Neurogenic Tumors of the Mediastinum Treatment & Management
- Author: Dale K Mueller, MD; Chief Editor: Mary C Mancini, MD, PhD, MMM more...
While most tumors and cysts of the mediastinum are treated surgically, medical therapy is the primary form of treatment in several diseases.
Benign schwannomas and neurofibromas
Treatment for these lesions is surgical resection. This includes the plexiform varieties and melanotic schwannoma.
Granular cell tumors
Treatment for this rare lesion is surgical in nature.
Malignant schwannoma and neurofibrosarcoma
Surgical resection is the primary mode of therapy. Radiation therapy may be used postoperatively to control residual disease, but the benefit of this is unknown. No known chemotherapeutic regimens are effective against these tumors.
Treatment is surgical in nature.
Neuroblastoma and ganglioneuroblastoma
Treatment of mediastinal neuroblastoma is based on the evaluation of a number of risk factors that are used to assign a stage to the disease according the INSS. This is identical to the staging system used for neuroblastoma occurring elsewhere in the body. Patients at INSS stages 1 and 2 are considered candidates for resection. For patients with more advanced disease (INSS stage 3, 4, or 4S), a combination of surgery and chemotherapy is recommended. High-risk patients rarely benefit from surgery. Intense chemotherapy with whole-body irradiation or myeloablative chemotherapy is administered, followed by autologous bone marrow transplant.
Neuroblastoma occurs much less frequently in adults than in children and infants but is a much more aggressive disease. Stage 1 disease is treated surgically, while irradiation is recommended for stage 2 disease. Chemotherapy has been tried for disseminated disease in adults, although no proven benefit has been observed.
These tumors are also graded using the INSS. Surgical resection is indicated in those with early disease, and chemotherapeutic therapy is added for those with more advanced disease.
Surgical resection is the only recommended treatment.
Surgical resection followed by irradiation and chemotherapy is recommended in all cases. Some studies have used myeloablative chemotherapy or whole-body irradiation followed by autologous bone marrow transplant, but, to date, benefits of this aggressive therapy have not been identified.
Chemodectomas are primarily treated with surgical resection. Preoperative embolization may be indicated because of the excessive vascularity of these tumors. Radiation therapy has also been used and is an acceptable alternative to surgical resection.
In cases of benign neoplasms, complete excision of the lesion itself is generally sufficient. Benign neurofibroma requires some resection in addition to the lesion itself, that being resection of the associated nerve. All benign neoplasms that are encapsulated should be resected without violation of the capsule. VATS resection is now commonplace for these benign tumors. Shorter hospital stay and more rapid return to work have been demonstrated with this method.
When surgical resection of malignant neoplasms of the mediastinum is the primary treatment, bloc resection of the tumor should be performed whenever possible. Regional lymphadenectomy should accompany surgical resection of operable neuroblastomas.
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 (eg, phrenic, vagus, 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 an additional impact on recovery and perioperative risk.
Several mediastinal tumors can produce important effects that should be taken into account preoperatively. Neurogenic tumors that secrete catecholamines require special consideration.
Perform preoperative treatment on individuals with pheochromocytoma in order to prevent a catecholamine surge and an intraoperative hypertensive crisis.
Most authors recommend the administration of the alpha-blocker phenoxybenzamine. This medication is initiated approximately 2 weeks preoperatively, beginning at doses of 10 mg twice a day and increasing the dose every other day until a normotensive or near-normotensive state, with minimization or elimination of paroxysmal episodes, is achieved. Most patients require 40-120 mg/d to achieve this effect. Because of its prolonged half-life, reduction of the dose 24-48 hours before surgery is recommended, otherwise postoperative hypotension may occur after the source of excess catecholamine production is removed.
Other drugs that may be used instead are prazosin (a selective alpha-blocker) or labetalol (an alpha- and beta-blocker). Alpha-methylparatyrosine has been used successfully in a few patients who cannot tolerate alpha-blockade with other agents.
Preoperative beta-blockade can also be performed but is indicated only if persistent tachycardia or supraventricular arrhythmias are present. Beta-blockade should be started only after alpha-blockade is stabilized to prevent unopposed beta-blockade.
Atropine should not be given with preoperative medication. Anesthetic induction with good oxygenation should be rapid and unimpaired. Most commonly, thiopentone is used for induction; however, fentanyl and alfentanil can also be used because they do not result in histamine release, as do other agents. The choice of muscle relaxant is important because some (eg, tubocurarine, atracurium) can cause histamine release and others (eg, pancuronium) can release catecholamine stores. Vecuronium is the drug of choice because it produces none of these effects.
