Neurogenic Tumors of the Mediastinum

Updated: Nov 03, 2015
  • 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.

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History of the Procedure

Although the entire field of surgery is an ancient one, successful surgical procedures within the thorax are a relatively recent advancement. 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.

A few surgeons in the late 1800s and early 1900s attempted and described surgical approaches to the mediastinum. In 1888, Nassiloff first showed that the esophagus was accessible using a posterior approach. In this time frame, with no ability to manage the airway or to ventilate safely, such a surgical approach had to remain completely extrapleural because perforation of the pleura would result in a fatal pneumothorax.

In 1893, Bastinelli described the removal of an anterior mediastinal dermoid cyst. The procedure required resection of the manubrium, but the patient recovered.

In 1897, Milton wrote extensively on mediastinal surgery using the median sternotomy approach. He tried this approach first on human cadavers, finding that median sternotomy gave him excellent access to the mediastinum. He then used the same approach to explore the mediastinum of a live goat. Although he did enter the pleural cavity of the animal, he was able to perform a tracheostomy and give artificial respiration through it. This support enabled him to successfully explore the mediastinum and allowed the animal to have an uneventful recovery. Milton then described a human case in which he resected most of a tuberculous sternum plus 2 large tuberculous lymph nodes from the mediastinum, successfully avoiding the pleural spaces. This patient did well.

In 1940, Heuer published a monograph on mediastinal tumors. Most of the cases referenced in it were from the 1920s and 1930s, and, in spite of Milton's previously described work, no reference was made to the use of median sternotomy as an acceptable surgical approach to the mediastinum.

Heuer noted that at that time dermoid cysts and teratomas were the most commonly found tumors of the mediastinum. He also described successful removal of neurogenic tumors from the posterior mediastinum and described several types of thymic tumors.

In 1939, Alfred Blalock reported the first case in which symptoms of myasthenia gravis were completely relieved by removal of a thymic tumor, thus initiating a surgical option in the treatment of that disease. [1]

In 1995, video-assisted removal of neurogenic tumors was reported in combination with microneurosurgical techniques.

Recently, isolated reports of robotic resection of neurogenic tumors have also been reported. [2]

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Problem

Any discussion of masses and tumors of the mediastinum requires delineation of the boundaries of that area. When 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. The mediastinum is limited bilaterally by the mediastinal parietal pleura and extends from the diaphragm inferiorly to the level of the thoracic inlet superiorly. [3]

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 3 spaces or compartments (ie, anterior, middle, posterior) when discussing the location or origin of specific masses or neoplasms. The anterior compartment extends from the posterior surface of the sternum to the anterior surface of the pericardium and great vessels. The middle compartment, or middle mediastinum, is located between the posterior limit of the anterior compartment and the anterior longitudinal spinal ligament. The posterior mediastinum is the area posterior to the heart and trachea and includes the paravertebral sulci.

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.

While 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 is cystic structures associated with a developmental abnormality of the primitive foregut or the precursors of the pericardium or pleura. [4]

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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Epidemiology

Frequency

A review of collected series reveals that many mediastinal neoplasms and masses vary in incidence and presentation depending on patient age. 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 considering all age groups, 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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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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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 tracheobronchial tree and lungs, esophagus, superior vena cava, pleura and chest wall, and any adjacent intrathoracic nerves. Pathophysiologic changes that can be produced by invasion of specific structures are obstructive pneumonia and hemoptysis; dysphagia; superior vena cava syndrome; pleural effusion; and 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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Presentation

Many mediastinal tumors and cysts produce no symptoms and are found incidentally during chest radiographs or other imaging studies of the thorax performed for another reason. Symptoms are present in approximately one third of adult patients with a mediastinal tumor or cyst but are seen more commonly in the pediatric population, in which nearly two thirds present with some symptoms. In adults, asymptomatic masses are more likely to be benign.

Symptoms associated with the respiratory tract predominate in pediatric patients because airway compression is more likely. This occurs because of the significant malleability of the airway structures and the small size of the chest cavity in infants and children. Symptoms most often observed include persistent cough, dyspnea, and stridor. If the location and size of the mass produces partial or complete obstruction, obstructive pneumonia can also occur. Infectious symptomatology, and even signs of sepsis, can occur if a mediastinal cyst becomes infected.

Constitutional symptoms, such as weight loss, fever, malaise, and vague chest pain, commonly occur with malignant tumors in pediatric patients.

