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Acta Médica Costarricense
On-line version ISSN 0001-6002Print version ISSN 0001-6012
Acta méd. costarric vol.55 n.3 San José Jul./Sep. 2013
Original
Mediastinal germ cell tumors. Surgical experience with
twenty nine patients
José A. Mainieri-Hidalgo1,Valeria
Rees-Alpízar2, Isabel
Gamboa-González2 y Marcelo Mainieri-Breedy2
Work done at the Thoracic Surgery Department, “Dr. R. A. Calderón Guardia” Hospital. Caja Costarricense de Seguro Social Authors´ affiliation: 1Thoracic Surgery Department “Dr. R. A. Calderón Guardia” Hospital. 2Medical students.
Abstract
Background: To review and inform
about the experience acquired
with management of germ cell tumors of the mediastinum
at the
Methods: Twenty-nine patients with mediastinal
germ cell tumors were operated between 1986 and
Results: Subjects were predominantly
young males with
a gender ratio of 13.5:1 and a mean age of 26. Masses were located in
the
anterior mediastinum in 28 cases and in
the middle mediastinum in 1 case.
Twenty-seven cases were suspected
due tomediastinal widening on chest x-ray
examination, 1 to pleural effusion and 1 to pleural effusion and mediastinal widening. The most frequently found
symptoms
were dyspnea, retrosternal
chest pain, fever, cough, weight loss, superior vena cava syndrome, hemoptysis and gynecomastia
in
one male with coriocarcinoma. Tissue for
diagnosis
was obtained in 14 cases by mediastinotomy,
in 8 by thoracotomy, in 4 by video
assisted thoracoscopy,
in 1 by sternotomy, in 1 by mediastinoscopy
and in 1 by bronchoscopy.
Conclusion: Germ cell tumors of the mediastinum are infrequent, with higher
prevalence in young
males. Complete surgical excision remains the treatment of choice for resectable tumors, which are usually of more
benign
histology. Cure is not guaranteed by apparent total resection of
malignant germ
cell tumors, therefore primary or adjuvant chemotherapy should always
be
considered given that it was curative for some partially resected
tumors and others with apparent total resection recidivated.
Keywords: Germ cell tumors, extragonadal
germ cell tumors, tumors of the mediastinum.
Germ cell
tumors are more common in young men, they
are very rare in women, they are often malignant and symptomatic, and
like
other mediastinal tumors they are usually
detected by
chest x-ray which where there is a widening of the mediastinum.
Compression symptoms are usually present, the most common are: retrosternal pain, cough, dyspnea,
dysphonia, diaphragmatic paralysis, hemoptysis and superior vena cava syndrome. It
is also
expected the presence of symptoms, such as fever, weight loss and
malaise. Some
patients have gynecomastia, due to the
production of
beta-gonadotropin humana.3
The
radiographic finding of a tumor is usually a large
tumor, sometimes very large, which can range from an injury with
well-defined
edges that rejects mediastinal structures
or the
lungs; to lesions that frankly invade and surround the thoracic organs, that can be associated with pleural
effusion. CT
scan is useful to assess these characteristics; the mass is often
heterogeneous, which implies the existence of necrotic areas, or the
presence
of various tissues of different consistency. To observe calcifications
or bone
structure formation is typical of teratomas.4
Like
tumors originated in gonads, they are classified
into seminoma and nonseminoma
tumors. Nonseminomas most common are: teratoma, teratocarcinoma,
embryonal carcinoma, choriocarcinoma
and yolk sac tumor. In many cases they have a mixed pattern, and they
may show
a part malignant and part benign pattern. This feature is of great
importance
in relation with the management, where the malignant part responds well
to chemotherapy,
and it is not unusual to remove later the benign portion that remains
after
treatment.5
Mixed
tumors are the most common, followed by teratoma,
seminoma and embryonal
carcinoma, but choriocarcinomas
are rare. Like gonadal origin tumors, some
mediastinal germ cell tumors produce
substances that can be
used as tumoral serological markers and
may be used
as a diagnostic element. Yolk sac tumors, teratocarcinomas
and embryonal carcinoma tend to raise
serum
alpha-fetoprotein. Choriocarcinomas often,
and very
few seminomas, increase beta human
chorionic gonadotropin. Pure seminomas
rarely elevate biomarkers, but in some cases there is elevated lactate dehydrogenase. The presence of these biomarkers
is of great
help in the diagnosis and monitoring of patients, as they tend to
become
negative after appropriate treatment. It is important; when you have
these
markers, to rule out tumors in the gonads. The pelvic or testicular
ultrasound
is mandatory before treatment.5
The
anterior mediastinostomy
and videothoracoscopy are useful
procedures to take a
biopsy, but one must consider the possibility of mixed tumors that are
not
represented in the obtained tissue.6
The
histological finding often correlates to the
treatment. Teratomas, in most cases, are
usually
surgically removed in a first approach; while the rest of tumors tend
to
present as an invasive pattern, but have a good prognosis using
chemotherapy.7
In some cases, surgical resection of the residual tumor is
necessary,
being of a good prognosis the finding of necrotizing tissue.8,9
The aim of
this study was to review the experience in
the management of mediastinal germ cell
tumors, in
the Hospital “Dr. R. A. Calderón
Guardia”; to describe the clinical presentation, the procedure to
establish the diagnosis, treatment and outcome of patients with these
tumors,
during the period of 26 years: between 1986 and 2012.
Methods
Prior
approval of the protocol by the Ethics and
Research Committee of the Hospital, we conducted a retrospective
analysis of
all cases diagnosed with germ cell tumor, and operated in the Thoracic
Surgery
Department at the HCG between January 1986 and December 2012. The study
did not
include patients with germ cell tumors diagnosed by hormonal laboratory
studies, which did not require biopsy or surgical resection and that
were
treated by the Medical Oncology Department.
