizing pneumonia is widely recognized but the in-
creasing number of reported variant morphologies of or-
ganizing pneumonia, shown to advantage on CT, need
to be borne in mind if the diagnosis is not to be over-
looked.

References
1. Colby TV (1998) Bronchiolitis. Patho-
logic considerations. Am J Clin Pathol
109:101–109
2. Geddes DM (1991) BOOP and COP.
Thorax 46:545–547
3. Hansell DM (1992) What are bronchio-
litis obliterans organizing pneumonia
(BOOP) and cryptogenic organizing
pneumonia (COP)? Clin Radiol
45:369–370
4. Cordier JF (2000) Organizing pneumo-
nia. Thorax 55:318–328
5. Davison AG, Heard BE, McAllister
WA, Turner-Warwick ME (1983) Cryp-
togenic organizing pneumonitis. Q J
Med 52:382–394
6. Epler GR, Colby TV, McLoud TC,
Carrington CB, Gaensler EA (1985)
Bronchiolitis obliterans organizing
pneumonia. N Engl J Med 17:152–158
7. Du Bois RM, Geddes DM (1991)
Obliterative bronchiolitis, cryptogenic
organizing pneumonitis and bronchioli-
tis obliterans organizing pneumonia:
three names for two different condi-
tions. Eur Respir J 4:774–775
8. Woodhead MA, du Bois RM (1991)
Bronchiolitis obliterans, cryptogenic
organizing pneumonitis and BOOP.
Respir Med 85:177–178
9. Myers JL, Colby TV (1993) Pathologic
manifestations of bronchiolitis, con-
strictive bronchiolitis, cryptogenic or-
ganizing pneumonia, and diffuse pan-
bronchiolitis. Clin Chest Med
14:611–622
10. Cordier JF (1993) Cryptogenic orga-
nizing pneumonitis. Bronchiolitis obli-
terans organizing pneumonia. Clin
Chest Med 14:677–692
11. Travis WD, King TE, Bateman ED,
Lynch DA, Capron F, Center D, Colby
TV, Cordier JF, DuBois RM, Galvin J,
Grenier P, Hansell DM, Hunninghake
G, Kitaichi M, Myers JL, Muller NL,
Nagai S, Nicholson A, Raghu G,
Wallaert B ATS/ERS International con-
sensus classification of idiopathic in-
terstitial pneumonias (in preparation)
12. Colby TV (1992) Pathologic aspects of
bronchiolitis obliterans organizing
pneumonia. Chest 102 (Suppl 1):38–43
13. Uner AH, Rozum-Slota B, Katzenstein
AL (1996) Bronchiolitis obliterans-
organizing pneumonia (BOOP)-like
variant of Wegener’s granulomatosis.
A clinicopathologic study of 16 cases.
Am J Surg Pathol 20:794–801
14. Epler GR (2001) Bronchiolitis obliter-
ans organizing pneumonia. Arch Intern
Med 22:158–164
15. Floyd R (1922) Organization of pneu-
monic exudates. Am J Med Sci
163:527–548
16. Chastre J, Raghu G, Soler P, Brun P,
Basset F, Gibert C (1987) Pulmonary
fibrosis following pneumonia due to
acute Legionnaires’ disease. Clinical,
ultrastructural, and immunofluorescent
study. Chest 91:57–62
17. Prabhu MB, Barber D, Cockcroft DW
(1991) Bronchiolitis obliterans and
Mycoplasma pneumonia. Respir Med
85:535–537
18. Seggev JS, Levin S, Schey G (1986)
Unusual radiological manifestations of
Q fever. Eur Respir Dis 69:120–122
19. Camp M, Mehta JB, Whitson M (1987)
Bronchiolitis obliterans and Nocardia
asteroides infection of the lung. Chest
92:1107–1108
20. Diehl JL, Gisselbrecht M, Meyer G,
Israel-Biet D, Sors H (1996) Bronchio-
litis obliterans organizing pneumonia
associated with chlamydial infection.
Eur Respir J 9:1320–1322
21. Jeon JS, Yi HA, Ki SY, Jeong SW,
Uh ST, Jin SY, Park JS, Choi DL, Kang
CH, Kim JS, Park CS (1997) A case of
bronchiolitis obliterans organizing
pneumonia associated with adenovirus.
