CASE REPORT

Metastatic Hepatocellular Carcinoma With Associated

Spinal Cord Compression
Jan Vargas, BS, Mathew Gowans, BA, William A. Vandergrift, MD, Jason Hope, MD
and Pierre Giglio, MD

Abstract: Metastatic hepatocellular carcinoma is a rare occurrence in
the United States. The prognosis is poor, with a survival time of months
from the time of diagnosis. This article reports a case of myelopathy
that developed from metastases in a patient with no significant medical
history. The patient was treated with decompressive laminectomy
followed by adjuvant radiotherapy. A review of the literature demon-
strated that most cases from hepatocellular carcinoma metastasizing to
the spinal cord involve either the thoracic or lumbar levels and arise
from the right liver lobe or both lobes. Major risk factors included
positive hepatitis B virus serologies. This article also discusses current
trends in management of epidural spinal cord compression. Although
treatment with chemotherapy has not shown any benefit, surgical
management has been shown to decrease morbidity and mortality in
some patients.
Key Indexing Terms: Epidural spinal cord compression; Metastatic
hepatocellular carcinoma; Spine. [Am J Med Sci 2011;341(2):148152.]
S pinal cord compression from metastatic hepatocellular car-
cinoma (HCC) is a rare occurrence in the United States,
unlike other regions of the world where a higher prevalence of
HCC is seen. The exact cause for this discrepancy is unknown
but may include genetic and environmental factors. We report
a patient with HCC and vertebral metastasis who initially had
no complaints of the typical bone pain or neurologic compli-
cations seen with metastatic HCC until an acute injury involv-
ing his thoracic spine. After imaging confirmed the metastatic
spread, a rapid decline in the patients health ensued, which
corresponds to the poor prognosis of weeks to months of life
after initial diagnosis of HCC.
posterior elements of the fourth thoracic vertebra (T4). The CT
scan of the abdomen showed liver changes consistent with
cirrhosis, bilateral adrenal nodules and an enlarged right retro-
peritoneal lymph node. Multiple lytic lesions in the vertebra
throughout the spine were noted. CT scan of the pelvis showed
multiple lytic lesions in the pelvic bones, a pathologic fracture
within the fifth lumbar vertebra (L5) and a soft tissue mass
within the right iliac wing.
The patient was provided referral to the Medical University
of South Carolina/Hollings Cancer Center Brain & Spine Tumor
Program. On evaluation, the patient had complaints of leg weak-
ness and pain in the lower back. Magnetic resonance imaging of
the cervical, thoracic and lumbar spine showed multiple areas of
metastatic deposits involving the entire spine. However, most
prominent was a lesion at the T4 level (Figures 1 and 2) with
significant compression of the spinal cord.
On physical examination, the patient appeared cachectic
with slight scleral icterus. No lymph nodes were palpable in the
neck, supraclavicular, axillary or groin regions. Lung exami-
nation showed clear, bilateral breath sounds, and a small 3- to

CASE PRESENTATION
A 50-year-old man with no pertinent medical history
except for excessive alcohol abuse presented with complaints
of ongoing chest and back pain that had been present for
approximately 2 months and a 30-lb weight loss during this
same period. The symptoms began after a lifting episode with
his dog, after which he described a crunching feeling in his
mid-back. The patient subsequently underwent 4 sessions with
a chiropractor. After the last session, his pain worsened,
prompting him to visit an emergency department near his
residence. The emergency department performed a computed
tomography (CT) scan of the chest, abdomen and pelvis. The
CT of the chest showed diffuse osseous lytic lesions and
expansile lesions in the right second and third ribs and in the

From the College of Medicine (JV, MG), Medical University of South

Carolina,; Departments of Neurosciences (WAV, PG) and Pathology and
Laboratory Medicine (JH), Medical University of South Carolina, Charles-
ton, South Carolina.
Submitted July 19, 2010; accepted in revised form August 13, 2010.
Correspondence: Pierre Giglio, MD, Department of Neurosciences,
Medical University of South Carolina, 96 Jonathan Lucas Street, Suite 307 FIGURE 1. T2-weighted magnetic resonance imaging showing
CSB, Charleston, SC 29425 (E-mail: giglio@musc.edu). the spinal metastasis and compression of the spinal cord (arrow).

