• What is it:
  • Cryptogenic Organizing Pneumonia (COP) is a
    • non-infectious
    • inflammatory lung disease
  • characterized by:
    • granulation tissue plugs in the
      • bronchioles
      • alveolar ducts and
      • alveoli
  • Associated with
    • chronic inflammation in the
      • Surrounding interstitium.
  • It is classified as an
    • idiopathic condition but
    • can resemble
      • infectious pneumonia
      • clinically and on
      • imaging
• Etymology:
  • Cryptogenic means of unknown origin.
  • Derived from the Greek word organizein (to arrange), referring to the fibroblastic granulation tissue organizing in the airways.
• AKA:
  • Idiopathic Bronchiolitis Obliterans Organizing Pneumonia (BOOP).
• What causes it:
  • The exact cause is
    • unknown, but it is considered
    • idiopathic.
  • Pathophysiologically, COP involves:
    • Chronic inflammation
      • Fibroblast proliferation,
      • Intra-alveolar fibrosis
    • .
• What is the result:
  • Impaired gas exchange and respiratory symptoms due to:
    • Although there is granulation tissue in the airways small airway obstruction is not a hallmark of COP,
  • If untreated, it may progress to:
    • Chronic respiratory dysfunction, or
    • Rarely, pulmonary fibrosis.
• How is it diagnosed:
  • Clinical findings:
    • Gradual onset of symptoms over weeks to months.
    • Symptoms include:
      • Persistent dry cough,
      • Dyspnea,
      • Fever, and
      • Fatigue.
  • Imaging studies:
    • Applied Anatomy Diverse Findings
      • Parts: Respiratory bronchioles, alveolar ducts, alveoli.
      • Size: Lesions often span multiple secondary pulmonary lobules.
      • Shape: Rounded, nodular, linear, or perilobular.
      • Position: Can involve any lung region without lobar preference.
      • Character:
        • Ground-glass opacities
        • Reticulations
        • Consolidation,
        • Atoll sign (reverse halo sign):
          • Central ground-glass opacity surrounded by a
          • ring of consolidation,
          • historically considered characteristic but not pathognomonic.
        • Nodules
        • Masses
        • Despite involvement of bronchioles mosaic attenuation and air trapping is not a common feature
      • Time: Subacute onset over weeks to months.
    • Chest X-ray:
      • Patchy, peripheral consolidations, often mimicking infectious pneumonia.
    • Chest CT:
      • Parts:
        • Patchy airspace consolidations and
        • nodules
        • GGO’s.
      • Size: Ranges from
        • diffuse lung involvement
        • segmental lesions to .
        • focal  subsegmental
      • Position:
      • Peripheral and basal lung field
      • but can involve upper lung fields
      • subpleural or
      • peribronchial distribution,
      • .
      • Character:
        • consolidations
        • ground-glass opacities,
        • nodular densities which can uncommonly cavitate
        • interstitial changes.
        • Atoll sign (reverse halo sign):
          • Central ground-glass opacity surrounded by a
          • ring of consolidation,
          • historically considered characteristic but not pathognomonic.
      • Time: Persistent over weeks but responsive to corticosteroid treatment.
  • Pulmonary Function Test (PFT):
    • COP typically shows a restrictive pattern (reduced total lung capacity and vital capacity).
      • Obstructive patterns, such as reduced forced expiratory volume in 1 second (FEV1) and FEV1/forced vital capacity (FVC) ratio, are less common but may be seen in cases with significant small airway involvement.
  • Histopathology (gold standard):
    • Fibroblastic plugs in
      • bronchioles  alveoli and (Masson bodies).
    • Interstitial mononuclear inflammation and mild fibrosis.
  • Exclusion of other causes:
    • Rule out infectious pneumonia, malignancy, and systemic diseases.
• How is it treated:
  • First-line therapy:
    • Corticosteroids (e.g., prednisone): Rapid improvement in symptoms and imaging findings in most cases.
  • Second-line options (for refractory cases):
    • Immunosuppressive agents (e.g., azathioprine, cyclophosphamide).
  • Supportive care:
    • Oxygen therapy for hypoxemia.
    • Pulmonary rehabilitation for chronic cases.
  • Monitoring:
    • Serial imaging to assess response to treatment and detect relapse.
• Radiological implications:
  • COP mimics infectious pneumonia on imaging but lacks microbiological evidence of infection.
  • Serial imaging shows rapid improvement with corticosteroid therapy.
  • Persistent or recurrent opacities may indicate incomplete response or relapse.
• Key points and pearls:
  • Not infectious: Clinical history and microbiology are critical to differentiate COP from pneumonia.
  • Imaging Has Diverse findings:
    • • OP can appear as
        • bronchial wall thickening
          ground-glass opacities
        • patchy consolidations,
        • nodules,
        • masses , or combinations thereof.
          • Atoll sign (reverse halo sign): Once thought to be pathognomonic, it is now known to occur in other conditions (e.g., invasive fungal infections, vasculitis).
          • Arcade like Sign
            • Perilobular pattern
        • Can present as focal masses, raising suspicion for malignancy.
  • Relapse is common: Close follow-up is necessary, as up to 50% of patients may experience recurrence.
  • Early treatment with corticosteroids prevents progression to fibrosis.
  • Exclude secondary organizing pneumonia (e.g., associated with connective tissue disease, drugs, or malignancy).