Korean J Intern Med 12:70–74
22. Winterbauer RH, Ludwig WR,
Hammar SP (1977) Clinical course,
management, and long-term sequelae
of respiratory failure due to influenza
viral pneumonia. Johns Hopkins Med J
141:148–155
23. Peramaki E, Salmi I, Kava T,
Romppanen T, Hakkarainen T (1991)
Unilateral bronchiolitis obliterans orga-
nizing pneumonia and bronchoalveolar
lavage neutrophilia in a patient with
parainfluenza 3 virus infection. Respir
Med 85:159–161
24. Allen JN, Wewers MD (1989) HIV-as-
sociated bronchiolitis obliterans orga-
nizing pneumonia. Chest 96:197–198
25. Dreis DF, Winterbauer RH, Van
Norman GA, Sullivan SL, Hammar SP
(1984) Cephalosporin-induced intersti-
tial pneumonitis. Chest 86:138–140
26. Piperno D, Donne C, Loire R, Cordier
JF (1995) Bronchiolitis obliterans orga-
nizing pneumonia associated with mi-
nocycline therapy: a possible cause.
Eur Respir J 8:1018–1020
27. Cameron RJ, Kolbe J, Wilsher ML,
Lambie N (2000) Bronchiolitis obliter-
ans organizing pneumonia associated
with the use of nitrofurantoin. J Com-
put Assist Tomogr 24:259–261
28. Williams T, Eidus L, Thomas P (1998)
Fibrosing alveolitis, bronchiolitis obli-
terans, and sulfasalazine therapy. Chest
81:766–768
29. Cohen MB, Austin JH, Smith-Vaniz A,
Lutzky J, Grimes MM (1989) Nodular
bleomycin toxicity. Am J Clin Pathol
92:101–104
30. Conte SC, Pagan V, Murer B (1997)
Bronchiolitis obliterans organizing
pneumonia secondary to amiodarone:
clinical, radiological and histological
pattern. Monaldi Arch Chest Dis
52:24–26
31. Camus P, Lombard JN, Perrichon M,
Piard F, Guerin JC, Thivolet FB,
Jeannin L (1989) Bronchiolitis obliter-
ans organizing pneumonia in patients
taking acebutolol or amiodarone.
Thorax 44:711–715
32. Heard BE, Cooke RA (1968) Busulfan
lung. Thorax 23:187–193
33. Bense L, Wiman LG, Steiner E, Hjerpe
A (1986) Pulmonary side effects after
treatment with barbiturates. Eur J Re-
spir Dis 69:61–62
34. Copland GM, Kolin A, Shulman HS
(1974) Fatal pulmonary intra-alveolar
fibrosis after paraquat ingestion. N
Engl J Med 8:290–292
35. Patel RC, Dutta D, Schonfeld SA
(1987) Free-base cocaine use associat-
ed with bronchiolitis obliterans orga-
nizing pneumonia. Ann Intern Med
107:186–187

36. Morley TF, Komansky HJ, Adelizzi
RA, Giudice JC (1984) Pulmonary
gold toxicity. Eur J Respir Dis
65:627–632
37. Angle P, Thomas P, Chiu B, Freedman
J (1997) Bronchiolitis obliterans with
organizing pneumonia and cold agglu-
tinin disease associated with phenytoin
hypersensitivity syndrome. Chest
112:1697–1699
38. Gammon RB, Bridges TA, al-Nezir H,
Alexander CB, Kennedy JI Jr (1992)
Bronchiolitis obliterans organizing
pneumonia associated with systemic
lupus erythematosus. Chest
102:1171–1174
39. Ippolito JA, Palmer L, Spector S, Kane
PB, Gorevic PD (1993) Bronchiolitis
obliterans organizing pneumonia and
rheumatoid arthritis. Semin Arthritis
Rheum 23:70–78
40. Imasaki T, Yoshii A, Tanaka S, Ogura
T, Ishikawa A, Takahashi T (1996)
Polymyositis and Sjogren’s syndrome
associated with bronchiolitis obliterans
organizing pneumonia. Intern Med
35:231–235
41. Knoell KA, Hook M, Grice DP,
