Sigmoid colon metastasis from hepatocellular carcinoma.
ABSTRACT Hepatocellular carcinoma (HCC) is a major health problem worldwide, and it has a poor prognosis. Extrahepatic metastasis from HCC is not unusual, with direct invasion representing the main spreading mode. Sites that are frequently involved are the lung, bone, and lymph nodes. There are few reports of HCC invading the distant gastrointestinal tract, especially hematogenously. Herein we report a case of sigmoid colon metastasis from HCC. The patient was diagnosed with HCC and treated with transcatheter arterial chemoembolization (TACE). Eighteen months after TACE the patient presented with abdominal pain on the left lower quadrant, and a CT scan showed an enhanced mass on the sigmoid colon. Immunohistochemical staining revealed that a tumor cell was positive for polyclonal carcinoembryonic antigen and weakly positive for hepatocyte antigen, supporting the diagnosis of HCC metastasis. The patient underwent anterior resection for the metastatic HCC.
- [show abstract] [hide abstract]
ABSTRACT: Estimates from the year 2000 indicate that liver cancer remains the fifth most common malignancy in men and the eighth in women worldwide. The number of new cases is estimated to be 564,000 per year, including 398,000 in men and 166,000 in women. In high-risk countries, liver cancer can arise before the age of 20 years, whereas, in countries at low risk, liver cancer is rare before the age of 50 years. Rates of liver cancer in men are typically 2 to 4 times higher than in women. The incidence of primary liver cancer is increasing in several developed countries, including the United States, and the increase will likely continue for some decades. The trend is a result of a cohort effect related to infection with hepatitis B and C viruses, the incidence of which peaked in the 1950s to 1980s. In selected areas of some developing countries, the incidence of primary liver cancer has decreased, possibly as a result of the introduction of hepatitis B virus vaccine. The geographic variability in incidence of primary liver cancer is largely explained by the distribution and the natural history of the hepatitis B and C viruses. The attributable risk estimates for the combined effects of these infections account for well over 80% of liver cancer cases worldwide. Primary liver cancer is the first human cancer largely amenable to prevention using hepatitis B virus vaccines and screening of blood and blood products for hepatitis B and C viruses.Gastroenterology 12/2004; 127(5 Suppl 1):S5-S16. · 12.82 Impact Factor
Article: Hepatocellular carcinoma.[show abstract] [hide abstract]
ABSTRACT: Hepatocellular carcinoma (HCC) is the fifth most common cause of cancer, and its incidence is increasing worldwide because of the dissemination of hepatitis B and C virus infection. Patients with cirrhosis are at the highest risk and should be monitored every 6 months. Surveillance can lead to diagnosis at early stages, when the tumour might be curable by resection, liver transplantation, or percutaneous treatment. In the West and Japan, these treatments can be applied to 30% of patients, and result in 5-year survival rates higher than 50%. Resection is indicated among patients who have one tumour and well-preserved liver function. Liver transplantation benefits patients who have decompensated cirrhosis and one tumour smaller than 5 cm or three nodules smaller than 3 cm, but donor shortage greatly limits its applicability. This difficulty might be overcome by living donation. Most HCC patients are diagnosed at advanced stages and receive palliative treatments, which have been assessed in the setting of 63 randomised controlled trials during the past 25 years. Meta-analysis shows that only chemoembolisation improves survival in well-selected patients with unresectable HCC.The Lancet 01/2004; 362(9399):1907-17. · 39.06 Impact Factor
- Hepatology 04/2002; 35(3):519-24. · 12.00 Impact Factor
The Korean Journal of Hepatology 2010;16:397-400
Sigmoid colon metastasis from hepatocellular carcinoma
Dong-Jun Yoo1, Young-Hwa Chung1, Yoon-Seon Lee1, Sung Eun Kim1, Young-Joo Jin1,
Yu Mi Lee1, Mi-Jung Kim2
1Department of Internal Medicine and 2Department of Pathology, Asan Medical Center,
University of Ulsan College of Medicine, Seoul, Korea
Hepatocellular carcinoma (HCC) is a major health problem worldwide, and it has a poor prognosis. Extrahepatic metastasis from
HCC is not unusual, with direct invasion representing the main spreading mode. Sites that are frequently involved are the lung,
bone, and lymph nodes. There are few reports of HCC invading the distant gastrointestinal tract, especially hematogenously.
