Hepatoma in a child with methotrexate-induced hepatic fibrosis

During autopsy, an 11-year-old girl with acute lymphocytic leukemia was found to have hepatic fibrosis with a 2.5-cm nodule of hepatocarcinoma. For 5 1/2 of the six years of treatment, chemotherapy consisted of daily orally administered methotrexate with monthly doses of vincristine sulfate and prednisone. The cumulative dose of methotrexate was 2.5 g. To our knowledge, this report constitutes the first association of hepatoma with methotrexate-induced hepatic fibrosis. A careful follow-up of patients receiving methotrexate for malignant neoplasms is urged; caution is suggested in the prolonged use of methotrexate when treating benign disease.