HRCT of fibrosing lung disease: problems and pitfalls

David M HansellRoyal Brompton Hospital

London UK

ILD Postgraduate Course, Porto - April 2016

• HRCT interpretation of fibrosing lung disease– Basic HRCT signs and their reliability

• Practical HRCT approach to differentiating between fibrosing lung diseases

• Significance of new abnormalities on HRCT in idiopathic pulmonary fibrosis– Focal: nodule or mass

– Diffuse: ground glass opacification

Usual Interstitial Pneumonia

Language used when NOT a definite UIP pattern on CT

• Numerous adjectives beginning

with P….

• Possible, Potential, Permissible, Plausible, Practically, Probable, Portuguese, Perhaps, Presumed, etc.

One radiological classification of UIP

• HRCT Definitely is UIP

– classic UIP pattern

• (n.b. not synonymous with IPF - c.f. chronic HP)

• HRCT Could be UIP

– a fibrosing lung disease, no honeycombing or contradictory (“inconsistent with”) features

• HRCT Definitely not UIP

– clear signs of another diagnosis

Starting point

• Common to all three situations is features of “a fibrosing lung disease” on HRCT

• So, the first step: Does the HRCT show a predominantly fibrosing lung disease?

– What are the HRCT signs of fibrosis?

– How reliable are these HRCT signs?

Which one is a fibrosing lung disease?

UIP on lung biopsy

✓

✗

✗

OP (nitrofurantoin)

Pulmonary oedema

BASICS The HRCT signs of a predominantly fibrotic lung disease:

• Honeycombing

• Traction bronchiectasis

• Volume loss

Reliability of HRCT signs of fibrotic lung disease(++++ = complete certainty)

• Honeycomb pattern

+++(+)

• Traction bronchiectasis

++(+)

• Volume loss

+

++++

Honeycombing

Identification of honeycombing on HRCT - cardinal sign of UIP

• False positive identification

– Severe traction bronchiolectasis

– Centrilobular/paraseptal emphysema e.g. superimposed on NSIP

– Oedema/infection superimposed on emphysema

– Other cystic conditions e.g. Langerhans CH

Lung biopsy: Fibrotic NSIP and centrilobular emphysema

Interobserver variability in the CT assessment of honeycombing in the lungs

• 43 observers (!)

• Honeycombing present definitely yes (5) thro’ definitely not (1)

• Agreement with reference standard moderate κ=0.43-0.58

• In 29% disagreement on presence/absence

• Sources of disagreement: traction bx, cysts and superimposed emphysema

Watadani et al Radiology 2013;266:207

Historically poor: Lynch et al (2005) κ=0.31

Traction bronchiectasis

Identification of traction bronchiectasis on HRCT

• False positive identification

– Within honeycombing

– Dilated bronchi within OP / DAD

– Conspicuous, but not dilated, bronchi within GGO

• “False negative”

– Within honeycombing (advanced)

– Severity of traction reduced if coexistent emphysema

Traction bronchiectasis - identification by CALIPER software:

…differentiation from honeycombing unreliable

• Fibrotic IIPs (UIP and NSIP) – Edey 2011 Eur Radiol

• Rheumatoid Arthritis-related FLD – Kim 2010 Eur Respir J

• Chronic hypersensitivity pneumonitis – Walsh SL 2012 Eur Radiol

• All comers connective tissue disease FLD– Walsh SL 2014 Thorax

Kappas for traction bronchiectasis = 0.58-0.69

Observer agreement for traction bronchiectasis in various FLD

Volume loss

Honeycombing

Traction bronchiectasis

Volume loss

Back to the specifics of a UIP pattern…

UIP pattern

= Unusual Interstitial Pneumonia

Characteristic/Definite UIP pattern on CT

• Subpleural

• Basal

• Honeycombing

Supportive CT features (unofficial)…

• “Propeller blade” cranio-caudal distribution

• Nodular ossifications within fibrosis

• Asymmetric distribution of fibrosis

• Component of pleuroparenchymal fibroelastosis (PPFE)

Supportive/ancillary features of UIP on CT:

• Propeller blade distribution*– Subpleural disease anterior in upper lobes

– Subpleural disease posterior in lower lobes

*so-called because of its lack of resemblance to a propeller

Supportive/ancillary features of UIP on CT:

• Nodular ossification (white spots) in fibrosis

– 29% prevalence (c.f. 8% in non-IPF/UIP) [in press]

• R to L asymmetry of fibrosis [anecdotal]

PleuroparenchymalFibroelastosis (PPFE)

+UIP

Supportive/ancillary features of UIP on CT:

PPFE associated with lower zone UIP in 32% of patients [unpublished data]

UIP pattern(all four features)

Possible UIP pattern(all three features)

Inconsistent with UIP pattern (any one of seven features)

Subpleural basal predominance

Subpleural basal predominance

Upper or mid lung predominance

Peribronchovascular predominance

Reticular abnormality Reticular abnormality Extensive ground glass abnormality (extent > reticular abnormality)

Profuse micronodules (bilateral, predominantly upper lobes)

Honeycombing with or without traction bronchiectasis

Discrete cysts (multiple bilateral, away from areas of honeycombing)

Diffuse mosaic attenuation/air trapping (bilateral in three or more lobes)

Absence of features listed as inconsistent with UIP pattern

Absence of features listed as inconsistent with UIP pattern

Consolidation in broncho-pulmonary segment(s)/lobe(s)

