Lung Biopsy Interpretation
Case 6 -
Bronchiolitis Obliterans Organizing Pneumonia (BOOP) (Cryptogenic Organizing Pneumonia)
Anna-Luise A. Katzenstein & Jeffrey L. Myers
This 67 year old South American physician presented with a 9 month history of episodic cough and
malaise associated with shortness of breath. Chest x-ray showed nonspecific patchy bilateral air-space
opacities. Pulmonary function studies showed moderate restriction (FVC 51% of the predicted value) with
reduction in diffusing capacity (DLCO 48% of the predicted value) and desaturation at rest and during
exercise (O2 saturation 79% at rest and 72% after exercise). He underwent thoracotomy and open lung
Case 6 - Figure 1 - Low magnification photomicrograph showing an area of intraluminal fibrosis ("organizing pneumonia").
Case 6 - Figure 2 - Higher magnification view showing the polypoid configuration of the intraluminal fibroblastic plugs characteristic of BOOP.
Case 6 - Figure 3 - Photomicrograph showing another area of organizing pneumonia, here associated with prominent foamy histiocytes in surrounding air spaces. Although not specific, the presence of foamy histiocytes is characteristic of BOOP and is sometimes a helpful clue to the diagnosis.
Your section from his thoracoscopic lung biopsy show a distinctive pattern of intraluminal fibrosis.
The striking finding is the presence of polypoid plugs of immature appearing fibroblastic tissue within
distal bronchioles, alveolar ducts, and peribronchiolar air spaces. There is associated nonspecific
alveolar septal thickening largely limited to the areas of intraluminal fibrosis. Thickened alveolar
septa contain a mild infiltrate of mononuclear inflammatory cells and demonstrate hyperplasia of alveolar
Bronchiolitis obliterans organizing pneumonia (BOOP) was the term proposed in 1985 by Epler and
colleagues for a distinctive clinicopathological syndrome that had been previously described under a
variety of terms including cryptogenic organizing pneumonitis, bronchiolitis obliterans with classical
interstitial pneumonia (BIP), and bronchiolitis obliterans and organizing pneumonia-like process. Since
then yet additional synonyms have been proposed including idiopathic intraluminal organizing pneumonia
and seasonal cryptogenic organising pneumonia. The previously referenced consensus statement sponsored
by the American Thoracic Society (see Case 1 – UIP) suggests use of the term cryptogenic organizing
pneumonia (COP). By whatever name, idiopathic BOOP is a specific clinicopathological syndrome that must
be distinguished from UIP.
Idiopathic BOOP affects males and females equally and occurs most commonly in middle aged adults with
a peak incidence in the sixth decade. Most patients present with cough and shortness of breath of
several weeks duration which are frequently accompanied by fevers. The classical description has been
expanded by recognition of seasonal variation in some patients (so-called "seasonal cryptogenic
organising pneumonia"). A minor subset of patients has also been identified associated with a more
fulminant course, although it may be extremely difficult to separate this syndrome from acute
interstitial pneumonia. The most common radiographic finding is patchy bilateral air space opacities
which may have a "ground glass" appearance. Patients in this group have an excellent prognosis and
nearly all recover with corticosteroid therapy. Localized air space opacities resembling lung neoplasms
also can occur, as seen in this patient. Less commonly patients present with bibasilar interstitial
opacities that mimick those seen in idiopathic pulmonary fibrosis. This latter radiographic pattern may
be more common in patients with associated collagen vascular diseases and tends to be associated with a
The main pathologic abnormality is the presence of intraluminal fibrosis within distal airways,
alveolar ducts, and peribronchiolar alveolar spaces. The intraluminal fibrosis consists of polyploid
plugs of immature fibroblastic tissue which resemble granulation tissue. The intraluminal plugs show a
characteristic configuration at low magnification resulting from their distribution within distal
airways. Larger terminal bronchioles and peribronchiolar alveolar spaces also show varying degrees of
involvement. At higher magnification the fibrosis consists of concentrically arranged spindle cells
associated with a pale staining basophilic matrix. Chronic inflammatory cells and capillaries can also
be identified within the granulation tissue plugs. An acute and chronic bronchiolitis is usually present
away from the areas of intraluminal fibrosis and consists of a peribronchiolar infiltrate of acute and
chronc inflammatory cells associated with varying degrees of epithelial necrosis. An acute inflammatory
exudate may also be present within bronchiolar lumens.
A number of secondary changes accompany the intraluminal fibrosis. Foamy alveolar macrophages are
present within peribronchiolar alveolar spaces and reflect the presence of proximal airway obstruction
(i.e. endogenous lipid pneumonia). Interstitial pneumonia is present in most cases and is characterized
by an alveolar septal infiltrate of mononuclear inflammatory cells with varying degrees of septal
thickening and epithelial hyperplasia. For the most part, however, the areas of interstitial pneumonia
are limited to the areas of intraluminal fibrosis and are not present in unaffected pulmonary parenchyma.
Ultrastructurally BOOP resembles other forms of acute lung injury. The main abnormality is necrosis
of bronchiolar, alveolar duct, and alveolar epithelium resulting in denudation of the underlying basal
lamina. Fibroblasts and myofibroblasts migrate from the interstitial compartment into the airways and
peribronchiolar alveolar spaces through the damaged basement membranes, thus forming intraluminal
fibroblastic plugs. Proliferating bronchiolar cells and type 2 pneumocytes eventually incorporate the
fibroblastic plugs back into the interstitial compartment where they are broken down by mechanisms that
are not yet well defined.
It should be emphasized that organizing pneumonia is a relatively nonspecific reaction to lung injury
that can occur as a secondary finding adjacent to other pathologic processes or as a component of other
primary pulmonary disorders (see Table). This is particularly important to bear in mind when
interpreting small biopsy specimens, such as transbronchial or even thoracoscopic biopsies.
Cryptococcosis, Wegener's granulomatosis, and eosinophilic pneumonia are three important conditions that
can be associated with broad areas of organizing pneumonia.
Table 1: Clinical Syndromes Associated with Organizing Pneumonia ("BOOP")
| Collagen vascular diseases|
| rheumatoid arthritis|
| systemic lupus erythematosus|
| mixed connective tissue disease|
| Toxic injuries|
| inhalants (NO2 -- silo fillers disease)|
| systemic (drugs -- bleomycin, amiodarone)|
| radiation (external beam irradiation for breast carcinoma)|
| Chronic ("organizing") infection|
| bacteria (legionella, nocardia)|
| viruses (influenza, CMV)|
| Pneumocystis carinii|
| Idiopathic (BOOP; cryptogenic organizing pneumonia)|
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