Nonpalpable testicular pure seminoma with elevated serum alpha-fetoprotein presenting with retroperitoneal metastasis: a case report
Iwatsuki et al. Journal of Medical Case Reports
Nonpalpable testicular pure seminoma with elevated serum alpha-fetoprotein presenting with retroperitoneal metastasis: a case report
Shoichiro Iwatsuki 0
Taku Naiki 0
Noriyasu Kawai 0
Toshiki Etani 0
Keitaro Iida 0
Ryosuke Ando 0
Takashi Nagai 0
Atsushi Okada 0
Keiichi Tozawa 0
Yosuke Sugiyama 1
Takahiro Yasui 0
0 Department of Nephro-urology, Graduate School of Medical Sciences, Nagoya City University , 1, Kawasumi, Mizuho-cho, Mizuho-ku, 467-8601 Nagoya , Japan
1 Department of Pharmacy, Nagoya City University Hospital , Nagoya , Japan
Background: Patients with a primary pure seminoma in the testis who have elevated serum alpha-fetoprotein are rare and should be treated as patients with nonseminomatous germ cell tumors. However, nonpalpable testicular tumors in this condition have never been reported. We describe a case of nonpalpable pure testicular seminoma with elevated serum alpha-fetoprotein presenting retroperitoneal metastasis. Case presentation: A 29-year-old Asian man was referred to our hospital with right flank pain. Computed tomography showed a mass located between his aorta and inferior vena cava, but a testicular tumor was not detected. His serum levels of lactate dehydrogenase, alpha-fetoprotein, and DUPAN-2 were high. Although no tumor or nodule was palpable in his testis, ultrasonography revealed multiple low echoic lesions in his right testicular parenchyma. He was diagnosed with right testicular cancer with retroperitoneal lymph node metastasis and underwent right high orchiectomy. A pathological examination revealed pure seminoma and no nonseminomatous components were found in the specimen. Three courses of induction systemic chemotherapy (cisplatin, etoposide, and bleomycin) normalized his serum alpha-fetoprotein and DUPAN-2 levels. Three additional courses of chemotherapy (etoposide and bleomycin) were performed, and treatment was completed with laparoscopic retroperitoneal lymph node dissection. Pathology of the dissected specimen showed fibrous and necrotic tissue with no viable cells. He is alive without recurrence 54 months after orchiectomy. Conclusions: We report a case of pure testicular seminoma with elevated serum alpha-fetoprotein and DUPAN-2 presenting retroperitoneal metastasis. We recommend an ultrasound examination of bilateral testes when large retroperitoneal tumors are detected in young men, even if a mass is not palpable in the scrotum.
Alpha-fetoprotein; DUPAN-2; Testicular tumor; Retroperitoneal lymph node dissection; Seminoma; Burned-out tumor; Case report
Testicular cancers are categorized into seminomatous
and non-seminomatous germ cell tumors (NSGCTs),
each with a 50 % incidence. Distinguishing NSGCTs
from seminomas is important because the therapeutic
strategy is different. Many patients with NSGCT have
elevated serum tumor markers, such as lactate
dehydrogenase (LDH), alpha-fetoprotein (AFP), and
human chorionic gonadotropin (hCG). Since
seminoma does not induce AFP production, the guidelines
recommend that cases with increased AFP levels be
treated as cases of NSGCT [
]. Because, there is a
possibility that a hidden focus of NSGCTs like yolk
sac tumor is somewhere present. However, in the
literature, few cases have been described of patients
with histologically pure seminoma presenting with
elevated serum AFP levels [
We report a case of a 29-year-old Asian man with
nonpalpable testicular cancer presenting retroperitoneal
lymph node metastasis. Although his testicular histology
showed pure seminoma at orchiectomy, preoperative
serum AFP levels were elevated.
A 29-year-old Asian man with no remarkable past
history was referred to our hospital presenting with
right flank pain. He had an episode of right flank
pain 2 weeks before the first visit. Computed
tomography (CT) revealed a retroperitoneal mass (52×36×31
mm) located between his aorta and inferior vena cava
(Fig. 1a), but a testicular tumor was not detected in
his testis. His serum levels of LDH, AFP, and
DUPAN-2 were high (327 U/l, 29.6 ng/ml, and higher
than measurable range, 1600 U/ml, respectively).
Serum levels of other tumor markers, such as hCG,
carcinoembryonic antigen, carbohydrate antigen 19–9,
and soluble interleukin 2 receptor, were within the
normal range (1.1 mIU/ml, 2.7 ng/ml, 27.9 U/ml, and
157 U/ml, respectively). Although no tumor or nodule
was palpable in either testis, ultrasonography revealed
multiple low echoic lesions in his right testicular
parenchyma (Fig. 1b). He was diagnosed with right
testicular cancer with retroperitoneal metastasis, and
underwent right high orchiectomy (Fig. 2a). A
pathological examination revealed pure seminoma (Fig. 2b);
fibrous foci were diffusely observed (Fig. 2c) and no
nonseminomatous components were found in the
specimen. Because his preoperative serum AFP levels
were high, induction chemotherapy combining
cisplatin, etoposide, and bleomycin (BEP), was
performed. After three courses, his serum AFP and
DUPAN-2 levels were normalized. The volume of his
retroperitoneal mass decreased to 15×10×7 mm after
three additional courses of chemotherapy combining
etoposide and cisplatin (EP). Finally, laparoscopic
retroperitoneal lymph node dissection (RPLND) was
performed, and pathology of the dissected specimen
showed fibrous and necrotic tissue with no viable
cells (Fig. 3d). He is alive without recurrence 54
months after orchiectomy.
