CPC: Case Study

CPC #3: Answer

The differential diagnosis for this patient is quite broad. The patient has multifocal airspace disease with peripheral accentuation demonstrated radiographically, without lymphadenopathy or pleural effusions. The patient was apparently well prior to her illness, and developed fever and malaise that preceded the development of cough and a raw throat. The patient's illness has a subacute, non-toxic, non-fulminant pace. The overall sense is that this patient has an inflammatory or infectious process, though the history of breast carcinoma raises the specter of metastasis.

Major concerns in the clinical differential diagnosis included infection, specifically with fungal organisms such as histoplasmosis or tuberculosis. Another possibility would be a slowly resolving bacterial or viral pneumonia. Multiple pulmonary emboli could give peripherally centered infiltrates as was seen in this case, and pulmonary emboli are always a concern in a patient with a history of carcinoma. Eosinophilic pneumonia could present in this fashion, though the pulmonary infiltrates are not the classic "inverse pulmonary edema" pattern. Malignancy was a major concern. Pulmonary lymphoma could present with bilateral airspace infiltration, though the absence of lymphadenopathy argues against this. Carcinoma growing in a bronchioloalveolar pattern could also account for the radiographic findings. A primary bronchioloalveolar carcinoma would be possible, though the concern in this case would be metastatic breast carcinoma growing in a bronchioloalveolar pattern. Finally, bronchiolitis obliterans organizing pneumonia (BOOP) would fit both the clinical and radiographic findings.

The diagnostic procedure was a transbronchial biopsy. The biopsy showed patchy intraluminal plugs of fibrosis adjacent to normal appearing surrounding lung. The plugs of fibrosis extended from distal bronchioles into adjacent alveolar ducts and airspaces, yielding a branching pattern (Figure 1,2,3). The plugs are characterized by elongated bland-appearing fibroblasts in a myxoid matrix. Mitotic activity was absent, and the cells do not morphologically resemble the mammary carcinoma previously diagnosed. These findings are those of bronchiolitis obliterans organizing pneumonia (BOOP).

Figure 1

Figure 2

Figure 3

Bronchiolitis obliterans organizing pneumonia (BOOP) is a non-specific manifestation of acute lung injury. In this sense, it is similar to diffuse alveolar damage, except that it is focal and peribronchiolar as opposed to diffuse. BOOP represents organization (abnormal healing with scarring) of a bronchiolar and alveolar exudates that reflect injury to the distal bronchiole, alveolar ducts, and peribronchiolar alveoli. This is in contrast to resolution of the exudates resulting from an injury, which implies a return to normal histology.

It is somewhat hard to appreciate all the features of BOOP on a small transbronchial biopsy. The architecture and distribution of BOOP are better appreciated in an open lung biopsy. Examples of sections from open lung biopsies taken from other patients with BOOP are shown below. Figure 4 demonstrates the patchy distribution of BOOP. In this section, the plugs of fibroblastic tissue are centered on a large arteriole. While the airway is not evident in this section, we know that airways typically accompany arterioles within the lung, and hence the fibrosis must be centered upon an airway. Figure 5 shows an intraluminal plug of granulation tissue involving a bronchiole. Extension of these plugs of granulation tissue out of the bronchiole and into the adjacent alveoli and ducts is demonstrated in Figure 6, where the branching nature of BOOP is seen.

Figure 4

Figure 5

Figure 6

BOOP may be accompanied by secondary pathologic phenomena within the lung. First, BOOP may be associated with air trapping (hyperinflation), resulting from partial bronchiolar obstruction by the plugs of fibroblastic tissue (Figure 7) Second, BOOP may be associated with atelectasis and accumulation of macrophages in the distal lung when the BOOP completely obstructs the airway (Figure 8). Remember, macrophages enter the lung from the pulmonary circulation, but exit via the airspaces. If the airspaces are blocked by the plugs of fibroblastic tissue of BOOP, the macrophages will accumulate distally within the lung.

Figure 7

Figure 8

The diagnosis of BOOP on a transbronchial biopsy requires close clinical correlation. It should be remembered that BOOP is a purely descriptive pathologic term of a histologic finding that can be encountered in a variety of situations. These can be broken down into three categories. First, BOOP may be the primary cause of the respiratory illness. This can occur when BOOP is a result of organization of a prior infection such as viral or bacterial infections, the result of a toxic inhalation, the result of drug toxicity (i.e., sulfasalazine), secondary to collagen vascular disease, the result of bronchial obstruction, the result of chronic aspiration, or idiopathic. Second, BOOP may be a non-specific reaction at the periphery of an unrelated pathologic process, such as a tumor, granuloma or infarct. Third, BOOP may be focal finding in another pathologic disease process. For example, BOOP may be a minor manifestation of eosinophilic pneumonia, hypersensitivity pneumonitis, non-specific interstitial pneumonitis, or eosinophilic granuloma. In a transbronchial biopsy specimen, it is particularly important to exclude categories two and three before concluding that BOOP is primary given the limited sampling of pulmonary tissue.

The possibility of metastatic carcinoma was a major concern to the patient. However, the clinical course was entirely consistent with primary idiopathic BOOP, and the transbronchial biopsy supported that impression. Therefore, the patient was treated with 1mg/kg of prednisone and followed closely. Over the course of several months, her symptoms and radiographic findings completely resolved, and her steroids were tapered slowly. The patient is currently free of disease and healthy off of steroids. Hence, the clinical course in conjunction with the histopathologic findings, establish the diagnosis of idiopathic primary BOOP in this case.

Return to Top