Lung
Other interstitial pneumonitis / fibrosis
Cryptogenic organizing pneumonia
Topic Completed: 1 November 2017
Minor changes: 21 December 2020
Copyright: 2002-2021, PathologyOutlines.com, Inc.
PubMed Search: Cryptogenic organizing pneumonia[TI] lung
Table of Contents
Definition / general | Essential features | Terminology | ICD coding | Epidemiology | Sites | Pathophysiology | Etiology | Clinical features | Diagnosis | Laboratory | Radiology description | Radiology images | Prognostic factors | Case reports | Treatment | Gross description | Gross images | Microscopic (histologic) description | Microscopic (histologic) images | Virtual slides | Positive stains | Negative stains | Electron microscopy description | Videos | Differential diagnosis | Additional references | Board review style question #1 | Board review style answer #1Cite this page: Yoshikawa A, Fukuoka J. Cryptogenic organizing pneumonia. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/lungnontumorBOOP.html. Accessed January 17th, 2021.
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 coding
- J84.116 Cryptogenic organizing pneumonia
Epidemiology
- Incidence of cryptogenic organizing pneumonia is 6 - 9 per 100,000 person years (Medicine (Baltimore) 1995;74:201)
- No sex predominance
- Median age at onset is 50 - 60 years old (N Engl J Med 1985;312:152, Chest 2011;139:893, Int J Tuberc Lung Dis 2007;11:689)
- No association with smoking history
- Most patients are previously healthy individuals and lack history of lung disease
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
- Organizing pneumonia can be a complication or lung manifestation of other diseases (Thorax 2000;55:318, Chest 2011;139:893, Int J Tuberc Lung Dis 2007;11:689, J Thorac Imaging 2006;21:22)
- Idiopathic: cryptogenic organizing pneumonia
- Infection: bacterium / fungus / virus / parasite, pneumonia, lung abscess, empyema
- Other interstitial lung disease: nonspecific interstitial pneumonia, hypersensitivity pneumonitis, eosinophilic pneumonia, diffuse alveolar damage
- Autoimmune disease: rheumatoid arthritis, Sjögren syndrome, polymyositis / dermatomyositis, Sweet disease, etc.
- Aspiration
- Drug reaction, fume and toxic exposure
- Radiation
- Inflammatory bowel disease: Crohn's disease, ulcerative colitis
- Neoplasm: primary or metastatic lung cancer, lymphoma / leukemia, myelodysplastic syndrome (MDS)
- Lung infarction
Clinical features
- Mild and slowly progressive respiratory failure (Chest 2011;139:893, N Engl J Med 1985;312:152, Int J Tuberc Lung Dis 2007;11:689)
- Dry cough
- Dyspnea
- Malaise, fatigue and fever
- Duration of symptoms more than 3 months
- Abnormal chest auscultation
- End inspiratory fine crackles in affected lobes
- Restrictive pattern is often observed in pulmonary function tests; however, the abnormality is slight or within the normal range in 30% (Chest 2011;139:893, N Engl J Med 1985;312:152)
- Decreased forced vital capacity (FVC)
- Decreased diffusing capacity of the lung for carbon monoxide (DLCO)
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
- Typical pattern
Radiology images
Images hosted on other servers:
Typical organizing pneumonia
Chest radiograph
Focal organizing pneumonia
Infiltrative organizing pneumonia
Prognostic factors
- Good prognosis but frequent relapse; 20 - 58% with both cryptogenic organizing pneumonia and secondary organizing pneumonia relapse (Chest 2011;139:893, N Engl J Med 1985;312:152, Int J Tuberc Lung Dis 2007;11:689)
- Relapse predictors (Respiration 2007;74:624, Tuberc Respir Dis (Seoul) 2015;78:190, Am J Respir Crit Care Med 2000;162:571, Chest 1998;114:1599):
- Delay of corticosteroid administration
- Shorter maintenance of corticosteroid dose
- Hypoxemia: lower PaO2, lower PaO2/FiO2 ratio
- Lower serum total protein
- Lower forced vital capacity (FVC)
- Multifocal opacity on radiology
- Relapse predictors (Respiration 2007;74:624, Tuberc Respir Dis (Seoul) 2015;78:190, Am J Respir Crit Care Med 2000;162:571, Chest 1998;114:1599):
