Lung - nontumor
Other interstitial pneumonitis / fibrosis
Cryptogenic organizing pneumonia

Author: Akira Yoshikawa, Junya Fukuoka, M.D., Ph.D. (see Authors page)
Editor: Andrey Bychkov, M.D., Ph.D.

Revised: 7 December 2017, last major update November 2017

Copyright: (c) 2002-2017, PathologyOutlines.com, Inc.

PubMed Search: Cryptogenic organizing pneumonia[TI] lung
Cite this page: Yoshikawa, A., Fukuoka, J. Cryptogenic organizing pneumonia. PathologyOutlines.com website. http://pathologyoutlines.com/topic/lungnontumorBOOP.html. Accessed December 18th, 2017.
Definition / general
  • Since 1901, organizing pneumonia (OP) has been described with the name "bronchiolitis obliterans" as an interstitial lung disease with granulation tissue plugs within alveolar ducts and small airways secondary to a variety of causes, including infection, fume exposure, drugs, collagen vascular disease, allergic reactions and obstruction (Chest 1983;83:161)
  • Davison et al. (1983) and Epler et al. (1985) reported a series of cases with organizing pneumonia and no evidence of infection or other aetiological agents; after that, the term "bronchiolitis obliterans organizing pneumonia (BOOP)" was commonly used for a while (Q J Med 1983;52:382, N Engl J Med 1985;312:152)
  • In 2002, the American Thoracic Society / European Respiratory Society suggested the term "cryptogenic organizing pneumonia (COP)" to avoid confusion with airway disease, such as constrictive bronchiolitis obliterans, and categorized cryptogenic organizing pneumonia into acute / subacute interstitial pneumonia (Am J Respir Crit Care Med 2002;165:277, Am J Respir Crit Care Med 2013;188:733)
Essential features
  • Organizing pneumonia pattern is one of the most commonly seen lung lesions in a variety of diseases, such as infections and systemic diseases
  • Cryptogenic organizing pneumonia is a relatively rare disease; however, physicians need to consider this entity as one of the differential diagnoses because its clinical and radiological manifestations are often varied and nonspecific
  • Histologically, both cryptogenic organizing pneumonia and secondary organizing pneumonia are characterized by polypoid fibroblastic aggregations which plug alveolar sacs, ducts and bronchioles
Terminology
  • Broad term "organizing pneumonia" can refer to clinicopathological diagnosis (cryptogenic organizing pneumonia and secondary organizing pneumonia), histological pattern (organizing pneumonia pattern) or microscopic findings (e.g. Masson body)
  • Cryptogenic organizing pneumonia (COP) has also been called bronchiolitis obliterans, bronchiolitis obliterans organizing pneumonia (BOOP), idiopathic BOOP and cryptogenic organizing pneumonitis
ICD-10 coding
  • J84.116 Cryptogenic organizing pneumonia
Epidemiology
Sites
  • Bilateral or unilateral lobes of the lung
Pathophysiology
  • Organizing pneumonia is a repair process (wound healing) of the lung in response to preceding alveolar injury (Thorax 2000;55:318, Eur Respir J 2006;28:422)
    • Injury to capillary endothelial cells and alveolar epithelial cells results in the leakage of plasma protein, especially coagulation factors
    • Intra-alveolar coagulation of proteins and coagulation factors generates fibrin clotting on alveolar surfaces
    • Fibroblasts / myofibroblasts migrate into the damaged area, proliferate and generate loose fibrosis in the form of a small polyp
  • IL6, IL8 and TGFβ1 may play an important role in pathogenesis (Adv Exp Med Biol 2016;911:77)
  • Galectin 9 and regulatory T cells are increased in the lung with cryptogenic organizing pneumonia (Lung 2015;193:683)
Etiology
Clinical features
Diagnosis
  • Based on clinical features, radiology and histopathology (Am J Respir Crit Care Med 2002;165:277)
    • Because organizing pneumonia is a nonspecific manifestation seen in a wide variety of diseases and often secondary to them, it is important to investigate the cause of respiratory failure or other disease
    • Surgical lung biopsy or transbronchial lung biopsy is required to establish a firm diagnosis since the clinical and radiological findings are often not specific
    • However, a biopsy may not be necessary if the clinical and radiological features are suggestive enough
Laboratory
  • Increased serum surfactant proteins A and D
  • Negative serum antibodies of connective tissue diseases and hypersensitivity pneumonitis
Radiology description
  • Simple chest radiography
    • Bilateral or unilateral ground glass opacity and consolidation
  • High resolution computed tomography (Respirology 2016;21:810, Chest 2017;151:1356)
    • Typical pattern
      • Patchy ground glass opacity and consolidation with / without air bronchogram
      • Often peripheral and migratory
      • Size varies from a few centimeters to a whole lobe
      • Typical organizing pneumonia sometimes looks similar to eosinophilic pneumonia, pulmonary lymphoma and lepidic adenocarcinoma
    • Less common patterns
      • Focal organizing pneumonia: nodular or mass-like consolidation mimicking lung cancer (Int J Clin Exp Pathol 2015;8:511)
      • Infiltrative organizing pneumonia: diffuse infiltrative opacity
      • Reversed halo sign: central ground glass opacity surrounded by round consolidation
Radiology images

