Answer: Pulmonary eosinophilic granuloma (Langerhans cell histiocytosis)

Histology: There are scattered, stellate (“starfish”) shaped interstitial scars. There are clusters of cells with nuclear grooves, located around bronchioles in the interstitium and in the subpleural area. These cells are immunoreactive for CD1a and S100.

Discussion: The clue to the diagnosis in this case is the presence of scattered, distinctly interstitial stellate (“starfish”) shaped scars. Active and diagnosable disease was present only in one area in one of five sections taken of the biopsy. This phenomenon reflects the patchy nature of the disease and the necessity for examining multiple sections at multiple levels.

This patient smoked cigarettes, (as do most patients with pulmonary eosinophilic granuloma) and that activity is reflected in the presence of “respiratory” or “smoker’s,” bronchiolitis as well. Pulmonary eosinophilic granuloma (PEG) is a patchy and upper lung zone disease with a very characteristic appearance on CAT scan. PEG is unusual in that it is one of two interstitial lung disease disorders in which the chest radiograph will show enlarged lungs rather than the small lung volumes seen in most interstitial fibrotic lung disorders. The cystic changes seen on radiographic images are related to scar emphysema around areas of stellate fibrosis.

The diagnosis is made by light microscopy when one finds clusters of Langerhans’ cells with their characteristic nuclear grooves around bronchioles, in the interstitium or in the subpleural area. Langerhans’ cells are negative with PAS staining (unlike pulmonary alveolar macrophages) and generally react with immunostains directed against S-100 protein or the CD1a antigen. In some cases, the only diagnostic clue will be the stellate interstitial scars and the chest radiographic appearance.

The differential diagnosis here is limited. The usual interstitial pneumonitis histologic pattern of Idiopathic Pulmonary Fibrosis is characterized by temporal variability in a pattern of interstitial inflammation and scarring. The process is accentuated beneath the pleura and is accompanied by the presence of microscopic honeycombing. Radiographically, the lung volumes are small and the process is accentuated in the lower lung zones as opposed to the upper zone distribution of PEG. Bronchiolitis obliterans organizing pneumonia is an airway-airspace disorder and is not characterized by stellate interstitial scars. Lymphangioleiomyomatosis (LAM) is the other interstitial lung disorder associated with radiographically enlarged lungs. The characteristic microscopic features are those of random proliferation of a peculiar smooth muscle cells. These cells have a clear cytoplasm and resemble the smooth muscle seen in angiomyolipoma. In fact, they may be the same cells since they also stain with HMB 45 antibodies. Smooth muscle proliferation in LAM is not limited to the interstitium; it involves blood vessels, airways and any other area in which smooth muscle normally appears in the lung. S-100 and CD1a staining is helpful in the diagnosis of pulmonary eosinophilic granuloma although, unfortunately, in old scarred areas that staining is usually lost.