Stanford School of Medicine

Surgical Pathology Criteria

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Lymphocytic Interstitial Pneumonitis


  • Chronic lung disease characterized by interstitial lymphocytic infiltration

Alternate/Historical Names

  • LIP
  • Lymphocytic interstitial pneumonia

Diagnostic Criteria

  • Clinical
    • Gradual onset of dyspnea, cough
      • Most have symptoms >6 months
    • May occur at any age
    • Frequently associated with immune related diseases
      • Autoimmune diseases including collagen vascular
      • Immunodeficiency including AIDS and common variable immunodeficiency
      • Multicentric Castleman disease
      • Drug reactions
    • 80% have polyclonal gammopathy
    • 33-50% 5 year mortality
  • High resolution computed tomography (HRCT)
    • Ground glass opacities
    • Perivascular cysts
    • Perivascular honeycombing in late stages
  • Histopathologic features
    • Diffuse cellular expansion of interlobular and alveolar septa
      • Does not preferentially track along lymphatic routes (bronchovascular bundles)
    • Polymorphous infiltrate of lymphocytes, plasma cells and macrophages
      • Small and large lymphocytes, mostly T cells
      • Germinal centers may be seen in some cases along bronchovascular bundles
      • Lymphocytes and plasma cells are polyclonal
      • Histiocytes may be multinucleated or epithelioid
    • May progress to interstitial fibrosis and honeycomb change

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

Differential Diagnosis

Lymphocytic Interstitial Pneumonitis Nonspecific Interstitial Pneumonia, Cellular Type
Prominent interstitial lymphoid infiltrate Mild to moderate interstitial lymphoid infiltrate
Occasional follicles may be seen Follicles rare
The distinction may not be well defined in some cases


Lymphocytic Interstitial Pneumonitis Extranodal Marginal Zone B Cell Lymphoma
Polymorphous infiltrate Monomorphous infiltate
Predominantly T cells Predominantly B cells
Involvement of pleura and cartilage rare Pleura and cartilage may be involved
Dutcher bodies not seen Dutcher bodies may be seen
Polyclonal Monoclonal


Lymphocytic Interstitial Pneumonitis Hypersensitivity Pneumonitis
Diffuse involvement of alveolar septa Predominantly peribronochiolar
Marked infiltrate Patchy, less dense infiltrate
No BOOP-like foci BOOP-like foci common
Both may have loose granulomas and develop honeycomb change


Lymphocytic Interstitial Pneumonitis Follicular Bronchiolitis
Predominantly T cell infiltrate Prominent B cell follicles
Predominantly interalveolar Predominantly peribronchiolar
Occasional caess will show features of both


Lymphocytic Interstitial Pneumonitis Nodular Lymphoid Hyperplasia
Diffuse involvement of alveolar septa Discrete nodule(s)
Germinal centers, if present, are a minor component Prominent germinal center hyperplasia

Classification / Lists

Idiopathic Interstitial Lung Diseases

Other Diffuse Parenchymal Lung Diseases



  • 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.
  • Guinee DG Jr. Update on nonneoplastic pulmonary lymphoproliferative disorders  and related entities. Arch Pathol Lab Med. 2010 May;134(5):691-701.
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