Download enormous mixed germ cell tumor of the testis with four

2009
ENORMOUS MIXED GERM CELL TUMOR OF
THE TESTIS WITH FOUR DIFFERENT TYPES
OF TUMORS: TERATOMA, SEMINOMA,
EMBRYONAL CANCER AND YOLK SAC TUMOR
M. Tzvetkov*, G. Venkov*, A. Vlahova**, T. Dikov**
*Clinic of Urology, ** Department of Pathology, Medical University, Sofia
Keywords: testicular cancer, teratoma testis, yolk sac tumоr, embryonal carcinoma, seminoma
Address for correspondence: G. Venkov, Medical University, Clinic of Urology, 1, St. Georgi Sofiiski Street,
1431 Sofia, Bulgaria, Tel.: +359 877626588, e-mail: [email protected]
Abstract: Objective: We report a case of enormous mixed germ cell tumor of the testis with four different types
of tumors: teratoma, seminoma, embryonal cancer and yolk sac tumor with a clearly defined histology pattern.
Materials and methods: A rare case of a 15-year-old boy with giant tumor of the left testis is presented. At the time
of presentation the tumor measured 18x10x9cm. The tumor markers were increased, serum alpha-fetoprotein was over
350.00 ng/ml and human chorionic gonadotropin (beta-HCG) in serum was 125.96mlU/ml. The patient was treated
with left inguinal orchiectomy. The tumor was histologically and immunohistochemically verified. Histologically, four
different types of tumors were found: teratoma, seminoma, embryonal cancer and yolk sac tumor. The treatment was
continuеd with chemotherapy courses.
Other cases from world literature are reviewed.
Case report
We report a rare case of a 15-year-old boy with
complaints of swelling and pain in the left testicle
detected on self examination. The symptoms had
begun two years before and had gradually increased.
For this period of time the swelling of the testicle
had enlarged and the organ had reached the size of
a melon. For unknown reasons, probably religious,
the boy hadn’t reached for medical help. The general
condition of the boy was good. No pathological
finding was found in the lungs and other organs.
Local status: the examination detected a giant
growth of the left testis sized 18x10x9cm. The skin of
the testis was blush, at places livid. Venous blood
vessels were wide and could be seen through the
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skin. When palpated, the consistence of the testicle
was hard elastic. Fig.1
The surface groin lymphatic nodes were not
palpably enlarged. Laboratory tests were in normal
values.
The tumor markers were highly elevated. His alphafetoprotein (AFP) in serum was over 350.00ng/ml
and human chorionic gonadotropin (beta-HCG) in
serum was 125.96mlU/ml.
The computer tomography (CT) of scrotum and
pelvis showed an enormous tumor mass which
originated from the left testicle. The tumor was with
infiltrate growth and heterogeneous structure and
calcificates. Fig.2
2009
Enormous Mixed Germ Cell Tumor of the Testis
Fig.1 Tumor of the testicle – outside look of the formation
By moving right arteria illiaca comunis enlarged
lymphatic nodes were found in the pelvis. Fig.3
Fig.2 Computer tomography of the scrotal tumor.
CT of the chest showed no sign of metastatic
disease. Left inguinal orchiectomy was performed.
During the operation liquid tumor materials leaked
from the lower pole of the testis. At this place the
skin of the scrotum was very thin and the tumor
extended through tunica albuginea involving tunica
vaginalis. The tumor had invaded the spermatic cord.
Fig.4
Fig.3 CT scan of pelvis. Enlarged lymphatic nodes.
Morphological research proved there were four
different types of tumor cells.
Fig.4 Extraction of the tumor from scrotum.