Patients with elevated serum AFP levels and a
primary pure seminoma are treated as patients with
NSGCTs, because some nonseminomatous
components are presumed to be present either in the testis
or at a metastatic site. Therefore, we treated the
current case as NSGCTs, and induction chemotherapy
followed by RPLND was performed after orchiectomy
as in stage IIB NSGCTs. Peterson et al. [
42 cases with pure seminoma at orchiectomy and
showing elevated serum AFP levels. They performed
combination chemotherapy based on platinum reagent
followed by RPLND. Viable cancer cells were
observed in the retroperitoneal lymph nodes of 15
patients (37.5 %) with pure seminoma showing elevated
serum AFP levels. In general, 16.9 % of patients with
stage II or greater pure seminoma without elevated
serum AFP levels have viable cancer cells in their
retroperitoneal lymph nodes [
]; of the patients with
NSGCTs who have retroperitoneal lymph node
metastases, 12.2 % have viable cancer cells in their
retroperitoneal lymph nodes after chemotherapy [
Therefore, pure seminomas with elevated serum AFP
levels have a relatively lower sensitivity to
chemotherapy than pure seminomas without elevated serum
AFP levels or NSGCTs. Fortunately, the pathological
examination of the retroperitoneal lymph nodes in
our patient did not reveal viable cancer cells; the
long-term good prognosis suggests that six courses
of BEP and EP chemotherapy were effective in this
DUPAN-2 is a well-known tumor marker for
pancreatic, bile duct, and colorectal cancers [
]; in our case,
serum DUPAN-2 levels, as well as AFP, were increased
before orchiectomy. In the literature, only two cases of
embryonal carcinomas with elevated serum DUPAN-2
levels have been reported [
]. Kamoshida et al.
reported immunohistochemical analyses of DUPAN-2
expression using paraffin-embedded specimens of 30
testicular germ cell tumors, and DUPAN-2 was
expressed in all of the specimens from nine patients
with embryonal carcinoma [
]. In our case, before
orchiectomy, our patient’s DUPAN-2 level was higher
than the measurable upper limit and it decreased to
within the normal range after chemotherapy
induction, suggesting that DUPAN-2 in our patient was
produced by a nonseminomatous component like an
Seminomas typically appear as solid, round,
homogeneous, low reflective masses contained within
testes, without calcification inside the tumors. On the
other hand, embryonal carcinomas and teratomas
appear as inhomogeneous masses with calcification
inside the tumor mass and, generally, a normal gonadal
stroma does not contain calcifications. Miller et al.
reviewed 3854 testicular ultrasound examinations;
they hypothesized that intratesticular
microcalcifications outside the margin of the tumor might
represent a phenomenon of burned-out tumor [
]. In our
case, an ultrasound examination revealed rough
microcalcifications around the intratesticular tumor;
in the orchiectomy specimen (Fig. 1c), many
calcifications and fibrous tissues were detected around the
seminomatous tumor (Fig. 2c). Those findings
suggest that the testicular mass might result from a
burned-out phenomenon of an embryonal carcinoma.
Therefore, we performed immunohistochemical
analyses for DUPAN-2 and AFP on the orchiectomy
specimen and retroperitoneal mass. Immunohistochemical
analyses showed no positive cells for DUPAN-2 or
AFP in the orchiectomy specimen and
retroperitoneal mass (Fig. 3). If we had obtained a biopsied
retroperitoneal specimen in the first diagnosis, we
might have been able to detect positive cancer cells.
In conclusion, here we report a case of pure testicular
seminoma with elevated serum AFP and DUPAN-2
presenting retroperitoneal metastasis. We
recommend an ultrasound examination of bilateral testes
when large retroperitoneal tumors are detected in
young men, even if a mass is not palpable in the
We report a case of pure testicular seminoma at
orchiectomy with elevated serum AFP and DUPAN-2 presenting
retroperitoneal metastasis. When a retroperitoneal mass
is detected and a testicular tumor is not palpable, we
recommend consideration of the possibility of a testicular
tiny tumor or of a burned-out phenomenon.
Written informed consent was obtained from the patient
for publication of this case report and any accompanying
images. A copy of the written consent is available for
review by the Editor-in Chief of this journal.
AFP: alpha-fetoprotein; BEP: cisplatin, etoposide, and bleomycin;
CT: computed tomography; EP: etoposide and cisplatin; hCG: human
chorionic gonadotropin; LDH: lactate dehydrogenase; NSGCTs:
nonseminomatous germ cell tumors; RPLND: retroperitoneal lymph node
The authors declare that they have no competing interests.
Each author participated sufficiently in the work to take public responsibility
for appropriate portions of the content. SI diagnosed this case and drafted
the manuscript. TNai critically revised the manuscript. NK, RA, TE, KI, TNag,
AO, KT, and YS carried out the acquisition of data, coordination, and helped
to draft the manuscript. TY supervised this manuscript. All authors read and
approved the final manuscript.
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