Lung
Interstitial lung diseases
Nonspecific interstitial pneumonia
Last author update: 1 March 2017
Last staff update: 22 August 2022
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PubMed search: nonspecific interstitial pneumonia / fibrosis
Table of Contents
Definition / general | Essential features | Terminology | ICD coding | Epidemiology | Sites | Pathophysiology / etiology | Diagrams / tables | Clinical features | Diagnosis | Laboratory | Radiology description | Radiology images | Prognostic factors | Case reports | Treatment | Gross description | Microscopic (histologic) description | Microscopic (histologic) images | Positive stains | Differential diagnosis | Additional referencesCite this page: Yoshikawa A. Nonspecific interstitial pneumonia. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/lungnontumornonspecificintpneumo.html. Accessed November 27th, 2024.
Definition / general
- #2 most common type of interstitial pneumonia
- Katzenstein et al. in 1994 first proposed the idea of NSIP, as not fitting any known pattern of idiopathic interstitial pneumonia (Am J Surg Pathol 1994;18:136)
- NSIP initially was a "provisional disease" in the 2002 ATS / ERS classification (Am J Respir Crit Care Med 2002;165:277); then a statement of idiopathic NSIP was published from an ATS / ERS working group (Am J Respir Crit Care Med 2008;177:1338); finally idiopathic NSIP was considered a defined disease in the 2013 ATS / ERS classification (Am J Respir Crit Care Med 2013;188:733)
Essential features
- An interstitial lung disease with a histologic NSIP pattern, due to a variety of etiologies
- The NSIP pattern is the second most common pattern, and always part of the differential diagnosis of the usual interstitial pneumonia (UIP) pattern, but NSIP has a better prognosis than UIP
- Multidisciplinary discussion is necessary to make the diagnosis and decide treatment direction
Terminology
- NSIP is the name of the morphologic (histologic) pattern
- When no specific cause is identified, the clinical, radiological and pathological diagnosis of "idiopathic NSIP" is rendered
ICD coding
- Idiopathic nonspecific interstitial pneumonia: J84.113
Epidemiology
- Idiopathic NSIP is the second most common idiopathic interstitial pneumonia, following idiopathic pulmonary fibrosis
- The mean onset is 50 - 60 years old
- Female predominant
- No clear association with tobacco use
Sites
- Bottom of lower lobes of bilateral (or "bibasilar") lung
Pathophysiology / etiology
- NSIP pattern is often present in connective tissue diseases, hypersensitivity pneumonitis, drug induced injury and infectious diseases
- Idiopathic form of NSIP is rare; most idiopathic NSIP appear to be an early manifestation of undifferentiated connective tissue disease (Am J Resp Crit Care Med 2007;176:691, Chest 2015;147:165, Eur Respir J 2011;38:384)
- Neovascularization promoted by the expression of VEGF-A and MMP-2 may play a role in fibrosis of NSIP (Pathol Int 2013;63:237)
Diagrams / tables
Images hosted on other servers:
Schema of NSIP pattern
Clinical features
- Chronic and slowly progressive respiratory failure
- Shortness of breath
- Dyspnea on exertion
- Cough
- Fatigue
- Weight loss
- Abnormal chest auscultation
- End inspiratory fine crackles in bibasilar lung
- Restrictive pattern in pulmonary function tests:
- Decreased forced vital capacity (FVC)
- Decreased diffusing capacity of the lung for carbon monoxide (DLCO)
Diagnosis
- It is often challenging to make the diagnosis for cases with an NSIP pattern, since it includes a variety of diseases
- Therefore, two levels of diagnosis are recommended: histological diagnosis of NSIP pattern and multidisciplinary (clinical-radiological-pathological) diagnosis for its etiology (i.e. idiopathic, connective tissue, etc.), based on:
- Clinical features, including laboratory tests