Pathology report:
Macroscopical outlook: A testis filled with tumor
formation with versicoloured cut surface. Gross
examination revealed an enlarged testis measuring
18х10х9cm due to extensive involvement by tumor
with variegated cut surface: confluent greyish–
white, yellowish-brown and hemorrhagic zones,
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2009
Enormous Mixed Germ Cell Tumor of the Testis
variably sized cysts, necrotic zones, calcifications, no
detectable engagement of the coverings. Fig.5
Fig.6 Histological look of the first component immature teratoma
Fig.5 Macroscopical outlook and tumor formation
Histological finding of a mixed germ-cells
tumor. Histology slides disclose diffent types of
tumour tissue, determining the diagnosis mixed
germ cell tumor. The largest area is occupied by
i m m ature teratoma, composed of immature tissue
and organoid components derived from all three
germinal layers. Endo- and ecto-dermal structures
are abundantly represented: hair follicules,
keratinous cysts, epithelial-like glandular formations,
islands of primitive neuroepithelium; all these are
unproportionally admixed with immature-appearing
mesenchyme and cartilage of mesodermal origin.
Fig.6
Roughly quantified, second in size to the teratoma,
is a tumor tissue composed of monomorphic cells
with abundant clear cytoplsms and centrally placed
nuclei; nesting pattern is discernible by tiny fibrous,
lymphocyte-rich, septae. Part of these nests contain
single moderately pleomorphic, multinucleated
tumor cells, and the immunohistochemistry (IHC)
assay verified their syncytiotrophoblastic origin
(hCGT; code N1534, Dako). The finding is consistent
with seminoma with syncytiothrophoblast cells. Fig.7
The histology picture is further varied by the
presence of yolk sac tumor - relatively minor areas
with papillary-reticular and microcystic appearance;
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with interspersed single, ill-formed, pathognomic
Schiller-Duvall bodies. Fig.8
Fig.7 Histology of the second component seminoma with syncytiothrophoblast cells
Totaling less than 5% of the whole tumor tissue
is the embryonal carcinoma – solid and glandular
areas are noted composed of highly pleomorphic
cells, exhibiting vesicular nuclei with prominent
nucleoli; necrotic parts and calcium depositions are
encountered. Fig.9
2009
Enormous Mixed Germ Cell Tumor of the Testis
The patient was diagnosed with Stage IIA
pT3N1M0S1 mixed-germ cell tumor of the left testis.
The treatment was continued with primary
chemotherapy courses. Retroperitoneal lymph node
dissection was not performed. A new staging was
planned after primary chemotherapy.
Fig.8 Histology of the third component – yolk sac tumor
Post-operative period went without complications
and the wound healed completely. To stage correctly
the disease, a second examination was performed
with spiral computer tomography (SCT). Two
paraaortal enlarged lymphatic nodes were found
under the left renal vena. Fig.10
In the pelvis two more enlarged lymphatic nodes
were found over the inguinal ligament, one on each
side. Fig.11
Fig.9 Histology of the forth component - embryonal carcinoma
Fig.10 SCT scan shows two enlarged paraaortal
lymphatic nodes in the left side under left vena renalis.
Дискус
ия
Fig.11 SCT scan enlarged lymphatic nodes in pelvis
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2009
Enormous Mixed Germ Cell Tumor of the Testis
Discussion
Approximately 95% of all testicular neoplasms
are of germ cell origin. For unclear reasons, there
has been a world-wide increase in the incidence
of these tumors1. Testicular germ cell tumors are
the most common solid malignancies in men
between the 20 and 45 years of age2. Testicular
neoplasms account for 1-2% of all malignancies in
male population3. According to regional cancer
registries in Europe, about 90% of the patients are
with low-stage disease (TNM stages I-IIB)4. Most
of the patients with testis cancer (61-78%) have
clinical stage I disease confined to the testis with
normalized markers after orchiectomy5,6. More than
half of the germ cell tumors are a mixture of two
or more of the basic germ cell tumor types, with
the exception of spermatocytic seminoma. The
mixed types that contain seminoma occur at a later
age compared to those without seminomatous
components. Histologically, 59% of mixed germ cell
tumors contain seminoma, 41% contain yolk sac
tumor, and 47% contain embryonal carcinoma and
teratoma. Syncytiotrophoblastic cells are present in
42%7. The most well documented risk factor for the
development of germ cell tumors is cryptorchidism.
