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Abstract
Background: Primary malignant mediastinal germ cell tumor (PMMGCT) is rare and sometimes the prognosis of
the patients with PMMGCT is not very satisfactory.
Methods: A total of 54 patients with PMMGCT in a follow-up from 1990 to 2009. We evaluated the role of the
surgical treatment and the effect of multimodality treatment strategy for patients with PMMGCT.
Results: Fifty-two patients underwent surgical resections, while the other two patients just received
chemoradiotherapy. Among the 52 patients, 28 cases received preoperative adjuvant therapy and 24 cases
underwent surgery as initial treatment; 30 cases with complete resections, 18 cases with partial resections and 4
cases with only biopsies. There was no perioperative mortality. Histopathologic results revealed 18 cases of
seminomas and 36 cases of nonseminomatous germ cell tumors (NSGCT). The last follow-up showed that 17
patients were alive, including 11 patients with seminoma and 6 patients with NSGCT. The 5-year overall survival rate
of patients with seminomas was 87.7%. The 3-year and 5-year overall survival rates of patients with NSGCT were
47.4% and 23.0%, respectively.
Conclusions: It could be concluded that a complete surgical resection of PMMGCT after chemoradiotherapy showed
favorable long-term survival. Patients with pure seminomas have a better prognosis compared with that with NSGCT.
Virtual slides: The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/
1676987232116837.
Keywords: Mediastinum, Nonseminomatous germ cell tumor, Seminoma
© 2014 Liu et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative
Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and
reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain
Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article,
unless otherwise stated.
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cancer cells in the residual mass after standard Table 1 Initial symptoms and clinical data in 18 patients
cisplatin-based chemotherapy and conventional selv- with seminoma and 36 patients with nonseminomatous
age chemotherapy and seldom results in a long-term germ cell tumor
disease-free status. Therefore, surgical resection of the Seminoma NSGCT
residual mass after chemotherapy plays an important Symptom No. of patients (%) No. of patients (%)
role in controlling mediastinal NSGCT. This multi- Chest pain 6 (33.3) 18 (50.0)
mdimensional treatment strategy serves to assess re- Dyspnea 3 (16.7) 15 (41.7)
sponse, to remove chemotherapy-resistant disease,
Cough 3 (16.7) 13 (36.1)
and to guide additional chemotherapy. Controversy
Back or shoulder pain 1 (5.6) 2 (5.6)
still exists regarding the effectiveness between surgical
resection and chemotherapy, but multidimensional Hemoptysis 0 (0) 6 (16.7)
treatment has become the standard treatment for me- Hoarsness 0 (0) 1 (2.8)
diastinal NSGCT. We retrospectively reviewed our Super vena cava syndrom 1 (5.6) 2 (5.6)
19-year experience with 54 PMMGCT patients to Fever 1 (5.6) 6 (16.7)
evaluate the efficacy and safety of the multidimen-
Weight loss 2 (11.1) 4 (11.1)
sional therapy.
Asymptomatic 2 (11.1) 1 (2.8)
NSGCT: nonseminomatous germ cell tumor.
Patients and methods
Patients
A medical records database in our department was diagnosis of mediastinal NSGCT. The initial clinical
searched retrospectively to identify patients with PMM diagnosis of mediastinal NSGCT was shown among 31
GCT. Records for operations and pathology reports were patients, and other patients were diagnosed as thymoma,
specially reviewed. Between 1990 and 2009, a total of 2152 thymic carcinoma, and mediastinal tumor, respectively.
patients with mediastinal tumors were evaluated at the
Department of Thoracic Surgery, Provincial Hospital Affil- Methods
iated to Shandong University, China. Among these pa- All statistical analyses were performed with SPSS 10.0
tients, there were 54 patients with continuous PMMGCT, statistical software (SPSS, Chicago, IL, USA). Survival
including 47 males and 7 females ranging from 14 to rate was calculated with the Kaplan–Meier method and
58 years old (average age was 27 and 28.6 years old re- difference in survival between groups was calculated by
spectively). Patients were further divided into seminoma using the log-rank test. Differences were considered to
group and NSGCT group. Seminoma mixed with other be statistically significant when the P value was less than
histologic type was classified as NSGCT. 0.05.