Herein we report a case of sigmoid colon metastasis from HCC. The patient was diagnosed with HCC and treated with
transcatheter arterial chemoembolization (TACE). Eighteen months after TACE the patient presented with abdominal pain on the
left lower quadrant, and a CT scan showed an enhanced mass on the sigmoid colon. Immunohistochemical staining revealed that
a tumor cell was positive for polyclonal carcinoembryonic antigen and weakly positive for hepatocyte antigen, supporting the
diagnosis of HCC metastasis. The patient underwent anterior resection for the metastatic HCC. (Korean J Hepatol 2010;
Keywords: Hepatocellular carcinoma; Metastasis; Sigmoid colon
Received February 12, 2010; Revised July 1, 2010; Accepted July 13, 2010
Abbreviations: HCC, hepatocellular carcinoma; GI, gastrointestinal; TACE, transarterial chemoembolization; CT, computed tomography; HBV, hepatitis
B virus; HBsAg, hepatitis B virus surface antigen; HBeAg, hepatitis B virus e antigen; AFP, alpha-fetoprotein; CEA, carcinoembryonic antigen
Corresponding author: Young-Hwa Chung
Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, 388-1, Poongnap-2dong, Songpa-gu,
Seoul 138-736, Korea
Tel. +82-2-3010-3184, Fax. +82-2-476-0824, E-mail; email@example.com
Copyrights Ⓒ 2010 by The Korean Association for the Study of the Liver
The Korean Journal of Hepatology∙pISSN: 1738-222X eISSN: 2093-8047
Hepatocellular carcinoma (HCC) is a serious health problem
and has a poor prognosis. HCC accounts for 5.6% of all human
cancers with more than 1 million deaths annually and the
incidence of HCC is increasing.1,2 Despite the implementation of
surveillance programs for early HCC, most tumors are diagnosed
at intermediate or advanced stages, and only 30% of patients
benefit from curative therapies such as resection, liver trans-
plantation, or percutaneous ablation.2,3
In the previous autopsy series, extrahepatic metastasis was
present in 30~70% of cases and the major organs involved were
lung, lymph nodes, bone, and the adrenal gland.4,5 Interestingly,
involvement of the gastrointestinal (GI) tract from HCC seldom
occurs, being found in only 4~6% of cases in the same series4,5
and 0.5~2% of cases in another series.6,7 Among the GI meta-
stasis from HCC, colon metastasis, especially the left-sided
colon, is very rare and mostly occurs through direct invasion.8,9
Here, we report on a HCC patient who was treated with trans-
arterial chemoembolization (TACE) and had a solitary metastatic
tumor from HCC on his sigmoid colon one and a half years after
A 47-year-old man was admitted with a hepatic mass
incidentally detected by ultrasound. A computed tomography
(CT) scan revealed a 1.7 cm-sized mass in the hepatic segment
VI with enhancement on the arterial phase and early washout on
the portal phase (Fig. 1A), and a tiny enhancing nodule on the
arterial phase without early washout on the portal phase in segment
IV (Fig. 1B). The patient was a hepatitis B virus (HBV) carrier.
Upon physical examination, superficial lymphadenectasis,
icteric sclera, liver palm, or spider telangiectasias were not
observed. The laboratory findings showed a slight elevation of
transaminase (aspartate aminotransferase: AST 78 IU/L, alanine
398 The Korean Journal of Hepatology Vol. 16. No. 4, December 2010
Figure 1. CT scans performed at the initial diagnosis of HCC. (A) The hepatic mass was a 1.7 cm-sized mass with arterial enhancement
(arrow) mass in hepatic segment VI, with a patent portal vein and no metastatic lesion evident on CT scans. (B) A tiny subcapsular
arterial enhancement (arrow) without early washout was noted in segment IV.
Figure 2. Endoscopy image and CT scan of metastatic HCC. (A) Endoscopy revealed a bulging contoured mass at 20 cm from the
anal verge without a mucosal defect or diverticulum. (B) The CT scan revealed a 4×3.5 cm eccentric mass (arrow) abutting the sigmoid
colon without lymph node enlargement.
aminotransferase: ALT 50 IU/L) and a mild decrease in platelet
count (113,000/mm3). All other values including white blood
cell, hemoglobin, protein, albumin, bilirubin, and prothrombin
time were within normal limits. HBV surface antigen (HBsAg)
and HBV e antigen (HBeAg) were positive but anti-hepatitis C
virus antibody was negative. The alpha-fetoprotein (AFP) level
was 365 ng/mL. A percutaneous needle biopsy was performed on
the mass in segment VI and the pathologic diagnosis of HCC,
Edmonson-Steiner grade 3, was made. The patient underwent
transcatheter arterial angiography and chemoembolization (TACE)
to treat the HCC and differentiate the tiny enhancing nodule from
another HCC. On angiography, the enhancing nodule was identi-
fied as an AP shunt. After TACE, there had been no evidence of
tumor recurrence on follow-up CT scans and AFP levels for one
and a half years. In one and a half years, the patient presented
with abdominal pain around the left lower quadrant. Physical
examination was unremarkable and all laboratory findings
including an AFP level were within normal limits except a mild
elevation of liver enzymes: AST 46 IU/L and ALT 68 IU/L. On
colonoscopy, a bulging contoured hard mass was noted in the
sigmoid colon but the overlying mucosa was intact (Fig. 2A).