Hendrix JD Jr (1999) Dermatomyositis
associated with bronchiolitis obliterans
organizing pneumonia (BOOP). J Am
Acad Dermatol 40:328–330
42. Stey C, Truninger K, Marti D, Vogt P,
Medici TC (1999) Bronchiolitis obli-
terans organizing pneumonia associat-
ed with polymyalgia rheumatica. Eur
Respir J 13:926–929
43. Kaufman J, Komorowski R (1991)
Bronchiolitis obliterans organizing
pneumonia in common variable immu-
nodeficiency syndrome. Chest
100:552–553
44. Zackrison LH, Katz P (1993) Bronchi-
olitis obliterans organizing pneumonia
associated with essential mixed cryo-
globulinaemia. Arthritis Rheum
36:1627–1630
45. Kanda Y, Takahashi T, Imai Y,
Miyagawa K, Ohishi N, Oka T, Chiba
S, Hirai H, Yazaki Y (1997) Bronchio-
litis obliterans organizing pneumonia
after syngeneic bone marrow trans-
plantation for acute lymphoblastic
leukemia. Bone Marrow Transplant
19:1251–1253
46. Chaparro C, Chamberlain D, Maurer J,
Winton T, Dehoyos A, Kesten S (1996)
Bronchiolitis obliterans organizing
pneumonia (BOOP) in lung transplant
recipients. Chest 110:1150–1154
47. Verberckmoes R, Verbeken E,
Verschakelen J, Vanrenterghem Y
(1996) BOOP (bronchiolitis obliterans
organizing pneumonia) after renal
transplantation. Nephrol Dial Trans-
plant 11:1862–1863
48. Camus P, Piard F, Ashcroft T, Gal AA,
Colby TV (1993) The lung in inflam-
matory bowel disease. Medicine (Balti-
more) 72:151–183
49. Strobel ES, Bonnet RB, Werner P,
Schaefer HE, Peter HH (1998) Bron-
chiolitis obliterans organizing pneumo-
nia and primary biliary cirrhosis-like
lung involvement in a patient with pri-
mary biliary cirrhosis. Clin Rheumatol
17:246–249
50. Robinson BW, Sterrett G (1992) Bron-
chiolitis obliterans associated with
polyarteritis nodosa. Chest
102:309–311
51. Tenholder MF, Becker GL, Cervoni MI
(1990) The myelodysplastic syndrome
and bronchiolitis obliterans. Ann Intern
Med 1:714–715
52. Vaiman E, Odeh M, Attias D, Ben-Arie
Y, Oliven A (1999) T-cell chronic lym-
phocytic leukaemia with pulmonary in-
volvement and relapsing BOOP. Eur
Respir J 14:471–474
53. Safadi R, Berkman N, Haviv YS,
Ben-Yehuda A, Amir G, Naparstek Y
(1997) Primary non-Hodgkin’s lym-
phoma of the lung presenting as bron-
chiolitis obliterans organizing pneumo-
nia. Leuk Lymphoma 28:209–213
54. Spiteri MA, Klenerman P, Sheppard
MN, Padley S, Clark TJ, Newman-
Taylor A (1992) Seasonal cryptogenic
organizing pneumonia with biochemi-
cal cholestasis: a new clinical entity.
Lancet 1:281–284
55. Crestani B, Valeyre D, Roden S,
Wallaert B, Dalphin JC, Cordier JF
(1998) Bronchiolitis obliterans orga-
nizing pneumonia syndrome primed by
radiation therapy to the breast. Am J
Respir Crit Care Med 158:1929–1935
56. Arbetter KR, Prakash UB, Tazelaar
HD, Douglas WW (1999) Radiation-
induced pneumonitis in the “nonirradi-
ated” lung. Mayo Clin Proc 74:27–36
57. Camus P, Nemery B (1998) A novel
cause for bronchiolitis obliterans orga-
nizing pneumonia: exposure to paint
aerosols in textile workshops. Eur Re-
spir J 11:259–262
58. Bates C, Read RC, Morice AH (1997)
A malicious mould. Lancet 31:1598
59. Epler GR (1992) Bronchiolitis obliter-