The
information was obtained from the database of the
Department. We selected all patients with histologically
confirmation of mediastinal germ cell
tumor, during
the study period. General information was extracted regarding age,
gender,
clinical presentation and radiological diagnostic or surgical
procedure,
complications, surgical mortality and histological diagnosis. Clinical
records
were reviewed to take information on the signs and symptoms, medical
treatment,
special studies performed and evolution. Since serological markers were
not
shown properly in the medical records, they were excluded from the
study.
From the
data obtained we report the frequency with
which each was presented, and despite being a small number of cases, we
report
the trend, according to the histological subtype and response to
treatment.
Results
We studied
29 cases, 2 females and 27 males, with a
ratio of 1:13.5, that had ages between 15 and 40
years-old,
with an average of 26 years-old. The location corresponded in 28 cases,
to the
anterior superior mediastinum, and one in
the middle mediastinum.
The
presentation, in 27 cases, was with widened of the
mediastinum at the chest X-rat, one with a
pleural
effusion and one with pleural effusion and widened of the mediastinum.
Only in 24 cases adequate clinical information was found about symptoms
in the
clinical record; 4 patients were asymptomatic, 20 were symptomatic and
the most
common symptoms were: 16 cases with dyspnea,
12 cases
with retrosternal pain or discomfort, 11
cases had
fever, 9 cases had cough, 8 cases had weight loss, 8 cases had superior
vena
cava syndrome, 1 case had hemoptysis and 1
case had
male gynecomastia in a patient with choriocarcinoma.
The sample
for histological diagnosis was obtained in
14 cases, using an anterior mediastinostomy,
8 cases
with thoracotomy, 4 cases with video-thoracoscopy, 1 case with sternotomy,
1 mediastinoscopy and 1 bronchoscopy.
The
histological finding is shown in Table 1, where
the highest frequency was mixed tumors, then followed by teratomas
and seminomas, and it is less frequent to
find coriocacinomas and yolk sac tumors.
Twenty
patients were operated with the intent to
remove the tumor: 12 by thoracotomy 6 by sternotomy and 2 by videothoracoscopy.
12 patients underwent an apparent complete resection and 8 had a
partial
resection or biopsy only, considering it an unresectable
lesion. Out of the 20 operated patients, 14 received pre-or
postoperative
chemotherapy. At the time of the study, it was found that out of 12
patients
with apparently complete resection, 8 were found alive without disease
(VSAT),
1 patient was alive but with tumor activity (VCAT) and 3 patients died
with
tumor activity (MCAT). Out of the 8 patients with incomplete resection,
4 were
MCAT, 2 VSAT and 2 VCAT. In 9 cases that were considered unresectable
at the moment of surgery, a biopsy was performed and they were treated
with
chemotherapy. Of these, 6 were MCAT and 3 VSAT.
Overall
survival of all patients at the time of the
study was 65%, with the longest survival of 26 years. Of the 19
patients who
had more than five years after been treated, 11 were alive and 8 died,
which
represents a survival of 58% at five years. It was found that the 10
patients
with mixed tumors, regardless of whether complete resection, incomplete
or biopsy alone were performed, only two
were alive. The three
patients with teratocarcinomas were MCAT,
the
patients with choriocarcinoma: one was
VSAT and one
MCAT; and the patient with embryonal
carcinoma was
VCAT. By contrast, the 5 patients with teratomas
and
the two patients with yolk sac tumors were VSAT and the 6 patients with
seminomas: 5 were VSAT and 1 was VSAT.
Discussion
Germ cell
tumors of the mediastinum
are relatively infrequent.10 The Thoracic Surgery
Department of HCG,
is a reference center, and in a period of 26 years only 29 patients
were
operated with a rate of 1.1 case per year.
Some tumors
were diagnosed and treated using exclusively serological markers, so
the
frequency is higher than the one reported.11 In
a study by Navarro et al, in metropolitan hospitals in
The
frequency was much higher in young men, aged
between 15 and 40 years old. Most of the patients had symptoms when
they were
diagnosed, and these symptoms are the same as other tumors of the mediastinum described in literature.13 Diagnosis
is performed when looking at an abnormal widening of the mediastinum
and CT scan provides valuable information regarding the particular
characteristics of the tumor, especially to plan the route to take a
biopsy or
to perform a surgical approach.14
The
anterior mediastinostomy
is the most practical and effective method to take a representative
sample in
order to make the histological diagnosis, in this study had no
mortality and
with the exception of one case that required a video-assisted thoracoscopy, in the remaining 13 cases it was
sufficient
for the diagnosis.15, 16
It should
be noted that because of the high frequency
of mixed tumors, although a clear histological diagnosis established by
biopsy
of a specific mediastinal germ cell tumor,
one must
consider the possibility that in another site of the tumor, there is a
different histological finding. This should encourage pathologists to
study
with multiple cuts, both biopsies and excised mediastinal
masses, and oncologists, to keep it in mind.6
It was
found that the main prognostic factor was the
histological characteristics, where mixed tumors and the teratocarcinomas
had the worst prognosis. It was also found that benign teratomas
and seminomas, had a very good response to chemotherapy. Out
of the 19
patients who had more than five years after been treated, 11 were alive
and 7
died: a survival of 58% at five years.9
Surgical
excision is still the treatment of choice for
resectable tumors, which are usually histologically more benign, however, the
apparent complete
resection is not a guarantee, therefore in all cases adjuvant
chemotherapy
should be considered; and it showed be more useful, since a number of
partially
resected tumors were cured with
chemotherapy, and
some with apparent complete resection relapsed. 17
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