The majority of GCT originates from gonad, whereas a minority may occur in the extragonadal places such as mediastinum, retroperitoneum and pineal gland . Primary GCT of the mediastinum is relatively rare and accounts for 10-15% of the mediastinal tumors. While PMMGCT is rather rare and only accounts for 1-4% of the mediastinal tumors . The exact pathogenesis of GCT in the mediastinum is still uncertain. Retroperitoneal germ cell tumors are generally considered to be metastases from primary gonadal lesions, whereas the origin of primary mediastinal and pineal lesions has been a matter of speculation. It is hypothesized that extragonadal germ cell tumor (EGCT) is either a consequence of an abnormal migration of germ cell along the midline from the yolk sac to the embryonic gonadal ridge during embryogenesis or result from germ cells that are distributed physiologically in the liver, bone marrow and brain in order to provide regular functions or convey hematologic or immunologic information . Thus, the midline structures, the anterior mediastinum especially, are the most common occurrence site of EGCT. EGCT can be developed as primary neoplasm in the pineal gland, retroperitoneum, sacral area and hence they may also be in gonadal originallyv .
PMMGCT are rare and occur predominantly in young adults . In our cases, male patients account for the vast majority, the mean age at the time of diagnosis was 27 years. PMMGCT are divided into two broad groups, seminomas and NSGCT. Seminomas retain the morphology of spermatogonial germ cells and are extremely sensitive to treatment by radiation as well as chemotherapy [10, 13]. NSGCT includes yolk sac tumor, embryonal carcinoma, choriocarcinoma, immature teratoma, terato- carcinoma and mixed tumors with both differentiated and undifferentiated elements . They are, as a group, still sensitive to chemotherapy, although they are less sensitive to radiationtherapy than seminomas . Seminomas are the most common mediastinal malignant GCT . Cesar A et al. reported that primary mediastinal seminomas accounted for approximately 37% of all mediastinal GCT  and Clamon and Economon et al. reported that one-half of malignant GCT are seminomas [15, 16]. In our series, seminomas occupy 33.3% of all malignant tumors. A higher incidence of NSGCT was found, this may attribute to the cases of immature teratoma. Cesar A reported that yolk sac tumor is the most common NSGCT of the mediastinum, accounting for 12% of all GCT in this location . We retrospectively reviewed 54 cases of continuous PMMGCT in our hospital, including 11 yolk sac tumors.
PMMGCT is often prone to be misdiagnosed, because of their nonspecific clinical symptoms. The presenting symptoms are cough, chest pain, hemoptysis, and/or dyspnea which are second to compression of adjacent tissues. In addition, some patients presented without any symptoms, and the diagnosis was made by a routine physical or radiographic examinations. Sometimes, the diagnosis of PMMGCT may be confused with thymoma, thymic carcinoma and Hodgkin’ disease. In this case, a careful clinical history and the serum levels of β-HCG and AFP may be helpful in making accurate diagnosis. The elevated serum markers of β-HCG and/or AFP will ultimately favor a diagnosis of NSGCT. Takeda S et al. reported that approximately 90% of their patients with NSGCT had elevated STM levels . In our series, the patients with elevated β-HCG and/or AFP are all histologic NSGCT. Some patients were treated with chemotherapy according to the elevated levels of STM. It has also been reported that the STM levels can be survival predictive . Furthermore, the definite diagnosis of PMMGCT relies on pathological examinations. Sometimes, PMMGCT are morphologically indistinguishable from some other malignant tumors, but immunohistochemical studies will ultimately lead to the correct diagnosis. For decades, the preoperative cytologic examination by percutaneous fine-needle biopsy has become the common method to diagnose the mediastinal mass. But sometimes, the needle biopsy samples are too small to do immunohistochemical studies, so the preoperative needle biopsy is usually unreliable. Furthermore, it also increases the possibility of needle track implantation. In our series, 19 patients had needle biopsy, only 7 patients with accurate diagnoses. In this regard, biopsy via mediastinoscopy or thoracoscopy is required for the final diagnosis of highly suspected PMMGCT,but the risk also increases. In addition, GCT could have a mixed histology, so the diagnosis of seminoma based on small biopsy specimens should be considered clinically as well as histopathologically.
