Lymphomas, Endocrine, Mesenchymal, and Other Rare Tumors of the Mediastinum Treatment & Management
- Author: Mary C Mancini, MD, PhD, MMM; Chief Editor: John Geibel, MD, DSc, MSc, MA more...
While most tumors and cysts of the mediastinum are treated surgically, medical therapy is the primary form of treatment in several diseases.
Hodgkin disease of the mediastinum is treated primarily by radiation or a combination of radiation and chemotherapy. Mediastinal Hodgkin disease in the very early stages (stage PS IA) may be treated with radiation therapy only. Disease at unfavorable stages I or II benefits more from a combination of radiation and chemotherapy. Stage III and IV disease is treated with chemotherapy.
Most chemotherapy for Hodgkin disease is performed using a regimen of doxorubicin, vinblastine, bleomycin, and dacarbazine (ABVD) alone or a regimen in which ABVD is alternated with nitrogen mustard, vincristine, procarbazine, and prednisone (MOPP). An alternative method suggested by some authors is a combination of low radiation doses (3500 cGy) plus chemotherapeutic agents that do not include alkylating agents. This is suggested as a regimen that may lessen the undesirable late effects of the more traditional chemotherapy protocols.
Non-Hodgkin lymphoma of the mediastinum is treated with the same chemotherapy regimens as prescribed for the disease found in other areas of the body.
Treatment of this aggressive lymphoma is most often performed with high doses of cyclophosphamide, doxorubicin, vincristine, and methotrexate followed by leucovorin rescue. Specific treatment of the central nervous system is performed in these regimens because a high level of disease involvement occurs in this area.
In most cases, surgical resection, if possible, is the treatment of choice. Radiation therapy has been used postoperatively with some benefit in cases of malignant fibrous histiocytoma. It has also been used in rhabdomyosarcoma, with uncertain results.
Chemotherapy has been used in some cases of liposarcoma preoperatively to downsize a previously inoperable tumor. It has also been attempted in angiosarcoma, with uncertain benefit. Chemotherapy, with or without radiotherapy, is the recommended treatment for cases of localized mediastinal rhabdomyosarcoma and is shown to improve the disease-free survival rate. In the remaining mesenchymal tumors of the mediastinum, chemotherapeutic treatment has either proven ineffective or not been studied.
Ectopic endocrine tumors of the mediastinum
Surgical resection is the treatment of choice for parathyroid adenomas and carcinomas of the mediastinum.
Treat thyroid neoplasms with surgical resection. Other treatment modalities used for unresectable mediastinal tumor are identical to those used for metastatic thyroid disease from the cervically located gland.
Surgical resection is the treatment of choice for most neoplasms that occur in the mediastinum.[37, 38]
In cases of benign neoplasms, complete excision of the lesion itself is generally sufficient. All benign neoplasms that are encapsulated should be resected without violation of the capsule.
Resect intrathoracic thyroid goiters.
When surgical resection of malignant neoplasms of the mediastinum is the primary treatment, perform en bloc resection of the tumor whenever possible.
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. For safe management of the airway distorted or narrowed by a mediastinal mass, consider detailed preoperative assessment of the airway and ensure adequate visualization and readily available supplementary equipment (eg, flexible bronchoscope). 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 easy availability of necessary blood products (all of paramount importance) before surgery is begun.
Involvement of associated intrathoracic structures by tumor may mandate their resection. Pulmonary resection; excision of nervous structures such as the phrenic, vagus, or sympathetic chain; or even resection of major vascular structures (eg, superior vena cava) may be required. Importantly, 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 before any type of operative procedure, even simple biopsy, is entertained.
Superior vena cava syndrome
SVCS can occur in association with several 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 preoperative patient, treatment with bedrest, elevation of the head, and oxygen administration can be helpful. Salt restriction and diuretics are not generally indicated. Use corticosteroids only for the treatment of associated laryngeal edema or in the presence of brain metastases producing increased intracranial pressure.
Take care 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. Do 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.
Perform intubation 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. Consider this during transport; positioning of the patient must be taken into account.
As with all thoracic surgery, position the patient properly for the indicated procedure. Tumors or cysts located in the anterior mediastinum are generally 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 video-assisted thoracoscopy (VATS).
