Histopathologic Features of IPF

Histopathologic Features of Usual Interstitial Pneumonia, Small

Used with permission from McGraw-Hill Companies, Inc. Copyright © 2007 McGraw-Hill Companies, Inc.

Surgical Lung Biopsy

In patients in whom HRCT is non-diagnostic for IPF, lung biopsy is required for a definite IPF diagnosis.8 Transbronchial biopsies via fiberoptic bronchoscopy are of low yield in the diagnosis of IPF and are not recommended.8 Biopsies of multiple lobes via thoracoscopic or open approaches are preferred and necessary to obtain adequate tissue for histologic diagnosis.8

Again, the decision to pursue surgical lung biopsy must take into account underlying comorbidities, poor pulmonary function, and patient preference.8

The histopathologic lesion associated with IPF is UIP.12 Just as the 2011 guidelines placed the radiographic features of UIP into 1 of 3 categories, a similar schema was applied to the histopathologic features of UIP.40 As shown in Table 4 and described below, the histopathologic features of lung biopsy were placed in 1 of 4 categories: definite UIP pattern, probable UIP pattern, possible UIP pattern, and not UIP pattern.8

Table 4.
Histopathologic criteria for usual interstitial pneumonia. Reprinted with permission of the American Thoracic Society. Copyright © 2014 American Thoracic Society. Raghu G, Collard HR, Egan JJ, et al. An official ATS/ERS/JRS/ALAT statement: idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and management. Am J Respir Crit Care Med. 2011;183:788-824. Official Journal of the American Thoracic Society. Note: this document was published in 2011 and is currently in revision. Certain aspects of this document may be out of date and caution should be used when applying these in clinical practice or other usages.

UIP Pattern
(all 4 criteria)
Probable UIP Pattern Possible UIP Pattern
(all 3 criteria)
Not UIP Pattern
(any of the 6 criteria)
Evidence of marked fibrosis/architectural distortion ± honeycombing in a predominately subpleural/paraseptal distribution Evidence of marked fibrosis/architectural distortion ± honeycombing Patchy or diffuse involvement of lung parenchyma by fibrosis, with or without interstitial inflammation Hyaline membranes*
Presence of patchy involvement of lung parenchyma by fibrosis Absence of either patchy involvement or fibroblast foci, but not both Absence of other criteria for UIP (see UIP pattern column) Organizing pneumonia*
Presence of fibroblast foci Absence of features against a diagnosis of UIP, suggesting an alternate diagnosis (see 4th column) Absence of features against a diagnosis of UIP, suggesting an alternate diagnosis (see 4th column) Granulomas
Absence of features against a diagnosis of UIP, suggesting an alternate diagnosis (see 4th column) OR
Honeycomb changes only
  Marked interstitial inflammatory cell infiltrate away from honeycombing
      Predominant airway-centered changes
      Other features suggestive of an alternate diagnosis

UIP, usual interstitial pneumonia.
*Can be associated with acute exacerbation of IPF.
An isolated or occasional granuloma and/or a mild component of organizing pneumonia pattern may rarely be coexisting in lung biopsies with an otherwise UIP pattern.
This scenario represents end-stage fibrotic lung disease where honeycombed segments have been sampled but where a UIP pattern might be present in other areas.

UIP Pattern

As seen in Figure 4a,12 the chief diagnostic criterion of UIP is a variegated pattern at low magnification in which patchy areas of pulmonary parenchymal fibrosis with scarring and honeycomb changes alternate with areas of less affected or normal parenchyma.84445

Similar to the radiologic changes, histopathologic changes often affect the subpleural and paraseptal parenchyma most severely.8 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 cysts.12 As seen in Figure 4b, 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 foci.1244 Although initially considered discrete areas of fibrosis, recent investigation has suggested that fibroblastic foci may reflect a reticulum of scar tissue extending from the pleura to the central portions of lung.46 Areas of honeycomb change are composed of cystic fibrotic airspaces that are frequently lined by bronchiolar epithelium and filled with mucus and inflammatory cells.844 These findings, observed together, are diagnostic of definite UIP, assuming atypical findings are absent (Table 4).8

Figure 4.
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.

Histopathologic Features of Usual Interstitial Pneumonia

Probable UIP pattern

The following features are suggestive of a probable UIP pattern (Table 4)8:

  • Honeycomb changes only 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 an alternative diagnosis

Possible UIP Pattern

A possible UIP pattern includes all of the following criteria (Table 4)8:

  • Patchy or diffuse fibrosis involving the lung parenchyma, with or without interstitial inflammation
  • Absence of other criteria signifying UIP
  • Absence of features classified as “not UIP pattern” and suggestive of an alternative diagnosis

Not UIP Pattern

Certain histologic features are inconsistent with a UIP pattern (Table 4).8 Features such as hyaline membranes, granulomas, marked interstitial inflammatory cell infiltrate apart from honeycombing, predominant airway-centered changes, and other features suggestive of an alternate diagnosis should lead to the consideration of other diseases.8 It is important to recognize that UIP may be superimposed on other lung diseases, such as COPD or sarcoidosis. In these cases, changes of both diseases are expected to be present.

Notably, the UIP pattern is not limited to IPF and can be found in several other diseases.12 UIP can be seen in the following conditions12:

  • Connective tissue diseases
  • Asbestosis
  • Chronic hypersensitivity pneumonitis
  • Hermansky-Pudlak syndrome
  • Drug toxicities

Correlation with clinical history is needed to distinguish IPF from other disorders that are associated with a UIP pattern.8

Content contributed by:
Ryan Hadley, MD
University of Michigan