You are in: eMedicine Specialties > Thoracic Surgery > Tumors Mediastinal SeminomaArticle Last Updated: May 4, 2006AUTHOR AND EDITOR INFORMATIONSection 1 of 11
  Author: Shabir Bhimji, MD, PhD, Locum Cardiothoracic and Vascular Surgeon, Saudi Arabia and Middle East Hospitals Shabir Bhimji is a member of the following medical societies: American Cancer Society, American College of Chest Physicians, American Lung Association, and Texas Medical Association Editors: Jeffrey C Milliken, MD, Chief, Division of Cardiothoracic Surgery, University of California at Irvine Medical Center; Clinical Professor, Department of Surgery, University of California at Irvine School of Medicine; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; Shreekanth V Karwande, MBBS, Chair, Professor, Department of Surgery, Division of Cardiothoracic Surgery, University of Utah School of Medicine and Medical Center; Rajalaxmi McKenna, MD, FACP, Consulting Staff, Department of Medicine, Southwest Medical Consultants, SC, Good Samaritan Hospital, Advocate Health Systems; Mary C Mancini, MD, PhD, Director of Cardiothoracic Transplantation, Professor, Department of Surgery, Louisiana State University Health Sciences Center Author and Editor Disclosure Synonyms and related keywords: mediastinal seminoma, germ cell, germ cell tumor, germ-cell tumor, germ cell mass, germ-cell mass, malignant germ cells of the mediastinum, seminoma, radiation, mediastinum, gonads, mediastinal mass, cisplatin-based chemotherapy, respiratory compromise, intrathoracic mass, anterior mediastinal mass, extragonadal malignancy, totipotential cells, spermatogenesis, median sternotomy, median sternotomy exploration, teratoma, radiation, chemotherapy, cisplatin, vinca alkaloids, etoposide, ifosfamide, bleomycin, combination chemotherapy, induction chemotherapy, mediastinum cancer, mediastinal cancer, malignant seminoma, benign seminoma INTRODUCTIONSection 2 of 11
  Germ cell tumors of the mediastinum are uncommon. Less than 5-7% of germ cells occur outside the gonads, but of the extragonadal sites, the mediastinum is the most common location for germ cell tumors. Other areas where germ cell tumors can occur are the retroperitoneum, the intra-abdominal cavity, and the chest. The exact mechanism whereby germ cell tumors originate in the mediastinum remains unknown. Germ cell tumors in the mediastinum were first reported nearly 50 years ago. Pathological studies from autopsy data revealed that the tumors were usually large and frequently locally invasive. The first theory on extragonadal malignant germ cell tumors postulated that the tumors developed from primitive germ cells in the endoderm of the yolk sac or from the urogenital ridge. These cells normally move into the scrotum during development, but when this migration fails, the cells may remain localized to either the mediastinum or the retroperitoneum. Other researchers hypothesized that these totipotential cells become detached during embryogenesis and result in primitive masses, which may develop into germ cell tumors. So far, however, no theory is proven. No research documents that these cells metastasize from gonadal tissue. Mediastinal germ cells tumors are now postulated to be autonomous oncologic entities. For excellent patient education resources, visit eMedicine's Procedures Center and Cancer and Tumors Center. Also, see eMedicine's patient education articles Bronchoscopy and Cancer: What You Need to Know. FrequencyMalignant germ cell tumors of the mediastinum are rare, accounting for approximately 10% of all mediastinal tumors. These tumors occur almost exclusively in males, and the age at presentation is generally 20-35 years. More than a third of all malignant germ cell tumors are pure seminomas. All types of malignant germ cell masses are more prevalent in males, and most of these males are symptomatic. Benign germ cell tumors, on the other hand, are distributed equally between the sexes, and most develop in the third decade of life. In children, mediastinal germ cell tumors can occur at any age and are equally divided between boys and girls. EtiologyExperimental evidence suggests that the cells responsible for mediastinal tumors are derived from germinal cells that transmigrate to the mediastinum from the urogenital ridge during embryonic life; however, not all authorities agree with this view of presupposed metastatic disease. Nevertheless, it is always important to make sure, through physical examination of the groin and scrotum, that no gonadal tumors are simultaneously present. Ultrasound is sensitive for examination of the scrotal area, and CT scanning is essential to evaluate the retroperitoneum. Although