Neurogenic Tumors of the Mediastinum

Updated: Nov 02, 2017
  • Author: Dale K Mueller, MD; Chief Editor: Mary C Mancini, MD, PhD, MMM  more...
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Overview

Background

Several tumors of neurogenic origin can occur in the mediastinum. Tumors that occur in this area of the chest can present in many different ways clinically and can produce many different pathologic processes. An understanding of the embryology of this area and of the anatomic relationships of the normal structures within the mediastinum is essential in the proper determination of the exact nature of a mass or tumor located in this area.

Although the entire field of surgery is an ancient one, successful surgical procedures within the thorax are a relatively recent advance. [1] Until the era when the airway and ventilation could be controlled artificially, the mediastinum, like other parts of the thorax, was deemed a dangerous area to approach.

Use of video-assisted thoracoscopic surgery (VATS) technology has entered the armamentarium of the thoracic surgeon with respect to the treatment of numerous mediastinal diseases. [2, 3, 4]  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. [5]

Numerous advances have also been made in the areas of diagnostic imaging and biologic analysis. Diagnostic modalities such as positron emission tomography (PET) and various 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.

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Anatomy

Any discussion of masses and tumors of the mediastinum requires delineation of the boundaries of that area. In defining the location of specific mediastinal masses, the portion of the thorax defined as the mediastinum extends from the posterior aspect of the sternum to the anterior surface of the vertebral bodies and includes the paravertebral sulci. It is limited bilaterally by the mediastinal parietal pleura and extends from the diaphragm inferiorly to the level of the thoracic inlet superiorly. [6]

Because some mediastinal tumors and other masses are most often found in particular mediastinal locations, many authors have artificially subdivided the area for better descriptive localization of specific lesions. Most commonly, the mediastinum is subdivided into three spaces or compartments for this purpose, as follows:

  • The anterior compartment, or anterior mediastinum, extends from the posterior surface of the sternum to the anterior surface of the pericardium and great vessels; it normally contains the thymus gland, adipose tissue, and lymph nodes
  • The middle compartment, or middle mediastinum, is located between the posterior limit of the anterior compartment and the anterior longitudinal spinal ligament; it contains the heart, pericardium, ascending and transverse portions of the aorta, brachiocephalic vessels, main pulmonary arteries and veins, superior and inferior vena cavae, trachea and mainstem bronchi, numerous lymph nodes, and various neural structures (eg, phrenic nerves)
  • The posterior compartment, or posterior mediastinum, is the area posterior to the heart and trachea and includes the paravertebral sulci; it contains the descending thoracic aorta and ligamentum arteriosum, esophagus, thoracic duct, azygos vein, and numerous neural structures (including autonomic ganglion and nerves, lymph nodes, and adipose tissue)

Common anterior mediastinal tumors include thymomas, lymphomas, germ cell tumors, and mesenchymal tumors. Benign conditions include goiters and lymphangiomas. Most anterior mediastinal tumors are thymomas.

Whereas neoplasms of the middle mediastinum are most commonly of lymphatic origin, neurogenic tumors also may occasionally occur in this area. Another significant group of masses identified in this compartment consists of cystic structures associated with a developmental abnormality of the primitive foregut or the precursors of the pericardium or pleura. [7]

Almost all tumors of neurogenic origin occupy the posterior portion of the mediastinum. Although neurogenic tumors are by far the most common neoplasm of the posterior mediastinum, tumors originating from lymphatic, vascular, or mesenchymal tissues can also be found in this compartment.

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Pathophysiology

Tumors and cysts of the mediastinum can produce abnormal effects at both systemic and local levels.

Local pathophysiology

Because of the malleable nature and small size of the pediatric airway and other normal mediastinal structures, benign tumors and cysts can produce abnormal local effects. These effects are more evident in children than in adults. Compression or obstruction of portions of the airway, the esophagus, or the right heart and great veins by an enlarging tumor or cyst can easily occur and can result in a number of symptoms. Infection can occur primarily within some of these mediastinal lesions, particularly those of a cystic nature, or can occur secondarily in nearby structures, such as the lungs, as a result of local compression or obstruction.