148 The American Journal of the Medical Sciences Volume 341, Number 2, February 2011
 Hepatocellular Carcinoma With Spinal Cord Compression

TABLE 1. Laboratory data of the patient

Normal Range
Hematology
White blood cell count (K/mm3) 4.74 4.810.8
Red blood cell count (M/mm3) 4.53 4.706.10
Hemoglobin (g/dL) 14.9 14.018.0
Hematocrit (%) 44.50 42.052.0
Platelet counts (K/mm3) 147 140.0440.0
Tumor markers
Alphafetoprotein 323.9 (ng/mL) 8.0
Carbohydrate antigen 199 198 037.0
Blood chemistry
Aspartate aminotransferase 146.0 12.038.0
(IU/L)
Alanine aminotransferase 84.0 10.045.0
(IU/L)
Total bilirubin (mg/dL) 1.9 0.21.3
Direct bilirubin (mg/dL) 0.7 0.11.3
Total proteins (g/dL) 7.2 6.08.0
albumin (g/dL) 3.3 3.54.8
FIGURE 2. T2-weighted T Spine magnetic resonance imaging Blood urea nitrogen (mg/dL) 13.0 8.020.0
showing the spinal lesion (arrow) compressing the spinal cord. Cr (mg/dL) 0.9 0.71.3
Patient had bilateral lower extremity weakness. Na (mmol/L) 137.0 135.0145.0
K (mmol/L) 3.80 3.505.0
Cl (mmol/L) 99.0 98.0107.0
Glucose (mg/dL) 134 70.0100.0
4-cm mass was palpated near the anterior end of the third and
fourth ribs. Cardiovascular and abdominal examinations were
unremarkable with no hepatosplenomegaly noted; however, on
spinal palpation, there were 2 areas of pain in the mid-thoracic DISCUSSION
and upper lumbar levels. His extremities showed no signs of Liver cancer is the fifth most common cancer in the
edema, clubbing or cyanosis. world and has the third highest mortality.1 In the United States,
The neurologic examination revealed that deep tendon 90% of primary liver cancers are HCCs. The incidence and
reflexes in his lower extremities were present and symmetric; mortality of HCC has been steadily increasing over the de-
however, bilateral proximal weakness was noted, greater on the cades. Altekruse et al2 found that age-adjusted incidence rates
right. No complaints of bladder or bowel dysfunction were noted. tripled from 1975 to 2005, increasing from 1.6 per 100,000 to
On further examination, weakness on dorsiflexion of the right 4.9 per 100,000, and reported an increase in liver cancer
lower extremity was noted, but there was no evidence of sensory
loss anywhere except the third division the right trigeminal nerve.
Pupils were equal and reactive to light and accommodation.
Cranial nerves II to XII were otherwise intact. Laboratory values
for the patients blood chemistries are given in Table 1.
Because of the patients neurologic deficit and the sig-
nificant findings on imaging, the patient underwent an emergent
T4 laminectomy to prevent continued cord compression. The
pathology report from a specimen sent at the time of surgery
was consistent with HCC (Figure 3). This diagnosis was made
using immunostains including polyclonal carcinoma embryonic
antigen, common acute lymphocytic leukemia antigen, cyto-
keratin antibody 5.2 (all positive) and alpha fetoprotein (AFP,
negative). The biopsy demonstrated malignant cells forming
solid and pseudoglandular patterns with bile pigment evident
(Figs. 3 and 4). Adjuvant treatment with radiation was recom-
mended, and the patient underwent palliative radiation to the
thoracic and lumbosacral spine with 30 gray in 10 fractions
over a period of 2 weeks. The patient reported an improvement
of his leg weakness and had adequate pain control. He was FIGURE 3. Pathology; a biopsy of the epidural lesion showing
followed up by a local oncologist but unfortunately died 212 bile production that is consistent with HCC metastasis. (Hemo-
months after his initial diagnosis from the progression of his toxylin-eosin; original magnification 40). Arrow demonstrates
systemic disease. bile pigment formation.

