Lung
Other interstitial pneumonitis / fibrosis
UIP / IPF


Topic Completed: 1 June 2017

Minor changes: 17 August 2020

Copyright: 2003-2020, PathologyOutlines.com, Inc.

PubMed Search: usual interstitial pneumonia OR idiopathic pulmonary fibrosis

Akira Yoshikawa, M.D.
Andrey Bychkov, M.D., Ph.D.
Page views in 2019: 19,422
Page views in 2020 to date: 10,801
Cite this page: Yoshikawa A. UIP / IPF. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/lungnontumorUIP.html. Accessed September 30th, 2020.
Definition / general
  • Idiopathic pulmonary fibrosis (IPF) is a specific form of chronic interstitial lung disease of unknown cause, associated with histologic and radiologic pattern of usual interstitial pneumonia (UIP)
Essential features
  • Chronic and progressive respiratory failure due to fibrosis in the lung
  • One of the most common and most lethal lung diseases
  • Characterized by bibasilar patchy fibrosis and honeycomb
Terminology
  • UIP is the name of morphological pattern in histology and radiology, and also seen in other etiologies such as connective tissue diseases and hypersensitivity pneumonia
  • IPF was previously called chronic interstitial pneumonitis or cryptogenic fibrosing alveolitis
ICD coding
  • J84.112
Epidemiology
Sites
  • Bottom of lower lobes of bilateral (or "bibasilar") lung
Pathophysiology / etiology
  • Damage of alveolar epithelium (or pneumocytes) is a key event
  • Aberrant Wnt / β-catenin signaling pathway may be related to abnormal remodeling
  • Increased TGF-β1 activity likely has role in abnormal fibrosis
  • Although the etiology is still unknown, studies report several potential risk factors:
Diagrams / tables

Images hosted on other servers:
Schema of UIP pattern

Schema of UIP pattern

Clinical features
  • Manifestations of chronic respiratory syndrome:
    • Chronic dyspnea
    • Dry cough
    • Fatigue
    • Digital clubbing
  • Abnormal chest auscultation
    • End inspiratory fine crackles in bibasilar lung
  • Restrictive pattern in pulmonary function tests:
    • Decreased total lung capacity (TLC)
    • Decreased forced vital capacity (FVC)
    • Decreased diffusing capacity of the lung for carbon monoxide (DLCO)
    • Reduced diffusing capacity is mainly due to ventilation-perfusion mismatch from ventilation of lung tissue with capillary destruction and perfusion of under ventilated alveoli; smaller component due to reduced diffusion across a fibrotic alveolar septa
Diagnosis
  • Diagnosis of UIP / IPF is often challenging and strict criteria are still being discussed
  • Based on clinical features (including laboratory tests), high resolution computed tomography (HRCT) and surgical lung biopsy (SLB)
    • It is necessary to rule out other etiologies such as particle exposure, connective tissue diseases and hypersensitivity pneumonia
    • Transbronchial lung biopsy is sometimes performed instead of SLB, however pathologic diagnosis becomes more difficult due to the size of sample
  • The guidelines suggest multidisciplinary decision by physicians, radiologists and pathologists, especially when there is a discrepancy in between (Am J Respir Crit Care Med 2011;183:788)
  • Current guidelines do not recommend lung biopsy for cases with typical UIP pattern on HRCT; nevertheless histopathology remains an important diagnostic modality (Eur J Radiol 2014;83:20, Am J Respir Crit Care Med 2004;170:904, Eur Respir J 2010;35:1322, Thorax 2003;58:143)
Laboratory
Radiology description
  • Chest Xray can detect lesions: however, it is usually not sensitive enough to render the diagnosis
  • UIP pattern on HRCT:
    • Subpleural bibasilar reticular opacity
    • Honeycomb change; clustered cystic airspaces, 3 - 10 mm in diameter (Eur J Radiol 2014;83:27)
    • Traction bronchiectasis is often seen
Radiology images

Images hosted on other servers:
UIP pattern UIP pattern UIP pattern

UIP pattern

Prognostic factors
Case reports
Treatment
Gross description
  • Fibrotic changes in lower lobes
    • Shrunken lung with "hobnailed" pleura due to scarring
    • Elastic hard consistency
    • Diffuse (relatively subpleural dominant) destruction of lung mesenchyme
    • Multiple air cysts due to honeycomb change
    • Traction bronchiectasis can be seen
Gross images