Pheochromocytomas are highly vascular tumors. Adequate availability of blood products is a key feature in the treatment of these patients.
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 is 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 VATS incision or 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.
Specific management of neurogenic tumors with intraspinal extension should be mentioned. Evaluation of all patients with tumors of the posterior mediastinum preoperatively is essential to rule out intraspinal extension. Combined management by neurosurgical and thoracic surgical teams is warranted when intraspinal extension is suggested. If intraspinal extension is first identified at the time of thoracotomy and was not considered prior to this, the outcome could prove disastrous. The approach to these tumors usually requires laminectomy for resection of the intraspinal portion of the tumor and thoracotomy for the intrathoracic portion. In cases in which laminectomy must be performed at multiple levels, some form of stabilization of the vertebral column is undertaken. Laminectomy combined with VATS and thoracoscopy have also been reported for neurogenic tumors involving the spinal column.
A consideration for the resection of pheochromocytomas is that manipulation of a pheochromocytoma during surgical resection may result in a sudden introduction of catecholamines into the circulation. This can occur even in the presence of preoperative preparation with alpha- and beta-blockers. Early in the dissection, care must be taken during surgery to manipulate these tumors as little as possible and to control venous outflow.
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. Some patients require ventilatory support for a longer time and 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 is a critical factor in postoperative management after thoracic surgery. Adequate cough effort and ventilatory excursion cannot be maintained without satisfactory pain control. The administration of analgesic agents via a thoracic epidural catheter is an excellent and highly effective method of pain management. Lumbar or thoracic epidural catheters can also 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. PCA is not as efficient for pain control as epidural analgesia.
Continuous infusion of 0.25% bupivacaine at 4 mL/h through the ON-Q elastomeric infusion pump is a safe and effective adjunct to pain management after thoracotomy. The use of the ON-Q Pain Relief System 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 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. Intermittent chest radiographs are obtained and evaluated for findings of residual undrained collections, complete pulmonary expansion, lobar atelectasis and infiltrates, and other abnormalities. When drainage from the chest tubes is less than 400 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 followed 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 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. Optimal follow-up treatment for patients with thoracic malignancy has not been demonstrated in randomized controlled trials. Computed tomography of the chest has been suggested as a surveillance tool for children with high-risk neuroblastoma.
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. 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 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 it occurs without the presence of infection, simple washout, debridement, and rewiring can be performed. 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 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, the prognosis is generally excellent. This group of tumors includes such neoplasms as thymolipomas, benign teratomas, benign neurilemomas and neurofibromas, ganglioneuromas, benign paragangliomas, benign mesenchymal tumors (eg, fibromas, angiomas, lymphangiomas), ectopic benign thyroid tissue and tumors, 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.
Survival numbers in pediatric patients with neuroblastoma have been studied in depth and analyzed with reference to a number of clinical and biological prognostic factors. This analysis is beyond the scope of this text. However, intrathoracic neuroblastomas generally have a more favorable outcome than extrathoracic types. The overall survival rate for thoracic neuroblastomas is greater than 70% at 5 years and greater than 60% at 10 years.
These tumors are generally less aggressive than neuroblastomas. They are evaluated using the same prognostic and staging criteria as neuroblastoma. Ganglioneuroblastomas have a better prognosis because a large percentage of them manifest as an asymptomatic solitary mass and can be completely resected in many cases.
Neuroblastomas and ganglioneuroblastomas are extremely rare but much more aggressive in adults. Neuroblastoma exhibits wide local and distant spread and is rapidly fatal, while ganglioneuroblastoma may, in some cases, be treated with surgical resection.
Askin or peripheral neuroectodermal tumor
These are very rare but very aggressive tumors. Survival is commonly less than 1 year, and long-term survival, even with aggressive therapy, is rare.
Malignant nerve sheath tumors
Malignant schwannomas occurring in patients with von Recklinghausen disease have a poorer prognosis than do those that occur in the absence of that disease.
The long-term survival rate after resection approaches 50% for this neoplasm; however, individuals with associated von Recklinghausen disease have a high incidence of local or distant recurrence within 2 years.
