Poorly differentiated neuroendocrine carcinoma of
the seminal vesicle
Yutaka Yasunaga,1Takafumi Ueda,2Yoshinori Kodama3and Toshitsugu Oka1
Departments of1Urology,2Orthopedics and3Pathology, National Hospital Organization Osaka National Hospital, Osaka, Japan
Abbreviations & Acronyms
NEC = neuroendocrine
NET = neuroendocrine
NSE = neuron-specific
PSA = prostate-specific
SV = seminal vesicle
Yasunaga M.D., Ph.D.,
Department of Urology,
National Hospital Organization
Osaka National Hospital,
1-24-41 Hoenzaka, Chuo-ku,
Osaka 540-0006, Japan. Email:
Received 12 August 2011;
accepted 4 December 2011.
Online publication 29 December
humeral bone tumor resulting in a pathological fracture. Positron emission tomography
vesicle. Laboratory data showed an elevation of neuron-specific enolase, despite the
normal prostate-specific antigen. Transrectal needle biopsy showed a poorly differenti-
ated carcinoma of the right seminal vesicle and the metastasis of the pelvic lymph node.
Immunohistochemical results were compatible with the features of neuroendocrine car-
cinoma; synaptophysin, chromogranin A and CD 56 were positive. The previously biop-
sied bone tumor was finally diagnosed as a metastasis. A systemic chemotherapy using
etoposide and cisplatin failed. The patient died of cancer one-and-a-half years later.
We describe an extremely rare case of poorly differentiated neuroendo-
neuroendocrine carcinoma, poorly differentiated, seminal vesicle.
Primary tumors of the seminal vesicle are uncommon. Exclusively, NET arising from the
seminal vesicle is extremely rare. Here, we show a case of poorly differentiated NEC of the
seminal vesicle with bone metastasis, and discuss the problems related to the diagnosis and
treatment of this tumor.
A 67-year-old man presented at the Department of Orthopedics with a left upper arm tumor
resulting in a pathological fracture. A needle biopsy of the left humeral bone disclosed an
undifferentiated carcinoma. A subsequent positron emission tomography scan using fluo-
rodeoxy glucose as a tracer to screen the primary site of the carcinoma showed the hot spot
accumulated behind the urinary bladder, suspected to be in either the prostate or seminal
vesicle. An additional examination including chest X-ray and abdominal computed tomog-
raphy scan resulted in no other abnormal findings as the primary site. The patient was then
referred to the Department of Urology, and examined physically and clinically. The digital
rectal examination showed an enlarged prostate with a smooth surface.A large mass behind
the right lobe of the prostate was also palpable without apparent distinction from the right
SV. Transrectal ultrasonography showed an irregular tumor in the right SV extending to the
prostate, as well as a large lymph node swelling in the pelvic cavity. Magnetic resonance
imaging scan also featured a large, 4 cm in size and irregular tumor of the right SV (Fig. 1)
accompanying lymph node metastasis aside the right internal iliac artery, and additional
bone metastases in the lumbar and sacral regions.
Laboratory tests showed anemia (hemoglobin 11.4 g/dL and hematocrit 34.9%) and
elevations of C-reactive protein (6.53 mg/dL), and alkaline phosphatase (419 IU/L) with a
antigen, squamous cell carcinoma antigen, CA19-9 and CA125 were all within the normal
range, showing 1.4 ng/mL, 1.3 ng/mL, 7 U/mL and 9.3 U/mL, respectively. PSA was also at
normal levels (1.72 ng/mL). NSE was the only positive tumor marker (22.0 ng/mL).
International Journal of Urology (2012) 19, 370–372 doi: 10.1111/j.1442-2042.2011.02944.x
© 2011 The Japanese Urological Association
To determine histological diagnosis, a transrectal needle
biopsy was carried out. Under microscopy, the specimens
disclosed a poorly differentiated carcinoma presenting aside
the normal seminal vesicle (Fig. 2a). The tumor cells com-
posed of pleomorphic nuclei featured an irregular growth
pattern, suggesting a highly-aggressive carcinoma (Fig. 2b).
Immunohistochemical analysis showed that the tumor cells
expressed positive immunoreactivities with synaptophysin,
chromogranin A and CD 56. Nuclear labeling index of
MIB-1 staining showed 25% (Fig. 2c). In contrast, the com-
plete absence of immunolabeling was found using epithelial
membrane antigen, CAM5.2, AE1/AE3, CA125 or PSA.
Additional immunohistochemical analysis using somatosta-
tin receptor type 2 also showed negative staining.The speci-
men taken from the adjacent lymph node showed the same
findings, whereas all specimens taken systematically from
the prostate showed no evidence of malignancy. The afore-
mentioned phenotype and immunohistochemical profile
were consistent with the diagnosis of a poorly differentiated
NEC arising from the seminal vesicle.