Associated syndromes, such as hematologic malignancies (leukemia or myelodysplastic syndrome) have already been reported in some patients with PMMGCT . In addition, NSGCT is occasionally associated with klinfelter syndrome . However, the reasons for these associations in mediastinal NSGCT remain to be clarified. We didn’t notice such associated syndromes in any of our cases.
In the last two decades, several authors have reported the effectiveness of cisplatin-based chemotherapy, which has become the standard therapy for PMMGCT [4, 8, 9]. The role of surgical resection has been changed into multidimensional therapy for PMMGCT. Recently, the treatment of PMMGCT with cisplatin-based chemotherapy followed by surgical resection of residual disease is currently one of the most successful approaches of multidimensional therapy .
We currently believe that most of the patients with PMMGCT can not be diagnosed definitely before operation, but only can be assured by intraoperative biopsy or resected specimens. Primary surgical resection is still the most important way. Particularly to the patients with small and resectable tumors without any invasion, we should first perform thoractomy for radical resection, followed by postoperative chemotherapy and/or radiotherapy. In fact, patients really benefit from surgery when complete excision can be performed, but partial resection has not been demonstrated beneficial . In our cases, partial resection or partial response to chemotherapy resulted in a subsequent rapid progression of the disease. Therefore, complete resection must be the surgical target in every case. But to the patients with locally advanced tumors, which involved adjacent organs and couldn’t be completely resected, systematic chemotherapy could be recommended to reduce the tumor mass and prevent metastases outside the mediastinum, if necessery, selvage resection could be performed thereafter.
It is well known that seminomas are radiosensitive tumors . Primary or adjuvant radiations for mediastinal seminomas have been effective in the local control of the tumors [4, 9, 15]. Based on our observations, it appears that complete surgical resection of mediastinal seminomas followed by local radiation and cisplatin-based combination chemotherapy would be the very effective treatment for these patients. Nevertheless, NSGCT are relatively resistant to radiotherapy which is not recommended. To the patients of NSGCT with large mediastinal mass, aggressive cisplatin-based chemotherapy followed by resection of the residual tumor has become the best approach to improve the survival of these patients. This approach avoids demanding or incomplete resections and unnecessary resections. Thoracic surgery was typically delayed for 4 weeks after chemotherapy, which allowed the patient, in particular, to have the bone marrow to recover.
Most of the patients with PMMGCT have large mediastinal mass, even extensive involvement of the adjacent organs. Not infrequently, the mediastinal mass is adherent to the mediastinal surfaces of the cardiac chambers, surgery is technically demanding. Nonetheless, we should perform aggressive resection in the patients with PMMGCT if anatomically feasible, including, if necessary, the artificial vascular replacement,great vein and alternative cardiac chamber resection. In our cases, the two patients who had been performed the artificial vascular replacements had a better prognosis. Although the success of chemotherapeutic regimens in PMMGCT is important, skilled thoracic surgery is an equally important component for successful multidimensional therapy. In this series, patients with PMMGCT who underwent initial tumor resection had higher complete response rate and disease-free survival compared with those who had only biopsy or partial resection. But the role of initial tumor resection needs further evaluation in prospective studies.
Wright CD et al. had emphasized the importance of normalization of STM before surgical extirpation of residual disease in patients with NSGCT . The patients whose STM remained elevated after first-line chemotherapy should receive second-line chemotherapy. But Kesler KA et al.  reported that operable patients should undergo surgical extirpation of residual disease after first-line chemotherapy, regardless of STM status. In our series, the STM levels were not measured in some patients before or after surgery,more experiences would be required to evaluate the role of surgery in patients with an elevated and increasing STM before surgical resection.
In conclusion, the prognosis of patients with seminomas is significantly better than that of patients with NSGCT. The results of multidimensional therapy for PMMGCT depend on both successful chemotherapy and surgery. The complete resection of the tumor is important, with wide surgical margins including great vein and adjacent structures, if necessary. New therapeutic strategies are currently being studied in the treatment of the patients with PMMGCT to minimize operative morbidity and to improve the long-term survival equivalent to that of testicular NSGCT.