Interstitial pneumonia induced by sorafenib in a patient with hepatocellular carcinoma: An autopsy case report

Abstract

Sorafenib is a multikinase inhibitor currently approved in Japan for the treatment of unresectable hepatocellular carcinoma. Interstitial pneumonia induced by sorafenib may have a fatal outcome, and therefore, has recently been the focus of many studies. The current report presents an autopsy case of diffuse alveolar damage (DAD) that occurred in a 59-year-old male, who had been treated with sorafenib. The patient had been given sorafenib for six months and had exhibited no respiratory symptoms during this time. However, 19 days after sorafenib treatment was resumed, acute interstitial pneumonia developed. In previously reported cases, the first symptoms of pulmonary toxicity appeared following a limited treatment duration with sorafenib; this was in contrast to the patient in the current study, who developed the first symptoms after eight months. We therefore conclude that physicians must be aware of interstitial pneumonia as a potential pulmonary toxicity associated with sorafenib treatment when treatment with sorafenib is resumed, even after prolonged use. In addition, to best of our knowledge, this is the first case of a postmortem examination reported in patient with interstitial pneumonia induced by sorafenib treatment.

Keywords: diffuse alveolar damage; drug-induced interstitial pneumonia; hepatocellular carcinoma; molecular-targeted agent; sorafenib.

Figure 1

Clinical course of the patient after the administration of sorafenib. Serum AFP and PIVKA-II reduced after TACE. On day 19 of sorafenib readministration, the patient developed progressive dyspnea, and was admitted to hospital. The oxygen saturation was 81% despite oxygen supplementation. There was a clinical worsening, and the patient succumbed to the disease three days after admission. AFP, α-fetoprotein; PIVKA-II, protein induced by vitamin K absence or antagonist II; TACE, transcatheter arterial chemoembolization; CRP, C-reactive protein.

Figure 2

Chest X-ray on admission.

Figure 3

Gross features of the lungs at autopsy.

Figure 4

Microscopic findings in the lungs. Diffuse alveolar damage with hyaline membranes superimposed on a fibrotic lung background (hematoxylin and eosin stain). (A) Early exudative stage: Injury of type II pneumocytes with sloughing into alveolar lumens and hyaline membrane formation. (B) Proliferative stage: Organization of exudates composed of proliferating type II pneumocytes and fibroblasts with squamous metaplasia. (C) Late organizing fibrotic phase: Interstitial fibrosis with widening of alveolar septa and disappearance of the hyaline membranes.