Histopathology Features

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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 should undergo a lung biopsy to reach a definite IPF diagnosis1
 
The decision to pursue lung biopsy must take into account underlying comorbidities, pulmonary function, and patient preference1

1. Raghu G et al. Am J Respir Crit Care Med. 2011;183(6):788-824. 

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

A biopsy should take samples from multiple lobes, preferably via thoracoscopic or open approaches to obtain adequate tissue for histologic diagnosis1
 
Transbronchial biopsies via fiberoptic bronchoscopy are not recommended in diagnosing IPF due to low yield1,2
 
1. Raghu G et al. Am J Respir Crit Care Med. 2011;183(6):788-824.
2.Meltzer EB et al. Orphanet J Rare Dis. 2008;3:1-15.

There are 4 categories of UIP pattern in histopathology

The histopathologic features of lung biopsy fall into 1 of 4 categories1:
–Definite UIP pattern
–Probable UIP pattern
–Possible UIP pattern
–Not UIP pattern
 
1. Raghu G et al. Am J Respir Crit Care Med. 2011;183(6):788-824.

Definite UIP pattern

Evidence of marked fibrosis/architectural distortion ± honeycombing in a predominantly subpleural/paraseptal distribution
AND
Presence of patchy involvement of lung parenchyma by fibrosis
AND
Presence of fibroblast foci
AND
Absence of features against a diagnosis of UIP, suggesting an alternate diagnosis (see Not UIP section)

1. Raghu G et al. Am J Respir Crit Care Med. 2011;183(6):788-824.

The chief diagnostic criterion of UIP is a variegated pattern at low magnification

UIP shows alternating areas of patchy pulmonary parenchymal fibrosis with scarring and honeycomb changes and less affected or normal parenchyma3,4

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.2

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

Histopathologic changes in IPF often affect the subpleural and paraseptal parenchyma most severely

The involved areas of the lung show complete distortion of normal architecture, with sheets of dense collagen replacing normal lung tissue and occasional microscopic honeycomb cysts2
 
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.2

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

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 cells4 
 
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.2
 
2. Meltzer EB et al. Orphanet J Rare Dis. 2008;3:1-15.
4. Katzenstein AL et al. Am J Respir Crit Care Med. 1998;157(4 Pt 1):1301-1315. 

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 foci2-4

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.2
 
2. Meltzer EB et al. Orphanet J Rare Dis. 2008;3:1-15.
3. Travis WD et al. Am J Surg Pathol. 2000;24(1):19-33.
4. 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 fibrosis5

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

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.

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

Definite UIP is not limited to IPF

The UIP pattern can be found in several other diseases, including2:
–Connective tissue diseases
–Asbestosis
–Chronic hypersensitivity pneumonitis
–Hermansky-Pudlak syndrome
–Drug toxicities
 
Clinical history is essential for distinguishing IPF from other disorders that also produce a UIP pattern on biopsy1

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

UIP may occur simultaneously with patterns of other lung diseases

  • It is important to recognize that UIP may be present along with other patterns consistent with other lung diseases, such as emphysema6,7
  • In these cases, changes characteristic of each disease are expected to be present7
 
6. Jankowich M et al. Chest 2012;41(1):222-231.
7. Awano N et al. Histopathology 2017;70(6):896-905.

Probable UIP pattern

The following features are suggestive of a probable UIP pattern1:

Honeycomb changes 
OR
Marked fibrosis  and architectural distortion with or without honeycombing
AND
Absence of fibroblastic foci or patchy involvement (not both)
AND
Absence of features classified as “not UIP pattern” and suggestive of alternative diagnosis

1. Raghu G et al. Am J Respir Crit Care Med. 2011;183(6):788-824.

Possible UIP pattern

A possible UIP pattern includes all of the following criteria1:
 
Patchy or diffuse fibrosis involving the lung parenchyma, with or without interstitial inflammation
AND
Absence of other criteria signifying UIP
AND
Absence of features classified as “not UIP pattern” and suggestive of an alternative diagnosis

1. Raghu G et al. Am J Respir Crit Care Med. 2011;183(6):788-824.

Not UIP pattern

Presence of any of the following 6 features is considered “not UIP” and should lead to the consideration of other diseases1

Organizing pneumonia
Hyaline membranes
Predominant airway-centered changes
Marked interstitial inflammatory cell infiltrate apart from honeycombing
Granulomas
Other features suggestive of an alternate diagnosis

1. Raghu G et al. Am J Respir Crit Care Med. 2011;183(6):788-824.

Summary

  • IPF may exhibit a range of UIP patterns on histopathologic samples1
  • UIP pattern can indicate other pathologies in addition to IPF1
  • 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
MDD, multidisciplinary discussion.

1. Raghu G et al. Am J Respir Crit Care Med. 2011;183(6):788-824.

References

1. Raghu G et al. Am J Respir Crit Care Med. 2011;183(6):788-824. 
2. Meltzer EB et al. Orphanet J Rare Dis. 2008;3:1-15.
3. Travis WD et al. Am J Surg Pathol. 2000;24(1):19-33.
4. Katzenstein AL et al. Am J Respir Crit Care Med. 1998;157(4 Pt 1):1301-1315.
5. Cool CD et al. Am J Respir Crit Care Med. 2006;174(6):654-658.
6. Jankowich M et al. Chest 2012;41(1):222-231.
7. Awano N et al. Histopathology 2017; 70(6):896-905.