The radiological differential diagnosis of the UIP pattern

5th International Conference on Idiopathic Pulmonary Fibrosis, Modena, 2015, June 12th The radiological differential diagnosis of the UIP pattern Simon Walsh King s College Hospital Foundation Trust London, United Kingdom

The radiological differential diagnosis of the UIP pattern Very short lecture..

Scope Suggest an algorithmic approach to HRCT diagnosis in the setting of fibrotic lung disease Within this, discuss The radiological differential diagnosis of the UIP pattern Challenges making a radiologic diagnosis of UIP/IPF

How do we make a radiologic diagnosis in the setting of fibrotic lung disease?

Making a HRCT diagnosis in fibrotic lung disease: key questions. Is it a fibrotic lung disease? If so, is it classical UIP? If its not UIP, what are the alternatives? alternatives

Making a HRCT diagnosis in fibrotic lung disease: key questions.

Revision: HRCT patterns of fibrosis (++++ = complete certainty) Honeycombing +++(+) Traction bronchiectasis ++(+) Volume loss +

Revision: HRCT patterns of fibrosis (++++ = complete certainty)

Traction Bronchiectasis

Traction Bronchiectasis Non-tapering airway surrounded by abnormal lung parenchyma

Revision: HRCT patterns of fibrosis (++++ = complete certainty)

Volume loss can be difficult to appreciate.

Making a HRCT diagnosis in fibrotic lung disease: key questions.

3 diagnosis categories UIP pattern ( definite, classic ) Possible UIP pattern Inconsistent with a UIP pattern Raghu et al. AJRCCM 2011;183:788

Subpleural basal honeycombing UIP

Accuracy of a CT diagnosis of UIP/IPF

What do these atypical cases look like?

Spectrum of atypical radiologic appearances of biopsy proven UIP Sverzellati et al. Radiology 2009;254:987 Most common radiologic diagnoses in 34 patients with biopsy proven UIP whose CT does not meet radiologic criteria for definite UIP (i.e. basal, subpleural honeycombing).. NSIP 18 CHP 4 Sarcoidosis 3 OP Other 1 8

Pitfalls.. IMPORTANT: confidence accuracy

MDT diagnosis = chronic hypersensitivity pneumonitis

MDT diagnosis = fibrotic NSIP

MDT diagnosis = fibrotic pulmonary sarcoidosis

Recap: Radiologic presentation of UIP/IPF 50% Definite UIP Radiologic presentation: Subpleural, basal honeycombing 50% Atypical UIP Radiologic presentation: Fibrotic NSIP (most common) CHP (rare) Fibrotic Sarcoidosis (very rare) 95+% accurate CAVEAT: In <5% of cases, a classic UIP pattern on CT may end up with a diagnosis of fibrotic NSIP, CHP or even sarcoidosis (rare) at MDT

HRCT diagnosis fibrotic lung disease

Diffuse fibrotic lung diseases - non-classic UIP options.. Atypical UIP (discussed previously) Fibrotic NSIP Chronic hypersensitivity pneumonitis Fibrotic Sarcoidosis Fibrotic variant of Organizing Pneumonia

Diffuse fibrotic lung diseases - non-classic UIP options..

IPF, fibrotic NSIP, CHP HRCT challenge. Characteristic CT features of chronic HP, IPF and fibrotic NSIP allow confident distinction between these entities in approximately 50% of patients. Silva et al, Radiology 2008;246:288

An Official ATS/ERS/JRS/ALAT Statement: Idiopathic pulmonary fibrosis: Evidence-based Guidelines for Diagnosis and Management Definite UIP Atypical UIP or fibrotic NSIP Chronic hypersensitivity pneumonitis Raghu et al. AJRCCM 2011;183:788

Chronic hypersensitivity pneumonitis

Silva et al, Radiology 2008;246:288

Upper lobe predominance Lobular areas of low attenuation (reflects small airways disease) Bronchocentricity Silva et al, Radiology 2008;246:288

BRONCHOCENTRICITY IPF CHP

Fibrotic NSIP

RELATIVE SUBPLEURAL SPARING Silva et al, Radiology 2008;246:288 MacDonald et al, Radiology 2001;221:600