Images hosted on other servers:
Honeycomb lung

Honeycomb lung

Microscopic (histologic) description
  • Major findings consistent with UIP pattern
    • Dense fibrosis
      • The lesion representing UIP pattern is mainly composed of hyalinized collagen
      • Often destructs alveolar architecture
      • Smooth muscle and elastofibrosis are often present
      • Mild to moderate infiltration by inflammatory cells can be seen
    • Patchy and peripheral / perilobular involvement
      • Temporal heterogeneity of the lesions evident on low power
      • Fibrosis tends to be remarkable in perilobular or subpleural area
      • Normal lung parenchyma can remain in the center of the lobule
    • Honeycomb
      • Cystic spaces lined by bronchiolar epithelium and fibrotic wall
      • The lung in the end stage fibrosis is called "honeycomb lung"
    • Fibroblastic foci
      • Active fibrotic lesions composed of myofibroblasts
      • Aggregation of spindle cells with gray to pale purple matrix adjacent to dense fibrosis
  • Clinical guidelines suggest 4 levels of certainty for pathologic diagnosis (Am J Respir Crit Care Med 2011;183:788)
    • Definite UIP pattern
      • Marked fibrosis / architectural distortion
      • Patchy involvement
      • Fibroblast foci
    • Probable UIP pattern
      • Either:
        • A: marked fibrosis / architectural distortion AND [patchy involvement OR fibroblastic foci]
        • Or B: honeycomb change only
    • Possible UIP pattern
      • Patchy or diffuse involvement of fibrosis
    • Not UIP pattern (whenever any of findings below is present)
      • Hyaline membranes
      • Organizing pneumonia
      • Granulomas
      • Marked interstitial inflammatory cell infiltrate away from honeycombing
      • Predominant airway centered changes
      • Other features suggestive of an alternate diagnosis
    • Some criteria of these findings (e.g., how many granulomas to be considered significant) are still not clear
  • Additional findings
    • Squamous metaplasia: squamoid epithelium without cilia, predictor of acute exacerbation (USCAP 2016)
    • Interstitial emphysema: a cystic space without epithelial lining, predictor of pneumothorax (Am J Surg Pathol 2014;38:339)
    • Respiratory bronchiolitis macrophage: accumulation of macrophages in air spaces, especially in smokers; marked lesion is called desquamative interstitial pneumonia-like reaction
    • Pulmonary alveolar proteinosis-like change: eosinophilic and fine granular proteinaceous material in airspace (Respir Investig 2016;54:272)
    • Centriacinar emphysema, especially in smokers
    • Peribronchiolar metaplasia, replacement of bronchiolar epithelium in alveolar walls and terminal bronchioles (Am J Surg Pathol 2005;29:948)
    • Fat metaplasia
    • Bone metaplasia
    • Kuhn's hyaline (Mallory's hyaline): dense, waxy, eosinophilic clumps within cytoplasm of reactive type 2 pneumocytes (Hum Pathol 1980;11:59)
    • Fibrin deposition
Microscopic (histologic) images

Scroll to see all images.

Contributed by Akira Yoshikawa, M.D. and Yale Rosen, M.D.
Low power magnification

Low power magnification

Peripheral dense fibrosis adjacent to normal parenchyma

Peripheral dense fibrosis adjacent to normal parenchyma

Honeycomb

Honeycomb

PAP-like change within honeycomb

PAP-like change within honeycomb

Fibroblastic focus

Fibroblastic focus

Respiratory bronchiolitis macrophage

Respiratory bronchiolitis macrophage


Low power magnification

Low power magnification

Dense fibrosis with smooth muscle hyperplasia

Dense fibrosis with smooth muscle hyperplasia

Fat metaplasia

Fat metaplasia

Fibroblastic focus

Fibroblastic focus

Peribronchiolar metaplasia

Peribronchiolar metaplasia

Peripheral / perilobular involvement of dense fibrosis

Peripheral / perilobular involvement of dense fibrosis


Peripheral / perilobular elastosis on elastic van Gieson staining

Peripheral / perilobular elastosis on elastic van Gieson staining

Low power magnification

Low power magnification

Perilobular involvement

Perilobular involvement

Honeycomb

Honeycomb

Peribronchiolar metaplasia

Peribronchiolar metaplasia

Squamous metaplasia

Squamous metaplasia


Bone metaplasia

Bone metaplasia

Fibroblastic foci Fibroblastic foci Fibroblastic foci Fibroblastic foci Fibroblastic foci

Fibroblastic foci


Fibroblastic foci Fibroblastic foci

Fibroblastic foci



Images hosted on other servers:
Findings in UIP pattern

Findings in UIP pattern

Dense fibrosis and honeycomb

Fibroblastic foci Fibroblastic foci

Fibroblastic foci

Honeycomb Honeycomb

Honeycomb


Patchy and peripheral involvement Patchy and peripheral involvement Patchy and peripheral involvement Patchy and peripheral involvement

Patchy and peripheral involvement

Peripheral / perilobular involvement Peripheral / perilobular involvement

Peripheral / perilobular involvement


Peripheral / perilobular involvement

Peripheral / perilobular involvement

Case with UIP

Case with UIP

Positive stains
Electron microscopy description
  • Fibrosis due to migration of activated mesenchymal cells through defects in epithelial lining and its basement membrane from interstitial to intraluminal compartment
  • Replacement of alveolar type I cells by hyperplastic alveolar type II cells
Videos


Pathogenesis of IPF
Differential diagnosis
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