2011 Lippincott Williams & Wilkins 149

Vargas et al
FIGURE 4. Pathology; pseudoglandular arrangement of malig-
nant cells demonstrating a prominent single nucleolus, an ir-
regular nuclear membrane, and finely granular eosinophilic cy-
toplasm, consistent with metastatic hepatocelluar carcinoma.
mortality from 1992 to 2005, rising from 3.3 deaths per
100,000 to 4.0 deaths per 100,000.
Risk factors for the development of HCC include
chronic viral hepatitis, cirrhosis, exposure to aflatoxin and
alcohol, diabetes, nonalcoholic fatty liver disease, primary
biliary cirrhosis and autoimmune hepatitis. Of these, cirrhosis
is believed to be the greatest risk factor, followed by chronic
viral hepatitis.3,4 The main causative agent for HCC in Asian
countries is chronic infection with the hepatitis B virus (HBV),
which accounts for 70% to 80% of cases.5 Infection with the
hepatitis C virus (HCV) accounts for 80% of cases. More than
70% of all newly diagnosed liver cancers occur in Asia, a
region accounting for 75% of all those who are chronically
infected with the HBV in the world. China alone accounts for
55% of all cases of HCC worldwide. In Australia and the
United States, traditionally low-incidence areas, there has been
a 2- to 3-fold increase over the last 25 years in the incidence of
HCC, most likely because of the immigration of people from
areas of high prevalence rates of chronic HBV infection, among
other factors. Two observations are evident in all Asian coun-
tries. First is the male to female ratio of 3:1 of HCC. Second is
the age of onset in the Asian population, which starts to
increase at the age of 35 to 40 years and usually peaks in the
sixth or seventh decade of life.5
There is mounting evidence of other significant risk
factors that include aflatoxin ingestion, alcohol intake and
diabetes. Aflatoxins, one of the most potent hepatocarcinogens
in animals, are found in moldy grains and are prominent in
areas of Africa and Southeast Asia. There is limited informa-
tion about the relationship to HCC and aflatoxins in the United
States. In a pilot study, 3 of 19 cases of HCC were positive for
aflatoxin B1 DNA adducts, whereas 5 of 5 patients with HCC
tested positive for aflatoxin B1 albumin adducts.6 Diabetes is
also investigated as an important contributor to HCC, although
the mechanisms remain unclear. One possible mechanism is
through damage caused by oxidative stress that leads to hepatic
inflammation, fibrosis and eventual cirrhosis. Several studies
have provided evidence that viral hepatitis, alcohol and diabe-
tes interact synergistically in affecting the development of
HCC.6 This patients HBV and HCV status were unknown; he
had no history of diabetes or aflatoxin exposure. Therefore,
150
heavy alcohol use and subsequent cirrhosis were the main
known risk factors for HCC in the current case.
Metastasis to the musculoskeletal system occurs in 5%
to 13% of patients with HCC and most commonly involves the
ribs, spine and femur, with the most common presenting
symptom being bone pain.711 Although cases of vertebral
metastases have been reported in the literature, nerve root and
spinal cord compression because of metastatic HCC are rare
complications, occurring in 1% of cases.12 In a case series by
Liaw et al,13 6 of 395 patients with HCC presented with spinal
cord compression. In this case, the patient did not have the
typical presentation of bone pain usually associated with met-
astatic HCC and only began experiencing sciatic-like pain in
his right leg and bilateral lower extremity weakness about 1