Fifty-one patients had symptoms at the time of diagnosis:
chest pain in 24 cases, dyspnea in 18 cases, cough in 16 Follow-up
cases, fever in 7 cases, hemoptysis in 6 cases, weight loss in After discharge from the hospital, all patients in this
6 cases, back or shoulder pain in 3 cases, superior vena cava series were evaluated every 3-month for the first 5 years
obstruction syndrome in 3 cases, and hoarseness in 1 case and 6-month intervals thereafter, as well as their clinical
(Table 1). All male patients had normal testicles. history, physical examination, laboratory analysis, CT
All patients received standard chest X-rays and com- scan. There were 6 patients out of follow-up. The date
puted tomography (CT) scans. It showed that all the tu- of death or last follow-up was defined as the endpoint.
mors were located in the anterior or anterosuperior
mediastinum. Preoperative histologic diagnosis was car- Results
ried out in 19 patients by fine needle biopsy guided by Among these 54 patients, 52 patients underwent surgical
ultrasound or CT. As a result, histologic evaluations re- resections, while the other 2 patients only received che-
vealed 7 cases of mediastinal NSGCT, 12 cases of poorly moradiotherapy. Among 52 patients treated with sur-
differentiated carcinoma or no diagnosable cells were gery, 22 patients received cisplatin-based chemotherapy
found. Serum levels of tumor markers, beta-human as basic treatment on the basis of a serologic diagnosis
chorionic gonadotropin (β-HCG) and alpha-fetoprotein or the needle biopsy followed by surgical resection; 6 pa-
(AFP), were tested in 30 patients, among which 7 pa- tients received preoperative radiotherapy, which was not
tients with elevated β-HCG, 15 patients with elevated very effective, then followed surgical resection thereafter;
AFP levels, 4 patients with elevated both β-HCG and 24 patients underwent surgery as basic treatment
AFP levels. Elevated serum in tumor markers (STM) (Table 2). Of all these 52 patients with surgery, 30 pa-
strongly indicated NSGCT. Preoperative elevated levels tients were treated with complete resection, 18 patients
of β-HCG or AFP and needle biopsy supported the with partial resection and 4 patients had only biopsy.
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Table 2 Initial therapy of 18 patients with seminoma and 36 Patients with nonseminomatous germ cell tumor
Seminoma NSGCT
No. of Complete response Partial response No. of Complete response Partial response
patients or resection or resection patients or resection or resection
Surgery 8 7 1 16 9 7
Chemotherapy 4 2 2 18 5 13
Radiotherapy 6 2 4 2 0 2
NSGCT: nonseminomatous germ cell tumor.
