Brain Metastases from Hepatocellular Carcinoma in US Patients

Abstract

Hepatocellular carcinoma (HCC) is a disease on the rise in the United States, due to the epidemic of hepatitis C-induced liver disease. Better chemotherapy options, aggressive surgery, and liver transplantation have led to improved patient survival and an increase in late-appearing, distant metastases from HCC. Brain metastases, although formerly thought of as rare manifestations of HCC, may be more likely to come to clinical and pathological attention than extrahepatic metastases in other sites since they often produce clinical symptoms that necessitate neurosurgical intervention and metastasis removal. In addition, brain metastases from HCC are frequently associated with mass-producing hemorrhage, further requiring evacuation. Hence, pathologists are relatively more likely to encounter brain metastases from HCC as surgical specimens than metastases from HCC to some other common sites of spread, such as bone, lymph nodes, or adrenal. Brain metastases from HCC are being increasingly documented in areas of the world with high endemic rates such as Asia, but thus far have only very rarely been reported in patients native to the United States. We describe our institution's experience with three Caucasian US males, two with hepatitis C as risk factors, who developed metastatic HCC to the brain. We expect clinicians and pathologists will encounter more patients with HCC and extrahepatic metastases, particularly those to brain, in the near future.

Little Response of Cerebral Metastasis from Hepatocellular Carcinoma to Any Treatments

“…One of the noticeable features is that brain metastasis from HCC had a tendency of bleeding as in the previous reports 1,2,4,9,10,13,14,16,18,21) , though no patients were classified as Child-Pugh grade C, and had a delayed prothrombin time in this study. Thus, 70.0% of the patients had stroke-like presentation due to tumor bleeding, and over 90% of the lesions had the hemorrhagic components in or near the mass on MR images and/or CT scan.…”

“…Though brain metastasis from HCC is a rare occurrence even in the endemic areas, it may become a major health problem in the near future due to the increasing incidence of HCC, especially in the western and European countries, and the prolonged survival due to the recent development of advanced therapeutic techniques 5,7,10,11,[20][21][22] . And, the incidence of brain metastases from HCC seems to be more higher than the previous estimations of 0.26% of the study of Chang et al 1) considering the report of 2.2% in Japanese autopsy series 14) .…”

“…Such a tendency of bleeding may be due to the pathological feature of brain metastasis of HCC of a trabecular or sinusoidal pattern and interspersed vascular channels 21) . Considering that all four patients with incomplete surgical resection experienced recurrent ICH during or immediately after adjuvant WBRT, complete surgical resection should be obtained.…”

“…Hepatocellular carcinoma (HCC) is a notorious cancer due to its aggressive clinical course and short survival time in Asian populations, and over the past two decades it has been a growing public health problem worldwide because its incidence has substantially increased 5,7,21,22) . Therefore, HCC currently ranks as the fifth most common type of cancer in men worldwide, though it was formerly considered to be a rare disease in Western and European countries 6,7,22) .…”

Bevacizumab Safety in Patients with Central Nervous System Metastases

“…However, CNS metastases from HCC have an inherent tendency to bleed because patients with HCC are likely to have coagulopathy due to impaired liver function, resulting in cerebral hemorrhage incidences of up to 87.5%, independent of the type of therapy received (10)(11)(12)(13).…”