□ CASE REPORT □

Diffuse Liver Infiltration by Melanoma of Unknown

Primary Origin: One Case Report and Literature Review

Guo-Dong Shan, Guo-Qiang Xu, Li-Hua Chen, Zhao-Ming Wang, En-Yun Jin, Feng-Ling Hu
and You-Ming Li

Abstract
Diffuse liver infiltration by melanoma of unknown primary origin is rare. We encountered a unique case of
diffuse liver infiltration by melanoma of unknown primary origin in our hospital. A 62-year-old woman was
referred to our hospital for anorexia of 6 months duration and abdominal distension for 1 month. Ultra-
sonography (US), computerized tomography (CT) and magnetic resonance imaging (MRI) revealed an obvi-
ous enlarged liver without detectable nodules. She was diagnosed as liver metastasis by melanoma of un-
known primary origin via percutaneous liver biopsy. The report demonstrates the difficulty of making a non-
invasive diagnosis of diffuse hepatic infiltration on metastatic melanoma.

Key words: liver metastasis, melanoma, unknown primary origin

(Inter Med 48: 2093-2096, 2009)

(DOI: 10.2169/internalmedicine.48.2542)

Introduction
Liver metastases are diagnosed in 10%-20% of patients
with melanoma, and are associated with a bad prognosis and
short survival time rates (1). Since masses in the liver have
a previous history of melanoma, most liver metastases from
melanoma are easy to diagnose.
We present here a case of melanoma of unknown primary
origin which was diagnosed by percutaneous liver biopsy. In
this case, US, CT and MRI showed a hepatomegaly without
detectable nodules. To our knowledge, only two cases of
diffuse liver infiltration by skin melanoma have been previ-
ously reported (2, 3). In order to facilitate a better under-
standing of melanoma, we report this case and review the
literature.
Case Report
A 62-year-old woman was referred to our hospital for
anorexia of 6 months duration and abdominal distension for
1 month. Abdominal ultrasound examination in a local hos-
pital showed hepatomegaly and ascites. She had no fever or
night sweats, and no contact with sick persons or animals.
Her past medical history revealed neck pain for over 1 year,
which was treated occasionally with Chinese traditional
medicine. She had no history of liver disease, alcohol abuse
or pulmonary tuberculosis. Her family history was not sig-
nificant. Physical examination showed that her vital signs
were normal, and no pigmentation nor superficial nodular
lesion was observed in her body. Her skin and sclera were
slightly yellow colored. The liver was palpable 10 cm below
the costal margin and the spleen was not palpable. Viral se-
rological and autoimmune markers were all negative. Serum
tumor markers of alpha-fetoprotein (AFP), carcinoembryonic
antigen (CEA) and cancer antigen 199 (CA199) were all
normal except for elevated cancer antigen 125 (CA125)
(49.87 U/mL, normal range <35 U/mL). PPD test was nega-
tive. The ascites was clear light yellow, and no malignant
cells were detected. The serum-ascites albumin gradient
(SAAG) was 11.9 g/L. Ziehl-Neelsen stain of the ascites
was negative for TB. The remaining biochemical parameters
were normal. An abdominal CT and MRI revealed hepa-
tomegaly without focal lesions, a small amount of ascites
and a slightly depressed inferior vena cava due to the en-
larged liver (Figs.1 and 2). CT scan showed no tumors in
the lung or head. No tumor was found by gastroscopy,
colonoscopy, or video capsule endoscopy. No tumor was

Department of Gastroenterology, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
Received for publication June 2, 2009; Accepted for publication August 17, 2009
Correspondence to Dr. Guo-Qiang Xu, xgqhangzhou@sohu.com

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 Inter Med 48: 2093-2096, 2009 DOI: 10.2169/internalmedicine.48.2542

Fi
gur
e1 . Contr
ast-
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found by urogenital, otolaryngologic, and ophthamologic ex-

aminations. Because of uncertainty of her diagnosis, the pa-
tient was treated symptomatically with fluid restriction,
Transmetil and Diammonium Glycyrrhizinate (JiangsuChia-
Tai Tianqing Pharmaceutical Co., Ltd., China).
A percutaneous liver biopsy was performed which dem-
onstrated hepatic intrasinusoidal infiltration by malignant
melanoma cells (Fig. 3). Immunohistochemically, the tumor
cells were immunostained positive for HMB-45 and MelanA
proteins.
The patient’s clinical course continued to worsen after ad-
mission and he became markedly jaundiced and showed en-
cephalopathy on the 23rd hospital day; the patient died of
hepatic failure on the 31st hospital day. Her biochemical
course is summarized in Table 1. After a definitive diagno-
sis, she received a herbal remedy and refused to receive any
Western medication.
Discussion
Malignant melanoma is a cancer of melanocytes, usually
in skin. It can be highly aggressive, with as many as 20% of
patients developing metastases (4). Liver metastasis, in par-
ticular, has been shown to portend a grave prognosis, with a
median survival time of approximately 4 months (5). Mela-
noma occasionally occurs as apparent metastasis to lymph
nodes or viscera without a detectable or known primary le-
sion. Such melanomas of unknown primary site (MUP) are
estimated to comprise between 3.7% and 6% of all incident
melanomas (6-14). Diagnostic criteria for MUP initially
were proposed in 1963 by Dasgupta et al (6). Contemporary
criteria for the diagnosis include the following: 1) metastatic
melanoma confirmed clinically, histologically, and immuno-
histochemically; 2) the absence of a previous cutaneous tu-
mor, pigmented or not, destroyed or excised without his-

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 Inter Med 48: 2093-2096, 2009 DOI: 10.2169/internalmedicine.48.2542

