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Thymic Tumors Treatment & Management

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

Approach Considerations

The National Comprehensive Cancer Network (NCCN) has published guidelines on the treatment of thymoma and thymic carcinoma.[8]

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Medical Therapy

While most tumors and cysts of the mediastinum are treated surgically, medical therapy is the primary form of treatment in several diseases. Thymic neoplasms are discussed as follows:

Thymoma

Although surgical resection is the preferred treatment for thymoma, patients with clinically unresectable extrathoracic disease require radiation therapy, chemotherapy, or both. Radiation therapy is an essential part of the treatment of any thymoma with invasive characteristics. Controversy exists regarding the use of radiation therapy for patients with stage I tumors; however, it is recommended for those with tumors in more advanced stages, although a recent study demonstrated no advantage for stage II thymic tumors.[9] Radiation therapy has also been used preoperatively to facilitate the resection of bulky tumors; however, this role is usually played by chemotherapy.

Cisplatin-based chemotherapy regimens are often recommended for patients with unresectable stage III disease or with disseminated stage IV disease. Chemotherapy is also a useful induction agent for locally advanced thymomas to facilitate resection of these bulky tumors.[10] Cisplatin-based regimens have shown promise for improving both resectability and long-term patient survival.

Thymic carcinoma

Because the number of these cases is limited, limited data are available regarding specific modes of treatment. Radiotherapy may be indicated for thymic carcinoma, as some long-term patient survival has been achieved even with radiation as a primary modality of treatment.

Cisplatin-based chemotherapy protocols have been used in some cases of undifferentiated mediastinal carcinoma and may be applicable to cases of recurrent or metastatic disease.[10] Because cases are limited, the effectiveness of treatment regimens is difficult to evaluate. Several cases describe some long-term survivors.

Neuroendocrine tumors of the thymus

Radiation and chemotherapy have not been found beneficial in the treatment of thymic neuroendocrine malignancies. Radiation therapy has been reported to provide local control and help limit symptoms due to paraneoplastic syndromes.

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Surgical Therapy

Surgical resection is the treatment of choice for most neoplasms that occur in the mediastinum.

In cases of benign neoplasms, complete excision of the lesion itself is generally sufficient. Thymoma is one exception to this principle because, in addition to removal of the tumor, total thymectomy is indicated for all thymomas. All benign neoplasms that are encapsulated should be resected without violating the capsule.

In cases of malignant neoplasms, complete resection including local extension should be included as indicated. Pericardium, brachiocephalic vein, superior vena cava, lung, pleura, sternum, ribs, phrenic nerve, and diaphragm have all been resected with extensive malignant thymomas.

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Preoperative Details

Standard preoperative management applicable to all thoracic surgical cases applies to the preoperative treatment 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. Safe management of the airway distorted or narrowed by a mediastinal mass involves (1) performing a detailed preoperative assessment of the airway, (2) achieving adequate visualization, and (3) having supplementary equipment (eg, flexible bronchoscope) readily available. Placement of a double-lumen endotracheal tube to provide single-lung ventilation is usually 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 extremely important, before surgery is begun.

Involvement of associated intrathoracic structures by tumor may mandate their resection. Pulmonary resection, excision of nervous system structures (eg, phrenic, vagus, sympathetic chain), sternum, rib, or even resection of major vascular structures (eg, superior vena cava, brachiocephalic vein) 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.

Several mediastinal tumors can produce important effects that should be taken into account preoperatively.

Indications and results of salvage surgery in mediastinal tumors are still unclear. Mediastinal salvage surgery is defined as surgical resection of persistent or recurrent primary mediastinal tumors after previous local treatments with curative intent or exclusive chemotherapy in case of bulky tumors. A recent study concluded that mediastinal salvage surgery can offer a chance of curative treatment in selected patients with an acceptable morbidity and mortality.[11] Thymic tumors obtain the best results in term of long-term survival.

Superior vena cava syndrome

Superior vena cava syndrome (SVCS) can occur in association with a variety of 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 the syndrome.

