• AKA:
  • NSIP, Uniform Interstitial Pneumonia.
• Etymology:
  • The term non-specific reflects the lack of unique histological features compared to other interstitial lung diseases (e.g., UIP).
• What is it:
  • NSIP is a chronic inflammatory disease and a subtype of interstitial lung disease (ILD).
• Characterized by:
  • Diffuse or patchy interstitial inflammation and/or fibrosis with:
    • Lower lobe predominance,
    • Bronchovascular distribution,
    • Ground-glass opacity,
    • Subpleural sparing, and
    • Absence of honeycombing.
  • Occurs in two forms:
    • Cellular NSIP: Predominantly inflammatory changes with minimal fibrosis.
    • Fibrotic NSIP: More pronounced fibrosis with associated structural remodeling.
• Anatomically affecting:
  • Bronchovascular bundles (peribronchial and perivascular interstitium).
  • Interstitial spaces (including alveolar septa and interlobular regions).
  • Alveolar ducts (connecting airways to alveoli).
  • Alveoli (air sacs responsible for gas exchange).
• What causes it:
  • Idiopathic NSIP:
    • Cause unknown; classified as an idiopathic interstitial pneumonia.
  • Secondary NSIP:
    • Often associated with systemic autoimmune diseases, such as:
      • Systemic sclerosis,
      • Sjögren’s syndrome, and
      • Polymyositis/dermatomyositis.
    • Other potential causes include:
      • Drug-induced lung injury (e.g., chemotherapy, immunotherapy),
      • Environmental exposures (e.g., dusts or fumes), and
      • Chronic viral infections (e.g., HIV).
• What is the result:
  • Persistent inflammation and fibrosis result in:
    • Impaired gas exchange,
    • Restriction of lung expansion,
    • Development of traction bronchiectasis and bronchiolectasis in advanced cases.
• How is it diagnosed:
  • a) Clinical findings:
    • Symptoms include:
      • Gradual onset of progressive dyspnea,
      • Chronic dry cough, and
      • Fatigue, often over months to years.
  • b) Imaging studies:
    • Chest X-ray:
      • Diffuse reticular opacities, often bilateral and symmetrical.
    • Chest CT:
      • Parts: Diffuse or patchy ground-glass opacities, reticulations, and peribronchovascular thickening.
      • Size: Variable, from focal regions to diffuse lung involvement.
      • Shape: Homogeneous or reticular.
      • Position:
        • Lower lobe predominance and bronchovascular distribution.
        • Subpleural sparing, a key distinguishing feature of NSIP.
      • Character:
        • Minimal or absent honeycombing (distinguishing it from UIP).
        • Traction bronchiectasis and bronchiolectasis in advanced fibrotic cases.
      • Time:
        • Slowly progressive but may stabilize or improve with treatment.
  • c) Laboratory findings:
    • Autoimmune markers: ANA, anti-Ro/SSA, anti-La/SSB for associated systemic diseases.
    • Exclude infections with serologies for chronic viral infections (e.g., HIV, hepatitis).
• How is it treated:
  • First-line therapy:
    • Corticosteroids (e.g., prednisone): Typically effective in reducing inflammation.
  • Second-line options:
    • Immunosuppressive agents (e.g., mycophenolate mofetil, azathioprine) for refractory or progressive disease.
  • Supportive care:
    • Oxygen therapy and pulmonary rehabilitation for advanced disease.
  • Monitoring:
    • Serial imaging and pulmonary function tests to assess response to treatment and detect progression.
• Radiological implications:
  • NSIP findings include symmetrical ground-glass opacities, fine reticulations, and subpleural sparing.
  • Lower lobe predominance and bronchovascular distribution are hallmark features.
  • Honeycombing is rare, further distinguishing NSIP from UIP.
  • Traction bronchiectasis and bronchiolectasis reflect advanced fibrotic changes and chronicity.
• Key points and pearls:
  • NSIP is often associated with systemic autoimmune diseases, particularly systemic sclerosis.
  • Lower lobe predominance and subpleural sparing are highly characteristic.
  • The prognosis is better than UIP, as many patients stabilize or improve with corticosteroids or immunosuppressive therapy.
  • Histopathology and imaging are critical for distinguishing NSIP from other ILDs.

In a Nutshell Buzz (NB)

 

Fibrotic NSIP

Starts Central and Spreads Outward Along the Bronchovascular bundle

peribronchovascular

symmetric

ground glass

reticulation

traction bronchiectasis

loss of volume

subpleural sparing 60-65%

confluent

reticular

consolidations

honeycomb rare

Interlobular septa
can be thickened.