month after his initial injury. At no time during his treatment
did he experience any bowel or bladder dysfunction.
A review of the literature revealed 4 case series11,14 16
and 6 case reports12,1721 of metastatic HCC that caused spinal
cord compression, for a total of 26 cases. Eight of 13 cases had
evidence of previous HBV infection, whereas 3 of 9 had
positive HCV serology. In 4 cases, both HCV and HBV titers
were negative, and in 1 case, both were positive. In 11 cases,
data on hepatitis serologies were not available. Of the 26 cases,
3 involved the cervical vertebrae, 15 involved the thoracic, 11
involved the cord at the lumbar level and 1 case described
compression of the conus medullaris and the cauda equina.
Serum AFP levels were significantly increased in 13 of 18
cases reviewed. Eight cases did not have AFP levels available.
In 12 of 14 cases, the primary carcinoma was located in either
the right liver lobe or involved both hepatic lobes. These
findings are summarized in Table 2.11,12,14 21
In a case series by Liaw et al,13 19 patients presented
with bone metastases of which 10 had an HCC primary in the
right lobe of the liver and 9 had a primary tumor in both lobes.
Okazaki et al described 14 patients with bone metastases and
noted that in all but in 1 of the cases, the primary tumor was
located in the right lobe of the liver. When examined with
hepatic angiography, the authors noted that in all cases, the
primary originated from the right anterior superior segment,
and the authors theorized that tumor invasion of these veins
allows for systemic dissemination because this segment is
located between the right and middle hepatic veins.22 In our
review of the literature, we also found a predominance of
primary liver cancers arising from either the right liver lobe or
from both lobes.
The prognosis in this case was typical for HCC, with the
mean survival rate of weeks to months and even lower if
metastasis to bone is present.18 Negative staining of the meta-
static lesions for AFP suggests that the tumor lost the ability to
produce AFP on metastasis, thus implying a more de-differen-
tiated population of tumor cells. This would correlate with a
poor prognosis.
Traditionally, the management of epidural spinal cord
compression has been with corticosteroids and high-dose radi-
ation. The role of chemotherapy is still being established. In a
study by Kim et al, patients with HCC presenting with bone
metastases were stratified into an untreated control group
that received palliative radiotherapy and a treatment group
that received intra-arterial chemotherapy, systemic chemo-
therapy or a combination of intra-arterial and systemic
chemotherapy. Kim et al23 found no statistical difference
between the medial survival times of the 2 groups and noted
that the only independent prognostic factor for these patients
was the presence of ascites.
Volume 341, Number 2, February 2011
 TABLE 2. Summary of literature review
Age Primary Survival
Study Location of SCC AFP level (normal range) HBV/HCV Treatment (yr) Site of metastasis tumor time
Doval et al9 T2,3 500 IU/mL (10 IU/mL) HbsAg/ PEBR, OC (capecitabine and 55 T23, L1,5, S1,3 R lobe 5 mo
thalidomide)
T6 3540 - 7920 IU/mL (10 IU/mL) HbsAg/ Palliative OC (gemcitabine and 52 R seventh rib, L third rib, R lobe 11 mo
cisplatin), PEBR, T5,6 LPF T3, T5
T4,5 250 IU/mL (10 IU/mL) / OC (gemcitabine and cisplatin), 70 T4,5 vertebra L lobe 4 mo
T14 LPF, EBR
L4 121 IU/mL (10 IU/mL) / PEBR 62 C5, C6, T912, L4 R lobe 3 mo

