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Teratomas and Other Germ Cell Tumors of the Mediastinum Treatment & Management

  • Author: Dale K Mueller, MD; Chief Editor: Mary C Mancini, MD, PhD, MMM  more...
 
Updated: Nov 02, 2015
 

Medical Therapy

While most tumors and cysts of the mediastinum are treated surgically, medical therapy is the primary form of treatment in several diseases.

Germ cell seminomas

Radiation therapy is the primary treatment for seminoma. A dose range of 3000-4500 cGy is recommended. Chemotherapy often is used in patients older than 35 years or those with features of advanced disease. Cisplatin-based chemotherapy regimens are found very effective in seminoma. Some evidence suggests that chemotherapy should become the primary form of treatment for seminoma and that radiotherapy should be used for the treatment of locoregional areas of involvement. Surgery has almost no indication in seminoma except for purposes of diagnosis. Patients should receive radiotherapy even if complete resection appears to have been achieved.

Nonseminomatous germ cell tumors of the mediastinum

Benign teratomas of the mediastinum are the only mediastinal nonseminomatous germ cell tumors for which surgical resection is indicated as primary treatment.

A number of cisplatin-based chemotherapeutic protocols are used as primary treatment of malignant mediastinal nonseminomatous germ cell tumors. Initial regimens last 3-4 months with re-staging performed after completion of treatment. Recurrence develops in about 20% of cases, and salvage chemotherapy regimens are used in these patients. Surgical resection of residual disease within the chest may be required primarily for diagnosis after initial chemotherapy treatment. As many as 75% of patients requiring resection have benign teratoma, nonviable tumor, or fibrosis found.

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Surgical Therapy

Surgical resection is the treatment of choice for most neoplasms that occur in the mediastinum, except for malignant germ cell neoplasms.

The most common mediastinal tumors for which nonsurgical forms of therapy are considered the primary treatment are seminomas, malignant nonseminomatous germ cell tumors, lymphoma, and advanced-stage neuroblastoma in children.

In cases of benign neoplasms, complete excision of the lesion itself generally is sufficient. Benign teratomas are tumors for which surgical excision is adequate therapy. All benign neoplasms that are encapsulated should be resected without violation of the capsule. VATS techniques have been introduced in teratoma resection with promising results.

Surgical resection is advised in nonseminomatous malignant germ cell tumors of the mediastinum when radiographic studies show residual mediastinal disease present after appropriate chemotherapeutic treatment has been administered. Residual masses are observed in 10-20% of cases after treatment. Resection of residual masses in these cases is performed to determine the presence or absence of residual malignancy. If the former is the case, additional chemotherapeutic treatment may or may not be considered.

In cases of seminoma, some controversy exists regarding resection of residual posttreatment masses. Some authors state that no surgical intervention is needed and that radiographic follow-up is the appropriate course of action. Others state that residual masses greater than a specified size should be resected.

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Preoperative Details

Standard preoperative management applicable to all chest surgical cases applies to the preoperative management of individuals undergoing resection of mediastinal tumors. Airway management is of paramount importance when dealing with tumors that can produce a mass effect on these structures. Consider detailed preoperative assessment of the airway, as well as adequate visualization and readily available supplementary equipment (eg, flexible bronchoscope), for safe management of the airway distorted or narrowed by a mediastinal mass. Placement of a double-lumen endotracheal tube to provide single-lung ventilation usually is preferred for any procedure in which a thoracotomy approach is used.

Some mediastinal tumors may require extensive resection of adjacent tissues, and blood loss may be substantial in these cases. Provide for adequate intravenous access, appropriate monitoring capability, and necessary blood products (all of paramount importance) before the operation is begun.

Involvement of associated intrathoracic structures by tumor may mandate their resection. Pulmonary resection, excision of nervous structures (eg, phrenic, vagus, sympathetic chain), or even resection of major vascular structures (eg, superior vena cava) may be required. The surgeon must be prepared for this, and the patient must be informed preoperatively that such resection may be required because this may have additional impact on recovery and perioperative risk.

Although uncommon in cases of germ cell tumors for which surgical resection is the indicated treatment, several mediastinal tumors can produce important effects that should be taken into account preoperatively.

Superior vena cava syndrome

Superior vena cava syndrome (SVCS) can occur in association with various thoracic neoplasms. While bronchial carcinoma represents the most common cause of this problem, lymphoma, germ cell malignancies, thymic neoplasms, and a host of the less common mediastinal malignancies can produce it.

If this syndrome is noted to be acute in a patient preoperatively, treatment with bed rest, elevation of the head, and oxygen administration can be helpful. Salt restriction and diuretics generally are not indicated. Use corticosteroids only for treatment of associated laryngeal edema or in the presence of brain metastases that produce increased intracranial pressure.