- High resolution computed tomography (HRCT)
- Surgical lung biopsy
- The guidelines suggest multidisciplinary discussion by experienced physicians, radiologists and pathologists, especially when they disagree (Am J Respir Crit Care Med 2011;183:788, Am J Respir Crit Care Med 2004;170:904, Thorax 2003;58:143)
- Some NSIP cases with inconclusive autoimmune features may fit the criteria for idiopathic NSIP under current guidelines, or be classified as interstitial pneumonia with autoimmune features (IPAF) (Eur Respir J 2015;46:976)
- Some cases with NSIP pattern may be included in the newly described category of "Unclassifiable interstitial pneumonia (UCIP)" (Respirology 2016;21:51)
Laboratory
- Serological autoantibody tests: can be positive but not conclusive for connective tissue disease
- Antinuclear antibody
- Rheumatoid factor
- Anti-CCP antibody
- Anti-SS-A, B antibody
- Anti-Sm antibody
- Anti-Scl-70 antibody
- Anti-ARS antibody
- Antibodies tests of hypersensitivity pneumonitis: pertinent negative for idiopathic NSIP (Am J Respir Crit Care Med 2012;186:314)
- Avian antigens: pigeon, parakeet, budgerigar, chicken
- Fungus: trichosporon, aspergillus
- Bacteria: actinomycete
- Mycobacteria: Mycobacterium avium-intracellulare
- Chemicals
- Increased serum KL-6 (normal limit is < 500 IU)
Radiology description
- Chest xray and HRCT can detect lesions: however, it is usually not sensitive enough to render the diagnosis (PLoS One 2016;11:e0166168, Thorax 2003;58:143)
- HRCT findings suggestive for NSIP pattern:
- Diffuse ground glass opacity
- Reticular opacity
- Traction bronchiectasis
- Not suggestive findings:
- Irregular linear opacity
- Honeycombing
- Nodular opacity
Radiology images
Images hosted on other servers:
NSIP pattern on HRCT
Prognostic factors
- Better prognosis than UIP / IPF, with a 5 year survival of ~ 70% for all NSIP (Am J Respir Crit Care Med 1998;157:199)
- Survival rate depends on the background etiology (Eur Respir J 2015;45:746)
- 5 year survival of 61% for idiopathic NSIP
- 5 year survival of 42% for NSIP with chronic hypersensitivity pneumonitis
- 5 year survival of 77% for autoimmune NSIP
Case reports
- 11 year old boy with NSIP after peripheral blood stem cell transplantation (J Thorac Imaging 2009;24:59)
- 24 year old woman and 38 year old man with connective tissue diseases and NSIP overlapping organizing pneumonia (Int J Clin Exp Pathol 2015;8:11230)
- 29 year old man and 41 year old woman with NSIP and amyopathic dermatomyositis (Clin Rheumatol 2007:26;436)
- 58 year old man with NSIP overlapping UIP (Diagn Pathol 2012;7:167)
- 64 year old woman with NSIP who developed Kaposi sarcoma after steroid therapy (Pathol Res Pract 2006;202:113)
- 66 year old man with NSIP and emphysema, which improved after smoking cessation (Respir Med Case Rep 2014;14:7)
- 73 year old woman with NSIP and bullous pemphigoid (Chest 2012;141:795)
Treatment
- There is no standard treatment for idiopathic NSIP, although 80% of cases could be improved or stabilized by glucocorticoids with / without other immunosuppressive drugs such as azathioprine and cyclophosphamide (Am J Respir Crit Care Med 1998;158:1286, Respir Med 1999;93:113)
- Treat background diseases, including autoimmune diseases
- Remove suspicious drugs; reduce inhalation exposure to possible disease promoters
Gross description
- Diffuse involvement with mild to moderate increase in lung weight
- Fibrotic changes in lower lobes
- Homogeneous and diffuse compared to UIP
- Shrunken lung
- Traction bronchiectasis can be seen
- Honeycomb change can be seen but limited
Microscopic (histologic) description
- Since there are few specific findings for NSIP pattern, it is essential to exclude other lung diseases on histology (Am J Respir Crit Care Med 2008;177:1338)