Malignant mediastinal paragangliomas and pheochromocytomas
Extraadrenal pheochromocytomas are rare but have a higher malignant potential than their adrenal counterparts. Malignancy can occur in as many as 10% of these tumors. These tumors are commonly aggressive locally, and metastases may occur even after a long disease-free period following resection.
Future and Controversies
Numerous 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.
Numerous biologic 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 technology has entered the armamentarium of the thoracic surgeon with respect to the treatment of numerous mediastinal diseases.[22, 11] This modality is already used commonly for biopsy of masses and lymph nodes. It has also been commonly used for resection of various mediastinal cysts, mediastinal parathyroid adenomas, and localized benign tumors of the posterior mediastinum such as ganglioneuromas.
Robotic resection has also been used for general thoracic surgical procedures, including thymectomy and extirpations of benign mediastinal masses. Its use may be limited by lack of appropriate instrumentation.
Blalock A, Mason MF, Morgan HJ, Riven SS. Myasthenia Gravis and Tumors of the Thymic Region: Report of a case in which the Tumor was Removed. Ann Surg. 1939 Oct. 110(4):544-61. [Medline].
Laurent F, Latrabe V, Lecesne R, Zennaro H, Airaud JY, Rauturier JF, et al. Mediastinal masses: diagnostic approach. Eur Radiol. 1998. 8(7):1148-59. [Medline].
Lentini S. Regarding neurogenic malignant tumors in the mediastinum. Thorac Cardiovasc Surg. 2011 Feb. 59(1):63-4. [Medline].
Strollo DC, Rosado-de-Christenson ML, Jett JR. Primary mediastinal tumors: part II. Tumors of the middle and posterior mediastinum. Chest. 1997 Nov 5. 112(5):1344-57. [Medline].
Mawatari T, Baba T, Satoh H, Morishita K, Izumiyama O, Watanabe A. Example of evoked potential monitoring for a neurogenic tumor positioned high in the mediastinum. Ann Thorac Cardiovasc Surg. 2011 Jun. 17(3):297-300. [Medline].
Giron J, Fajadet P, Sans N, Jarlaud T, Verhnet H, Galy-Fourcade D, et al. Diagnostic approach to mediastinal masses. Eur J Radiol. 1998 Mar. 27(1):21-42. [Medline].
Durand C, Baudain P, Nugues F, Bessaguet S. Mediastinal and thoracic MRI in children. Pediatr Pulmonol Suppl. 1999. 18:60. [Medline].
Nakazono T, White CS, Yamasaki F, Yamaguchi K, Egashira R, Irie H, et al. MRI findings of mediastinal neurogenic tumors. AJR Am J Roentgenol. 2011 Oct. 197(4):W643-52. [Medline].
Protopapas Z, Westcott JL. Transthoracic hilar and mediastinal biopsy. J Thorac Imaging. 1997 Oct. 12(4):250-8. [Medline].
Serna DL, Aryan HE, Chang KJ, Brenner M, Tran LM, Chen JC. An early comparison between endoscopic ultrasound-guided fine-needle aspiration and mediastinoscopy for diagnosis of mediastinal malignancy. Am Surg. 1998 Oct. 64(10):1014-8. [Medline].
Rieger R, Schrenk P, Woisetschlager R, Wayand W. Videothoracoscopy for the management of mediastinal mass lesions. Surg Endosc. 1996 Jul. 10(7):715-7. [Medline].
Demmy TL, Krasna MJ, Detterbeck FC, Kline GG, Kohman LJ, DeCamp MM Jr, et al. Multicenter VATS experience with mediastinal tumors. Ann Thorac Surg. 1998 Jul. 66(1):187-92. [Medline].
Canvasser DA, Naunheim KS. Thoracoscopic management of posterior mediastinal tumors. Chest Surg Clin N Am. 1996 Feb. 6(1):53-67. [Medline].
Cansever L, Kocaturk CI, Cinar HU, Bedirhan MA. Benign posterior mediastinal neurogenic tumors: results of a comparative study into video-assisted thoracic surgery and thoracotomy (13 years' experience). Thorac Cardiovasc Surg. 2010 Dec. 58(8):473-5. [Medline].
Bodner J, Wykypiel H, Wetscher G, Schmid T. First experiences with the da Vinci operating robot in thoracic surgery. Eur J Cardiothorac Surg. 2004 May. 25(5):844-51. [Medline].
Marchevsky AM. Mediastinal tumors of peripheral nervous system origin. Semin Diagn Pathol. 1999 Feb. 16(1):65-78. [Medline].
