Histopathology Features

Diagnosing IPF:Histopathologic features of IPF

Only a subset of possible IPF cases are candidates for a lung biopsy

Patients whose HRCT results are non-diagnostic for IPF may undergo a surgical lung biopsy to reach a definite IPF diagnosis1-3ab

 

 

 

The decision to pursue lung biopsy must take into account underlying comorbidities, pulmonary function, and patient preference1,2

1. Raghu G et al. Am J Respir Crit Care Med. 2018;198(5):e44-e68. 2. Raghu G et al. Am J Respir Crit Care Med. 2011;183(6):788-824. 3. Lynch DA et al. Lancet. 2018;6(2):138-153. 

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a: Surgical lung biopsy is not indicated in patients at high risk for intra-, peri-, or postoperative complications (e.g., severe hypoxemia at rest and/or severe pulmonary hypertension with a diffusion capacity <25% after correction for hematocrit)

b: A multidisciplinary discussion is needed before a diagnosis of IPF is made

 

Choosing the right biopsy method is crucial for making an accurate diagnosis

A biopsy should take samples from multiple lobes, preferably via video-assisted thoracoscopic approaches to obtain adequate tissue for histologic diagnosis1-3

 

Transbronchial biopsies via fiberoptic bronchoscopy are not recommended in diagnosing IPF due to low yield2-4

 

Recommendations differ based on HRCT evidence of UIP or the potential for something other than UIP1:

 

1. Raghu G et al. Am J Respir Crit Care Med. 2018;198(5):e44-e68. 2. Raghu G et al. Am J Respir Crit Care Med. 2011;183(6):788-824. 3. Lynch DA et al. Lancet. 2018;6(2):138-153. 4. Meltzer EB et al. Orphanet J Rare Dis. 2008;3:1-15.

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There are 4 categories of UIP pattern in histopathology

The histopathologic features of UIP fall into 1 of 4 categories1,3:

 

1. Raghu G et al. Am J Respir Crit Care Med. 2018;198(5):e44-e68. 3. Lynch DA et al. Lancet. 2018;6(2):138-153.  

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UIP pattern1,3

Evidence of dense fibrosis with architectural distortion (i.e., honeycombing and/or destructive scarring) in a predominantly subpleural/paraseptal distribution

AND

Presence of patchy involvement of lung parenchyma by fibrosis

Presence of fibroblast foci

AND

AND

Absence of features to suggest an alternate diagnosis (see Alternate Diagnosis section)

1. Raghu G et al. Am J Respir Crit Care Med. 2018;198(5):e44-e68. 3. Lynch DA et al. Lancet. 2018;6(2):138-153.  

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Predominant subpleural and/or paraseptal distribution of fibrosis

AND

The chief diagnostic criterion of UIP is patchy dense fibrosis at low magnification1

UIP shows alternating areas of patchy pulmonary parenchymal fibrosis with scarring and honeycomb changes and less affected or normal parenchyma5,6

1. Raghu G et al. Am J Respir Crit Care Med. 2018;198(5):e44-e68. 4. Meltzer EB et al. Orphanet J Rare Dis. 2008;3:1-15. 5. Travis WD et al. Am J Surg Pathol. 2000;24(1):19-33. 6. Katzenstein AL et al. Am J Respir Crit Care Med. 1998;157(4 Pt 1):1301-1315.

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Histopathologic features of usual interstitial pneumonia. Reprinted from Fishman's Pulmonary Diseases and Disorders, 4th edition 2007. Meltzer, EB and Noble, PW: Chapter70, Idiopathic Pulmonary Fibrosis. Used with permission from McGraw-Hill Companies, Inc. Copyright © 2007 McGraw-Hill Companies, Inc.4

CHANGE_ME

Histopathologic changes in IPF often affect the subpleural and paraseptal parenchyma most severely1,3 
Histopathologic features of usual interstitial pneumonia. Reprinted from Fishman's Pulmonary Diseases and Disorders, 4th edition 2007. Meltzer, EB and Noble, PW: Chapter70, Idiopathic Pulmonary Fibrosis. Used with permission from McGraw-Hill Companies, Inc. Copyright © 2007 McGraw-Hill Companies, Inc.3
1. Raghu G et al. Am J Respir Crit Care Med. 2018;198(5):e44-e68. 3. Lynch DA et al. Lancet. 2018;6(2):138-153.  4. Meltzer EB et al. Orphanet J Rare Dis. 2008;3:1-15. 
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At high magnification, the detailed features of definite UIP are visible

Areas of honeycomb change are composed of cystic fibrotic airspaces that are frequently lined by bronchiolar epithelium and filled with mucus and inflammatory cells6 

 

4. Meltzer EB et al. Orphanet J Rare Dis. 2008;3:1-15. 6. Katzenstein AL et al. Am J Respir Crit Care Med. 1998;157(4 Pt 1):1301-1315.

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Histopathologic features of usual interstitial pneumonia. Reprinted from Fishman's Pulmonary Diseases and Disorders, 4th edition 2007. Meltzer, EB and Noble, PW: Chapter70, Idiopathic Pulmonary Fibrosis. Used with permission from McGraw-Hill Companies, Inc. Copyright © 2007 McGraw-Hill Companies, Inc.4

 

Hyperplastic alveolar epithelium

 

 

 

 

Fibroblasts

At high magnification, the detailed features of definite UIP are visible (cont.)

