organizing pneumonia: what is it? a conceptual approach and pictorial review

ARTICLE IN PRESS+ModelDIII-399; No. of Pages 7

Diagnostic and Interventional Imaging (2014) xxx, xxx—xxx

REVIEW / Thoracic imaging

Organizing pneumonia: What is it?A conceptual approach and pictorial review

M. Baque-Justona,∗, A. Pellegrina, S. Leroyb,C.H. Marquetteb, B. Padovania

a Department of Radiology, Hospital Pasteur, 30, avenue de la Voie-Romaine,06003 Nice cedex 1, Franceb Department of Respiratory Medicine, Hospital Pasteur, 30, avenue de la Voie-Romaine,06003 Nice cedex 1, France

KEYWORDSLung HRCT;Organizingpneumonia;Interstitial lung

Abstract Organizing pneumonia (formerly named bronchiolitis obliterans with organizingpneumonia or BOOP) is a clinical, radiological and histological entity that is classified as anInterstitial Lung Disease. The understanding of this family of diseases has seen great progressover the past twenty years. CT presentation of organizing pneumonia is polymorphous but afew patterns have been recently recognized as being more specific to this diagnosis. The aim

disease;Review

of this work is to summarize new understandings of the clinical and histological presentationof the disease and to review the most relevant CT features.© 2014 Éditions francaises de radiologie. Published by Elsevier Masson SAS. All rights reserved.

Introduction

Organizing pneumonia has been described as a pathological entity since the 1980s [1,2] andour now well-established understanding of the disease has continued to deepen throughhistological and radiological progress [3]. However, various conceptual changes have led

Please cite this article in press as: Baque-Juston M, et al. Organizing pneumonia: What is it? A conceptual approach andpictorial review. Diagnostic and Interventional Imaging (2014), http://dx.doi.org/10.1016/j.diii.2014.01.004

to some degree of confusion, partly due to a change in the name of the disease from BOOP(bronchiolitis obliterans with organizing pneumonia) to OP (organizing pneumonia) [4]. Thedifficulty also lies with the fact that there is an idiopathic form of the disease known ascryptogenic organizing pneumonia (COP), as well as several secondary forms [5].

Abbreviations: OP, Organizing pneumonia; COP, Cryptogenic organizing pneumonia; BOOP, Bronchiolitis obliterans with organizing pneu-monia; BAL, Bronchoalveolar lavage; UIP, Usual interstitial pneumonia; NSIP, Non-specific interstitial pneumonia; AIP, Acute interstitialpneumonia; ANCA, Antineutrophil cytoplasmic antibody.

∗ Corresponding author.E-mail address: [email protected] (M. Baque-Juston).

2211-5684/$ — see front matter © 2014 Éditions francaises de radiologie. Published by Elsevier Masson SAS. All rights reserved.http://dx.doi.org/10.1016/j.diii.2014.01.004

dx.doi.org/10.1016/j.diii.2014.01.004

dx.doi.org/10.1016/j.diii.2014.01.004

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In over 70% of cases, OP produces focal sub-pleural and/or

ARTICLEIII-399; No. of Pages 7

efinitions

P is a process of pulmonary tissue repair that can be either:cryptogenic;secondary to a lung injury such as infection, drug toxicity,inhalation of a pathogen (cocaine), inhalation of toxic gas,gastroesophageal reflux, collagenosis, organ transplant,or radiotherapy [5—8];it can be histologically associated with pulmonary lesionsof another nature such as vasculitis, lymphoma, lungcancer [9], hypersensitivity pneumonitis, eosinophilicpneumonia, acute interstitial pneumonia, non-specificinterstitial pneumonia, or usual interstitial pneumonia [5](Table 1).

These three different situations share the same terminol-gy, but they need to be distinguished based on their clinicalnd radiological features and their prognoses.

Histological diagnosis, in the same way as in other inter-titial lung diseases, is no longer considered to be the goldtandard [3]; it is the review of all available data in a mul-idisciplinary meeting that will allow the final diagnosis toe made and an underlying or associated aetiology to bexcluded.

athology of OP

P is initiated by lung injury: the alveolar epithelium reactso produce granulation tissue that is similar to that gener-ted during the healing process of a skin wound [10,11].nflammatory debris are filling the alveoli and spreading tohe alveolar ducts and terminal bronchioles, with character-stic endoluminal buds of granulation tissue known as Masson

Please cite this article in press as: Baque-Juston M, et al. Orgapictorial review. Diagnostic and Interventional Imaging (2014),

odies. These abnormalities can be associated with an inter-titial inflammatory infiltrate, which is why OP is classifieds an interstitial lung disease [3—5].