- Rarely progresses to severe respiratory failure and death
- Myelodysplastic syndrome (MDS) related organizing pneumonia may be associated with worse prognosis
- Cicatricial form of cryptogenic organizing pneumonia is more progressive or persistent and resistant to treatment (Hum Pathol 2017;64:76)
Case reports
- 43 year old woman with organizing pneumonia (OP) related to trastuzumab (Springerplus 2016;5:1964)
- 46 year old woman with OP related to MPO ANCA (Respirol Case Rep 2015;3:122)
- 58 year old man presenting with OP as a preceding symptom of rheumatoid arthritis (Case Rep Pulmonol 2014;2014:758619)
- 64 year old woman with OP related to pembrolizumab (Drug Target Insights 2016;10:9)
- 68 year old man with IgG4 related OP (Intern Med 2014;53:2701)
- 74 year old woman with rapidly progressive cryptogenic organizing pneumonia (COP) (Intern Med 2017;56:1185)
Treatment
- Most with cryptogenic organizing pneumonia and secondary organizing pneumonia completely recover with oral corticosteroids (N Engl J Med 1985;312:152, Chest 2011;139:893)
- Clarithromycin was recently suggested as an alternative regimen with fewer adverse events (PLoS One 2017;12:e0184739)
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
Contributed by Yale Rosen, M.D.
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:
Contributed by Akira Yoshikawa, M.D. and Yale Rosen, M.D.
Low power
Almost normal background
Medium power, organizing pneumonia
Organizing pneumonia
Cellular infiltration
Foamy macrophages
Low power
Medium power
Organizing pneumonia with hyalinizing change
Organizing pneumonia with hyalinizing change
Bronchiolitis obliterans with hyalinizing change
Organizing pneumonia (OP)
Organizing pneumonia (OP)
Organizing pneumonia (OP)
Masson body
Images hosted on other servers:
Bronchiolitis obliterans
Masson bodies (ball shaped, typical form of organizing pneumonia)
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Organizing pneumonia (OP)
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
- Type I pneumocyte necrosis is observed in the early phase (Thorax 2000;55:318)
Videos
Histology of cryptogenic organizing pneumonia
Differential diagnosis
- Acute interstitial pneumonia (AIP) / acute respiratory distress syndrome (ARDS):
- Diffuse alveolar damage (DAD) of AIP or ARDS may have a prominent organizing pneumonia (organizing DAD) radiologic pattern
- If organizing pneumonia is so diffusely distributed that it almost completely occupies the surgical sample, organizing DAD should be favored
- Hyaline membranes, architectural destruction and myofibroblastic aggregation with less extracellular matrix are other clues of DAD pattern
- Eosinophilic pneumonia: pink macrophages (not foamy), more fibrin, frequent type II pneumocyte atypia
- Granulomatosis with polyangiitis: geographic necrosis, hemorrhage, capillaritis, more eosinophils, more fibrin deposition
- Inflammatory myofibroblastic tumor: nodule / mass of spindle cells, more plasma cells, ALK+, SMA+, desmin+
- Inflammatory pseudotumor (IgG4 related / NOS): nodule / mass of spindle cells, SMA+, ALK+
- Nonspecific interstitial pneumonia (NSIP):
- Organizing pneumonia is often seen in NSIP pattern but it does not exceed more than 20% of area
- Interstitial change (cellular or fibrotic) is more predominant
- Spindle cell carcinoma (sarcomatoid carcinoma): nodule / mass of atypical spindle cells
- Usual interstitial pneumonia (UIP):
- Fibroblastic focus in UIP pattern is another type of myofibroblastic aggregation but usually adjacent to dense fibrotic lesion unlike in organizing pneumonia
- Dense interstitial fibrosis, architectural destruction and honeycomb change are other clues of UIP
Additional references
Board review style question #1
Which of the following two findings are against the histological diagnosis of organizing pneumonia?
- Dense interstitial fibrosis
- Fibrin deposition
- Fibroblastic focus
- Foamy macrophage accumulation
- Masson body
Board review style answer #1
A and C. Both A and C are findings suggestive for usual interstitial pneumonia (UIP) pattern.
