Ruptured hepatic metastases of cutaneous melanoma during treatment with vemurafenib: an autopsy case report.
BACKGROUND
The spontaneous rupture of hepatic metastases is rare compared to that of primary hepatic tumors. In addition, vemurafenib, a selective inhibitor of the mutant BRAF protein or gene product, has been reported to be extremely effective in patients with metastatic melanoma who harbor a BRAF V600E mutation.


METHODS
A 44-year-old female had previously undergone surgery for resection of a malignant melanoma in the lower right leg. Four years later, hepatic metastases became apparent, and transcatheter arterial embolization (TAE) was performed. Then she underwent treatment with vemurafenib. The size of the hepatic metastases markedly decreased. Two months later, they enlarged rapidly and ruptured, requiring emergency TAE. However, the patient developed hemorrhagic shock and died of renewed intra-abdominal bleeding on the 26th postoperative day.


CONCLUSIONS
This is a rare case of ruptured hepatic metastases of malignant melanoma during treatment with vemurafenib. Postmortem examination and immunohistochemical analysis indicated reactivation of the mitogen-activated protein kinase pathway in the metastatic tumor, suggesting secondary resistance to vemurafenib as the possible underlying mechanism.
Second Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Fukui, Japan.
Takuto
T
Nosaka
Second Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Fukui, Japan.
Katsushi
K
Hiramatsu
Second Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Fukui, Japan.
Tomoyuki
T
Nemoto
Second Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Fukui, Japan.
Yasushi
Y
Saito
Second Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Fukui, Japan.
Yoshihiko
Y
Ozaki
Second Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Fukui, Japan.
Kazuto
K
Takahashi
Second Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Fukui, Japan.
Tatsushi
T
Naito
Second Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Fukui, Japan.
Kazuya
K
Ofuji
Second Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Fukui, Japan.
Hidetaka
H
Matsuda
Second Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Fukui, Japan.
Masahiro
M
Ohtani
Second Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Fukui, Japan.
Hiroyuki
H
Suto
Department of Pathology, University of Fukui Hospital, Fukui, Japan.
Yoshiaki
Y
Imamura
Second Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Fukui, Japan.
Yasunari
Y
Nakamoto