If SVCS is noted to be acute in a preoperative patient, treatment with bedrest, elevation of the head, and oxygen administration can be helpful. Salt restriction and diuretics are generally not indicated. Corticosteroids can be useful for treatment of associated laryngeal edema or in the presence of brain metastases producing increased intracranial pressure. High-dose corticosteroids can result in a transient reduction in size of some mediastinal neoplasms, such as lymphomas, and may be useful as immediate treatment.

Care must be used in the placement of intravenous lines because venous inflow to the heart from the supracardiac great veins will be greatly altered. 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. Try to not place intravenous lines in the neck because jugular venous pressure may be markedly elevated and accidental extravasation of blood from these sites may lead to airway compromise.

Intubation must 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 because this produces increased intracerebral venous pressure. Take this factor into account during transport and positioning of the patient.

Myasthenia gravis

Approximately 30-50% of individuals with thymomas have some clinical evidence of myasthenia gravis. Attempts to stabilize neuromuscular symptoms associated with this disease with medical treatment prior to surgery are important. Medications used include pyridostigmine bromide (Mestinon), corticosteroids, and various immunosuppressive agents. If symptoms cannot be stabilized with medication, plasmapheresis is indicated. This preoperative management should be performed in conjunction with neurologist consultation.

Anesthetic considerations are directed at avoidance of perioperative myasthenic crisis and management of medications so that respiratory function and muscle strength are maximal at the completion of surgery. Usually, only a mild sedative and atropine are given preoperatively. Anticholinergic medications are avoided, as are muscle relaxants. Appropriate levels of anesthesia are obtained using inhalation agents and short-acting narcotics. Airway management with single-lumen endotracheal intubation is performed and presents no problem. Some centers use perioperative short courses of high-dose corticosteroids.

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Intraoperative Details

As with all thoracic surgery, the position of the patient is of paramount importance. Tumors or cysts located in the anterior mediastinum are generally approached through a median sternotomy. This approach is used for tumors of the thymus, although many incisions are appropriate. Tumors and cysts 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. Lateral thoracotomy and bilateral subcostal incision with transverse sternotomy (clamshell) have also been used in the treatment of thymomas. These incisions may be prudent for a small number of cases, including recurrent disease or tumor extension into the posterior mediastinum. Partial sternotomy and a transcervical approach have also been used; these approaches offer a cosmetic advantage. The da Vinci Surgical System (Intuitive Surgical, Inc., Sunnyvale, Calif) has been reported to be used for thymectomy.[12]

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, clamshell, and VATS.

VATS has been used for resection of selected tumors of the mediastinum. Thymectomy for encapsulated thymomas that range from small to moderate in size has been performed using this method, as has resection of various neurogenic tumors and foregut cysts. Regardless of the method chosen to accomplish thymectomy, this operation requires complete removal of all thymic tissue, which generally includes a large adipose component in the adult. When this is performed, certain mediastinal structures are virtually skeletonized. Care must be taken during these procedures to avoid damage to the phrenic nerves and to the brachiocephalic veins.

Extensive thymic tumors may be found to invade the superior vena cava or the brachiocephalic veins. Some of these structures may be resected with the tumor. Should this be necessary, a number of options are available for replacement of the superior vena cava or the innominate vein. Autologous venous, pericardial, and prosthetic grafts have been used.

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Postoperative Details

Care of patients after resection or biopsy of mediastinal tumors 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. Patients who require ventilatory support for a longer period should be treated accordingly.

Pulmonary toilet is an essential part of the postoperative management after any kind of chest surgery to prevent atelectasis and mobilize and clear any bronchial secretions. Various methods are available to assist with pulmonary toilet, including chest physiotherapy, incentive spirometry, and respiratory treatments with inhaled bronchodilators.

Pain control is also 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 via a thoracic epidural catheter is an excellent and highly effective method of pain management. Lumbar epidural catheters can also be used and, with proper choice of analgesic agents, can provide good pain relief. 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.

Patient-controlled analgesia 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 compared to epidural analgesia. At some point after oral intake has begun, pain medication can be converted to oral analgesic agents.

Wound management is straightforward. In most cases, operative dressings are removed after 24 hours. 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 do 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. Patients are monitored 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 mL in a 24-hour period, when no air leak is present, and when 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 followed for a short time (ie, 3-6 mo) postoperatively while wound healing and progression of patient activity are being monitored.