Alternatively All the S’s

subpleura

sparing

symmeteric

ground glass

scleroderma sle and all the other s’s arthritis, vasculitis

 

basal

? Interlobular septa

 

In general not progressive

May get better on Rx

 

Size

thickening of bronchovascular bundles

Shape

Position

subpleural (subpleural sparing,  specific for NSIP but other causes eg small airway disease)

relatively symmetric

apico-basilar gradient

Character

ground glass

fine reticulation

reticular opacities and irregular linear opacities (sometimes – minor subpleural reticulation)

Associated Findings

volume loss

traction bronchiectasis

Classical Subpleural Sparing

http://www.pathologyoutlines.com/

 

 

• 

  

  TYPICAL FINDINGS IN NSIP
  Spatially homogeneous pattern of fibrosis seen in non specific interstitial pneumonia (NSIP) (trichrome stain X40)
  Courtesy Medscape eMedicine

  Methotrexate-induced NSIP in a 41-year-old woman with rheumatoid arthritis who presented with dyspnea and decreased diffusing capacity of the lungs for carbon monoxide (Dlco). (a) High-resolution CT scan shows
  scattered ground-glass attenuation and thickened inter- and intralobular lines (arrow). (b) Photomicrograph (original
  magnification, 400; hematoxylin-eosin stain) of a specimen from lung biopsy shows patchy interstitial fibrosis, expansion of the interstitium by chronic inflammatory infiltrates, and reactive hyperplastic type II pneumonocytes (arrow), findings consistent with NSIP induced by the pulmonary toxic effects of methotrexate.
  Diffuse mucinous bronchioloalveolar carcinoma in a 78-year-old man. (a) High-resolution CT scan
  shows a bilateral crazy-paving pattern and centrilobular nodules. (b) Photomicrograph (original magnification,
  400; hematoxylin-eosin stain) of a specimen from open lung biopsy shows replacement of the alveolar epithelium
  by epithelial neoplastic cells with abundant intracytoplasmic mucin (arrows).
  Rossi, S.E et al “Crazy-Paving” Pattern at Thin-Section CT of the Lungs: RadiologicPathologic Overview Radiographics  Volume 23 – Number 6,  2003

• Cellular NSIP and Fibrotic NSIP

• NSIP can be divided into two subtypes based on the predominant histological pattern seen on lung biopsy: cellular NSIP and fibrotic NSIP.
  • In Cellular NSIP, the lung tissue is
  • relatively little fibrosis. In contrast,
    • CT
      •  patchy or diffuse ground-glass opacities
      • may be associated with a reticular pattern and
      • traction bronchiectasis
      • more pronounced in the
        • peripheral regions of the lungs, and may be
        • subpleural or
        • peribronchovascular
          • may also be consolidation in some areas of the lung.
  • In Fibrotic NSIP
    • presence of fibrosis or
    • scarring within the lung tissue.
    • worse prognosis c
    • more severe respiratory symptoms,
    • lower lung function, and a
    • greater likelihood of developing pulmonary hypertension.
      • CT
        • shows more pronounced and
        • diffuse reticular opacities and
        • traction bronchiectasis, with
        • less ground-glass opacities
        • fibrotic changes may be
          • more extensive and involve
          • larger areas of the lung tissue.
        • may also be
          • honeycombing in advanced cases.
• The fibrotic form of nonspecific interstitial pneumonia (NSIP) is a
  subtype characterized by a predominant pattern of lung fibrosis,
  with varying degrees of inflammation. Unlike the cellular form, the
  fibrotic form involves more extensive scarring of the lung
  interstitium, leading to thickening and stiffening of the lung tissue.
  This subtype is often associated with autoimmune diseases (like
  systemic sclerosis, rheumatoid arthritis, or dermatomyositis) and
  can also occur as an idiopathic condition. Diagnosis is based on
  high-resolution CT (HRCT) scans, which often reveal reticular
  opacities, traction bronchiectasis, and subpleural sparing, but
  typically lack honeycombing. A lung biopsy may be necessary to
  confirm the diagnosis. The fibrotic form of NSIP generally has a less
  favorable prognosis than the cellular form, as the extent of fibrosis
  limits the reversibility of the condition, though some patients may
  still respond to immunosuppressive therapies.

Radiopedia

Primarily idiopathic but the morphological pattern can be seen in association with a number of conditions:

• connective tissue disorders
  • systemic lupus erythematosus
  • systemic sclerosis
  • Sjögren syndrome
  • polymyositis ⁵
  • dermatomyositis ⁵
• other autoimmune diseases
  • rheumatoid arthritis
  • primary biliary cirrhosis
  • Hashimoto thyroiditis
  • antisynthetase syndrome
• drug-induced lung disease: especially chemotherapy agents ⁴
• hypersensitivity lung disease
• slowly healing diffuse alveolar damage (DAD)
• relapsing organizing pneumonia
• occupational exposure
• immunodeficiency (mainly HIV infection) ¹³
• graft versus host disease (GVHD) ¹³
• immunoglobulin G4 (IgG4)-related sclerosing disease, with or without overlap features with Rosai-Dorfman disease ¹³
• multicentric Castleman disease ¹³
• myelodysplastic syndrome ¹³

• • INTERSTITIAL PNEUMONIA , IP
    • • Usual interstitial pneumonia (UIP)
      • Nonspecific interstitial pneumonia (NSIP)
      • Cryptogenic organizing pneumonia (COP)
      • Desquamative interstitial pneumonia (DIP)
      • Respiratory bronchiolitis-interstitial lung disease (RB-ILD)
      • Acute interstitial pneumonia (AIP)
      • Lymphoid interstitial pneumonia (LIP)
      • Idiopathic pleuroparenchymal fibroelastosis (PPFE)

References and Links

Pathology Outlines

• TCV
  • NSIP Introduction
    • Cellular NSIP
    • Fibrotic NSIP
  • NSIP Cases 
  • ILD Map

Videos