After operation, 42 patients received cisplatin-based with disease-free survival for over 5 years, 1 patient with
chemotherapy and followed by radiotherapy in 14 cases, a disease-free survival for 46 months and 1 patient with a
5 patients received radiotherapy only. The patients with disease-free survival for 20 months), 5 patients died of
seminomas were treated with radiotherapy doses ranging tumor-related or other causes and 1 patient was out of
from 40 Gy to 50 Gy, while the patients with NSGCT follow-up. 2 patients with seminomas were treated only
were treated with radiotherapy doses ranging from 50 Gy by chemoradiotherapy, 1 patient with a disease-free sur-
to 54 Gy. vival for over 52 months and the other patient with a
Surgical incisions have been grouped by the anatomic disease-free survival for over 2 years, but out of follow-
region and extent of the tumor: median sternotomy in 26 up thereafter. Of the 36 patients with NSGCT, 26 pa-
cases, anterolateral thoracotomy in 15 cases and postero- tients died of tumor-related causes, 6 patients were alive
lateral thoracotomy in 11 cases. Pulmonary lobectomy (including 4 patients with disease-free survival for over
was performed in 4 cases and pulmonary wedge resection 5 years, 1 patient with a disease-free survival for over
in 7 cases, partial pericardial resection in 6 cases, ipsilat- 28 months, 1 patient was alive for 4 years but with devel-
eral phrenic nerve resection in 3 cases, local chest wall oped disease recurrence) and 4 patients were out of
resection in 3 cases, superior vena cava reconstruction in follow-up. Nevertheless, all patients with NSGCT treated
1 case, orthotopic great venous reconstruction with vas- with incomplete resection died or lost to follow-up
cular prosthesis placed from the remaining left innomin- within 2 years. The median survival in the incomplete re-
ate vein to the superior vena cava-right atria junction in section group was 7 months postoperatively (ranging
1 case. These two patients who received the artificial vas- from 4 to 22 months).
cular replacement have been surviving free of disease. The overall 5-year survival rate of the patients with
There were no perioperative deaths. Major postopera- mediastinal seminoma was 87.7%. The overall 3 and 5-
tive complications occurred in 9 patients: pulmonary in- year survival rates of the patients with NSGCT were
fection in 5 patients, phrenic nerve paralysis in 3 patients, 47.4% and 23.0%, respectively. The prognosis of the pa-
concurrent thrombosis of left innominate vein in 1 patient tients with seminoma was significantly better than that
and was successfully cured by anticoagulant therapy. of the patients with NSGCT (P < 0.0001, log-rank test,
The 2 patients who didn’t receive surgery were diag- Figure 1).
nosed as seminomas via fine needle biopsy. Six histopath-
ologic categories of tumor were found in 52 patients who Discussion
underwent surgical resection, including 16 pure semino- The majority of GCT originates from gonad, whereas a
mas, 14 immature teratomas, 11 yolk sac tumors, 3 em- minority may occur in the extragonadal places such as
bryonal cell carcinoma, 3 teratocarcinomas and 5 mixed mediastinum, retroperitoneum and pineal gland [10].
tumors (yolk sac tumor and immature teratoma in 2 Primary GCT of the mediastinum is relatively rare and
cases, embryonal cell carcinoma and yolk sac tumor in 1 accounts for 10-15% of the mediastinal tumors. While
case, yolk sac tumor and seminomas in 1 case and em-
bryonal cell carcinoma and seminoma in 1 case, Table 3). Table 3 Histologic classification of 54 patients with
primary mediastinal germ cell tumors
Follow-up data after surgery were available for 48 pa-
Tumor type No. of patients Percent (%)
tients and 6 patients were out of follow up. At the last
follow-up, 17 patients were still alive, including 11 pa- Seminoma 18 33.3
tients with seminoma and 6 patients with NSGCT. York sac tumor 11 20.4
Thirty-one patients died within the follow-up period, in- Embryonal carcinoma 3 5.55
cluding 27 patients with tumor-related causes and 4 pa- Immature teratoma 14 25.9
tients without tumor-related causes. Teratocarcinoma 3 5.55
Of the 16 patients with seminomas treated with
Mixed germ cell tumor 5 9.3
surgery, 10 patients were alive (including 8 patients
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associations in mediastinal NSGCT remain to be clari- surgery is technically demanding. Nonetheless, we should
fied. We didn’t notice such associated syndromes in any perform aggressive resection in the patients with PM
of our cases. MGCT if anatomically feasible, including, if necessary,
In the last two decades, several authors have reported the artificial vascular replacement,great vein and alterna-
the effectiveness of cisplatin-based chemotherapy, which tive cardiac chamber resection. In our cases, the two pa-
has become the standard therapy for PMMGCT [4,8,9]. tients who had been performed the artificial vascular
The role of surgical resection has been changed into replacements had a better prognosis. Although the suc-
multidimensional therapy for PMMGCT. Recently, the cess of chemotherapeutic regimens in PMMGCT is im-
treatment of PMMGCT with cisplatin-based chemother- portant, skilled thoracic surgery is an equally important
apy followed by surgical resection of residual disease is component for successful multidimensional therapy. In
currently one of the most successful approaches of this series, patients with PMMGCT who underwent ini-
multidimensional therapy [18]. tial tumor resection had higher complete response rate
We currently believe that most of the patients with and disease-free survival compared with those who had
PMMGCT can not be diagnosed definitely before oper- only biopsy or partial resection. But the role of initial
ation, but only can be assured by intraoperative biopsy or tumor resection needs further evaluation in prospective
resected specimens. Primary surgical resection is still the studies.
