A Case of Metastatic Testicular Cancer

Complicated by Tumour Lysis Syndrome

and Choriocarcinoma Syndrome
1.
2.
3.
4.
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7.

Koji Kawai1,
Ei-Ichiro Takaoka1,
Makito Naoi1,
Kensaku Mori2,
Manabu Minami2,
Toru Shimazui1 and
Hideyuki Akaza1

+Author Affiliations

1.

1.

Department of Urology and 2Department of Radiology, Institute of Clinical Medicine,

University of Tsukuba Graduate School of Comprehensive Human Sciences, Tsukuba,
Ibaraki, Japan
For reprints and all correspondence: Koji Kawai, Department of Urology, Institute of Clinical Medicine,
University of Tsukuba, 1-1-1 Tennodai, Tsukuba-City, Ibaraki 305, Japan. E-mail:rkawa@md.tsukuba.ac.jp

Received March 6, 2006.

Accepted May 1, 2006.

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Abstract
A 26-year-old man was referred to our hospital for treatment of metastatic testicular
cancer. The pathological diagnosis was choriocarcinoma with seminoma. Sequential
computerized tomography examinations revealed rapidly progressing bulky liver
metastases and a lung metastasis. Chemotherapy with bleomycin, etoposide and
cisplatin (BEP) was started on the day of admission. Subsequently, the patient suffered
from tumour lysis syndrome (TLS) and massive haemorrhage at metastatic sites. The
latter complication is also called choriocarcinoma syndrome. To our knowledge, this is
the first case report of testicular cancer complicated with both critical conditions.
Intensive care and radiological intervention barely prevented a fatal outcome. The
urological oncologist should be aware of the potential complications TLS and
choriocarcinoma syndrome in cases of rapidly progressive and high-volume
choriocarcinoma.

Key words

testicular cancer

tumour lysis syndrome

choriocarcinoma syndrome
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INTRODUCTION

Liver metastasis represents an independent, poor-risk prognostic factor in patients with

testicular cancer. Several investigators have reported improvement of the outcome by
multimodality treatments (1,2), but hepatic involvement itself, along with the biological
aggressiveness of the disease, sometimes requires intensive management. Here, we
report a case of testicular cancer with multiple liver metastases that showed extremely
rapid progression. The patient suffered from life-threatening complications including
tumour lysis syndrome (TLS), haemorrhagic manifestations from liver metastases and
small bowel infiltration, liver failure and disseminated intravascular coagulation (DIC)
during the first course of induction chemotherapy. Intensive medical care and
radiological intervention barely prevented a fatal outcome.
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CASE
A 26-year-old man complaining of left scrotal swelling underwent a high orchiectomy in
a local hospital. The pathology of the left testicular tumour was choriocarcinoma with a
seminoma element. Computerized tomography (CT) revealed multiple liver metastases
(Fig. 1) and a solitary lung metastasis of 3 cm in diameter. The patient was referred to
our hospital for treatment of metastatic disease 11 days after the surgery. Physical
examination at admission revealed hepatomegaly and gynecomastia. The LDH level and
hCG level had increased markedly to 2070 IU/ml and 2660000 IU/ml, respectively. The alphafetoprotein level was within normal limits (2 ng/ml). The CT on the admission day
revealed hepatomegaly with numerous masses replacing almost the entire liver, as
shown in Fig. 2. In contrast, there was no significant change in the lung metastasis.

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Figure 1.

Abdominal CT before orchiectomy. CT showed multiple liver metastases.

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Figure 2.

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Abdominal CT on the admission day. CT revealed marked progression of liver