After resection of a thymoma, patients may be monitored using CBC count, chest radiography, and chest CT studies at appropriate intervals. One published recommendation suggests monitoring postoperative patients with malignant thymoma every 6 months for the first 5 years and annually thereafter. According to this follow-up protocol, a CBC count and chest radiograph are performed every 6 months in the first year, and then these studies, along with chest CT scan, are performed annually.

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Complications

Appropriate preoperative, intraoperative, and postoperative antibiotic coverage is warranted. Sternal dehiscence occurs very rarely after sternotomy performed for noncardiac procedures. If dehiscence occurs in the absence of infection, the sternum can be debrided and rewired primarily. If infection is present, aggressive debridement of devascularized bone and cartilage is needed, as is vigorous irrigation of the area. 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. Omentum can also be used in these cases.

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

In infected cases, appropriate preoperative, intraoperative, and postoperative antibiotic coverage is warranted, usually with a third-generation cephalosporin unless a particular organism is isolated. In that case, antibiotic coverage is tailored to the sensitivities reported.

Injury to the phrenic nerve can occur, resulting in temporary or permanent diaphragmatic paralysis. This can cause the patient to have symptomatic dyspnea and atelectasis on the affected side.

Individuals with marginal pulmonary status from underlying pulmonary disease or those with neuromuscular abnormalities causing weakness of the muscles of respiration, such as those with myasthenia gravis, can experience significant respiratory difficulties from this complication.

Injury to a vagus nerve can also 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 is generally excellent. Thymic neoplasms included in this group are thymolipomas. Prognosis after treatment of malignant mediastinal tumors depends on the type of lesion, its biological behavior, and the extent of the disease present.

Thymoma

Thymomas are not considered benign neoplasms. Survival rates associated with tumors that are encapsulated or stage I is 95-97% at 5 years and 80-95% at 10 years. Invasive or stage II tumors are associated with a reduced 5-year survival rate of 60-70% and a 10-year survival rate of 40-50%. Survival rates for stage III tumors are reported to be less than 60% at 5 years and 14% at 10 years. Survival rates for stage IVA tumors have been reported at 40% for 5 years and 0% at 10 years.

Surgical resection should be considered for patients with recurrent thymoma.[13]

Other thymic malignancies

Squamous cell carcinoma of the thymus is quite rare, with fewer than 200 cases reported in the literature. Prognosis is considered excellent in cases of well-differentiated squamous cell tumors found and resected early. Poorly differentiated tumors have a uniformly poor prognosis.

The overall cure rate for neuroendocrine tumors of the thymus is low. One series reports a 13% 5-year survival rate.

The survival rate for patients with thymic epithelial neoplasms is 77% at 5 years. Risk factors with prognostic significance included staging and histologic type.

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Future and Controversies

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

Emerging diagnostic modalities such as PET scanning and other radionuclide studies may assist in the diagnosis of specific neoplasms and in posttherapy surveillance for recurrent disease. PET scanning has preliminarily demonstrated the ability to differentiate benign thymomas and malignant thymomas.

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 VATS and robotic technology has entered the armamentarium of the thoracic surgeon with respect to the treatment of a number of mediastinal diseases. This modality is already commonly used for biopsy of masses and lymph nodes. It has also been described for resection of various mediastinal cysts, mediastinal parathyroid adenomas, and localized benign tumors of the posterior mediastinum, such as ganglioneuromas. The success of these modalities will be determined by data obtained in the long-term follow-up of cases. Because these neoplasms grow slowly, these data are not yet available.

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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 Drugs & Diseases gratefully acknowledge the contributions of previous author Jane M Eggerstedt, MD, to the development and writing of this article.

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Posteroanterior chest film of a 34-year-old woman with large anterior mediastinal mass. Pathology results indicated malignant thymoma.
Lateral view of tumor in the image above (a 34-year-old woman with anterior mediastinal mass found to be a malignant thymoma). Note the fullness and haziness above the heart shadow.
CT scan view of tumor in the images above (a 34-year-old woman with large anterior mediastinal mass found to be a malignant thymoma). Arrow indicates the area in which the tumor (malignant thymoma) is invading the anterior chest wall.
 
 
 
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