Pulmonary histopathologic changes associated with melphalan therapy

A case of fatal pulmonary fibrosis and atypical epithelial proliferation (AEP) in a patient with multiple myeloma treated with melphalan is presented. Review of 10 other autopsied patients with myeloma treated with melphalan but no thoracic radiation, other cytotoxic agents, or highdose oxygen therapy revealed one other patient who died with extensive pulmonary fibrosis and AEP. Four other patients with AEP not associated with pneumonitis or fibrosis were also found, while no such changes were found in 11 autopsy controls or 11 patients with myeloma who did not receive cytotoxic agents. Melphalan should be added to the growing list of agents capable of causing severe fibrotic pulmonary reactions.