Table 1 Aetiologies of secondary organising pneumonia.

OP secondary to a lung injuryInfection BacteriaDrug toxicity Antibiot

AntiepilAntiarrhImmuno

Drug intoxication CocaineInhalation of toxic gas HydrogeAspiration of gastric contents GastroeCollagenosis PolymyoOrgan transplant Bone maRadiotherapy OP can

radiothe

OP associated with another lung pathologyVasculitis (Wegener’s granulomatosis) In these

with hisany douhas led

of a diff

Tumours (lymphoma, lung cancer)Pulmonary infarctHypersensitivity pneumonitisEosinophilic pneumoniaInterstitial lung diseases UIP, NSIP, AIP

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PRESSM. Baque-Juston et al.

linical features of OP

n the literature, the descriptions of the clinical picture ofP broadly report the signs of COP, as the symptoms ofecondary forms of OP can be clinically influenced by thenderlying pathology.

COP is a rare disease that affects both sexes indiscrim-nately between the ages of 50 and 60 with a relativerevalence of non-smoking patients [12]. Within a few days,he patient develops hyperthermia, malaise, cough, and dys-noea, all of which can become severe, associated with signsf inflammation and an increase in blood neutrophil lev-ls. Bronchoalveolar lavage is not specific but often showsn increase in lymphocytes. Symptoms regress quickly withteroid therapy but can return when treatment is stopped,r progress into a chronic and fibrosing form with a poorerrognosis.

adiology of OP

maging patterns of OP are well recognized and new char-cteristic features have recently been described, meaninghat an earlier diagnosis of OP is becoming easier to suggest.5].

In order to keep our descriptions succinct, the terms usedre in keeping with the definitions of the ‘‘Glossary of Termsor Thoracic Imaging’’ established by the Fleischner Societyn 2008 [13].

lassic form: fluctuating multifocalarenchymal consolidation

nizing pneumonia: What is it? A conceptual approach and http://dx.doi.org/10.1016/j.diii.2014.01.004

, viruses, parasites, fungiics: nitrofurantoineptics: Carbamazepineythmics: Amiodaronesuppressants: Interferon

inhalationn sulfide, industrial gasessophageal reflux, repeated micro-aspirationssitis, Dermatomyositisrrow transplant

grow away from the target site and after the end ofrapy treatment

conditions, histological pattern of OP may be associatedtological areas specific to the main pathology. If there isbt clinically, it is important to ensure that the biopsy thatto a diagnosis of OP is not only the periphery of a lesionerent nature

eribronchovascular consolidation areas, often bilateral andsymmetrical [5,14,15], usually described as predominating

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Organizing pneumonia: What is it? A conceptual approach an

in the lower lobes although some studies do not sup-port this [16] (Figs. 1, 2, 3). This may be associated withground glass opacities or areas of traction bronchiectasis(reversible under steroid treatment) and there may be an airbronchogram sign. These features are usually migratory,with some abnormalities disappearing spontaneously andnew areas of consolidation appearing simultaneously in dif-ferent sites.

A number of differential diagnoses may be consideredwhen multifocal parenchymal consolidation is present [17]:bronchioloalveolar carcinoma (Fig. 4), primary pulmonarylymphoma, eosinophilic pneumonia, multifocal pneumonia,


alveolar haemorrhage, multiple pulmonary infarcts, alveo-lar sarcoidosis, or ANCA-associated vasculitis, which can alltake on a similar appearance. The fluctuating appearance

Figure 1. OP presenting as multiple areas of sub-pleural and peri-bronchovascular consolidation.

Figure 2. Sub-pleural areas of consolidation, due to two foci ofOP.

Figure 3. Large area of sub-pleural consolidation in the right pos-terior lung base mimicking an infectious lung disease, secondary toOP. Regression of the lesions on steroid therapy.