Images hosted on other servers:

Typical organizing pneumonia


Chest radiograph

Focal organizing pneumonia

Infiltrative organizing pneumonia

Prognostic factors
Case reports
Treatment
Gross description
  • Multiple patchy fibrotic lesions
  • Ill defined, soft to firm gray areas
  • Volume of the lung is usually normal
  • Other changes are overlapped with secondary organizing pneumonia
Gross images

Images hosted on other servers:

Images contributed by Dr. Yale Rosen:

Cryptogenic organizing pneumonia

Organizing pneumonia

Microscopic (histologic) description
  • Organizing pneumonia (Semin Respir Crit Care Med 2012;33:462)
    • Fibroblastic plugs in alveolar sacs and ducts (organizing pneumonia) and bronchiolar lumen (bronchiolitis obliterans)
    • Formed by spindled fibroblasts in pale staining matrix of immature loose collagen with polypoid shape (Masson body) or serpiginous or elongated form
    • Organizing pneumonia sometimes extends from one alveolus to the next one through interalveolar fenestrae (butterfly pattern)
  • Mild to moderate cellular infiltrate in background (Eur Respir J 2006;28:422, Clin Med Insights Circ Respir Pulm Med 2016;9:123)
    • Thickened alveolar septa with lymphocytes, plasma cells and histiocytes
    • Alveolar architecture is usually preserved in cryptogenic organizing pneumonia
      • Because interstitial dense fibrosis, architectural destruction and honeycomb change are not components of cryptogenic organizing pneumonia, the organizing pneumonia lesion is likely to be secondary to other lung disease if these findings are mixed or overlapped (J Clin Pathol 2009;62:387)
  • Airspace changes (Thorax 2000;55:318)
    • Foamy macrophage accumulation in surrounding airspace may be present
    • Occasional fibrin deposition
      • If prominent, the lesion is more likely to be infection, eosinophilic pneumonia (especially after corticosteroids), vasculitis (e.g. granulomatosis with polyangiitis) or acute fibrinous organizing pneumonia (AFOP)
  • Cicatricial form of cryptogenic organizing pneumonia (Hum Pathol 2017;64:76)
    • Organizing granulation tissue is collagenized or hyalinized and harbors eosinophilic, lamellar and dense fibers
    • Airspaces can be filled with the collagenized organizing pneumonia but alveolar architecture is mostly preserved
Microscopic (histologic) images

Scroll to see all images:


Images hosted on PathOut server:

Images contributed by Akira Yoshikawa, Nagasaki University Hospital:

69 year old woman, ex smoker (60 pack years), initially presented 6 years ago
with abnormal chest radiograph in lower lobes and no symptoms
Currently, no infection, autoimmune disease or hypersensitivity pneumonia
Biopsy from S6 of the left lung shows cryptogenic organizing pneumonia:


Low power

Almost normal background

Medium power, organizing pneumonia

Organizing pneumonia


Cellular infiltration

Foamy macrophages



68 year old man, ex smoker (65 pack years), presented with abnormal chest radiograph
in middle and lower lobes of the lung 2 months ago in health checkup, without any symptoms
No findings of infection, autoimmune disease or hypersensitivity pneumonia
Biopsy from S6 of the right lung; cicatricial variant of cryptogenic organizing pneumonia:


Low power

Medium power

Organizing pneumonia with hyalinizing change


Bronchiolitis obliterans with hyalinizing change



Images hosted on other servers:

Bronchiolitis obliterans

Masson bodies (ball shaped, typical form of organizing pneumonia)


Organizing pneumonia (OP)



Images contributed by Dr. Yale Rosen:

Organizing pneumonia (OP)


Organizing pneumonia (OP)

Masson body



Images contributed by Dr. Semir Vranić:

Various images

Virtual slides

Images hosted on other servers:

Cryptogenic organizing pneumonia

Positive stains
  • Elastica van Gieson staining is helpful to evaluate if architecture of alveoli is preserved or not
Negative stains
  • Organizing polyps are negative for elastica van Gieson staining except in cicatricial variant
Electron microscopy description
Videos

Histology of cryptogenic organizing pneumonia

Differential diagnosis
Board review question #1
Which of the following two findings are against the histological diagnosis of organizing pneumonia?

  1. Dense interstitial fibrosis
  2. Fibrin deposition
  3. Fibroblastic focus
  4. Foamy macrophage accumulation
  5. Masson body
Board review answer #1
A and C. Both A and C are findings suggestive for usual interstitial pneumonia (UIP) pattern.