Tubular intranuclear inclusions in a patient with methotrexate-associated pulmonary fibrosis
A forty-six year old male, who had received methotrexate therapy for the past year for psoriasis of twenty years' duration, presented with a cough which had persisted for two to three months. There was a two year history of dyspnea upon exertion as well as intermittent fever, chills and sweats. The methotrexate treatment did not improve the skin condition and, because there was evidence of hepatic toxicity, the drug was discontinued. Radiological examination of the chest revealed diffuse bilateral interstitial fibrosis with extensive changes; a subseguent lung biopsy was obtained. Light microscopic evaluation demonstrated marked interstitial fibrosis, chronic inflammation, thickening of the alveolar septa, proliferation of alveolar macrophages, occasional fibrin deposits and multinucleated giant cells.Electron microscopic studies revealed massive fibrosis with a mixed population of infiltrating inflammatory cells. Some alveolar spaces were lined by metaplastic cuboidal epithelial cells, and in numerous residual type II pneumocytes, aggregates of branching tubules lined by trilaminar membranes were identified within the nucleus.