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. Manage patients who require ventilatory support for a longer time, 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. Several methods to assist with pulmonary toilet are available.
Pain control 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 can also be used, and, with proper choice of analgesic agents, they provide good pain relief. 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 as epidural analgesia for pain control. 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 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 24 hours, 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.
Patients who undergo resection of benign neoplasms or mediastinal cysts can be monitored for a short time (ie, 3-6 mo) postoperatively while wound healing and progression of patient activity is being monitored.
Because of the heterogeneity and the small numbers of malignant tumors found in the mediastinum, no single specific method has been described for the follow-up care of patients who undergo intended curative resection of a malignant neoplasm.
Treatment of mediastinal lymphomas is with chemotherapy and/or radiotherapy. Follow-up care is conducted according to standard lymphoma protocols.
Other malignant mediastinal neoplasms can be observed at appropriate intervals using chest radiographs and CT scans according to the physician's discretion.
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 prevention of these complications.
Wound infections after sternotomy or thoracotomy are rare. The chest wall has an excellent blood supply, and, with few exceptions, healing occurs readily. In addition, 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 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 sternal dehiscence occurs without the presence of infection, perform a simple washout, debridement, and rewiring. If infection is present, perform aggressive debridement of devascularized bone and cartilage and 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.
Injury to the phrenic nerve can occur, resulting in temporary or permanent diaphragmatic paresis. 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 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 stomach and pylorus is disrupted.
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. This group of tumors includes such neoplasms as thymolipomas; benign mesenchymal tumors such as fibromas, angiomas, and lymphangiomas; ectopic benign thyroid tissue, including intrathoracic extension of a cervical goiter; and parathyroid adenomas.
Prognosis after treatment of malignant mediastinal tumors depends on the type of lesion, its biological behavior, and the extent of the disease present.
Excellent survival rates are reported with appropriate chemotherapeutic treatment of Hodgkin disease. According to some reports, even patients with stage IV disease can have disease-free survival for more than 10 years in as many as 70% of cases.
Large cell lymphomas, including anaplastic varieties, are reported to have a more than 50% 3-year survival rate after chemotherapy, radiation therapy, or both.
MALTomas are rare indolent tumors for which long-term survival is good, even in the absence of chemotherapy.
Mantle cell tumors are rare but usually manifest with widespread disease. Median survival is approximately 4 years.
Malignant mesenchymal tumors
The prognosis for liposarcoma depends on several factors. Completely resected pseudoencapsulated tumors have a better prognosis compared to those that are nonencapsulated and invasive. Cell type and cell differentiation also play a role. Myxoid liposarcoma has a poorer prognosis. In one small series, approximately 30% of patients died of their disease after a mean period of less than 3 years.
Angiosarcomas of the mediastinum are rare but have a very poor prognosis, especially when they originate in the heart or great vessels.
Fibrosarcomas have a uniformly poor prognosis, and most patients die from their disease within a few years.
Primary leiomyosarcoma of the mediastinum has been described. In one reported series of 10 patients who underwent resection, 2 were alive and well at 4 and 6 years. Four of the others died of their disease or developed recurrence.
Rhabdomyosarcoma has the best long-term survival of all mesenchymal tumors because effective chemotherapeutic regimens have been identified. According to 1 report, 10-year actuarial survival rates range from 52-83% depending on the stage of disease at presentation and the existence of hematogenous metastases. Survival is much worse if the latter is present.
Mediastinal parathyroid carcinoma
Prognosis is generally good if complete resection can be accomplished.
Intrathoracic goiter with occult malignancy
Prognosis is generally good if complete resection of the gland can be accomplished.
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 scans, and other radionuclide studies may be able to assist in the diagnosis of specific neoplasms and in posttherapy surveillance for recurrent disease.
Angiographic techniques using localized intra-arterial injection of hypertonic contrast and embolization techniques have been used in several centers to obliterate mediastinal parathyroid adenomas. At present, this technology is used in patients who are considered a poor risk for surgery; however, with increased experience and skill, these methods may become useful in the treatment of many such lesions.
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 thoracoscopy (VATS) technology has entered the armamentarium of the thoracic surgeon with respect to the treatment of a number of mediastinal diseases. This modality is already used commonly 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. At several centers, thymectomy has been performed using this technology. The completeness of thymic resection remains to be seen.
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