Fi
gure3A. Pa t
holog
icalres
ult
:t he speci
men
wascove
red wit
h ala r
genumbero fme l
anoma
ce
ll
s（He ma t
oxyli
na ndEosi
ns t
aini
ng,orig
ina
l Fig
ure3C. Immuno
his
tochemi
cals
tai
ningo
fthel
ive
rbi
-
magni
fi
cati
on×400） opsys
pec
ime
nwi t
hHMB- 4
5 .

and B-ultrasonography, CT and MRI scan did not show a

Figur
e3 B. I
mmunohi
sto
chemi
cals t
aini
ng o
f opsy presented no sign of lymphoma. All of these findings
theli
verbi
ops
yspe
cime
nwi t
hMe l
anA.
tologic examination; and 3) exclusion of unusual primary
sites, including urogenital, otolaryngologic, or oph-
thamologic sites. A retrospective analysis of 40 patients di-
agnosed with melanoma as MUP revealed that 65% of the
patients presented with lymph node metastasis only, 28%
presented with visceral lesions, and 8% presented with sub-
cutaneous nodules (15). In the present patient, only liver
metastasis was found.
In the present case, imaging studies revealed hepa-
tomegaly and slight ascites accumulation. Liver function test
was slightly abnormal. Serum tumor markers of AFP, CEA,
and CA199 were normal. Hepatic tumor was initially con-
sidered to be impossible. Gynura root is widely used in Chi-
nese traditional medicine and it can lead to hepatic veno-
occlusive disease (HVOD) in some patients (16). The pre-
sent patient had in the past taken a lot of traditional medi-
cine to treat neck pain, however, she was not sure whether
she had ingested Gynura root. Because of her long-term use
of traditional medicine, gradually ascending bilirubin, hepa-
tomegaly and ascites, a clinical diagnosis of HVOD was not
excluded. The main clinical signs and symptoms of HVOD
were caused by portal hypertension. However, in this pa-
tient, esophageal varices was not indicated by endoscopy,
widened main portal vein (PV) and hepatic vein (HV) steno-
sis. So this case was not diagnosed as HVOD.
The liver is one of the most frequently involved organs in
disseminated non-Hodgkin’s lymphomas, and may be de-
tected in up to 40% of patients at the time of initial stag-
ing (17). Few patients with lymphoma have diffuse liver in-
filtration and present with hepatomegaly. The diagnosis of
lymphoma should be considered. However, in the present
patient, imaging studies and physical examination showed
no enlarged lymph nodes in the body and bone marrow bi-
ruled out lymphoma.
At last, liver biopsy was performed which demonstrated
hepatic intrasinusoidal infiltration by malignant melanoma
cells. But this patient had no previous history of melanoma.
In order to find the primary site, the patient was underwent
a series of examination including physical examination, im-
aging studies and endoscopy. However, various examinations
verified that the disease was confined to the liver. According
to the criteria for MUP, this patient was diagnosed as a
melanoma of unknown primary site.
Anbari et al reported that in 40 patients of MUP, 20%
had a history of regressed skin lesions. In none of those
cases was there a clinically apparent area of regression sug-
gestive of regressed melanoma. Dysplastic nevi were noted
in 22.5% of the patients in series. The prevalence of dys-
plastic nevi and regressed skin lesion in the MUP patients
suggested the likelihood of a primary cutaneous origin for
the metastatic melanoma (15).
Twenty days after the diagnosis, the present patient died
of fulminant hepatic failure. To our knowledge, only four
cases of fulminant hepatic failure secondary to malignant
melanoma were previously reported. Autopsy revealed that
the liver was almost completely occupied by melanoma cells
in these patients (2, 3, 18, 19). The increasing size of the
liver ruled out fulminant hepatitis as a cause, since the liver
would be expected to shrink in a patient with fulminant
hepatitis (20). The mechanisms of rapid liver failure here

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 Inter Med 48: 2093-2096, 2009 DOI: 10.2169/internalmedicine.48.2542

Ta
ble1
. Se
rum Bi
oche
mic
alPa
rame
ter
saf
terAdmi
ssi
on
Biochemical parameters(Normal values) day2 day9 day16 day23 day30
ALB(35-55g/L) 33.5 32.2 31. 28 27
ALT(3-50U/L) 17 117 286 578 1652
AST(3-40U/L) 53 120 473 942 2103
TB(1.0-22µmol/L) 80 88 99 153 306
DB(1-7µmol/L) 52 56 63 115 213
AP(30-115U/L) 134 171 221 493 1021
GGTP(0-54U/L) 178 192 354 702 1902
PT(10.5-14.0s) 12.8 14.2 15.1 28 120
LDH(150-450U/L) 88 349 562 1282 4365
Ammonia(10-47µmol/L) 21 44 71 98 134
ALB=albumin;ALT=lanine aminotransferase;AST=aspartate aminotransferase;TB=
total bilurubin; DB=direct bilurubin;
AP=alkalinephosphatase;GGTP=gamma-glutamyl transpeptidase;PT=prothrombin
time.LDH=lactate dehydrogenase

seemed more related to simple replacement of liver by mela-
noma rather than by a process of parenchymal infarction
and necrosis.
When imaging indicates diffuse liver enlargement without
an individual nodular lesion, it is difficult to differentiate
diffuse intrasinusoidal liver metastasis from other diseases,
such as fatty infiltration, hepatitis, lymphoma and HVOD.
The present case report demonstrates the difficulty of mak-
ing a noninvasive diagnosis of diffuse hepatic infiltration by
metastatic melanoma.

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Ⓒ 2009 The Japanese Society of Internal Medicine

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