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Usual Interstitial Pneumonia

Definition

  • Idiopathic interstitial lung injury demonstrating temporal and geographic heterogeneity

Alternate/Historical Names

  • Cryptogenic fibrosing alveolitis
  • Idiopathic pulmonary fibrosis
  • UIP

Diagnostic Criteria

  • Clinical
    • Insidious onset of dyspnea, cough
      • Most have symptoms >6 months
    • Rare under age 40
    • Pulmonary function tests: restrictive with decreased diffusing capacity
    • UIP is relentlessly progressive
      • Median survival 2.5-3.5 years
  • High resolution computed tomography (HRCT)
    • Changes predominantly basal and peripheral
    • Reticular, linear patterns, retraction bronchiectasis
    • Honeycombing usually present
    • Ground glass opacities focal but not widespread
    • Classic cases can be diagnosed by xray and do not need biopsy confirmation
  • Histopathologic features
    • Heterogeneous pattern of alternating honeycombing and normal lung with intermediate zones of inflammation and active fibrosis
    • Spatially heterogeneous fibrosis
      • Patchy honeycombing and severe architectural distortion predominantly subpleural and paraseptal
        • Enlarged, remodeled airspaces with thickened walls
        • Usually filled with mucus
    • Temporally heterogeneous fibrosis
      • Ranges from loose fibroblastic foci (septal fibromyxoid foci) to dense fibrosis
        • Foci of active fibroplasia next to mature collagenous scarring is characteristic
      • Increased number of fibroblastic foci has been proposed as a poor prognostic sign
        • Most studies in patients with clinically stable disease show no prognostic significance (Flaherty 2003, Hanak 2008)
    • Interstitial lympho-plasmacytic infiltrate usually mild
    • Organizing pneumonia may be present but not predominant
    • Smooth muscle hyperplasia may be prominent
  • The following features should not be present
      • Features of hypersensitivity reaction
        • Giant cells and or granulomas
        • Predominantly bronchiolocentric distribution
      • Features of other defined diseases such as:
        • Langerhans cell histiocytosis
        • Sarcoidosis
      • Marked inflammation
      • Marked eosinophilic infiltrate
      • Foreign material, especially asbestos
  • Patients with acute exacerbation may show a combination of features of diffuse alveolar damage (DAD)or cryptogenic organizing pneumonia and UIP
    • Defining feature of DAD
      • Hyaline membranes, intact or organizing
    • Features that should suggest superimposed DAD
      • Squamous metaplasia of respiratory bronchioles
      • Fibrin thrombi in small arteries
      • Type II pneumocyte hyperplasia
    • Intralumenal plugs of loose granulation tissue should suggest superimposed organizing pneumonia, cryptogenic or secondary to a known cause
    • Clinical and radiographic history is important
    • High mortality rate
  • Discordant features may be seen (UIP on one biopsy, NSIP on another)
    • Behaves as UIP
    • Multiple biopsies are recommended, if possible
  • The following must be ruled out in every case
    • Collagen vascular disease
      • Typically has more inflammation and follicles
      • Typically less fibroplasia and honeycombing
    • Drug reaction
    • Infection
      • Acid fast and fungal stain should be performed in every case
    • Radiation effect
    • Hermansky-Pudlak syndrome
      • Pulmonary fibrosis, granulomatous colitis, albinism, platelet defect

Gerald J Berry MD
Robert V Rouse MD
Department of Pathology
Stanford University School of Medicine
Stanford CA 94305-5342

Original posting/updates: 11/20/10, 12/29/12

Differential Diagnosis

Infection must be ruled out in every case

Usual Interstitial Pneumonia Nonspecific Interstitial Pneumonia
Temporal and spatial heterogeneity Temporal and spatial uniformity
Honeycomb change prominent Honeycomb change rare
Scant interstitial inflammation Prominent interstitial inflammation
Prominent fibroblastic foci Fibroblastic foci few, focal

 

Usual Interstitial Pneumonia Acute Interstitial Pneumonia
Temporal heterogeneity Temporally uniform
Honeycomb change prominent Honeycomb change only in late stage
Patchy distribution with subpleural accentuation Diffuse, uniform throughout
Hyaline membranes not seen Hyaline membranes prominent in early stage

 

Respiratory Bronchiolitis Associated Interstitial Lung Disease Usual Interstitial Pneumonia
Fibrosis does not destroy architecture, no honeycombing Fibrosis destroys architecture, honeycombing is prominent
No fibroblastic foci Frequent fibroblastic foci
Air spaces filled with macrophages Filling of airspaces with macrophages is not seen
HRCT shows centrilobular nodule pattern HRCT shows honeycombing, peripheral accentuation

 

Usual Interstitial Pneumonia Desquamative Interstitial Pneumonia
Intra-alveolar macrophages only focally present Diffuse intra-alveolar macrophages
Temporal heterogeneity Temporally uniform
Architecture destroyed, honeycomb change prominent Architecture preserved, honeycomb change uncommon
Fibroblastic foci common Fibroblastic foci absent
Interstitial fibrosis marked Interstitial fibrosis mild to moderate
Interstitial fibrosis variably distributed Interstitial fibrosis tends to be more uniform