The CT scan revealed a 4×3.5 cm sized, eccentric mass abutting the
sigmoid colon without any lymph node enlargement (Fig. 2B).
However, the scan did not show any evidence of recurrence in
the liver and the portal tract. The patient underwent anterior
resection and a well-defined subserosal mass, measuring
5.2×4×3.7 cm, was identified. The cut surface of the mass was
grayish white, solid, and granular with hemorrhage and necrosis
(Fig. 3A). The mass extended to the proper muscle layer, how-
ever, the overlying mucosa was intact. Histologic examination
Dong-Jun Yoo, et al. Sigmoid colonic metastasis from HCC 399
Figure 3. Histopathology of metastatic HCC. (A) Gross specimens
of sigmoid colon metastasis showing a well-defined subserosal
mass. (B) The tumor cells had eosinophilic granular cytoplasms
and large nuclei containing prominent nucleoli, resembling HCC
(hematoxylin-eosin stain; ×400), and (C) they were positive
for polyclonal carcinoembryonic antigen (pCEA) (×100).
demonstrated sheets of large polygonal tumor cells arranged
in a trabecular pattern. The tumor cells exhibited eosino-
philic, granular cytoplasm and large nuclei containing prominent
nucleoli, resembling HCC (Fig. 3B). The tumor cells were pos-
itive for polyclonal carcinoembryonic antigen (pCEA, 1:800, Dako,
Glostrup, Denmark) and weakly positive for hepatocyte antigen
(1:200, Dako, Denmark), supporting the diagnosis of HCC (Fig.
3C). There was no regional lymph node metastasis at the time
of surgery and the patient is free of recurrent disease to date for
over 4 months.
HCC with hematogeous metastasis to colon is very rare. This
case shows the typical findings of HCC metastasis to sigmoid
Extrahepatic metastasis of HCC is increasing with prolonged
survival and the most frequent sites of metastases are lung, bone,
and lymph nodes. On the other hand, GI involvement of HCC is
known to be not common. The major mode of metastasis to the
GI tract is direct invasion to the contiguous GI tract via adhesion
to the serosal side by a bulky tumor mass and the most frequently
involved site was the duodenum, followed by the stomach, colon,
and jejunum.6 Rarely, it is hypothesized that HCC may dissem-
inate hematogenously to distant GI tracts. Portal vein thrombosis
may be the key point of hematogenous spread to other sites.7,10 In
our case, it is notable that the HCC was initially a small sized sin-
gle mass without portal vein thrombosis and metastasized to the
left-sided colon one and a half years after TACE. Hematogenous
spread was suggested because the metastatic site was distant and
the lymph nodes were not involved.
Endoscopic findings of GI metastasis from HCC were varied,
such as a raised and centrally ulcerated lesion, mimicking gastric
carcinoma, polypoid tumor, or submucosal tumor.7,11 Therefore,
immunohistochemical findings are important to differentiate
HCC from adenocarcinoma in the diagnosis of GI metastasis.
Typically, in HCC, Cam 5.2 staining is positive whereas AE1/AE3
staining is negative.12 Polyclonal CEA is highly specific for the
lining of the biliary canaliculi.13 Similarly, AFP is another
reliable indicator for HCC and it has been reported to be positive
400 The Korean Journal of Hepatology Vol. 16. No. 4, December 2010
in 70~90% of cases.14 In this case, the colonoscopy showed a
bulging contoured tumor without any mucosal lesions, suspi-
cious of extrinsic compression. The histopathologic findings were
consistent with metastatic HCC, showing eosinophilic granular
cytoplasm and large nuclei containing prominent nucleoli with
immunopositivity for polyclonal CEA and hepatocyte antigen.
