Bronchiolitis obliterans organizing pneumonia

Clinical and functional characteristics and morphogenesis

The pathology has a number of specific clinical features. The disease often manifests after taking antibiotics. It is characterized by a subacute onset. The course of the process is undulating, but overall is assessed as relatively favorable. When assessing pulmonary function, prominent obstructive changes play a leading role, which is associated with damage to the small airways.

The morphogenesis of the disease represents a strict sequence of three stages:

1. At the initial stage, pathological activation of alveolar macrophages occurs directly within the bronchioles.
2. This activation is followed by marked exudation—the escape of fluid and cellular elements into the lumens of the bronchioles and alveoli.
3. The final stage of morphogenesis is the subsequent organization of the accumulated exudate, i.e., its gradual replacement by connective tissue.

Pathological anatomy and staging of the process

Bronchiolitis obliterans organizing pneumonia (also known as cryptogenic organizing pneumonia) differs fundamentally from other forms of idiopathic fibrosing alveolitis. The main difference lies in the clear localization of the lesion: the process exclusively affects the level of the terminal bronchioles and alveolar ducts.

Characteristic morphological features include:

• A combination of foci of carnification in the distal parts of the respiratory system (in the bronchioles, alveolar ducts, and the alveoli themselves).
• Presence of chronic, moderately severe interstitial inflammation.
• Strict preservation of the general architectonics of the lung tissue despite inflammation.
• Uniformity of the detected lesions at the microscopic level.

The pathological process is divided into two stages:

• Early stage. During this period, intraalveolar edema and pronounced exudation in the lumens of the alveoli and bronchioles come to the fore. The tissue is edematous, with lymphohistiocytic infiltration mixed with neutrophils. Young granulation tissue begins to form around the peribronchiolar zone (at the level of small bronchi and terminal bronchioles). Foci of pronounced basal cell hyperplasia are also recorded.
• Late stage. Characterized by the development of peribronchial sclerosis. Full-fledged foci of carnification form, in which the alveoli are irreversibly replaced by connective tissue. Deformation of the bronchioles occurs; their inner surface is lined with hyperplastic basal cells acquiring features of atypia. At the molecular level, there is an increase in the expression of growth factors—TGFβ and FGFb—by both epithelial and interstitial cells.

Dysregenerative epithelial changes

A crucial component of the pathological anatomy of BOOP is the remodeling of the epithelial lining. Dysregenerative changes are represented by three types of hyperplasia: goblet cell, basal cell, and atypical basal cell.

• Goblet cell hyperplasia. Normal epithelial cells are replaced by goblet cells. They are small in size, and their nuclei are displaced toward the basement membrane. The main function of these cells under pathological conditions is the hyperproduction of alcian-positive mucus. Interspersed between the goblet cells are columnar cells with dark cytoplasm containing small mucous granules in their apical parts.
• Basal cell hyperplasia. Manifests as an increase in the number of layers of basal cells (from 2 to 8 layers) located directly beneath the columnar epithelium. The cells themselves have a relatively large, centrally located darkly stained nucleus with a fine-meshed chromatin structure and smooth contours of the nuclear membrane. The cytoplasm is represented by a thin basophilic rim. This type of hyperplasia is characterized by a pronounced tendency for cells to mature in the direction from the basement membrane to the surface: as they move upward, the nuclei become lighter and the cytoplasmic rim wider.
• Atypical basal cell hyperplasia. This form is characterized by the appearance of clear signs of cellular atypia. Pronounced cellular and nuclear polymorphism is observed. The sizes of both the cells themselves and their nuclei are pathologically increased. In some cells, nucleoli become clearly distinguishable upon microscopy.

Briefly: answers to topical questions

Class and exam questions

What else to study on this topic

• Mechanisms of alveolar macrophage activation in the bronchioles at the initial stage.
• The role of TGFβ and FGFb growth factors in the development of peribronchial sclerosis.
• Differential diagnosis of BOOP and other forms of idiopathic fibrosing alveolitis.
• Histochemical features of alcian-positive mucus in goblet cell hyperplasia.
• Criteria for assessing cellular and nuclear polymorphism in atypical hyperplasia.

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