Krätzig T, Dreimann M, Klingenhöfer M, Floeth FW, Krajewski K, Eicker SO. Treatment of large thoracic and lumbar paraspinal schwannoma. Acta Neurochir (Wien). 2015 Mar. 157 (3):531-8. [Medline].
Bicakcioglu P, Demirag F, Yazicioglu A, Aydogdu K, Kaya S, Karaoglanoglu N. Intrathoracic neurogenic tumors. Thorac Cardiovasc Surg. 2014 Mar. 62 (2):147-52. [Medline].
Wheatley GH 3rd, Rosenbaum DH, Paul MC, Dine AP, Wait MA, Meyer DM, et al. Improved pain management outcomes with continuous infusion of a local anesthetic after thoracotomy. J Thorac Cardiovasc Surg. 2005 Aug. 130(2):464-8. [Medline].
Virgo KS, Johnson FE, Naunheim KS. Follow-up of patients with thoracic malignancies. Surg Oncol Clin N Am. 1999 Apr. 8(2):355-69. [Medline].
Federico SM, Brady SL, Pappo A, Wu J, Mao S, McPherson VJ, et al. The role of chest computed tomography (CT) as a surveillance tool in children with high-risk neuroblastoma. Pediatr Blood Cancer. 2015 Jun. 62 (6):976-81. [Medline].
Kaiser LR. Thoracoscopic resection of mediastinal tumors and the thymus. Chest Surg Clin N Am. 1996 Feb. 6(1):41-52. [Medline].
Burt M, Ihde JK, Hajdu SI, Smith JW, Bains MS, Downey R, et al. Primary sarcomas of the mediastinum: results of therapy. J Thorac Cardiovasc Surg. 1998 Mar. 115(3):671-80. [Medline].
Ishikawa E, Matsumura A, Ishikawa S, Nakamura K, Nose T. Combined minimally invasive approach using microsurgery and thoracoscopic surgery for resecting a dumbbell-type thoracic schwannoma. Minim Invasive Neurosurg. 2002 Dec. 45(4):251-3. [Medline].
Kaga K, Nishiumi N, Iwasaki M, Inoue H. Thoracoscopic diagnosis and treatment of mediastinal masses. Usefulness of the Two Windows Method. J Cardiovasc Surg (Torino). 1999 Feb. 40(1):157-60. [Medline].
Luketich JD, Ginsberg RJ. The current management of patients with mediastinal tumors. Adv Surg. 1996. 30:311-32. [Medline].
Meade RH. Surgery of the Mediastinum. A History of Thoracic Surgery. Springfield, Ill: Charles C. Thomas; 1961. 257-71.
Reardon MJ, Conklin LD, Fabre J, Reardon PR, Letsou GV. Thoracoscopic approach to posterior mediastinal neurogenic tumors in the adult. J Laparoendosc Adv Surg Tech A. 1999 Apr. 9(2):187-92. [Medline].
Reynolds M, Shields TW. Benign and Malignant Mediastinal Neurogenic Tumors in Infants and Children. Shields TW, LoCicero J III, Ponn RB, eds. General Thoracic Surgery. 5th ed. Philadelphia, Pa: Williams & Wilkins; 2000. Vol 2: 2301-12.
Saenz NC. Posterior mediastinal neurogenic tumors in infants and children. Semin Pediatr Surg. 1999 May. 8(2):78-84. [Medline].
Shapiro B, Orringer MB, Gross MD. Mediastinal Paragangliomas and Pheochromocytomas. Shields TW, LoCicero J III, Ponn RB, eds. General Thoracic Surgery. 5th ed. Philadelphia, Pa: Williams & Wilkins; 2000. Vol 2: 2333-55.
Shields TW. Overview of Primary Mediastinal Tumors and Cysts. Shields TW, LoCicero J III, Ponn RB, eds. General Thoracic Surgery. 5th ed. Williams & Wilkins: Philadelphia, Pa; 2000. Vol 2: 2105-9.
Shields TW. Benign and Malignant Neurogenic Tumors of the Mediastinum in Adults. Shields TW, LoCicero J III, Ponn RB, eds. General Thoracic Surgery. 5th ed. Philadelphia, Pa: Williams & Wilkins; 2000. Vol 2: 2313-27.
Whooley BP, Urschel JD, Antkowiak JG, Takita H. Primary tumors of the mediastinum. J Surg Oncol. 1999 Feb. 70(2):95-9. [Medline].