 

Usual Interstitial Pneumonia Cryptogenic Organizing Pneumonia
Temporal heterogeneity Temporally uniform
Honeycomb change prominent Honeycomb change rare
Interstitial fibrosing process Intralumenal fibrosing process
Fibroblastic foci adjacent to mature collagen, covered by epithelium Granulation tissue foci without significant collagen, not subepithelial
Random distribution Bronchiolocentric distribution
Predominantly collagenous fibrosis Predominantly fibroblastic fibrosis
Organizing pneumonia may be seen focally in UIP or in the setting of acute exacerbation of UIP

 

Usual Interstitial Pneumonia Hypersensitivity Pneumonitis
Lacks granulomas and giant cells Granulomas and giant cells generally present but may be infrequent in late stage
Random distribution Usually has some component of bronchiolocentric distribution even in late stage
  • Areas of chronic hypersensitivity pneumonitis may be identical to UIP
  • Identification of any of these features should prompt efforts to identify an allergen
  • Multiple biopsy specimens may be required

 

Langerhans Cell Histiocytosis Usual Interstitial Pneumonia
Scars frequently stellate and centrilobular with extension to subpleura Irregular subpleural scarring
Honeycomb change only occasionally seen Honeycomb change frequent
Frequently some typical active LCH lesions present Lacks peribronchiolar nodules of Langerhans cells
Langerhans cells are positive for CD1a and langerin CD1a and langerin negative
HRCT shows centrilobular nodule and cyst pattern HRCT shows honeycombing, peripheral accentuation

Classification / Lists

Idiopathic Interstitial Lung Diseases

Other Diffuse Parenchymal Lung Diseases

 

Bibliography

  • Travis WD, Colby TV, Koss MN, Rosado-de-Christenson ML, Müller NL, King TE Jr.  Non-neoplastic Disorders of the Lower Respiratory Tract, AFIP Atlas of Nontumor Pathology, First Series, Fascicle 2, 2002.
  • American Thoracic Society; European Respiratory Society. ATS/ERS International Multidisciplinary Consensus Classification of the Idiopathic Interstitial Pneumonias. This joint statement of the American Thoracic Society (ATS), and the European Respiratory Society (ERS) was adopted by the ATS board of directors, June 2001 and by the ERS Executive Committee, June 2001. Am J Respir Crit Care Med. 2002 Jan 15;165(2):277-304.
  • Flaherty KR, Toews GB, Travis WD, Colby TV, Kazerooni EA, Gross BH, Jain A, Strawderman RL 3rd, Paine R, Flint A, Lynch JP 3rd, Martinez FJ. Clinical significance of histological classification of idiopathic interstitial pneumonia. Eur Respir J. 2002 Feb;19(2):275-83.
  • Visscher DW, Myers JL. Histologic spectrum of idiopathic interstitial pneumonias. Proc Am Thorac Soc. 2006 Jun;3(4):322-9.
  • Travis WD, Matsui K, Moss J, Ferrans VJ. Idiopathic nonspecific interstitial pneumonia: prognostic significance of cellular and fibrosing patterns: survival comparison with usual interstitial pneumonia and desquamative interstitial pneumonia. Am J Surg Pathol. 2000 Jan;24(1):19-33
  • Monaghan H, Wells AU, Colby TV, du Bois RM, Hansell DM, Nicholson AG. Prognostic implications of histologic patterns in multiple surgical lung biopsies from patients with idiopathic interstitial pneumonias. Chest. 2004 Feb;125(2):522-6.
  • Fell CD, Martinez FJ, Liu LX, Murray S, Han MK, Kazerooni EA, Gross BH, Myers  J, Travis WD, Colby TV, Toews GB, Flaherty KR. Clinical predictors of a diagnosis of idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2010 Apr 15;181(8):832-7.
  • Song JW, Do KH, Kim MY, Jang SJ, Colby TV, Kim DS. Pathologic and radiologic differences between idiopathic and collagen vascular disease-related usual interstitial pneumonia. Chest. 2009 Jul;136(1):23-30.
  • Hanak V, Ryu JH, de Carvalho E, Limper AH, Hartman TE, Decker PA, Myers JL. Profusion of fibroblast foci in patients with idiopathic pulmonary fibrosis does  not predict outcome. Respir Med. 2008 Jun;102(6):852-6.
  • Enomoto N, Suda T, Kato M, Kaida Y, Nakamura Y, Imokawa S, Ida M, Chida K. Quantitative analysis of fibroblastic foci in usual interstitial pneumonia. Chest. 2006 Jul;130(1):22-9.
  • Flaherty KR, Colby TV, Travis WD, Toews GB, Mumford J, Murray S, Thannickal VJ, Kazerooni EA, Gross BH, Lynch JP 3rd, Martinez FJ. Fibroblastic foci in usual interstitial pneumonia: idiopathic versus collagen vascular disease. Am J Respir Crit Care Med. 2003 May 15;167(10):1410-5
  • Churg A, Wright JL, Tazelaar HD. Acute exacerbations of fibrotic interstitial  lung disease. Histopathology. 2010  [Epub ahead of print].
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