Figure 4. Bilateral sub-pleural areas of mixed density combin-ing consolidation and ground glass opacities. No regression of thelesions over a series of repeat studies, leading to the biopsy-c

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Figure 5. Female patient with history of right breast cancer who had usub-pleural area of consolidation and ground glass opacity; b: follow-up sproducing a reverse halo sign, in keeping with a delayed onset of OP sec

onfirmed diagnosis of multifocal adenocarcinoma.

f images over a series of repeat CT scans (Figs. 5a and 5b)s a distinguishing factor because it reduces the list ofifferential diagnoses to four aetiologies: OP, eosinophilicneumonia (similar CT features to OP but usually accompa-ied by raised blood and/or alveolar eosinophilia), alveolar


aemorrhage, and vasculitis [5].If other suggestive features of OP, as described below,

re present, they will contribute to greater diagnostic speci-city.

ndergone radiotherapy and chemotherapy six months previously. a:tudy three months later. The ground glass opacities have migratedondary to the radiotherapy.

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4 M. Baque-Juston et al.

Nodular form: solitary or multiple nodules ormasses

OP can present in the form of solid, mixed density (Fig. 6),or more rarely ground glass nodules (Fig. 7) that are onecentimetre or more in size [18]. The distribution of thesenodules is not specific, being scattered (Fig. 8) or peribron-chovascular, so the diagnosis of OP will rarely be suggestedat first, especially when there is underlying cancer or infec-tion. The nodules may have spiculated borders makingdistinction from a neoplasm difficult, especially since OP

Figure 6. Multinodular form of OP. Scattered nodules of over 1centimetre in size that are migratory and resolve spontaneously.

Figure 7. Non-resolving ground glass nodular opacity raising thepossibility of an adenocarcinoma. OP diagnosed on lung biopsy.

Figure 8. Multiple nodules and areas of parenchymal consoli-dation surrounded by ground glass opacity (halo sign) suggestingangio-invasive aspergillosis in an immunocompromised patient. Thediagnosis of OP was made after pulmonary biopsy.

often show increased uptake on PET scan. In an immuno-compromised patient, there is sometimes a halo sign (solidnodule surrounded by a ring of ground glass opacity) and inthis context, angio-invasive pulmonary aspergillosis is thefirst diagnosis to consider.

Excavated nodules are rare but may mimic tuberculosis orseptic embolism (Fig. 9). In rare cases, OP has a micronodu-lar appearance with milliary opacities or branching ‘‘tree inbud’’ micronodules.

When OP presents in a purely nodular form, the diagno-sis is thus rarely made at first, but if lesions are found tofluctuate and migrate, sometimes resolving spontaneously,they become highly suggestive of the diagnosis.

Atoll or reverse halo sign

The reverse halo sign is an area of ground glass opacitysurrounded by a crescent or ring of parenchymal consoli-dation [13] that may present smooth or spiculated borders(Figs. 10 and 11).

It was for a long time considered to be pathognomonicof OP, but this sign has now been described in other con-ditions such as granulomatous vasculitis associated withANCA (Wegener’s granulomatosis), sarcoidosis, paracoc-cidioidomycosis, pneumocystosis, tuberculosis, and lipoidpneumonia, as well as a complication of radio frequency

Figure 9. Solid and excavated nodules, rarely seen in OP. Diag-nosis made based on the spontaneously resolving and migratorycharacter of the abnormalities identified. The lesions resolved fullyunder steroid therapy.

Figure 10. Reverse halo sign: a ring of consolidation with smoothor spiculated borders surrounding an area of ground glass opacity,characteristic of OP, but not pathognomonic.

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Organizing pneumonia: What is it? A conceptual approach and pictorial review 5

Perilobular abnormalities

Characterised only recently, perilobular abnormalitiespresent as curved or arcade-like bands of parenchymalconsolidation with blurred borders, distributed along thestructures that surround the secondary pulmonary lobule[13] and often reaching the surface of the pleura (Fig. 14).

These abnormalities are characteristic and suggest thediagnosis of OP. In a series described by Ujita et al. [16]they were present in 57% of cases although they were oftennot very pronounced.

Bands of consolidation

Organizing pneumonia can also produce thick radial bandsof consolidation (>8 mm) extending towards the pleura,containing an air bronchogram that differentiates themfrom linear atelectasis [5] (Fig. 15) as well as sub-pleuralcurvilinear bands of consolidation parallel to the pleura(Fig. 16). These often-misunderstood signs are very evoca-tive of OP.

Crazy-paving sign

The presence of ground glass opacity adjacent to focal areasof consolidation is common and when it is seen in combi-

Figure 11. Reverse halo sign, also known as the atoll sign.

treatment [19]. It is, however, possible that the reversehalo sign seen in these cases may in fact be a histologicalparenchymal reaction of OP associated with or secondary tothese various aetiologies.