An additional needle biopsy of the sacral bone tumor,
which was suspected by the magnetic resonance imaging
scan, was found to be the NEC with multiple bone
(80 mg/m2on days 1–3) and cisplatin (70 mg/m2on day 1)
was introduced. The patient underwent two courses of
etoposide/cistplatin chemotherapy without any toxic events;
however, the tumor progressed, and NSE increased rapidly.
Another pathological fracture occurred in the lumbar bone,
resulting in impaired orthostasis. The best supportive care,
including palliative radiation, was introduced. The patient
died 5 months after the introduction of chemotherapy.
NET is a family of neoplasm including different subsets
of malignancies. The WHO classification 2000 recently
divided this entity into major three groups: well-
differentiated NET, well-differentiated neuroendocrine car-
cinoma (NEC),\ and poorly differentiated NEC.1NET or
tumors previously described as carcinoid tumors frequently
occur in the digestive tracts, such as the stomach, small
intestine, colon and pancreas.2Because of biological behav-
ior, particularly the presence of hormonal symptoms or
disorders, NET are regarded as “functional” gastroentero-
pancreatic tumors. Unlike functional NET, NEC cells are
clinically more aggressive and capable of distant tumor
spread resulting in metastasis. Poorly differentiated NEC is
characterized by extensive invasion, increased necrosis and
high mitotic activity measured by Ki-67/MIB-1 index,
resulting in clinically malignant behavior, such as multiple
metastases and poor prognosis.1NEC arise from not only
digestive tracts, but also from a wide variety of primary
sites, including the head and neck,3oral cavity,4and the
kidney.5The variant with neuroendrocrine differentiation of
prostatic adenocarcinoma has been cited during hormonal
treatment; however, primary NEC arising from the prostate
is extremely rare.6NEC originating from the SV was first
reported by Kreiner et al.7To our knowledge, this is the
second well-documented case of primary NEC of the SV.
When considering the extremely rare occurrence of
primary SV tumors, the precise location of the present
tumor was difficult to find. At first, two differential diag-
noses were supposed; primary SV adenocarcinoma with
neuroendocrine features or PSA-absent prostatic adenocar-
cinoma with neuroendocrine differentiation infiltrating
the seminal vesicle. To distinguish these two entities, the
samples from the SV and the prostate were independently
biopsied. Histological and immunohistochemical results
were consistent with the common features of poorly differ-
entiated NEC. A Ki-67/MIB-1 index of 25% shows high
aggressiveness of tumor cells and becomes the key factor for
therapeutic strategy after the diagnosis.
Like other organs previously reported in the literature,2
treatment for poorly differentiated NEC is very difficult.
Somatostatin analog, such as octreotide, can control the
tumor growth of NET or well-differentiated NEC;8
however, poorly differentiated NEC often lacks somatosta-
tin receptor expression. As seen in the present case, poorly
differentiated NEC does not respond to octreotide treat-
ment. As a result of a high rate of incidence of accompa-
nying metastasis, systemic chemotherapy is preferred to
surgical treatment alone. The combination regimen using
etoposide plus cisplatin was first introduced, but the effec-
tiveness was limited.9A recent survey using a three-drug
regimen by the addition of paclitaxel showed better survival
despite higher toxicity.10In the current case, etoposide che-
irregular tumor in the right seminal vesicle.
Magnetic resonance image (T2-weighted) showing an
Neuroendocrine carcinoma of seminal vesicle
© 2011 The Japanese Urological Association
motherapy failed to obtain any therapeutic effect in both
tumor reduction and NSE decline. A proposed better
regimen would be recommended.
The authors thank Dr Osamaura for immunohistochemical
analysis using somatostatin receptor type 2.
Conflict of interest
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Editorial Comment to Poorly differentiated neuroendocrine
carcinoma of the seminal vesicle
In this report,Yasunaga et al. showed am extremely rare case
of poorly differentiated neuroendocrine carcinoma of the
Neuroendocrine tumors (NET) are thought to arise from
neuroendocrine cells. They can arise in most epithelial
organs of the body, but are particularly well described in the
lung, tubular gastrointestinal tract and pancreas.
NET were thought to be benign tumors; however, some-
times NET show metastasis even without cellular and struc-
tural abnormality. Now NET are recognized as malignancy.
(b) The tumor cells composed of pleomorphic nuclei features an irregular growth pattern. (c) MIB-1 staining shows a nuclear labeling
index of 25%.
(a) A microscopic view of the biopsied specimen from the right seminal vesicle shows poorly differentiated carcinoma.
Y YASUNAGA ET AL.
© 2011 The Japanese Urological Association