Late BCNU lung: a light and ultrastructural study on the delayed effect of BCNU on the lung parenchyma

We describe eight patients who developed interstitial pulmonary fibrosis following BCNU (carmustine) therapy for cerebral tumours. The fibrosis presented 12-17 (mean 14) years after exposure to the drug. A distinctive pattern of pulmonary fibrosis with involvement of the apices and subpleural areas was seen in one patient dying of the disease. Light microscopy showed interstitial elastosis and intra-alveolar fibrosis which was often focal with an associated mild lymphoplasmacytic infiltrate, intra-alveolar oedema, macrophages, and some neutrophils. Ultrastructural studies showed electron lucency of type I pneumocytes, with breaks in the cytoplasmic membranes leaving a bare basement membrane. Degenerative change was also seen in endothelial cell cytoplasm along with lipofuscin deposition. While BCNU pulmonary fibrosis has been described up to 2 years after treatment, this complication so late after therapy, though rare, has important implications for the follow-up of patients receiving this drug.