The reverse halo sign should be distinguished from otherring-shaped areas of parenchymal consolidation containingmicronodules in their walls, seen in some granuloma-tous diseases such as tuberculosis or sarcoidosis [20](Figs. 12 and 13).


Figure 12. Ring of consolidation with micronodular wallsassociated with areas of branching micronodules secondary totuberculosis.

Figure 13. Coronal reconstruction of a micronodular ring ofconsolidation, secondary to tuberculosis.

nation with septal thickening, it produces a crazy-pavingappearance.

Figure 14. Multiple areas of perilobular consolidation in anarcade-like pattern, characteristic of OP due to amiodarone lung-toxicity.

Figure 15. Radial band of consolidation containing an air bron-chogram suggestive of OP to differentiate from linear atelectasisthat usually do not contain air bronchogram.

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6 M. Baque-Juston et al.

Figure 16. Sub-pleural curvilinear band of consolidation associ-ak

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rogressive fibrotic pattern

n approximately a quarter of cases, OP produces areasf sub-pleural reticulation and persistent architecturalistortion that have a similar appearance to findings in non-pecific interstitial pneumonia [5]. These fibrosing formseem to convey a poorer prognosis.

rganizing pneumonia: conceptualpproach and uncertainties

he appearances of OP on computed tomography are poly-orphic, and the most common features are areas of focal

onsolidation and ground glass opacities. The most specificigns are perilobular abnormalities, reverse halo sign, radialands of consolidation containing an air bronchogram (5) asell as evolution and migration of the lesions over time,ven in the absence of treatment. If nodules or areas ofon-specific consolidation are seen, other aetiologies suchs cancer, infection, or vascular causes must of course benvestigated before a diagnosis of OP can be made. However,hen these features are found together with more specific

igns, or when the lesions fluctuate, the diagnosis of OP canasily be suggested.

To assess whether OP is cryptogenic, the aetiologieshat can commonly be associated with this condition needo be excluded, and this will require additional investiga-ions including blood tests, BAL to look for infection, and

detailed patient history that covers environmental expo-ure, toxics and treatments.

If OP is secondary to radiotherapy, consolidation maye found either in the irradiated area (Fig. 17) or outsidet, including in the contralateral lung. It may appear whileadiotherapy is ongoing or several months after the end ofhe treatment.

OP is a relatively common pattern in drug-induced lungisease, especially with products based on nitrofurantoin,arbamazepine, interferon, and amiodarone. In amiodaroneoxicity, abnormalities can include OP with more diffuse


nterstitial lesions producing a clinical picture of UIP; thereas of consolidation in this case sometimes appear to bef increased density, and are often combined with increasedensity of the liver, spleen and/or thyroid parenchyma.

igure 17. Multifocal left lung consolidation areas in the field ofurrent radiotherapy for cancer of the left breast.

When several biopsy samples are taken from the sameatient, histological pattern of OP may also be seen in com-ination with other interstitial lung diseases such as chronicypersensitivity pneumonitis, UIP, NSIP or AIP. In adult respi-atory distress syndrome (ARDS), the pathological findings ofIP can show diffuse alveolar damage together with sites ofP [21]. Some authors suggest that diffuse alveolar dam-ge, OP and NSIP may be a spectrum of manifestations ofung injury and repair at different stages [5].

The diagnosis of OP requires multidisciplinary approachombining clinical and radiological expertise, with histo-athological evidences when a lung biopsy has beenerformed. If the scenario is not typical, it is important toemember that a histological finding of OP can be idiopathic,econdary to a determined injury or may be found at theeriphery of a coexisting lung lesion. It is sometimes neces-ary to take further biopsy samples from a wider area so thatn associated condition such as a lung cancer or vasculitis isot overlooked.

OP is a clinical, radiological and histological entity that islearly defined in the relatively rare context of COP, treatedy steroid therapy and associated with a good prognosis. It is

more complex and probably underestimated entity whent is found in association with, or secondary to, numerousther diseases. It is therefore crucial to assess any atypicaleature suggestive of an underlying pathology before even-ually applying the reassuring label of cryptogenic organizingneumonia.

isclosure of interest

he authors declare that they have no conflicts of interestoncerning this article.

eferences

[1] Davison AG, Heard BE, McAllister WA, Turner-Warwick ME. Cryp-togenic organizing pneumonitis. Q J Med 1983;52:382—94.