2011 Lippincott Williams & Wilkins

Tamaki Medullary cone to 220150 / Symptomatic 67 R parietal lobe of brain R lobe 12 d
et al19 cauda equina
Garcia and T9 1.39 ng/mL ( 44 ng/mL) / High dose corticosteroids and 49 T9 Both 26 d
Castillo18 radiation
Yang et al15 T12/L1 NA /NA PRT 37 T12, L1, L3, skull, pelvis Both 6 wk
T45 13,900 mg/L (0.044 mg/L) /NA L, palliative OC 47 T4, T5 Both 10 wk
T12 78,400 mg/L (0.044 mg/L) /NA PRT 31 T12, right pubic bone L lateral lobe 2 mo
T11L2 510 mg/L (0.044 mg/L) /NA PRT 64 T11L2 Both
C7 307 mg/L (0.044 mg/L) /NA PRT 55 C7 R lobe 1 mo
Dombrowski T710 10.3 g/L (WNL) NA/ RT 58 T710, bilateral adrenals Both 3 wk
et al17
Kantharia T10 8550 IU/mL (10) HbcAg/ Dexamethasone and RT 45 T10 Both 10 d
et al12
Lee16 C7 NA NA 50 C7 NA 2 mo
T7 NA NA 44 T7 NA 7 mo
T8,9 NA NA 38 T8,9 NA 7 mo
L1,2 NA NA 60 L1, L2 NA 9 mo
L2,3 NA NA 50 L2, L3 NA 4 mo
L4 NA NA 46 L4 NA 7 mo
L5 NA NA 31 L5 NA 4 mo
Chang and L4 NA L 9 L4 NA
Chen14 L4 NA 41 L4 NA
T1,2 NA L 60 T1,2 NA
C6T1 NA L 47 C6T1 NA
Pinazo Seron T11L2 346 mcg/L (10) / Dexamethasone and RT 55 T11L2 R lobe 3 mo
et al20
Melichar L4,5 WNL NA L, RT, regional OC 70 L4, L5, rib 11 mo
et al21 (doxorubicin, cisplatin, 5-FU)
5-FU, 5-fluorouracil; L, laminectomy; LPF, laminectomy with posterior fixation; NA, not available; OC, oral chemotherapy; PEBR, palliative external beam radiation; PRT, palliative radiotherapy;
WNL, within normal limits.

151
Hepatocellular Carcinoma With Spinal Cord Compression
Vargas et al
In addition, the role of surgery in the management of
epidural spinal cord compression is being reevaluated. Several
studies have shown that laminectomy and radiotherapy do not
affect outcome, when compared with radiotherapy alone. Since
then, radiotherapy has become the standard of care for patients
with metastatic epidural spinal cord compression. However, in
a randomized nonblinded trial, Patchell et al found that patients
treated with radiotherapy plus direct decompressive surgery
had statistically significant improvements in ambulatory rate,
maintenance of continence, muscle strength and survival time.
The authors reported no significant increase in morbidity or
mortality because of surgery.24 Furthermore, vertebral body
resection and stabilization with instrumentation have been
shown to be a good option in cases where there is spinal
instability and the tumor involves the vertebral body.25 Our
patient underwent a T4 laminectomy and resection of the
epidural lesion to relieve the symptoms of spinal cord com-
pression and had good symptomatic relief and preservation of
neurologic function.
CONCLUSIONS
We present a patient with an unusual complication of
HCC. Epidural spinal cord compression because of HCC is a
rare event in the United States, most likely due to the lower
incidence of HCC. When HCC does metastasize to bone, it
more commonly involves the ribs and the vertebrae. Our
review of 26 case reports supports this trend, and many of
the risk factors similar to those defined for development of
HCC were present in a majority of cases, namely infection
with HBV. AFP remains a good tumor marker for tracking
HCC recurrence.
Currently, the prognosis of metastatic HCC is poor. One
study cited a median survival period of 7 months.6 Better
screening techniques for at-risk patients with cirrhosis, ascites,
diabetes and liver function abnormalities may allow for earlier
detection and institution of medial care that could prolong the
life of the patients in the future. In addition, once discovered,
epidural spinal cord compression is associated with significant
morbidity and mortality. Given evidence from recent studies,
surgical therapies such as direct decompression of the tumor
followed by a course of radiotherapy or vertebral body resec-
tion with stabilization should be considered in patients in whom
surgery could be seen as a successful treatment.
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