Malignant mediastinal tumors can cause all of the same local effects as those associated with benign lesions but, in addition, can produce abnormalities by invasion of local structures. Local structures most commonly subject to invasion by malignant tumors include the following:

  • Tracheobronchial tree and lungs
  • Esophagus
  • Superior vena cava (SVC)
  • Pleura and chest wall
  • Adjacent intrathoracic nerves

Pathophysiologic changes that can be produced by invasion of specific structures include the following:

  • Obstructive pneumonia and hemoptysis
  • Dysphagia
  • SVC syndrome (SVCS)
  • Pleural effusion
  • Various neurologic abnormalities, such as vocal cord paralysis, Horner syndrome, paraplegia, diaphragmatic paralysis, and pain in the distribution of specific sensory nerves

Systemic pathophysiology

Certain mediastinal tumors can produce systemic abnormalities. Many of these manifestations are related to bioactive substances produced by specific neoplasms.

Tumors developing from autonomic nerve cells can produce several vasoactive substances. The most common of these is neuroblastoma, which produces excess amounts of the catecholamines, epinephrine, and norepinephrine. Ganglioneuroma and ganglioneuroblastoma can produce these substances but do so less often. Autonomic nerve tumors are also capable of producing excess amounts of vasoactive intestinal peptide. Neuroblastomas are thought to produce abnormal antibodies that are responsible for some unusual neurologic manifestations in some children with the tumor.

Some neurosarcomas have been associated with the production of an insulinlike substance that, in turn, can produce hypoglycemia.

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Etiology

Neurogenic tumors of the mediastinum arise from cells of the nerve sheath, paraganglionic tissue, and autonomic ganglia, all of which originate embryonically from the neural crest. Several tissues, including neural tissue, neural sheath tissue, and associated fibrous connective tissue of mesodermal origin, can be the source of these neoplasms.

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Epidemiology

A review of collected series reveals that many mediastinal neoplasms and masses vary in incidence and presentation depending on patient age. [8] Specific types of mediastinal tumors characteristically occur in specific areas within the mediastinum.

Historically, in adults, the most common type of mediastinal tumor or cyst found is the neurogenic tumor (21%), followed by thymic tumors (19%), lymphomas (13%), and germ cell tumors (10%). Foregut and pericardial cysts are the next most frequently occurring abnormality within this group. More recent data from several large series indicate that thymomas have become the most common mediastinal tumor. Some series also indicate that mediastinal lymphoma has passed neurogenic tumors in frequency.

In children and infants, neurogenic tumors are the most commonly occurring tumor or cyst, followed by foregut cysts, germ cell tumors, lymphomas, lymphangiomas and angiomas, tumors of the thymus, and pericardial cysts.

In adults, only approximately 1-2% of neurogenic tumors are malignant. In patients younger than 20 years or older than 40 years, approximately one third of mediastinal tumors are malignant, while in patients aged 20-40 years, roughly half are malignant. Benign lesions generally occur in individuals aged 20-50 years and occur slightly more frequently in women than in men.

Approximately two thirds of mediastinal tumors and cysts are symptomatic in the pediatric population, while only approximately one third produce symptoms in adults. The higher incidence of symptoms in the pediatric population is most likely related to the fact that a mediastinal mass, even a small one, is more likely to have a compressive effect on the small, flexible airway structures of a child.

When all age groups are considered, nearly 55% of patients with benign mediastinal masses are asymptomatic at presentation, compared to only approximately 15% of those in whom masses are found to be malignant.

Neurogenic tumors make up approximately 21% of all adult mediastinal tumors and 35% of all pediatric mediastinal tumors. Neurogenic tumors are the most common posterior mediastinal mass. Neurogenic tumors make up roughly 20% of all mediastinal tumors.

Almost all neurogenic tumors in adult patients are of nerve sheath origin, these being neurilemomas and neurofibromas.

Approximately 90% of pheochromocytomas occur in the adrenal medulla, and only approximately 2% of pheochromocytomas occur in the chest.

Roughly 10% of pheochromocytomas are associated with one of a variety of familial syndromes, the most noted of which are the multiple endocrine neoplasia syndromes. One interesting syndrome specifically associated with multiple extraadrenal pheochromocytomas is the Carney triad, in which these neoplasms occur in association with pulmonary hamartomas and gastric leiomyosarcomas. However, this syndrome does not appear to be familial.

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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.

Neuroblastoma

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.

Ganglioneuroblastoma

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.

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