- Characteristic findings of NSIP pattern
- Diffuse and uniform inflammation ("temporal homogeneity") on low power of alveolar wall, bronchovascular bundles and pleura
- There are usually no normal alveolar walls in the affected lobules
- Cellular or fibrotic change
- Lymphocytic or plasmacytic infiltration
- Loose fibrosis
- Lung architecture is frequently preserved
- "Cellular NSIP" or "fibrotic NSIP" can be stated specifically in pathologist report
- Diffuse and uniform inflammation ("temporal homogeneity") on low power of alveolar wall, bronchovascular bundles and pleura
- Features of interstitial pneumonia with autoimmune features (IPAF) (Chest 2010;138:251):
- Lymphoid aggregates with germinal center
- Extensive pleuritis
- Prominent plasmacytic infiltration
- Dense perivascular collagen
- It is quite rare to see pure NSIP on histology - typically there are focal findings of other interstitial lung disease (Histopathology 2014;65:549)
- Pertinent negative findings (Am J Respir Crit Care Med 2008;177:1338)
- UIP-like change
- Marked architectural distortion
- Dense fibrosis with smooth muscle hyperplasia or elastosis
- Fibroblastic foci
- Honeycomb change
- Hypersensitivity pneumonitis-like change
- Airway centered change
- Peribronchiolar metaplasia
- Granulomas or interstitial giant cells with cholesterol cleft
- Extensive organizing pneumonia (areas more than 20% of disease)
- Desquamative interstitial pneumonia-like change
- Aggregation of respiratory bronchiolitis macrophages in alveolar sacs and respiratory bronchioles
- Diffuse alveolar damage-like change
- Hyaline membrane
- Alveolar hemorrhage
- Lymphoid interstitial pneumonia-like change
- Marked and extensive infiltration of lymphocytes in alveolar wall
- Light chain restriction
- Smoking related interstitial fibrosis (J Clin Pathol 2013;66:882)
- Alveolar hyalinized septal thickening with little cellular infiltration
- Centriacinar emphysema
- UIP-like change
Microscopic (histologic) images
Scroll to see all images.
Contributed by Akira Yoshikawa, M.D.
Images hosted on other servers:
Contributed by Akira Yoshikawa, M.D.
Low power
Uniform involvement
Less inflamed
Lymphocytic infiltration and fibrosis
Lymphoid follicles with germinal center
Lymphoplasmacytic infiltration
Low power
Uniform involvement
Sparse architectural distortion
Peribronchiolar metaplasia
A few honeycomb changes
Dense fibrosis
Low power
Uniform involvement
Lymphocytic infiltration and fibrosis
Pleuritis
Organizing pneumonia
Lymphocytic aggregation
Airway centered change
Low power
Uniform involvement with lymphoid follicles
Lymphoid follicles with germinal center
Pleuritis with lymphoid follicles
Dense fibrosis are sparsely seen
Images hosted on other servers:
Diffuse and uniform inflammation
Cellular NSIP
Fibrotic NSIP
Pleuritis
Organizing pneumonia in NSIP
Series of slides of fibrotic NSIP
Positive stains
- Elastica van Gieson staining highlights the relative preservation of lung architecture
- Giemsa, Grocott and Ziehl-Neelsen stains rule out infectious diseases, if suspected
Differential diagnosis
- Desquamative interstitial pneumonia: smoking history, aggregates of alveolar macrophages
- Diffuse alveolar damage: hyaline membrane, alveolar hemorrhage
- Hypersensitivity pneumonitis: exposure to antigens, airway centered change
- Infectious disease (TB, fungal)
- Interstitial pneumonia with autoimmune features (IPAF): lymphoid aggregates with germinal center, extensive pleuritis, prominent plasmacytic infiltration, dense perivascular collagen
- Lymphoid interstitial pneumonia: viral infection such as HIV, CMV and HTLV1
- Organizing pneumonia: marked organizing pneumonia on histology
- Smoking related interstitial fibrosis: smoking history, acellular fibrosis
- UIP / IPF: patchy and peripheral involvement, fibroblastic focus, honeycomb change