Placement of intravenous lines should be planned carefully because venous inflow to the heart from the supracardiac great veins will be altered greatly. Many clinicians place intravenous lines in sites below the level of the heart to assure direct, rapid flow of medications and fluids to the heart. Intravenous lines in the neck should not be placed because jugular venous pressure may be elevated markedly, and accidental extravasation of blood from these sites may lead to airway compromise.

Intubation should be performed with care in individuals with SVCS because trauma to the airway may lead to disruption of small venous structures in the wall of the trachea. Normally, bleeding from these tiny vessels is self-limiting; however, in patients with SVCS, venous pressure is elevated, and bleeding may be more pronounced. Individuals with SVCS may not be able to lie comfortably in a supine position for an extended period of time because this produces increased intracerebral venous pressure. Consider this factor during transport and positioning of the patient.

Chronic SVCS can be treated with resection and interposition graft reconstruction if the patient is symptomatic.

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Intraoperative Details

As with all thoracic surgery, positioning the patient properly for the indicated procedure is of paramount importance. Tumors or cysts located in the anterior mediastinum generally are approached through a median sternotomy. This approach would be used for tumors of the thymus. Those located in the posterior or middle mediastinum and paravertebral sulci, such as most neurogenic tumors and foregut cysts, are approached through a posterolateral thoracotomy incision.

Standard single-lumen endotracheal intubation is appropriate for resections performed via the median sternotomy approach. Use of a double-lumen endotracheal tube for single-lung ventilation is preferable for those procedures performed through a thoracotomy incision and for all procedures performed using VATS. VATS techniques have been introduced in teratoma resection with promising results in several centers. Additional exposure includes a hemiclamshell thoracotomy with or without neck extension, which may be preferred for tumors in the anterior mediastinum with extensive involvement of the hemithorax.[7] A neck extension or supraclavicular extension can be incorporated with involvement that extends into the neck or subclavian vessels, respectively. A clamshell incision can also be used for tumors that extend into both hemithoraces. A tumor may extend to adjacent structures, and resection of the thymus, pericardium, lung, phrenic nerve, innominate vein, and superior vena cava can be appropriate.

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Postoperative Details

Care of patients after resection or biopsy of a mediastinal tumor is similar to that for any noncardiac surgery of the chest.

Extubation can be performed at the completion of the case or shortly thereafter in the postanesthesia recovery area. Some patients require ventilatory support for a longer time, and their cases should be managed accordingly.

Pulmonary toilet is an essential part of postoperative management after any kind of chest surgery to prevent atelectasis and to mobilize and clear any bronchial secretions. Various methods to assist with pulmonary toilet are available.

Pain control also is a critical factor in postoperative management after thoracic surgery. Adequate cough effort and ventilatory excursion cannot be maintained without satisfactory pain control. Administration of analgesic agents by thoracic epidural catheter is an excellent and highly effective method of pain management. Lumbar epidural catheters also can be used and, with proper choice of analgesic agents, can provide good pain relief. Patient-controlled analgesia (PCA) is another widely used method and is preferred to traditional intramuscular or intravenous administration of narcotics and other agents. It is not as efficient for pain control as epidural analgesia.

A continuous infusion of 0.25% bupivacaine at 4 mL/h through the ON-Q elastomeric infusion pump is also a safe and effective adjunct in postoperative pain management after thoracotomy. The use of the ON-Q Post-Op Pain Relief System (I-Flow Corporation, Lake Forest, Calif) results in decreased narcotic use and lower pain scores compared with continuous epidural infusion. At some point after oral intake has begun, pain medication can be converted to oral analgesic agents.

Wound management is straightforward. Operative dressings are removed after 24 hours in most cases. Thoracic surgical incisions heal well and have an extremely low rate of dehiscence and infection.

Chest tubes are managed in the same way as those used in other forms of thoracic surgery. Most cases of mediastinal tumor or cyst resection or biopsy will not involve pulmonary or esophageal resection. Chest tubes are maintained on minus 20 cm of water-seal suction, and drainage from the tubes is measured daily. Patient recovery is followed with daily chest radiographs that are evaluated for residual undrained collections, complete pulmonary expansion, lobar atelectasis and infiltrates, and other abnormalities. When drainage from the chest tubes is less than 50-100 cc in a 24-hour period, no air leak is present, and the chest radiograph shows full pulmonary expansion with no collections on the operated side, the chest tubes may be removed.

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Follow-up

Patients who undergo resection of benign neoplasms or mediastinal cysts can be observed for a short time (ie, 3-6 mo) postoperatively while wound healing and progression of patient activity is monitored.

