Lung nontumor
Other interstitial pneumonitis / fibrosis
Lymphoid interstitial pneumonia (LIP)

Author: Akira Yoshikawa M.D.
Editor: Andrey Bychkov, M.D., Ph.D.
Deputy Editor Review: Debra Zynger, M.D.

Revised: 29 June 2018, last major update May 2018

Copyright: (c) 2003-2018, PathologyOutlines.com, Inc.

PubMed search: lymphoid interstitial pneumonia [title]

Cite this page: Yoshikawa, A. Lymphoid interstitial pneumonia (LIP). PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/lungnontumorLIP.html. Accessed September 25th, 2018.
Definition / general
Essential features
  • Rare type of interstitial lung disease due to different diseases including Sjögren syndrome, rheumatoid arthritis and human immunodeficiency virus (HIV) infection
  • On histology, diffuse infiltration of polyclonal lymphocytes with scant interstitial fibrosis is characteristic
Terminology
  • Also called lymphocytic interstitial pneumonia
ICD-10 coding
  • J84.2: lymphoid interstitial pneumonia
Epidemiology
  • Rare
  • Typical onset at ages 40 - 70 years old but can occur at any age (Chest 2002;122:2150)
  • More common in women
  • No association with smoking history
Sites
  • Bilateral lower lobes of the lung
Pathophysiology
  • Pathogenic mechanisms of LIP are still unclear
  • Has aspects of lymphoproliferative disease and lymphoid hyperplasia of polyclonal T or B cells (Chest 2002;122:2150)
  • Although it may transform to lymphoma, especially MALT, the risk is lower than initially reported (Eur Respir J 2006;28:364)
Etiology
  • Associated with several systemic diseases and conditions (Chest 2002;122:2150, Respirology 2016;21:600, Eur Respir J 2006;28:364)
    • Autoimmune (most common)
      • Sjögren syndrome (SjS); 25% of LIP cases have SjS and 1% of SjS cases present with LIP
      • Rheumatoid arthritis
      • Systemic lupus erythematosus
      • Polymyositis / dermatomyositis
      • Hashimoto disease
      • Hypothyroidism
      • Castleman disease
      • Myasthenia gravis
      • Autoimmune hemolytic anemia
      • Pernicious anemia
      • Primary biliary cirrhosis
    • Infection
      • Human immunodeficiency virus (HIV)
      • Epstein-Barr virus
      • Human T cell lymphotropic virus type 1
      • Legionella pneumonia
      • Mycoplasma
      • Chlamydia
      • Tuberculosis
    • Immunodeficiency
      • Acquired immunodeficiency syndrome (AIDS); especially in children
      • Monoclonal or polyclonal gammopathy
      • Common variable immunodeficiency
    • Idiopathic LIP accounts for 20% of cases (Eur Respir J 2006;28:364)
Clinical features
  • Very slowly progressive respiratory symptoms
    • Dyspnea on exertion
    • Dry cough
    • Systemic symptoms such as malaise, fever and weight loss
    • Duration of the symptoms prior to diagnosis can exceed a year
  • Bibasilar inspiratory crackles on chest auscultation
Diagnosis
  • Based on clinical, radiological and pathological findings (multidisciplinary diagnosis)
  • No firm diagnostic criteria currently exist
Laboratory
  • Dysproteinemia is often present
    • Hypergammaglobulinemia is more common than hypogammaglobulinemia
  • Restrictive pattern on pulmonary function tests
    • Reduced forced vital capacity (FVC)
    • Reduced diffusing capacity of the lung for carbon monoxide (DLCO)
Radiology description
  • Chest radiography
    • Bibasilar opacities with lower lobe predominance
  • High resolution computed tomography (Eur J Radiol 2015;84:542, Respirology 2016;21:600)
    • Ground glass opacity with / without consolidation with lower lobe predominance
    • Cyst formation and thickening of bronchovascular bundle and interlobular septa are often present
    • Cysts often remain even after resolution of symptoms
Radiology images

Images hosted on other servers:

Chest radiograph

Ground glass opacity with cyst formation and nodules

Cyst formation

Prognostic factors
Case reports
Treatment
  • No treatment data from a controlled study is available so far (Respirology 2016;21:600)
    • Corticosteroid therapy is commonly used as a first line treatment and improves the symptoms in most cases
    • Immunosuppression (eg, cyclophosphamide, azathioprine, cyclosporine A) may be used as a second line
  • Treatment for underlying disease is also essential for secondary LIP
Gross description
  • Ill defined lesion
  • Mild increase in lung weight
Microscopic (histologic) description
  • Diffuse interstitial infiltration of polymorphous lymphocytes and plasma cells
    • Lymphoid follicles with germinal centers, histiocytes and macrophages are often present
    • Bronchovascular bundles and interlobular septa are usually involved
    • Alveolar structure is often inflated and disrupted
    • Typically CD8+ or CD4+ T cells or B cells predominate, with an admixture of other lymphocytes
    • Immunohistochemistry or molecular testing are necessary to confirm polyclonality
  • Additional findings
    • Loose ill defined epithelioid granulomas
    • Interstitial or intra-alveolar giant cells
    • Intra-alveolar macrophages
    • Type II pneumocyte hyperplasia
    • Cyst formation without marked fibrosis
  • Pertinent negative findings
    • Loose and dense fibrosis (more common in fibrotic / cellular nonspecific interstitial pneumonia (NSIP))
    • Fibroblastic focus (more common in usual interstitial pneumonia or fibrotic NSIP)
    • Honeycomb change (more common in usual interstitial pneumonia or fibrotic NSIP)
    • Organizing pneumonia (more common in hypersensitivity pneumonitis)
  • See: Respirology 2016;21:600, Chest 2002;122:2150, Am J Respir Crit Care Med 2002;165:277
Microscopic (histologic) images

Images hosted on PathOut server:

Contributed by Akira Yoshikawa M.D.

Low power

Bronchovascular bundle

Architectural destruction

Septal thickening

Massive lymphocytic infiltration


Giant cells and lymphocytes

Lymphocytes and histiocytes

Granuloma and lymphocytes

Lymphoid aggregate and histiocytes



Contributed by Dr. Yale Rosen

Diffuse cellular pattern

Lymphoplasmacytic infiltration



Images hosted on other servers:

LIP

Numerous lymphoid follicles

EBV related LIP

Cytology description
  • Increase in the number of lymphocytes (especially CD8 positive) of bronchoalveolar lavage, without clonality (Eur Respir J 2006;28:364)
Positive staining - disease
Molecular / cytogenetics description
  • EBNA ISH and EBER ISH are helpful to detect EBV infection
Differential diagnosis
  • Follicular bronchitis / bronchiolitis
    • Lymphocytic infiltration into bronchial / bronchiolar walls with multiple lymphoid follicles
    • No or slight lymphocytic aggregation in intralobular septa
  • Hypersensitivity pneumonitis (HP)
    • History of an antigen exposure such as animals, birds and chemicals
    • Less diffuse but bronchocentric distribution
    • Loose ill defined granuloma and giant cells can be seen in both LIP and HP
  • Lymphoma, especially mucosa (bronchus) associated lymphoid tissue lymphoma
    • Monomorphous infiltration of lymphocytes, distortion of alveolar architecture, Dutcher bodies, pleural infiltration are more common in lymphoma
    • Immunohistochemistry is often helpful
  • Nonspecific interstitial pneumonia
    • Lymphoplasmacytic infiltration is also seen in NSIP but less severe
    • Alveolar structure is usually preserved compared with LIP
Board review question #1
Which of following is not usually seen in this entity?

  1. Cyst formation
  2. Giant cells
  3. Honeycomb change
  4. Lymphocytic interstitial infiltration
  5. Nonnecrotizing granuloma
Board review answer #1
C. Honeycomb change. Lymphoid interstitial pneumonia is predominantly a cellular interstitial pneumonia. Fibrotic processes such as dense fibrosis or honeycomb change usually exclude a diagnosis of LIP.