the cause of these tumors is not known, men with Klinefelter syndrome have an increased prevalence of them. Individuals with this syndrome, consisting of an extra X chromosome, are known to develop mediastinal germ cell tumors at least 10 years earlier than persons without the syndrome. Further workup in these patients has shown abnormally low levels of testosterone and high levels of luteinizing hormone and estradiol. These discoveries suggest a primary germ cell defect, which may cause faulty spermatogenesis and a predisposition to extragonadal malignancies. PathophysiologyThe histology of mediastinal tumors is very similar to that of tumors in the gonadal tissues; however, most authorities believe that metastases from the gonadal area are not responsible for the growth of these tumors in the mediastinum. In adults, germ cell tumors are the third most common type of tumor in the anterior mediastinum; in children, they are the second most common anterior mediastinal mass. Fortunately, most of these lesions are benign teratomas. Of the germ cell tumors, benign teratomas (ie, dermoid cysts) are the most commonly diagnosed mediastinal mass and are present in 50-70% of infants and children with germ cell tumors. Seminomas are the predominant malignant lesions, accounting for nearly 50% of mediastinal lesions. Pathology Mediastinal seminomas are generally bulky tumors and tend to infiltrate into adjacent structures early in the growth process. The cells are large and contain variable amounts of glycogen. These tumors are composed of large cells with multiple nuclei, which closely resemble syncytiotrophoblasts. Unlike other germ cell tumors, seminomas tend to remain localized in the chest, and only occasionally invade adjacent structures. However, these tumors are sometimes discovered late, and extrathoracic spread is sometimes observed. The usual route of metastases is hematogenous, and the major organs to which metastases occur are the lungs, liver, and bones. ClinicalThe clinical manifestations of seminomas depend on their histology. In most benign cases, seminomas are discovered on a routine chest radiograph. Patients with malignant seminomas usually present with symptoms of compression or invasion of surrounding structures and, uncommonly, systemic effects of the tumors. Constitutional symptoms (eg, pain, weight loss, fever, fatigue, dyspnea) have all been described. Occasionally, mediastinal adenopathy and superior vena cava syndrome may occur. Unlike nonseminomas, most seminomas have a localized effect and remain intrathoracic. They are rarely associated with other syndromes. INDICATIONSSection 3 of 11
Surgery is not the prime treatment modality, and more than 50% of patients are deemed to have unresectable tumors. For this reason, surgery is usually reserved for only small mediastinal masses in asymptomatic patients. Even in this situation, surgery has been associated with a high rate of recurrence and must therefore be accompanied by some form of adjuvant therapy, even if the resection appears to be complete. When complete excision is not possible, a biopsy is performed to confirm the diagnosis and an alternative treatment is started. Because these tumors are quite responsive to radiation, performing high-risk surgery (with its potential for injuring mediastinal structures) is unnecessary. RELEVANT ANATOMYSection 4 of 11
Seminomas usually develop in the anterosuperior mediastinum and can develop into fairly large tumors. The tumors usually grow at the juncture of the innominate vein and the superior vena cava. As a tumor grows, it can compress the above structures and invade the adjacent fatty tissues. When a seminoma is large, differentiating the mass from the thymic fat and surrounding pericardium is difficult. CONTRAINDICATIONSSection 5 of 11
Surgery should not be undertaken without a tissue diagnosis because (1) seminomas respond poorly to surgery and have a high rate of recurrence and (2) the mediastinal mass may be a lymphoma (more common in young males) instead of a seminoma and lymphomas usually respond to chemotherapy. Furthermore, if the patient has severe tracheomalacia from prolonged compression of the trachea by the tumor, anesthesia is not recommended. Finally, if the patient has metastatic disease or numerous medical conditions, surgery is best avoided. WORKUPSection 6 of 11
Lab Studies
Imaging Studies
Diagnostic Procedures
TREATMENTSection 7 of 11