[2] Epler GR, Colby TV, McLoud TC, Carrington CB, Gaensler EA.


Bronchiolitis obliterans organizing pneumonia. N Eng J Med1985;17:152—8.

[3] American Thoracic Society/European Respiratory Society.International multidisciplinary consensus classification of the

dx.doi.org/10.1016/j.diii.2014.01.004

http://refhub.elsevier.com/S2211-5684(14)00005-9/sbref0005
























































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ARTICLEDIII-399; No. of Pages 7

Organizing pneumonia: What is it? A conceptual approach an

idiopathic interstitial pneumonias. Am J Respir Crit Care Med2002;165:277—304.

[4] Geddes DM. BOOP and COP. Thorax 1991;46:545—7.[5] Roberton BJ, Hansell DM. Organizing pneumonia: a

kaleidoscope of concepts and morphologies. Eur Radiol2011;21:2244—54.

[6] Epler GR. Bronchiolitis obliterans organizing pneumonia, 25years: a variety of causes, but what are the treatment options?Expert Rev Respir Med 2011;5(3):353—61.

[7] Gómez-Gómez A, Martínez-Martínez R, Gotway MB. Organizingpneumonia associated with swine-origin influenza A H1N1 2009viral infection. Am J Roentgenol 2011;196(1):103—4.

[8] Gudavalli R, Diaz-Guzman E, Arrossi AV, Chapman JT, Mehta AC.Fleeting alveolar infiltrates and reversed halo sign in patientswith breast cancer treated with tangential beam irradiation.Chest 2011;139(2):454—9.

[9] Eguchi T, Takasuna K, Fujiwara M, Yoshida K. Coexistence of apulmonary adenocarcinoma with a focal organizing pneumonia.Interact Cardiovasc Thorac Surg 2011;13(4):444—6.

[10] Cordier J-F. Cryptogenic organizing pneumonia. Eur Respir J2006;28:422—46.

[11] Peyrol S, Cordier JF, Grimaud JA. Intra-alveolar fibrosis ofidiopathic bronchiolitis obliterans-organizing pneumonia. Cell-


matrix patterns. Am J Pathol 1990;137:155—70.[12] Drakopanagiotakis F, Paschalaki K, Abu-Hijleh M, Aswad

B, Karagianidis N, Kastanakis E, et al. Cryptogenic andsecondary organizing pneumonia: clinical presentation,

[

PRESSctorial review 7

radiographic findings, treatment response, and prognosis.Chest 2011;139(4):893—900.

13] Hansell DM, Bankier AA, MacMahon H, McLoud TC, Müller NL,Remy J. Fleischner Society: glossary of terms for thoracic imag-ing. Radiology 2008;246(3):697—722.

14] Oikonomou A, Hansell DM. Organizing pneumonia: the manymorphological faces. Eur Radiol 2002;12:1486—96.

15] Lee JW, Lee KS, Lee HY, Chung MP, Yi CA, Kim TS, et al. Crypto-genic organizing pneumonia: serial high-resolution CT findingsin 22 patients. Am J Roentgenol 2010;195(4):916—22.

16] Ujita M, Renzoni ES, Veeraraghavan S, Wells AU, Hansell DM.Organizing pneumonia: perilobular pattern at thin-section CT.Radiology 2004;232:757—61.

17] Müller NL, Silva CI. Consolidation. Imaging of the chest.Philadelphia: Saunders Elsevier; 2008. p. 97—115.

18] Marques G, Annweiler T, Raoux D, Tiffet O, Vergnon JM,Bertoletti L. Nodular presentation of a cryptogenic organizingpneumonia. Rev Pneumol Clin 2011;67(5):314—7.

19] Marchiori E, Zanetti G, Escuissato DL, Souza Jr AS, MeirellesGde S, Fagundes J, et al. Reversed halo sign: high-resolutionCT scan findings in 79 patients. Chest 2012;141(5):1260—6.

20] Marchiori E, Zanetti G, Irion KL, Nobre LF, Hochhegger B,Mancano AD, et al. Reversed halo sign in active pulmonary


tuberculosis: criteria for differentiation from cryptogenic orga-nizing pneumonia. Am J Roentgenol 2011;197(6):1324—7.

21] Walsh SL, Hansell DM. Diffuse interstitial lung disease: overlapsand uncertainties. Eur Radiol 2010;20(8):1859—67.

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organizing pneumonia: what is it? a conceptual approach and pictorial review

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