ans organizing pneumonia: definition
and clinical features. Chest 102
(Suppl 1):2–6
60. Epler GR (1998) Heterogeneity of
bronchiolitis obliterans organizing
pneumonia. Curr Opin Pulm Med
4:93–97
61. Guerry-Force ML, Müller NL, Wright
JL, Wiggs B, Coppin C, Pare PD, Hogg
JC (1987) A comparison of bronchioli-
tis obliterans with organizing pneumo-
nia, usual interstitial pneumonia, and
small airways disease. Am Rev Respir
Dis 135:705–712
1495
62. Müller NL, Guerry-Force ML, Staples
CA, Wright JL, Wiggs B, Coppin C,
Pare P, Hogg JC (1987) Differential
diagnosis of bronchiolitis obliterans
with organizing pneumonia and usual
interstitial pneumonia: clinical, func-
tional, and radiologic findings. Radiol-
ogy 162:151–156
63. Chandler PW, Shin MS, Friedman SE,
Myers JL, Katzenstein AL (1986)
Radiographic manifestations of bron-
chiolitis obliterans with organizing
pneumonia vs usual interstitial pneu-
monia. Am J Roentgenol 147:899–906
64. Haddock JA, Hansell DM (1992) The
radiology and terminology of crypto-
genic organizing pneumonia. Br J
Radiol 65:674–680
65. Müller NL, Staples CA, Miller RR
(1990) Bronchiolitis obliterans orga-
nizing pneumonia: CT features in 14
patients. Am J Roentgenol
154:983–987
66. Lee KS, Kullnig P, Hartman TE,
Müller NL (1994) Cryptogenic orga-
nizing pneumonia: CT findings in 43
patients. Am J Roentgenol
162:543–546
67. Nishimura K, Itoh H (1992) High-reso-
lution computed tomographic features
of bronchiolitis obliterans organizing
pneumonia. Chest 102 (Suppl 1):26–31
68. Flowers JR, Clunie G, Burke M, Con-
stant O (1992) Bronchiolitis obliterans
organizing pneumonia: the clinical and
radiological features of seven cases and
a review of the literature. Clin Radiol
45:371–377
69. Cordier JF, Loire R, Brune J (1989)
Idiopathic bronchiolitis obliterans or-
ganizing pneumonia. Definition of
characteristic clinical profiles in a se-
ries of 16 patients. Chest 96:999–1004
70. Lohr RH, Boland BJ, Douglas WW,
Dockrell DH, Colby TV, Swensen SJ,
Wollan PC, Silverstein MD (1997)
Organizing pneumonia. Features and
prognosis of cryptogenic, secondary,
and focal variants. Arch Intern Med
23:1323–1329
71. Kohno N, Ikezoe J, Johkoh T, Takeuchi
N, Tomiyama N, Kido S, Kondoh H,
Arisawa J, Kozuka T (1993) Focal or-
ganizing pneumonia: CT appearance.
Radiology 189:119–123
72. Murphy J, Schnyder P, Herold C,
Flower C (1998) Bronchiolitis obliter-
ans organising pneumonia simulating
bronchial carcinoma. Eur Radiol
8:1165–1169
73. Domingo JA, Perez-Calvo JI, Carretero
JA, Ferrando J, Cay A, Civeira F
(1993) Bronchiolitis obliterans orga-
nizing pneumonia. An unusual cause of
solitary pulmonary nodule. Chest
103:1621–1623
1496
74. Haro M, Vizcaya M, Texido A, Aguilar
X, Arevalo M (1995) Idiopathic bron-
chiolitis obliterans organizing pneumo-
nia with multiple cavitary lung nod-
ules. Eur Respir J 8:1975–1977
75. Froudarakis M, Bouros D, Loire R,
Valasiadou K, Tsiftsis D, Siafakas NM
(1995) BOOP presenting with haem-
optysis and multiple cavitary nodules.
Eur Respir J 8:1972–1974
76. Cordier JF (1995) Cavitary bronchioli-
tis obliterans organizing pneumonia.