Medical therapyThe current therapy for seminomas depends on presenting features at the time of diagnosis and staging. Treatment usually involves a combination of surgery, radiotherapy, and systemic chemotherapy. RadiationIn the past, primary treatment with radiation often yielded survival rates of 50-60%. The standard radiotherapy protocols call for 40-50 Gy delivered by external beam radiation to the mediastinum and supraclavicular regions. The neck region is included in the field of radiation because of the tendency of seminomas to initially spread to the cervical lymph nodes. Some oncologists also incorporate the axilla in the radiation field when the cervical nodes are enlarged. The radiation therapy is administered at a daily dose of 45-60 Gy over a period of 6 weeks. A failure of radiation therapy is believed to be due to the development of distant metastases rather than local recurrences. Combination treatment with radiation and surgery is not logical because both are aimed at achieving local control only. Because these tumors are bulky at presentation, the radiation may not encompass the entire tumor. Complications The complications of radiation are well known and predictable. Rapidly dividing cells are affected most significantly; these include cells of the dermis and the GI tract. Patients may present with nausea, vomiting, general malaise, poor wound healing, eczema, and ulcerations. The most frequent adverse effect is esophagitis, which occurs in most patients following radiation to the chest. This complication usually occurs 2 weeks after the start of radiation and subsides 1-2 weeks after completion. All patients may have radiographic evidence of radiation-induced pneumonitis, but less than 5% of patients may be clinically symptomatic. Life-threatening pneumonitis occurs in less than 1% of patients. Late complications may include bone deformities, cataracts, sterility, lung fibrosis, chromosomal damage, and, perhaps, an increased risk of cancer. Although rare, the risks of radiation-induced myocarditis and pericarditis are directly related to the amount of cardiac tissue near the field of treatment. ChemotherapyIn the last decade, significant improvements in survival have been achieved with multimodal chemotherapy regimens involving bleomycin, cisplatin, and etoposide. Cisplatin-based chemotherapy has induced complete responses in a small number of patients with seminomas. Chemotherapy is administered in 4-6 cycles, and intermittent pulmonary function tests are performed in all patients because of the toxicity of bleomycin to the lungs. At present, cisplatin forms the basis of most combination chemotherapeutic regimens that are active against seminomas. Other agents used for chemotherapy are vinblastine, cyclophosphamide, and dactinomycin. The response rates are difficult to compare with most other study results because many of the studies on these 3 agents were not randomized. In addition, the patient populations have been heterogeneous, and the chemotherapeutic regimens have been different. Chemotherapy clearly exerts a biologic effect in patients with advanced disease. Whenever possible during clinical trials, patients should be treated with either newer agents or a combination of agents. At this time, chemotherapy is sufficiently justified for use in patients with advanced disease, provided its limitations and toxicity are understood. Cisplatin Cisplatin is an important agent in the treatment of seminomas and is generally administered in combination with other agents in divided doses over 3-5 days. Cisplatin is recognized as an excellent agent because of its superior activity and its only modest myelosuppression. It generally acts in synergy with other chemotherapeutic agents. For this reason, it forms the basis of most combination regimens. In addition, cisplatin can be administered with thoracic radiation without undue toxicity. Various platinum analogs, such as carboplatin and iproplatin, are now available. These agents induce greater response but may be more myelosuppressive than cisplatin. Vinca alkaloids Both vincristine and vinblastine have been used to treat seminomas. These agents act as mitosis inhibitors by binding to microtubules and causing arrest in the metaphase. Although these alkaloids share a similar structure, they have a wide spectrum of clinical activity and toxicity. They are almost always used in combination with other chemotherapeutic agents. Etoposide Etoposide, an epipodophyllotoxin, has only mild activity as a single agent but because of its synergy with other agents is always used in combination regimens. This agent shows phase-specific activity for cells in the dividing phase. The correct dosing is still being debated, but most authorities recommend long-term administration for weeks. Ifosfamide Ifosfamide is a non–cell-specific alkylating agent that is replacing cyclophosphamide in many studies. It can be used in higher