GROUND GLASS PREDOMINANT WITH FINE RETICULATION Silva et al, Radiology 2008;246:288 MacDonald et al, Radiology 2001;221:600

NO HONEYCOMBING Silva et al, Radiology 2008;246:288 MacDonald et al, Radiology 2001;221:600

Fibrotic sarcoidosis

Perihilar bronchovascular distortion - reaching out to the subpleural lung

The fibrosis is often mass-like

Posterior retraction of the hila like this is almost pathognomonic

Fibrotic variant of organizing pneumonia Small group of patients presenting with organizing pneumonia Progressive fibrotic course and a poor prognosis In order to suggest this diagnosis with any degree of certainty, previous imaging, demonstrating OP is needed BJ Roberton et al, Eur Radiol 2011;21:2244

Non-fibrotic organizing pneumonia Classic perilobular pattern of OP

Non-fibrotic organizing pneumonia Bronchocentric band like opacities containing air bronchograms

Fibrotic variant of organizing pneumonia

Fibrotic variant of organizing pneumonia Traction bronchiectasis.

Fibrotic variant of organizing pneumonia Perilobular pattern.

Fibrotic variant of organizing pneumonia Band-like opacities with air bronchograms.

Re-cap..

Is there evidence of a fibrotic lung disease?

Is there evidence of a fibrotic lung disease? Honeycombing Traction Bronchiectasis Volume loss

Is there evidence of a fibrotic lung disease? yes Is it classical UIP?

Is there evidence of a fibrotic lung disease? yes Is it classical UIP? Basilar predominant Subpleural Honeycombing >95% accuracy for histopathologic UIP (but remember caveats)

Is there evidence of a fibrotic lung disease? Is it classical UIP? No Alternative Diagnoses

Is there evidence of a fibrotic lung disease? Is it classical UIP? No Alternative Diagnoses Lobular areas of decreased attenuation within normal lung CHP Absence of lower lobe predominance ± Centrilobular nodules (?) ± Upper lobe predominance ± Bronchocentricity

Is there evidence of a fibrotic lung disease? Is it classical UIP? No Alternative Diagnoses Atypical UIP vs. Fibrotic NSIP A common diagnostic dilemma in terms of imaging alone Rule out CHP (areas of lobular decreased attenuation) Clearly not fibrotic sarcoid Importance of AGE : Fell et al, AJRCCM 2010;181:832

Is there evidence of a fibrotic lung disease? Is it classical UIP? No Alternative Diagnoses Fibrotic sarcoidosis Classic sarcoid Ancillary features e.g. calcified nodes

Is there evidence of a fibrotic lung disease? Is it classical UIP? No Alternative Diagnoses Fibrotic variant of Organizing pneumonia Previous Imaging Features of OP

Is there evidence of a fibrotic lung disease? yes Is it classical UIP? No Alternative Diagnoses Atypical UIP vs. Fibrotic NSIP CHP Fibrotic sarcoidosis Fibrotic variant of Organizing pneumonia

Back to UIP/IPF Radiological challenge

Subpleural, basal honeycombing = classic UIP Easy

ATS/ERS/JRS/ALAT guidelines: Radiologic misdiagnosis is a problem Clinicians perspective: majority of clinicians found a HRCT diagnosis of IPF to be reliable in less than a third of practicing radiologists.. AU Wells - straw poll, Berlin IPF AIR meeting, November 2011

ATS/ERS/JRS/ALAT guidelines: Radiologic misdiagnosis is a problem Radiologists perspective: 150 cases of fibrotic lung disease Classify each case as Definite UIP Possible UIP Inconsistent with UIP www.hrct-imaging.com Walsh, Calandriello, Sverzellati, Wells, Hansell and the fibrotic lung disease investigators

ATS/ERS/JRS/ALAT guidelines: Radiologic misdiagnosis is a problem Radiologists perspective: ESTI (European Society of Thoracic Imaging) BSTI (British Society of Thoracic Imaging) STR (Society of Thoracic Radiology) KSTR (Korean Society of Thoracic Radiology)