The most consistent chromosomal abnormality is an
isochromosome of the short arm of chromosome
12, i(12p), which is present in 56% of seminomas
and in 83% of nonseminomatous tumors8,9. The
most common mixed germ cell tumor is the
combination of teratoma, embryonal carcinoma,
yolk sac tumor, and syncytiotrophoblastic cells with
or without seminoma10-12. The strongest associations
of histological subtypes in mixed germ cell tumors
are seen between yolk sac tumor and teratoma13.
Patients with germ cell tumor (GCT) in one testicle
have a 500-1000-fold greater chance of developing a
contralateral testicular carcinoma. 0.5-7% of patients
will develop a contralateral testicular tumor. 80-85%
of bilateral tumors occur metachronously, at a mean
of 65.1 months after the first tumor14.
Review of the literature shows several reports of
enormous testicular tumors. The majority of these
reports came from Japan where the incidence of
these tumors is low. The largest tumor was reported
32x28x28 cm in size with a calculated weight of 7 kg
40
in a 38-year-old patient with serum levels of LDH, AFP
and ß-HCG of 2.040 U/l, 240ng/ml and 5.6 ng/ml,
respectively15. These authors’ review of 42 cases in the
Japanese literature reported that patient was treated
initially with 3 cycles of VIP chemotherapy, followed
by high orchiectomy and retroperitoneal lymph node
dissection. The histologic examination of resected
specimens revealed only necrosis and fibrosis. The
authors believed that initial chemotherapy followed
by surgery was the management approach of choice
for the condition. Some other case reports have
described enlarged teratomas, seminomas and a
malignant fibrous hystiocytoma16-21.
Approximately 70% of testicular GCTs tend to
metastasize through the lymphatics, with paraaortic
nodes the first to be involved. Hematogenous
spread goes often to the lungs and liver22. Total
tumor size was not significantly related to the
development of metastasis or to the presence of
vascular or lymphatic invasion23. The histology of
the metastasis may be different from that of the
primary tumor. Nonseminomatous germ cell tumors,
including mature and immature teratomas, have a
variegated appearance and often display hemorrhage
and necrosis. These tumors are biologically more
aggressive and radioresistant24. The histologic subtype
does not influence prognosis. In patients younger
than 15 years of age, approximately 90% of testicular
germ cell cancers are yolk sac tumors. In these types
of patients, the AFP is elevated at diagnosis and is
an excellent indicator of response to therapy and of
disease status25.
Treatment with surgical excision and cisplatin-based
chemotherapy provides cures in >90% of the cases.
Radical inguinal orchiectomy with initial high ligation
of the spermatic cord is the procedure of choice in
treating a malignant testicular mass26. Tumors that
have a mixture of seminoma and nonseminoma
components should be managed as nonseminomas27.
Evaluation of the retroperitoneal lymph nodes,
usually by CT scanning, is an important aspect of
treatment planning in adults with testicular cancer.
Patients with a negative result however, have a 25%
to 30% chance of having microscopic involvement
of the lymph nodes28. A meta-analysis review of the
histology of surgical specimens from 24 publications
2009
Enormous Mixed Germ Cell Tumor of the Testis
(996 patients) found that residual teratoma was
present after chemotherapy in 36% of cases29. Biologic
markers, including AFP, HCG, PLAP, and lactate
dehydrogenase (LD) are valuable in continued follow
up of the patient30.
In our case we completed a radical inguinal
orchiectomy. In this case surgical treatment was
complicated because of the size of the tumor. The
patient was diagnosed with Stage IIA pT3N1M0S1
mixed germ cell tumor of the left testis.
The treatment was continued with primary
chemotherapy courses with PEB. Retroperitoneal
lymph node dissection was not performed. A new
staging was planned after primary chemotherapy
according to the algorithm for patients with
advanced disease, according to the International
Germ Cell Cancer Consensus Group (IGCCCG)31.
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