Due to the heterogeneity and small numbers of malignant tumors found in the mediastinum, no single specific method has been described for the follow-up of patients who undergo intended curative resection of a malignant neoplasm.

Specific serum markers are very useful in posttreatment surveillance of patients with nonseminomatous germ cell tumors. These studies include alpha-fetoprotein (AFP) and beta human chorionic gonadotropin (bhCG). If serum levels are found to be elevated at some point after treatment, additional imaging studies, such as CT or PET scan of the chest, should be performed to evaluate the patient for recurrent disease. Because nearly all relapses occur within 2 years after therapy, monthly surveillance consisting of physical examination, chest radiograph, and assay of serum markers is recommended for the first year posttreatment. Surveillance is recommended every 2 months for the second year.

During follow-up for seminoma, the patient is observed for at least a 2-year period. Observation consists of a monthly physical examination and chest radiograph. If radiographic observation of a residual mediastinal mass is observed, a CT scan is performed every 3 months for the first year and then at 6-month intervals for the second year.

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Complications

Complications that occur after resection of mediastinal tumors are similar to those that can occur after any thoracic surgical procedure.

As with any thoracic surgical procedure, postoperative pulmonary complications are most common. Atelectasis is a common postoperative complication and can develop into pneumonia if not treated aggressively. As noted previously, aggressive pulmonary toilet and pain management are the key factors in the prevention of these complications.

Wound infections after sternotomy or thoracotomy are rare. The chest wall possesses excellent blood supply and, with few exceptions, healing occurs readily. Also, existing intrathoracic infection generally is not a factor during resection of any of the noted mediastinal tumors, and these operations are considered clean procedures. The exception to this might be in cases of resection of some foregut cysts that may have secondary infection present.

Appropriate preoperative, intraoperative, and postoperative antibiotic coverage is warranted. Sternal dehiscence occurs (very rarely) after sternotomy performed for noncardiac procedures. If it occurs without the presence of infection, simple washout, debridement, and rewiring can be performed. If infection is present, aggressive debridement of devascularized bone and cartilage should be performed, as well as a vigorous washout. Cases in which significant infection is present are best treated with rotation of muscle flaps, such as the pectoralis major and rectus abdominus muscles, to cover the wound. A wound vacuum-assisted closure (VAC) has also been successfully used in superficial wound infections.

Injury to the phrenic nerve can occur, resulting in temporary or permanent diaphragmatic paresis. This can cause the patient to have symptomatic dyspnea, as well as atelectasis, on the affected side. Diaphragmatic plication should be considered to prevent lower lobe atelectasis.

Young children or individuals with marginal pulmonary status from underlying pulmonary disease or those with neuromuscular abnormalities causing weakness of the muscles of respiration (eg, myasthenia gravis) can experience significant respiratory difficulties from this complication.

Injury to a vagus nerve also can occur during surgery of the mediastinum. Usually, only one vagus nerve is injured and the remaining intact nerve maintains parasympathetic input to the gut without symptoms. If both vagus nerves are injured, difficulties with gastric emptying may occur because the innervation to the pylorus is disrupted.

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Outcome and Prognosis

Prognosis after resection of a mediastinal tumor varies widely depending on the type of lesion resected.

After resection of mediastinal cysts and benign tumors, prognosis generally is excellent. Germ cell tumors included in this group are benign teratomas or dermoid cysts.

Prognosis after treatment of malignant mediastinal tumors depends upon the type of lesion, its biological behavior, and the extent of the disease present.

Prognosis for malignant germ cell neoplasms is listed below. Nonseminomatous histology, presence of nonpulmonary metastases, primary mediastinal germ cell tumor location, and elevated levels of beta human chorionic gonadotropin (bhCG) are independent prognostic factors for shorter patient survival.

Seminoma

Primary treatment for seminoma generally is radiotherapy or chemotherapy. A number of series reported cure rates of about 60-65% after primary radiotherapy and as much as an 87% long-term survival after chemotherapy is used as the primary form of treatment. Residual disease is present radiographically in 10-20% of cases after initial systemic treatment has been completed. Some controversy about the management of this problem exists. Some centers advocate close observation because many residual masses simply are fibrotic changes. However, many take an aggressive approach to radiologic evidence of residual disease and promote surgical resection.

Nonseminomatous mediastinal germ cell tumors

Long-term (longer than 24 mo) disease-free survival rates after completion of systemic chemotherapeutic treatment in these patients is about 42%. The best prognosis is for those patients who underwent resection after chemotherapy and normalized or decreased tumor marker levels.[8]

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Future and Controversies

Several exciting advances have been made in areas of diagnostic imaging, biologic analysis, and therapy.