metastases, and hepatomegaly from numerous masses, replacing almost the entire
liver.
Because of the aggressive nature of the disease, we started induction chemotherapy
with bleomycin, etoposide and cisplatin (BEP) (3) on the day of admission. On the
second day (Day 2), the serum UA level had increased to 8.7 mg/dl (normal range 7
mg/dl), and urinalysis revealed acid urine. Oral allopurinol (300 mg/day) and
intravenous sodium bicarbonate were begun under the clinical diagnosis of TLS. Since
blood chemistry on Day 5 showed further elevation of the serum UA level to 9.9 mg/dl
and a high serum phosphate level of 6.1 mg/dl (normal range 5.5 mg/dl), the
allopurinol dose was increased to 600 mg/day. During the following days, the
biochemical markers returned to normal levels. Although the transient and mild
elevation of serum creatinine level, which peaked on Day 5 at 1.21 mg/dl (normal range
1.1 mg/dl), was noticed, the development of renal failure was successfully avoided.
Together with the metabolic derangements, the patient suffered from several
complications. On Day 2, the patient complained of acute and transient abdominal pain.
Since the symptoms were accompanied by progression of anaemia, we suspected
intraperitoneal haemorrhage from the liver metastases. In addition, massive melena
developed on Day 4. Both upper gastrointestinal endoscopy and colonoscopy failed to
detect the origin of the melena, but the angiography revealed irregular staining with
extravasation originating from branches of the ileal artery (Fig. 3). Since the findings
suggested tumour infiltration to the small bowel, the region was considered to be
responsible for the melena, and embolization with gelfoam was performed. Despite the
successful control of the melena, the anaemia progressed further. The repeated
episodes of abdominal pain and accumulation of massive ascites made us suspect
considerable bleeding from liver metastases. Although the bleeding point could not be
identified by hepatic angiography, selective embolization of the left hepatic artery with
gelfoam was performed. This procedure achieved good control of the bleeding. The
subsequently developed DIC and liver failure required further intensive care, but the
patient retained an almost stable general condition. The blood cell count and blood
chemistry tests were normalized, except for mild hyperbilirubinaemia, and the second
cycle of BEP was started on Day 22. The patient received three cycles of BEP, followed
by four cycles of combination chemotherapy with paclitaxel, ifosfamide and cisplatin
(TIP) (4). The clinical course was uneventful, and all tumour markers normalized after
the chemotherapy. The CT demonstrated marked reduction of the liver metastases (Fig.
4). The patient underwent thoracotomy for the residual lung metastasis. Since the
histology of the residual lung metastasis revealed necrosis, further chemotherapy was
not indicated. The patient has remained well and is without evidence of disease 8
months after the last chemotherapy.

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Figure 3.

The angiography performed on Day 6. Angiography revealed irregular staining with

extravasation originating from branches of the ileal artery.

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Figure 4.

Abdominal CT after three courses of BEP and four courses of TIP. All residual and
regressed liver metastases showed apparent cystic changes. BEP: leomycin + etoposide
+ cisplatin; TIP: paclitaxel + ifosfamide + cisplatin.
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DISCUSSION
We present the clinical course of a testicular cancer patient with rapidly progressing
liver metastases who suffered from TLS and haemorrhage at the sites of the
metastases. To our knowledge, this is the first case report of testicular cancer
complicated with both critical conditions. The patient was successfully managed with
intensive supportive care and radiological intervention.
First, TLS is an oncological emergency that may occur during chemotherapy for highly
chemosensitive malignancies (5). The release of intracellular substances accompanying
extensive tumour cell death is considered to be the cause of this syndrome. In many
cases, it occurs within 48 h from the start of chemotherapy (5). The TLS patient may
develop hyperuricaemia, hyperkalaemia, hyperphosphataemia, and hypocalcaemia. The
production and excretion of a high volume of uric acid causes the deposition of uric acid
crystals in the collecting ducts, which results in the development of uric acid
nephropathy. Also, the hyperphosphataemia causes deposition of calcium phosphate,
and can promote renal failure. Therefore, the primary aim of the treatment of TLS is
prevention of hyperuricaemia and adequate systemic hydration. Testicular cancer is a
rapidly growing, chemotherapy-sensitive cancer that seems to have high risk for
development of TLS, but to our knowledge, only four germ cell cancer cases with TLS
were reported in the literature in English (69).
Secondly, the patient suffered from repeated haemorrhages from liver metastases.
Logothetis (10) has described haemorrhage at the site of metastases in advanced germ
cell cancer containing high-volume choriocarcinomatous elements. This was termed
choriocarcinoma syndrome. Acute pulmonary haemorrhage is the most frequent
manifestation; however, haemorrhage at any site of metastasis can develop (11). In the
present case, the extremely high serum hCG level suggested that choriocarcinoma was
the dominant element of metastatic sites. The patient also suffered from repeated and
massive melena. The arteriography revealed that neoplastic vessels originated from
branches of the ileal artery. Although the tumour was not detected by CT, angiographic

