Brain Pathology Case of the Month - February 2013


Metastatic hepatocellular carcinoma


Hepatocellular carcinoma (HCC) represents 84% of primary liver malignancies in the United States affecting over half a million persons worldwide. Major risk factors of HCC include hepatitis C virus, hepatitis B virus and heavy alcohol consumption. The incidence of HCC has continually increased since the mid 1980s, likely due to increased incidence of cirrhosis secondary to hepatitis C virus and to a lesser extent hepatitis B virus (1).

Late stage HCC typically metastasizes to regional lymph nodes, the lung and rarely to bone (2). The incidence of bone metastases in HCC is approximately 1.6-16% with vertebrae being most common, followed by the pelvis, ribs, and rarely the skull. One study of 673 cases of HCC reported 8 cases (1.2%) with skull involvement (2). Solitary skull base metastasis is extremely rare and concurrent metastases to the spine or other areas are almost always present (4,8). Studies have shown that the most frequent finding in metastatic HCC to the skull is a subcutaneous mass (57%), followed by neurological deficits including visual disturbances (51%), headache (15%) and seizure (3%) (4,7).

Metastatic HCC to the pituitary gland is rare with 3 reported cases where the initial presentation of metastatic HCC mimicked a nonfunctioning pituitary adenoma (3,5,6).

The diagnosis of HCC is made based on the histopathologic findings, including the characteristic trabecular vascular architectural pattern with plump cells that show abundant eosinophilic cytoplasm, round to oval nuclei with coarse chromatin and prominent nucleoli. In the current case, additional histologic findings suggestive of HCC included focal bile production and intracytoplasmic lipid droplets. Immunohistochemistry was performed to confirm the hepatocellular nature of the tumor cells and showed positive staining for Hepar, MOC31 and pankeratin. Immunostaining with a polyclonal anti-CEA antibody revealed a canalicular and luminal pattern of staining, characteristic of HCC.

Follow up testing showed serum alpha-fetoprotein levels elevated at 461,040.0 ng/ml (0.0 - 8.9 ng/ml). Serologies for hepatitis B and C viruses were negative. Additional imaging revealed multiple lesions within the liver and porta hepatic lymph nodes as well as numerous metastases to the spine and ribs.


  1. El-Serag HB (2004) Hepatocellular carcinoma: recent trends in the United States. Gastroenterology 127:S27-S34.
  2. Fukutomi M, Yokota M, Chuman H, Harada H, Zaitsu Y, Funakoshi A, Wakasugi H, Igushi H (2001) Increased incidence of bone metastases in hepatocellular carcinoma. Eur J Gastroenterol Hepatol 13:1083-1088.
  3. Hirsch D, Benbassat CA, Drozd T, Okon E, Blum I (2005) Pituitary and bilateral adrenal enlargement: an unusual presentation of hepatocellular carcinoma. J Endocrinol Invest 28:454-8.
  4. Hsieh CT, Sun JM, Tsai WC, Tsai TH, Chiang YH, Liu MY (2007) Skull metastasis from hepatocellular carcinoma. Acta Neurochir (Wien) 149:185-190.
  5. Karamouzis MV, Melachrinou M, Fratzoglou M, Labropoulou-Karatza C, Kalofonos HP (2003) Hepatocellular carcinoma metastasis in the pituitary gland: case report and review of the literature. J Neurooncol 63:173-177.
  6. Moreno-Perez O, Peiro FM, Lopez P, Boix E, Meoro A, Serna-Candel C, Aranda FI, Pico AM (2007) An isolated pituitary metastasis as presentation of a differentiated hepatocellular carcinoma mimicking a nonfunctioning macroadenoma. J Endocrinol Invest 30:428-33.
  7. Shim YS, Ahn JY, Cho JH, Lee KS (2008) Solitary skull metastasis as initial manifestation of hepatocellular carcinoma. World J Surg Oncol 6:66.
  8. Trivedi P, Gupta A, Pasricha S, Agrawal G, Shah M (2009) Isolated skull base metastasis as the first manifestation of hepatocellular carcinoma--a rare case report with review of literature. J Gastrointest Cancer 40:10-14.

Contributed by Thomas C. Wilson, MD, Patricia A. Kirby, MBBCh, MMed (Anat Path), FRCPath (Nu)

International Society of Neuropathology