Lung - nontumor
Other interstitial pneumonitis / fibrosis
Usual interstitial pneumonia (UIP) / Idiopathic pulmonary fibrosis (IPF)

Author: Akira Yoshikawa (see Authors page)
Editor: Andrey Bychkov, M.D., Ph.D.

Revised: 6 February 2017, last major update January 2017

Copyright: (c) 2003-2017, PathologyOutlines.com, Inc.

PubMed Search: usual interstitial pneumonia OR idiopathic pulmonary fibrosis
Cite this page: Usual interstitial pneumonia (UIP) / Idiopathic pulmonary fibrosis (IPF). PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/lungnontumorUIP.html. Accessed May 22nd, 2017.
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-10 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:
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
Prognostic factors
Case reports
Treatment
Clinical images

Images hosted on other servers:

UIP pattern

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:

End stage IPF

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.

Images hosted on PathOut server:

Contributed by Akira Yoshikawa:

Case 1:

Low power magnification

Peripheral dense fibrosis adjacent to normal parenchyma

Honeycomb

PAP-like change within honeycomb

Fibroblastic focus

Respiratory bronchiolitis macrophage



Case 2:

Low power magnification

Dense fibrosis with smooth muscle hyperplasia

Fat metaplasia

Fibroblastic focus


Peribronchiolar metaplasia

Peripheral / perilobular involvement of dense fibrosis

Peripheral / perilobular
elastosis on elastic
von Gieson staining



Case 3:

Low power magnification

Perilobular involvement

Honeycomb

Peribronchiolar metaplasia

Squamous metaplasia

Bone metaplasia



Contributed by Dr. Yale Rosen:

Dense fibrosis and architectural destruction

Dense fibrosis and honeycomb

Honeycomb


Fibroblastic foci



Images hosted on other servers:

Schema of UIP pattern

Findings in UIP pattern

Dense fibrosis and honeycomb


Fibroblastic foci

Honeycomb


Patchy and peripheral involvement


Peripheral / perilobular involvement

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