findings supported the presence of infiltration of choriocarcinoma rather than small

bowel angiodysplasia. Although small bowel metastasis from testicular cancer is rare,
there are five case reports of small bowel metastases from genital chroriocarcinoma,
teratocarcinoma and retroperitoneal choriocarcinoma (12). In the present case,
pulmonary haemorrhage, the typical presentation of choriocarcinoma syndrome, was
not revealed. This might be due to small tumour volume in the lung metastasis (3 cm in
diameter, solitary) in our case.
In conclusion, the present case indicates that TLS, although rare, is a possible and
treatable complication of chemotherapy for testicular cancer. The rapid progression of
choriocarcinoma metastases is considered to have contributed to the onset of the
critical complications in this case. Prompt chemotherapy before orchiectomy would have
been a better choice for this patient, but this option was not selected because no lifethreatening metastases were noticed at the initial presentation. The urological
oncologist should be aware of the potential complications presented here, TLS and
choriocarcinoma syndrome, in the treatment of testicular cancer with rapidly
progressive and high-volume choriocarcinoma.

2006 Foundation for Promotion of Cancer Research

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References
1.

1.
Rivoire M, Elias D, De Cian F, Kaemmerlen P, Theodore C, Droz JP. Multimodality treatment of patients
with liver metastases from germ cell tumors. Cancer2001;92:57887.
CrossRefMedlineWeb of Science

2.

2.
Copson E, Mckendrick J, Hennessey N, Tung K, Mead GZ. Liver metastases in germ cell cancer:
defining a role for surgery after chemotherapy. BJU Int 2004;94:5528.

3.

CrossRefMedlineWeb of Science

3.

Williams SD, Birch R, Einhorn LH, Irwin L, Greco FA, Loehrer PJ. Treatment of disseminated germ-cell
tumors with cisplatin, bleomycin and either vinblastine or etoposide. N Engl J Med 1987;316:143540.
MedlineWeb of Science

4.

4.
Motzer RJ, Sheinfeld J, Mazumdar M, Banis M, Mariani T, Bacik J, et al. Paclitaxel, ifosfamide and
cisplatin second-line therapy for patients with relapsed testicular germ cell cancer. J Clin
Oncol 2000;18:24138.

5.

Abstract/FREE Full Text

5.

Baeksgaard L, Sorensen JB. Acute tumor lysis syndrome in solid tumorsa case report and review of
the literature. Cancer Chemother Pharmacol 2003;51:18792.
MedlineWeb of Science

6.

6.
Barton JC. Tumor lysis syndrome in nonhematopoietic neoplasms. Cancer1989;64:73840.

7.

CrossRefMedlineWeb of Science

7.

Blanke CD, Hemmer MP, Witte RS. Acute tumor lysis syndrome with choriocarcinoma. South Med
J 2000;93:9169.
MedlineWeb of Science

8.

8.
Pentheroudakis G, O'Neill VJ, Vasey P, Kaye SB. Spontaneous acute tumour lysis syndrome in patients
with metastatic germ cell tumours. Report of two cases. Support Care Cancer 2001;9:5547.

9.

CrossRefMedlineWeb of Science

9.

Kattan J, Culine S, Tavakoli-Ravavi T, Kramar A, Droz JP. Acute tumor lysis syndrome in poor-risk germ
cell tumours: does it exist? Support Care Cancer 1994;2:12831.
CrossRefMedlineWeb of Science

10.

10.
Logothetis CJ: Choriocarcinoma syndrome. Cancer Bull 1984;36:11820.

11.

11.
Logothetis CJ, Samuels ML, Selig DE, Ogden S, Dexeus F, Swanson D, et al. Cyclic chemotherapy with
cyclophosphamide, doxorubicin, and cisplatin plus vinblastine and bleomycin in advanced germinal
tumors. Results with 100 patients. Am J Med1986;81:21927.
CrossRefMedlineWeb of Science

12.

12.
Harada N, Misawa T, Chijiiwa Y, Imazono Y, Fujishima H, Nawata H. A case of extragenital
choriocarcinoma in the jejunum. Am J Gastroenterol 1991;86:10779.
MedlineWeb of Science