Symptoms associated with compression of some portion of the respiratory tract can be produced by benign lesions in adults, but this occurs much less commonly than in children. Infectious symptoms or sepsis from infection of a mediastinal cyst can occur in adults, although this is also very unlikely in persons in this age group. However, malignant lesions are more likely to produce signs and symptoms of obstruction, compression, or both because they invade or transfix normal mediastinal structures.

Clinical findings associated with these malignant properties include cough, dyspnea, stridor, dysphagia, and even more dramatic findings such as superior vena cava syndrome. Invasion of the chest wall or pleura by a malignant neoplasm can produce persistent pleural effusions and a significant amount of local pain. Invasion of nearby nerves within the thorax can produce local and referred pain and a variety of other findings such as hoarseness from recurrent nerve paralysis, diaphragmatic paralysis from phrenic nerve paralysis, Horner syndrome from autonomic nerve invasion, and even motor paralysis from direct spinal cord involvement. Pain in the shoulder or upper extremity can occur from invasion of the ipsilateral brachial plexus. Systemic findings such as weight loss, fever, and malaise also occur.

In von Recklinghausen disease or neurofibromatosis, an inheritable disease, the individual may develop multiple tumors, generally neurofibromas.

Functioning mediastinal pheochromocytomas produce an excess of circulating catecholamines. The hallmark clinical finding in individuals with these neoplasms is hypertension. The hypertension may be persistent, paroxysmal, or persistent with paroxysmal episodes. Hypertensive crises may occur and may be triggered or exacerbated by anesthesia, trauma, and the onset of labor. The hypertension found in these individuals may be termed malignant and most often is resistant to any standard antihypertensive therapy. It certainly may lead to the usual complications of long-standing or severe hypertension such as stroke, cardiac failure, or renal function abnormalities.

In some patients, paroxysmal episodes can be accompanied by other symptoms, which include headaches, diaphoresis, anxiety, chest pain, palpitations, and pallor. Some patients also have an associated tachycardia.

Marked vasoconstriction from the excessive catecholamine discharge associated with these neoplasms creates a severely volume-contracted state in these individuals. This, in turn, produces the appearance of an elevated hematocrit value.

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Indications

Treatment selection for a given mediastinal tumor or cyst depends on the diagnosis of the lesion being investigated. [5] Surgical resection is the primary treatment of choice in a large percentage of cases of neurogenic tumors.

Surgical resection is the treatment of choice for tumors originating from nerve sheath tissue, including neurilemoma, neurofibroma, and neurogenic sarcoma. Complete resection of the more malignant forms of these tumors may not be possible, and additional treatment modalities may be required.

Primary resection is the treatment of choice for neurogenic tumors of paraganglionic origin, which include paraganglionoma, chemodectomas, and mediastinal pheochromocytoma. Approximately 10% of pheochromocytomas are malignant and may not be entirely resectable. Some, even though benign, may be incompletely resected because of their location and increased vascularity. Preoperative treatment including alpha and beta blockade to prevent malignant hypertension during dissection is critical to excision of these tumors.

Peripheral neuroectodermal tumors (PNET), otherwise known as Askin tumors, are rare tumors occurring in the posterior sulcus or chest wall of adolescent and young adult patients. They are believed to develop from intercostal nerve tissue. Standard therapy includes en bloc resection, with accompanying radiotherapy and chemotherapy if complete resection is not possible.

Treatment varies for neurogenic tumors originating from autonomic nervous tissues. Ganglioneuroma, the most mature and benign form of autonomic nerve tumor, is treated by surgical resection. Neuroblastoma and ganglioneuroblastoma identified at an early stage of disease also may be treated with primary resection. Advanced stages of these diseases are treated primarily with chemotherapy, and surgical resection is rarely indicated.

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Relevant Anatomy

When 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.

Traditionally, the mediastinum is artificially subdivided into 3 compartments for better descriptive localization of specific lesions. When the location or origin of specific masses or neoplasms is discussed, the compartments or spaces are most commonly defined as anterior, middle, and posterior.

The anterior compartment extends from the posterior surface of the sternum to the anterior surface of the pericardium and great vessels. The anterior compartment 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. This area 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 such as the phrenic nerves. A small percentage of neurogenic tumors occur in the middle mediastinal compartment.

The 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). Almost all tumors of neurogenic origin occupy this portion of the mediastinum.

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Contraindications

Surgical removal is not indicated as primary treatment for some specific mediastinal tumors and cysts. Advanced stages of neuroblastoma and ganglioneuroblastoma are the tumors of neurogenic origin for which surgical resection is not considered as primary treatment.

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