According to previous reports, the interval between the diag-
nosis of HCC and detection of GI tract involvement ranged from
3 months to 8 years.6,7,9 Mostly, GI metastasis is found in patients
with advanced staged HCC. The prognosis of GI involvement
from HCC is known to be poor with a median survival period of
7 months.15 However, it was suggested that treatment of extra-
hepatic metastases may improve survival in some selected HCC
patients who have good reserved function, intrahepatic tumor
stage (T0-T2), and negative portal vein invasion.16 Similarly, a
previous study reported that adrenalectomy for metastatic HCC
resulted in improved survival rate especially in patients with
well-controlled intrahepatic lesions at the time of adrenal meta-
stasis and good general condition.17 Although there is little data
regarding the efficacy of surgical treatment in patients with hae-
matogenous colon metastasis from HCC, our case was treated
with surgical management for the metastatic HCC because the
patient had good hepatic reserved function and no other meta-
static lesions. The patient has been free of recurrent disease to
date for over 4 months.
In conclusion, HCC with GI metastasis is uncommon and rarely
spreads hematogenously to distant GI tracts. To date, the
previously reported colonic metastases were located to the right
side of the colon. Herein, to the best of our knowledge, we report
the first case of solitary left-sided sigmoid colonic metastasis
from HCC treated with surgical resection.
1. Bosch FX, Ribes J, Díaz M, Cléries R. Primary liver cancer: worldwide
incidence and trends. Gastroenterology 2004;127(Supple 1):S5-S16.
2. Llovet JM, Burroughs A, Bruix J. Hepatocellular carcinoma. Lancet
3. Bruix J, Llovet JM. Prognostic prediction and treatment strategy in
hepatocellular carcinoma. Hepatology 2002;35:519-524.
4. Anthony PP. Primary carcinoma of the liver: a study of 282 cases in
Ugandan Africans. J Pathol 1973;110:37-48.
5. Nakashima T, Okuda K, Kojiro M, Jimi A, Yamaguchi R, Sakamoto K,
et al. Pathology of hepatocellular carcinoma in Japan. 232 consecutive
cases autopsied in ten years. Cancer 1983;51:863-877.
6. Lin CP, Cheng JS, Lai KH, Lo GH, Hsu PI, Chan HH, et al.
Gastrointestinal metastasis in hepatocellular carcinoma: radiological
and endoscopic studies of 11 cases. J Gastroenterol Hepatol 2000;15:
7. Chen LT, Chen CY, Jan CM, Wang WM, Lan TS, Hsieh MY, et al.
Gastrointestinal tract involvement in hepatocellular carcinoma: clinical,
radiological and endoscopic studies. Endoscopy 1990;22:118-123.
8. Nozaki Y, Kobayashi N, Shimamura T, Akiyama T, Inamori M, Iida H,
et al. Colonic metastasis from hepatocellular carcinoma: manifested by
gastrointestinal bleeding. Dig Dis Sci 2008;53:3265-3266.
9. Park MS, Kim KW, Yu JS, Kim MJ, Yoon SW, Chung KW, et al.
Radiologic findings of gastrointestinal tract involvement in hepatocellular
carcinoma. J Comput Assist Tomogr 2002;26:95-101.
10. Yang PM, Sheu JC, Yang TH, Chen DS, Yu JY, Lee CS, et al. Metastasis
of hepatocellular carcinoma to the proximal jejunum manifested by
occult gastrointestinal bleeding. Am J Gastroenterol 1987;82:165-167.
11. Sandler RS, Sartor RB, Bozymski EM. Endoscopic appearance of
cancer metastatic to the stomach. J Clin Gastroenterol 1981;3(Suppl
12. Hurlimann J, Gardiol D. Immunohistochemistry in the differential
diagnosis of liver carcinomas. Am J Surg Pathol 1991;15:280-288.
13. Koelma IA, Nap M, Huitema S, Krom RA, Houthoff HJ. Hepatocellular
carcinoma, adenoma, and focal nodular hyperplasia. Comparative
histopathologic study with immunohistochemical parameters. Arch
Pathol Lab Med 1986;110:1035-1040.
14. Kojiro M, Kawano Y, Isomura T, Nakashima T. Distribution of albumin-
and/or alpha-fetoprotein-positive cells in hepatocellular carcinoma. Lab
15. Natsuizaka M, Omura T, Akaike T, Kuwata Y, Yamazaki K, Sato T, et al.
Clinical features of hepatocellular carcinoma with extrahepatic metastases.
J Gastroenterol Hepatol 2005;20:1781-1787.
16. Uka K, Aikata H, Takaki S, Shirakawa H, Jeong SC, Yamashina K, et al.
Clinical features and prognosis of patients with extrahepatic metastases
from hepatocellular carcinoma. World J Gastroenterol 2007;13:414-420.
17. Park JS, Yoon DS, Kim KS, Choi JS, Lee WJ, Chi HS, et al. What is the
best treatment modality for adrenal metastasis from hepatocellular
carcinoma? J Surg Oncol 2007;96:32-36.