doses than cyclophosphamide, although hemorrhagic cystitis is still a major adverse effect. It can also cause renal and hepatic dysfunction. Ifosfamide is generally administered intravenously. Bleomycin Bleomycin belongs to the antibiotic classification of chemotherapeutic drugs. It is derived from Streptomyces and causes breaks in the DNA molecule. Bleomycin is used in combination therapy and is usually administered parenterally. Although it has a number of adverse effects, the most well known is pulmonary fibrosis. Complications of chemotherapy All chemotherapeutic agents have side effects. Most agents are associated with adverse effects, and some have specific organ toxicity. Most produce nausea, vomiting, and flulike syndromes. Cisplatin can cause renal dysfunction, and renal parameters must be constantly monitored. Cisplatin is also associated with ototoxicity, neurotoxicity, anaphylaxis, a Raynaud-type phenomenon, and local vesication. Ifosfamide can cause myelosuppression, renal and hepatic dysfunction, hemorrhagic cystitis, alopecia, and confusion. Etoposide can also cause myelosuppression and has been associated with bronchospasm, hypotension, and ileus. Bleomycin can cause fever and pulmonary fibrosis. Combination therapy with radiation and chemotherapyRecent clinical trials have demonstrated excellent results when multimodality chemotherapy is combined with radiation for large, localized mediastinal seminomas or extensive residual disease. In these cases, the patient is administered chemotherapy consisting of cisplatin, bleomycin, and etoposide. After the patient has recovered (4-6 wk), radiation is administered at a dose of 40-60 Gy for 4-6 weeks. A CT scan is then obtained to assess the response of the tumor to treatment. If only a small mass remains, it is excised. Follow-up careAfter radiation and/or chemotherapy, CT scans are delayed for 6 weeks to allow maximum reduction of the mass. Regular blood workups are obtained to assess the effects of chemotherapy on the bone marrow, kidneys, and liver. Residual disease as seen on radiographs following treatment is a medical dilemma. If CT scans reveal a residual mediastinal mass, surgery is offered; however, some patients still have viable seminomas or teratomas after excision If a small mediastinal mass remains after nonsurgical therapy, it must be excised; however, this treatment is not a universal protocol. Some oncologists instead prefer to monitor these masses with serial CT scans, a course that carries a risk of recurrent disease. Surgical therapyStrict airway maintenance is required whenever patients with large anterior mediastinal tumors are sedated because these tumors can compress the trachea and make intubation difficult. A rigid bronchoscopy cart must always be available during this procedure. All anesthesia must be reversed before extubating the patient. Some patients may require longer intubation and may be extubated slowly, after the administration of steroids and bronchodilators. An arterial line, a Foley catheter, and a dose of preoperative antibiotic are required. Preoperative detailsGenerally, most patients with seminomas are young, healthy males who have minimal comorbid disorders. The preoperative workup for patients with mediastinal tumors involves CT scanning, pulmonary function tests, and nutritional status assessment. Because the mass in the mediastinum has the tendency to compress the airways, knowing the extent of airway compromise before the operation is extremely important. Bronchoscopy must be performed if bronchomalacia is possible. If the airway is compromised, anesthesia must be induced with the patient in a semi-Fowler position and a long endotracheal tube that can bypass the obstructed site must be used. If the mass has produced symptoms of superior vena cava compression, MRI can be ordered. MRI does not require contrast and can help identify the site and extent of obstruction. In all patients with superior vena cava obstruction, lower extremity intravenous access must be available. Some surgeons also recommend that standby cardiopulmonary bypass be available when patients have tracheal compromise or superior vena cava syndrome. Intraoperative detailsDepending on the mass location, excision via a thoracotomy can be performed; however, the typical and preferred incision for anterior mediastinal tumors is the median sternotomy. The sternum is divided from the suprasternal notch to the xiphoid, and all bleeding from the sternum is stopped. Once hemostasis has been achieved, the tumor is palpated in the anterior mediastinum prior to any resection. Structures such as the superior vena cava, pericardium, innominate vein, pleura, and