Dacarbazine (DTIC)-induced human liver damage light and electron-microscopic findings

The first electron-microscopic description of DTIC-induced human liver injury is presented. A 61-year-old man developed signs of hepatic failure during the second treatment cycle with DTIC for malignant melanoma. Light-microscopic examination revealed extensive centrilobular liver necrosis. Terminal hepatic venules did not show any signs of vasculitis or thrombosis and there was a lack of inflammatory infiltration. At the ultrastructural level intracytoplasmic, membrane-bound, organelle-free vacuoles were found in the hepatocytes. Liver cells showed bleb formation. Bile canaliculi were dilated and their microvilli flattened. In the pericanalicular exoplasm electron-dense fibrillary material, thought to be of microfilamentous origin, accumulated. The patient received 250 mg methylprednisolone i.v. at the very onset of symptoms and was discharged 12 days after the peak rise of transaminases with normal liver parameters.