ATS/ERS/JRS/ALAT guidelines: Radiologic misdiagnosis is a problem Radiologists perspective: Observer agreement: 112 thoracic radiologists from 5 continents Kw = 0 47 ± 0.05 <0.4 = poor, 0.4-0.6 = satisfactory, 0.6-0.8 = good, >0.8 = excellent

ATS/ERS/JRS/ALAT guidelines: Radiologic misdiagnosis is a problem Radiologists perspective: Observer agreement: Thoracic radiologists > 25 years experience Kw = 0 37 ± 0.11 <0.4 = poor, 0.4-0.6 = satisfactory, 0.6-0.8 = good, >0.8 = excellent

Why?

Honeycombing.. 1. Cardinal CT sign of fibrosis 2. Important criterion for UIP 3. Important predictor of mortality in IPF However, it may not always be easy to confidently identify. Arakawa et al, AJR, 2011,196:773

Honeycombing? Paraseptal emphysema with coexistent honeycombing

Honeycombing? Traction bronchiectasis

43 Observers 27 Expert chest radiologists 80 single images Kw = 0.40-0.58 <0.4 = poor, 0.4-0.6 = satisfactory,0.6-0.8 = good,>0.8 = excellent Watadani et al, Radiology, 2013:266:936

Some inconsistency.. Weighted kappa s for honeycombing Lynch et al, AJRCCM, 2005:172:488 Kappa = 0.21-0.31 Sundaram et al, AJR, 2008:191:1032 Kappa = 0.25-0.56 Goldin et al, Chest, 2009:136:1333 Kappa = 0.39 <0.4 = poor, 0.4-0.6 = satisfactory, 0.6-0.8 = good, >0.8 = excellent

Some inconsistency.. Weighted kappa s for honeycombing Lynch et al, AJRCCM, 2005:172:488 Kappa = 0.21-0.31 315 patients with biopsy proven IPF Expert thoracic radiologists <0.4 = poor, 0.4-0.6 = satisfactory, 0.6-0.8 = good, >0.8 = excellent

A counter argument.. Endless discussion about definition and identification of honeycombing missing the point?

Richeldi et al, 2011 Study population n=432 (28% with lung biopsy) Definite UIP = 32.9% i.e. honeycombing present in only 1/3 patients, in practice may be 20-45%

Radiologist s Challenge: to clarify possible UIP status Are there specific CT features that predict histopathologic UIP? Raghu et al. AJRCCM 2011;183:788

Gruden et al 2013 Raghu et al 2014 Chung et al 2015

201 cases of fibrotic lung disease With SLB data available Categorized cases as: Definite UIP (same as 2013 classification) Probable UIP Indeterminate Inconsistent with UIP (same as 2013 classification) Chung et al, Chest 2015;147:450-459

201 cases of fibrotic lung disease With SLB data available Categorized cases as: Definite UIP (same as 2013 classification) Probable UIP Indeterminate ( possible UIP on 2013 classification) Inconsistent with UIP (same as 2013 classification) Chung et al, Chest 2015;147:450-459

Probable UIP.. Peripheral and basilar predominant fibrosis with little or no honeycombing and absence of features to suggest another diagnosis Chung et al, Chest 2015;147:450-459

Probable UIP (34/201) 82% had definite/probable UIP on histology Chung et al, Chest 2015;147:450-459

DA Lynch - STR meeting Carlsbad 2015

IPF or Non-IPF IIP?

Clinical predictors of IPF The importance of age 135 patients (UIP / IPF=97; other IIPs=38) HRCT, PFTs, 6MWT (within 6/12 of biopsy)? Clinical-radiological predictors of IPF In idiopathic fibrotic lung disease, increasing age increases likelihood of a diagnosis of IPF irrespective of CT presentation >70 years PPV 95% >75 years PPV 100% Age is on the CT! Fell et al. AJRCCM, 2010;181:832-837

New approach: Working diagnosis of IPF Takes CT appearance as starting point Typical for UIP Compatible with UIP Atypical for UIP Dynamic diagnostic process (not set in stone) Integrate other important non-radiological information, in particular AGE DISEASE BEHAVIOUR LAVAGE PROFILE