phrenic nerves are identified. Because seminomas are sensitive to radiation, unnecessary resection of vital structures must be avoided. When the entire mass is not resectable, adjuvant radiation is required. Once the mass (or appropriate portions thereof) is resected, complete hemostasis is obtained and mediastinal drainage tubes are inserted. Surgical clips are placed in the area where the mass was excised to allow for the radiation field to be mapped later. If the pleural space was inadvertently entered, chest drainage tubes are also placed. The sternum is closed with wires, and the patient is awakened from anesthesia. Postoperative detailsThe typical patient with an anterior mediastinal mass is observed in the ICU for a few hours and, if hemodynamically stable with minimal chest drainage, is transferred to a monitored floor. Postoperative chest radiographs are obtained in every patient to view the placement of the drainage tubes and endotracheal tube (if present) and to assess for pneumothorax. Intravenous fluids are kept to a minimum, and adequate pain control is maintained. Most drainage tubes are removed on the second postoperative day, and the patient is encouraged to ambulate. Daily chest radiographs are not required after the mediastinal drains have been removed, but they are obtained after the chest tubes are removed in order to evaluate for the presence of pleural fluid or pneumothorax. The average hospital stay after a routine median sternotomy exploration is approximately 2-4 days. COMPLICATIONSSection 8 of 11
Because surgery is usually performed for small tumors, complication rates are much lower. The usual complications following a median sternotomy include incision pain, atelectasis, injury to the phrenic nerve and/or vascular structures, and postoperative bleeding. A common complication is airway compression from the mediastinal mass. During anesthesia, intubation may prove to be very difficult. Additionally, some patients may not be able to be weaned off the respirator because the prolonged compression of the airways may have caused tracheobronchomalacia. These patients may remain intubated for prolonged periods and may even require stenting of the airways. When aggressive surgical resection is undertaken for a seminoma, injury to the phrenic nerve(s) can result in diaphragm paralysis; however, in young, healthy patients, the complication rates are negligible, and most patients have an uneventful recovery. OUTCOME AND PROGNOSISSection 9 of 11
Surgical results for mediastinal seminomas range from poor to borderline. All series in which a mediastinal mass has been completely resected have shown 5-year survival rates of less than 50%, with a greater than 40% chance of recurrence. However, most patients who present with seminomas have a large anterior mediastinal mass, and surgery is rarely the first choice of treatment. In the last decade, the general trend has been to refer all patients with seminomas, regardless of size, for radiation therapy and chemotherapy. In current practice, seminomas are curable with aggressive treatment. The treatment of pure seminomas today is nonsurgical; only the small, resectable tumors in asymptomatic patients should be completely excised and managed with postoperative radiation, with doses of 40-50 Gy. If distant metastases are detected at the time of diagnosis, the patient should be treated with intensive cisplatin-based combination chemotherapy. Even though these tumors are very sensitive to radiation, remissions are observed in only 50-70% of patients; therefore, combination chemotherapy is recommended for bulky disease and radiation is recommended for localized disease. For bulky tumors, induction chemotherapy is administered and any residual disease revealed on a CT scan is then resected to determine if a viable tumor remains. A finding positive for a tumor may dictate further therapy. If no lesion is observed on the CT scan, no further therapy is warranted and the patient can be monitored with serial CT scans every 6-12 months. Current treatment regimens provide remission in more than 80% of individuals, and the 5-year survival rate is reported to be approximately 60-80%. FUTURE AND CONTROVERSIESSection 10 of 11
Seminomas generally affect young males in their second or third decade of life. For localized seminomas, the current treatment is radiation. Surgery is reserved for patients with residual masses after successful treatment with radiation, chemotherapy, or both. Because most patients are young, an aggressive approach with newer, multimodality treatments should be the intent in all patients. REFERENCESSection 11 of 11
Article Last Updated: May 4, 2006 |