most important way. Particularly to the patients with small Wright CD et al. had emphasized the importance of
and resectable tumors without any invasion, we should normalization of STM before surgical extirpation of re-
first perform thoractomy for radical resection, followed by sidual disease in patients with NSGCT [22]. The patients
postoperative chemotherapy and/or radiotherapy. In fact, whose STM remained elevated after first-line chemo-
patients really benefit from surgery when complete exci- therapy should receive second-line chemotherapy. But
sion can be performed, but partial resection has not been Kesler KA et al. [20] reported that operable patients
demonstrated beneficial [21]. In our cases, partial resec- should undergo surgical extirpation of residual disease
tion or partial response to chemotherapy resulted in a sub- after first-line chemotherapy, regardless of STM status.
sequent rapid progression of the disease. Therefore, In our series, the STM levels were not measured in
complete resection must be the surgical target in every some patients before or after surgery,more experiences
case. But to the patients with locally advanced tumors, would be required to evaluate the role of surgery in pa-
which involved adjacent organs and couldn’t be com- tients with an elevated and increasing STM before surgi-
pletely resected, systematic chemotherapy could be rec- cal resection.
ommended to reduce the tumor mass and prevent In conclusion, the prognosis of patients with semino-
metastases outside the mediastinum, if necessery, selvage mas is significantly better than that of patients with
resection could be performed thereafter. NSGCT. The results of multidimensional therapy for
It is well known that seminomas are radiosensitive tu- PMMGCT depend on both successful chemotherapy
mors [6]. Primary or adjuvant radiations for mediastinal and surgery. The complete resection of the tumor is im-
seminomas have been effective in the local control of portant, with wide surgical margins including great vein
the tumors [4,9,15]. Based on our observations, it ap- and adjacent structures, if necessary. New therapeutic
pears that complete surgical resection of mediastinal strategies are currently being studied in the treatment of
seminomas followed by local radiation and cisplatin- the patients with PMMGCT to minimize operative mor-
based combination chemotherapy would be the very bidity and to improve the long-term survival equivalent
effective treatment for these patients. Nevertheless, to that of testicular NSGCT.
NSGCT are relatively resistant to radiotherapy which is
not recommended. To the patients of NSGCT with large Competing interests
The authors declare that they have no competing interests.
mediastinal mass, aggressive cisplatin-based chemother-
apy followed by resection of the residual tumor has be-
Authors’ contributions
come the best approach to improve the survival of these YL, ZW and YY conceived the study idea and designed the study. YL, ZW
patients. This approach avoids demanding or incomplete and YY reviewed the literature and performed statistical analyses. YL, ZW,
resections and unnecessary resections. Thoracic surgery ZMP and YY drafted the manuscript. YL and YY reviewed and edited the
manuscript. All authors read and approved the final manuscript.
was typically delayed for 4 weeks after chemotherapy,
which allowed the patient, in particular, to have the bone Received: 23 December 2013 Accepted: 3 February 2014
marrow to recover. Published: 19 February 2014
Most of the patients with PMMGCT have large medias-
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