Table 4

Raghu et al AJRCCM 2011;183:788

• Subpleural

• Basal

• Honeycombing

UIP pattern(all four features)

Possible UIP pattern(all three features)

Inconsistent with UIP pattern (any one of seven features)

Subpleural basal predominance

Subpleural basal predominance

Upper or mid lung predominance

Peribronchovascular predominance

Reticular abnormality Reticular abnormality Extensive ground glass abnormality (extent > reticular abnormality)

Profuse micronodules (bilateral, predominantly upper lobes)

Honeycombing with or without traction bronchiectasis

Discrete cysts (multiple bilateral, away from areas of honeycombing)

Diffuse mosaic attenuation/air trapping (bilateral in three or more lobes)

Absence of features listed as inconsistent with UIP pattern

Absence of features listed as inconsistent with UIP pattern

Consolidation in broncho-pulmonary segment(s)/lobe(s)

Table 4

Raghu et al AJRCCM 2011;183:788

Upper or mid lung predominance

Peribronchovascular predominance

Extensive ground glass abnormality (extent > reticular abnormality)

Profuse micronodules (bilateral, predominantly upper lobes)

Discrete cysts (multiple bilateral, away from areas of honeycombing)

Diffuse mosaic attenuation/air trapping (bilateral in three or more lobes)

Consolidation in broncho-pulmonary segment(s)/lobe(s)

• Observer agreement for each of these features?

• Extent at which these abnormalities become significant?

Column 3 as a checklist to differentiate UIP from “others”

• Not basal

• Bronchocentric

• GGO > reticular

• Nodules

• Cysts

• Mosaicism (lobules)

• Consolidation

Much of Column 3 is a checklist of features that differentiate UIP from CHP…

• Mosaicism (lobules)

• Not basal

• Bronchocentric

• Nodules

• GGO > reticular

• Cysts

• Consolidation

NSIP

HP

LIP

DIP/

RB-ILD

UIPOP

LIP

DIP/

RB-ILD

NSIP

HP

UIP

OP

LIP

DIP/

RB-ILD

NSIP

HP

UIP

OP

HRCT pointers to chronic hypersensitivity pneumonitis:

• Lobules of decreased attenuation in spared (non-fibrotic) lung

• Occasional septal thickening may be a bit more obvious than in other fibrotic IIPs

• x3 distributions of fibrosis: UZ, LZ or random - sometimes vague/subtle bronchocentricity if UZ

• Coexistent subacute changes - indistinct relatively low attenuation centrilobular nodules (rare)

Lobules of decreased attenuation in spared lung

Chronic HP

UIP

Septal thickening in chronichypersensitivity pneumonitis

Unusual distribution of fibrosis, particularly vague bronchocentricity when upper lobe predominant:

n.b. Bronchocentricity, when present,

is much more subtle than the

bronchocentric fibrosis in sarcoidosis

BAL lymphocytosis 27%

MDT diagnosis of Chronic HP

UIP on lung biopsy

MDT diagnosis of IPF

Coexisting chronic and subacute features of HP (rare)

Summary scheme for HRCT of fibrosing lung disease:

• Is it a fibrosing lung disease (3 signs)?

• If yes, is it classical/definite UIP?

• If no, what are the choices?

HRCT differential diagnosis of fibrosing lung disease:

• Usual interstitial pneumonia (UIP)

• Non-specific interstitial pneumonia (NSIP)

• Chronic hypersensitivity pneumonitis

• Fibrotic sarcoidosis

• Fibrosing variant of organizing pneumonia

For non-definite UIP, list in order of prevalence/importance:

• Non-honeycomb UIP -v- Chronic HP

• Fibrosing variant of OP

• Idiopathic NSIP

• Fibrotic sarcoidosis

www.diagnoseIPF.com

A practical guide to the CT imaging of fibrosing lung disease

New abnormality on background of fibrosing lung disease

• Focal - nodule/mass

• Diffuse - ground glass opacification (“grey lung”)

Focal abnormality on a background of fibrosing lung disease

• Considerations:

–Condensation of fibrosis

• ?PPFE component (not often OP)

– Lung cancer

• x8 relative risk, 5-15% prevalence

• Often masked by background fibrosis

– Tuberculosis

• Atypical manifestations: often focal

Probable PPFE - monitor

Lung cancer

Reactivation TB(!)

New “grey lung” on background of fibrotic IIP - what’s happening?

Progressive fibrosis versus incipient acute exacerbation

Interval?

One year

6 weekslater

Differential diagnosis for rapid onset “grey lung” on background of fibrotic IIP:

• Acute exacerbation of IPF/UIP

• Supervening heart failure (oedema)

• Opportunistic infection (PCP/CMV)

• Drug reaction – esp. novel drugs

• (Spurious – expiratory CT)

• (Spurious – contrast in CTPA)

3 weeks later

Acute Exacerbation

Pulmonary oedema

Pneumocystis pneumonia

Expiratory CT

CTPA (contrast)

Ideal:Pre-contrast HRCT (limited sections)

Summary• “Is it fibrosing lung disease or not?” is the

crucial first question

• CT differentiation between UIP and other fibrosing lung diseases can be difficult but the main distinction is UIP -v- CHP

• Not all new nodules in IPF patients are lung cancer

• Be aware of differential diagnosis of supervening ground glass opacification in IPF