As the region of scarred lung tissue encroaches upon the areas of normal lung tissue, the advancing edge of the young fibrosis contains specialized structures known as fibroblast foci4-6

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Histopathologic features of usual interstitial pneumonia. Reprinted from Fishman's Pulmonary Diseases and Disorders, 4th edition 2007. Meltzer, EB and Noble, PW: Chapter70, Idiopathic Pulmonary Fibrosis. Used with permission from McGraw-Hill Companies, Inc. Copyright © 2007 McGraw-Hill Companies, Inc.4

 

Hyperplastic alveolar epithelium

 

Fibroblasts

 

 

 

4. Meltzer EB et al. Orphanet J Rare Dis. 2008;3:1-15. 5. Travis WD et al. Am J Surg Pathol. 2000;24(1):19-33. 6. Katzenstein AL et al. Am J Respir Crit Care Med. 1998;157(4 Pt 1):1301-1315.

Fibroblastic foci may reflect a reticulum of scar tissue

Fibrosis may occur as a reticulum of scar tissue that extends from the pleura to the central portions of lung rather than existing as discrete areas of fibrosis7

 

Histopathologic features of usual interstitial pneumonia. Reprinted from Fishman's Pulmonary Diseases and Disorders, 4th edition 2007. Meltzer, EB and Noble, PW: Chapter 70, Idiopathic Pulmonary Fibrosis. Used with permission from McGraw-Hill Companies, Inc. Copyright © 2007 McGraw-Hill Companies, Inc.

These findings, observed together, are diagnostic of UIP, assuming atypical findings are absent1,2

1. Raghu G et al. Am J Respir Crit Care Med. 2018;198(5):e44-e68. 2. Raghu G et al. Am J Respir Crit Care Med. 2011;183(6):788-824. 7. Cool CD et al. Am J Respir Crit Care Med. 2006;174(6):654-658.

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Hyperplastic alveolar epithelium

Fibroblasts

UIP is not limited to IPF

The UIP pattern can be found in several other diseases, including3,4:

 

Clinical history is essential for distinguishing IPF from other disorders that also produce a UIP pattern on biopsy2

2. Raghu G et al. Am J Respir Crit Care Med. 2011;183(6):788-824. 3. Lynch DA et al. Lancet. 2018;6(2):138-153. 4. Meltzer EB et al. Orphanet J Rare Dis. 2008;3:1-15.

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UIP may occur simultaneously with patterns of other lung diseases

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It is important to recognize that UIP may be present along with patterns consistent with other lung diseases, such as emphysema8,9

 

In these cases, changes characteristic of each disease are expected to be present9

 

8. Jankowich M et al. Chest 2012;41(1):222-231. 9. Awano N et al. Histopathology 2017;70(6):896-905.

Probable UIP pattern

The following features are suggestive of a probable UIP pattern1,3:

 

 

 

 

 

 

 

Absence of features suggestive of an alternative diagnosis

AND

Some features of UIP, but precludes a definitive diagnosis of UIP/IPF

OR

1. Raghu G et al. Am J Respir Crit Care Med. 2018;198(5):e44-e68. 3. Lynch DA et al. Lancet. 2018;6(2):138-153.

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Honeycomb Changes

Indeterminate UIP pattern

An indeterminate UIP pattern includes all of the following criteria1,3:

 

Fibrosis with or without architectural distortion with features supporting a pattern other than UIP or UIP secondary to another causea

Features of UIP along with features suggesting an alternative diagnosisb

AND

1. Raghu G et al. Am J Respir Crit Care Med. 2018;198(5):e44-e68. 3. Lynch DA et al. Lancet. 2018;6(2):138-153.

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aGranulomas, hyaline membranes (other than when associated with acute exacerbation of IPF, which may be the presenting manifestation in some patients), prominent airway-centered changes, areas of interstitial inflammation lacking associated fibrosis, marked chronic fibrous pleuritis, organizing pneumonia. These features may not be easily seen to the untrained eye and often need to be specifically sought.

bThese include: cellular inflammatory infiltrate away from areas of honeycombing, prominent lymphoid hyperplasia including secondary germinal centers, and a distinctly bronchiolocentric distribution that could include extensive peribronchiolar metaplasia.

Alternative Diagnosis

Presence of the following features is considered indicative of an alternative diagnosis and should lead to the consideration of other diseases1,3

 

 

Histologic findings indicative of other diseases (sarcoidosis, Langerhans cell histiocytosis, hypersensitivity pneumonitis, LAM)

All biopsies have features of other histologic patterns of IIPs (absence of fibroblast foci, loose fibrosis)

1. Raghu G et al. Am J Respir Crit Care Med. 2018;198(5):e44-e68. 3. Lynch DA et al. Lancet. 2018;6(2):138-153.

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LAM, lymphangioleiomyomatosis.

Summary

IPF may exhibit a range of UIP patterns on histopathologic samples1

UIP pattern can indicate other pathologies in addition to IPF3

The observed histopathologic pattern should be considered together with the HRCT features, medical history, and clinical observations in the context of an MDD to produce a diagnosis1,3

 

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1. Raghu G et al. Am J Respir Crit Care Med. 2018;198(5):e44-e68. 3. Lynch DA et al. Lancet. 2018;6(2):138-153.

MDD, multidisciplinary discussion.

References

 

 

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