Emerging diagnostic modalities, such as PET, as well as other radionuclide studies, may be able to assist in the diagnosis of specific neoplasms and in posttherapy surveillance for recurrent disease.

Numerous biological markers have been identified for many tumors and will play a vital role in better identifying individual neoplasms so that treatment can be optimized.

Use of video-assisted thoracic surgical (VATS) technology has entered the armamentarium of the thoracic surgeon with respect to the treatment of a number of mediastinal diseases. This modality already is used commonly for obtaining biopsy of masses and lymph nodes. It also has been described for resection of various mediastinal cysts, mediastinal parathyroid adenomas, and localized benign tumors of the posterior mediastinum such as ganglioneuromas. At several centers, thymectomy has been performed using this technology. The completeness of thymic resection able to be achieved by this approach is the subject of some controversy. VATS technology has also been reported in resecting teratomas of the mediastinum.

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Contributor Information and Disclosures
Author

Dale K Mueller, MD Co-Medical Director of Thoracic Center of Excellence, Chairman, Department of Cardiovascular Medicine and Surgery, OSF Saint Francis Medical Center; Cardiovascular and Thoracic Surgeon, HeartCare Midwest, Ltd, A Subsidiary of OSF Saint Francis Medical Center; Section Chief, Department of Surgery, University of Illinois at Peoria College of Medicine

Dale K Mueller, MD is a member of the following medical societies: American College of Chest Physicians, American College of Surgeons, American Medical Association, Chicago Medical Society, Illinois State Medical Society, International Society for Heart and Lung Transplantation, Society of Thoracic Surgeons, Rush Surgical Society

Disclosure: Received consulting fee from Provation Medical for writing.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Daniel S Schwartz, MD, FACS Medical Director of Thoracic Oncology, St Catherine of Siena Medical Center, Catholic Health Services

Daniel S Schwartz, MD, FACS is a member of the following medical societies: Society of Thoracic Surgeons, Western Thoracic Surgical Association, American College of Chest Physicians, American College of Surgeons

Disclosure: Nothing to disclose.

Chief Editor

Mary C Mancini, MD, PhD, MMM Professor and Chief of Cardiothoracic Surgery, Department of Surgery, Louisiana State University School of Medicine in Shreveport

Mary C Mancini, MD, PhD, MMM is a member of the following medical societies: American Association for Thoracic Surgery, American College of Surgeons, American Surgical Association, Society of Thoracic Surgeons, Phi Beta Kappa

Disclosure: Nothing to disclose.

Additional Contributors

Richard Thurer, MD B and Donald Carlin Professor of Thoracic Surgical Oncology, University of Miami, Leonard M Miller School of Medicine

Richard Thurer, MD is a member of the following medical societies: American Association for Thoracic Surgery, American College of Chest Physicians, American College of Surgeons, American Medical Association, American Thoracic Society, Florida Medical Association, Society of Surgical Oncology, Society of Thoracic Surgeons

Disclosure: Nothing to disclose.

Acknowledgements

The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous author Jane M Eggerstedt, MD, to the development and writing of this article.

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A 25-year-old man is found to have an asymptomatic anterior mediastinal mass on a routine chest radiograph. This posteroanterior (PA) view shows the edges of the mass extending beyond the normal heart border. At surgery, the mass was found to be a benign teratoma.
Later chest radiograph (see previous image) of a 25-year-old man with an asymptomatic anterior mediastinal mass. The arrow indicates the area the mass occupies in the anterior mediastinum. This was found to be a benign teratoma.
Table 1. Staging for Primary Gonadal Malignancies Based on TNM Classification
Stage T N M S
Stage 0 pTis N0 M0 S0
Stage I pT1-4 N0 M0 SX
Stage IA pT1 N0 M0 S0
Stage IB pT2



pT3



pT4



N0



N0



N0



M0



M0



M0



S0



S0



S0



Stage IS Any pT/Tx N0 M0 S1-3
Stage II Any pT/Tx N1-3 M0 SX
Stage IIA Any pT/Tx



Any pT/Tx



N1



N1



M0



M0



S0



S1



Stage IIB Any pT/Tx



Any pT/Tx



N2



N2



M0



M0



S0



S1



Stage IIC Any pT/Tx



Any pT/Tx



N3 M0



M0



S0



S1



Stage III Any pT/Tx Any N M1 SX
Stage IIIA Any pT/Tx



Any pT/Tx



Any N



Any N



M1a



M1a



S0



S1



Stage IIIB Any pT/Tx



Any pT/Tx



N1-3



any N



M0



M1a



S2



S2



Stage IIIC Any pT/Tx



Any pT/Tx



Any pT/Tx



N1-3



Any N



Any N



M0



M1a



M1b



S3



S3



Any S



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