Eur Respir J 8:1822–1823
77. Bouchardy LM, Kuhlman JE, Ball WC
Jr, Hruban RH, Askin FB, Siegelman
SS (1993) CT findings in bronchiolitis
obliterans organizing pneumonia
(BOOP) with radiographic, clinical,
and histologic correlation. J Comput
Assist Tomogr 17:352–357
78. Akira M, Yamamoto S, Sakatani M
(1998) Bronchiolitis obliterans orga-
nizing pneumonia manifesting as mul-
tiple large nodules or masses. Am J
Roentgenol 170:291–295
79. Arakawa H, Kurihara Y, Niimi H,
Nakajima Y, Johkoh T, Nakamura H
(2001) Bronchiolitis obliterans with or-
ganizing pneumonia versus chronic
eosinophilic pneumonia: high-resolu-
tion CT findings in 81 patients. Am
J Roentgenol 176:1053–1058
80. Johkoh T, Muller NL, Cartier Y,
Kavanagh PV, Hartman TE, Akira M,
Ichikado K, Ando M, Nakamura H
(1999) Idiopathic interstitial pneumo-
nias: diagnostic accuracy of thin-sec-
tion CT in 129 patients. Radiology
211:555–560
81. Müller NL, Miller R (1995) Diseases
of the bronchioles: CT and histopatho-
logic findings. Radiology 196:3–12
82. Aquino SL, Gamsu G, Webb WR,
Kee ST (1996) Tree-in-bud pattern:
frequency and significance on thin
section CT. J Comput Assist Tomogr
20:594–599
View publication stats
83. Ikezoe J, Johkoh T, Kohno N, Takeuchi
N, Ichikado K, Nakamura H (1996)
High-resolution CT findings of lung
disease in patients with polymyositis
and dermatomyositis. J Thorac Imag-
ing 11:250–259
84. Akira M, Hara H, Sakatani M (1999)
Interstitial lung disease in association
with polymyositis-dermatomyositis:
long-term follow-up CT evaluation in
seven patients. Radiology 210:333–
338
85. Austin JH, Müller NL, Friedman PJ,
Hansell DM, Naidich DP, Remy-Jardin
M, Webb WR, Zerhouni EA (1996)
Glossary of terms for CT of the lungs:
recommendations of the Nomenclature
Committee of the Fleischner Society.
Radiology 200:327–331
86. Murphy JM, Schnyder P, Verschakelen
J, Leuenberger P, Flower CD (1999)
Linear opacities on HRCT in bronchio-
litis obliterans organising pneumonia.
Eur Radiol 9:1813–1817
87. Voloudaki AE, Bouros DE,
Froudarakis ME, Datseris GE,
Apostolaki EG, Gourtsoyiannis NC
(1996) Crescentic and ring-shaped
opacities. CT features in two cases of
bronchiolitis obliterans organizing
pneumonia (BOOP). Acta Radiol
37:889–892
88. Murata K, Khan A, Herman PG (1989)
Pulmonary parenchymal disease: eval-
uation with high-resolution CT. Radiol-
ogy 170:629–635
89. Johkoh T, Muller NL, Ichikado K,
Nakamura H, Itoh H, Nagareda T
(1999) Perilobular pulmonary opaci-
ties: high-resolution CT findings and
pathologic correlation. J Thorac Imag-
ing 14:172–177
90. Sheehan RE, Wells AU, Milne DG,
Hansell DM (2000) Nitrofurantoin-in-
duced lung disease: two cases demon-
strating resolution of apparently irre-
versible CT abnormalities. J Comput
Assist Tomogr 24:259–261
91. Preidler KW, Szolar DM, Moelleken
S, Tripp R, Schreyer H (1996) Distri-
bution pattern of computed tomogra-
phy findings in patients with bronchi-
olitis obliterans organizing pneumo-
nia. Invest Radiol 31:251–255
92. Cohen AJ, King TE Jr, Downey GP
(1994) Rapidly progressive bronchio-
litis obliterans with organizing pneu-
monia. Am J Respir Crit Care Med
149:1670–1675
93. Sulavik SB (1989) The concept of
“organizing pneumonia”. Chest
96:967–969
94. Katzenstein AL, Myers JL, Prophet
WD, Corley LS III, Shin MS (1986)
Bronchiolitis obliterans and usual in-
terstitial pneumonia. A comparative
clinicopathologic study. Am J Surg
Pathol 10:373–381
95. Myers JL, Katzenstein AL (1988)
Ultrastructural evidence of alveolar
epithelial injury in idiopathic bronchi-
olitis obliterans-organizing pneumo-
nia. Am J Pathol 132:102–109
96. Katzenstein AL (1988) Pathogenesis
of “fibrosis” in interstitial pneumonia:
an electron microscopic study. Hum
Pathol 16:1015–1024
97. Myers JL, Katzenstein AL (1988)
Epithelial necrosis and alveolar col-
lapse in the pathogenesis of usual in-
terstitial pneumonia. Chest
94:1309–1311
98. Vracko R (1972) Significance of basal
lamina for regeneration of injured
lung. Virchows Arch A Pathol Pathol
Anat 355:264–274
99. Battersby S, Anderson TJ (1985)
Myofibroblast activity of radial scars.
J Pathol 147:33–40
100. Gosink BB, Friedman PJ,
Liebow AA (1973) Bronchiolitis obli-
terans. Roentgenologic–pathologic
correlation. Am J Roentgenol Radium
Ther Nucl Med 117:816–832