1. Variety of Imaging Findings:
   • COP can manifest as patchy consolidations, ground-glass opacities, nodules, masses, reticular opacities, and perilobular patterns.
   • These findings can be focal, multifocal, or diffuse, with no strict lobe predilection.
   • Specific signs like the Atoll sign (reverse halo sign) or the arcade-like sign are characteristic but not pathognomonic, as they are also seen in other conditions.
2. Overlap with Other Diseases:
   • Infectious pneumonia, particularly viral or fungal infections.
   • Other interstitial lung diseases (e.g., NSIP, UIP).
   • Neoplastic conditions like lung masses and lymphangitic carcinomatosis.
   • Drug-induced lung injury or autoimmune-related organizing pneumonia.
3. Mimics of Infectious Pneumonia:
   • COP often clinically and radiologically resembles bacterial or atypical infections, especially when presenting as patchy consolidations or nodules.
4. Dynamic Nature:
   • Lesions may change with corticosteroid therapy, further complicating the diagnosis if there is partial resolution.

Diagnostic Challenges:

• Non-specific Findings: The common imaging findings are not exclusive to COP, requiring clinical, imaging, and sometimes histopathological correlation.
• Need for Biopsy: In cases where the imaging findings are ambiguous, a lung biopsy is often required to confirm the diagnosis.

Takeaway:

COP’s protean nature on imaging reinforces the importance of a multidisciplinary approach, combining clinical history, laboratory results, and imaging findings to reach a diagnosis.

Buzz  The COPS are Everywhere and can Disguise as almost anything

• Structural
• peribronchial consolidation
  • Interstitial
    • alveoli
    • bronchioles
  •   COPS  All Lung Zones  COPS can go anywhere
    • bronchovascular
    • peripheral
• Path
  • interstitial inflammation
  • globs of tissue Masson bodies in in distal airspaces and bronchioles
• Imaging CT
  • Ground Glass
  • Patchy Consolidation
  • Atoll Inverted Halo
  • Nodules which can cavitate

“When an underlying cause is unknown it is classified as cryptogenic organizing pneumonia (COP; also referred to as primary organizing pneumonia) whereas if a cause is known it is then termed a secondary organizing pneumonia.”

Pathology –  “characterized by granulation tissue polyps within alveolar ducts and alveoli and with chronic inflammation involving the adjacent lung parenchyma. ”

Most cases are cryptogenic

• Small Airway Disease – Organizing Pneumonia – Terminal Bronchiole

  

  • cryptogenic or secondary organizing pneumonia (OP),

  • 

COP Pattern

• 

Case of a patient in remission from adult T-cell lymphoma/leukemia, now with multiple PET, AVID lung nodules  Pathology showed Acute organizing pneumonitis which could be part of any condition in the lung such as an infection.  CT showed cavitating nodules and solid nodules which were PET AVID The conclusion was that even though the pathology showed organizing pneumonitis, it could still be a response to the infection

Cavitating and solid nodules  PATH Acute organizing pneumonitis

 

COP vs NSIP

1 Year Later

 

COP vs NSIP
57 year old female presents 1 year later with similar CT findings of basilar bronchovascular infiltrates, almost symmetrical, associated with mediastinal and axillary adenopathy.
Pathological report was complex but suggested a diagnosis of cryptogenic organizing pneumonia
Ashley Davidoff MD TheCommonVein.net

References and Links

Tiralongo et al  Cryptogenic Organizing Pneumonia: Evolution of Morphological Patterns Assessed by HRCT Diagnostics 2020, 10(5), 262;

 

Radiopaedia
Wiki

Radiopaedia

• TCV
  • ILD Map
• Cases
  • 005Lu Cryptogenic Organizing Pneumonia
  • 65Lu Honeycomb predominant ILD COP RA UIP
  • 70Lu Amyloid Consolidative Nodular Septal