Teratomas and Other Germ Cell Tumors of the Mediastinum

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

Background

The mediastinum is an area of the body in which a wide range of tissue variability exists. Tumors that occur in this area therefore can represent many different clinical entities and pathologic processes. An understanding of the embryology of this area, as well as 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.

The mediastinum is the most common extragonadal location in which germ cell tumors are found. About 5-10% of all germ cell tumors are found in the mediastinum. Germ cell tumors can be benign or malignant. Benign germ cell tumors are referred to as benign teratomas or dermoids if they primarily are solid in consistency. If the tumors chiefly are cystic in nature, they are referred to as epidermoid or dermoid cysts, terms that should not detract from the fact that these truly are neoplasms.

Malignant germ cell tumors are subdivided into seminomas and nonseminomatous. Nonseminomatous tumors also are termed malignant teratomas and are divided further by cell type into choriocarcinomas, embryonal carcinomas, mixed tumors, teratocarcinomas, and yolk sac carcinomas.

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History of the Procedure

Although the entire field of surgery is an ancient one, successful surgical procedures performed within the thorax are relatively recent. 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. During this time, with no ability to manage the airway or ventilation 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 provided him excellent access to the mediastinum. He then used the same approach to explore the mediastinum of a live goat. Although the pleural cavities of the animal were entered, he was able to perform a tracheostomy and provide artificial respiration through it. This support enabled him to explore the mediastinum successfully and allowed the animal to have an uneventful recovery. He 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.

Heuer, in 1940, 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 at that time that 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.

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Problem

Discussion of masses and tumors of any part of the mediastinum requires delineation of the boundaries of that area. 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 when defining the location of specific mediastinal masses. The mediastinum is limited bilaterally by the mediastinal parietal pleura and extends from the diaphragm inferiorly to the level of the thoracic inlet superiorly.

Because a number of mediastinal tumors and other masses are found most commonly in particular mediastinal locations, many authors have subdivided the area artificially for better descriptive localization of specific lesions. Usually, the mediastinum is subdivided into 3 spaces or compartments (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 comprises the area posterior to the heart and trachea and includes the paravertebral sulci.

The most common tumors found in the anterior mediastinal compartment are of thymic, lymphatic, or germ cell origin. More rarely, masses associated with aberrant parathyroid or thyroid tissue are found. Neoplasms and other masses originating from vascular or mesenchymal tissues also may be found.

The vast majority of extragonadal germ cell tumors are found in the mediastinum, and, of these, roughly 95% are located in the anterior mediastinal 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. Also, as noted previously, numerous mediastinal tumors characteristically occur in specific areas within the mediastinum.

  • When considering mediastinal tumors or cysts in adults, germ cell tumors rank fourth in frequency, following neurogenic tumors, thymic tumors, and lymphomas. About 10% of mediastinal tumors in adults are germ cell tumors, and about 85% of these are benign.
  • In adults, germ cell tumors occur most commonly between the second and fourth decades of life and are found in equal numbers in both sexes.
  • In children and infants, neurogenic tumors also are the most commonly occurring tumors or cysts, followed by foregut cysts. Germ cell tumors rank third, followed by lymphomas, lymphangiomas and angiomas, tumors of the thymus, and pericardial cysts. Germ cell tumors make up about 25% of the mediastinal tumors found in children.
  • Seminoma represents more than 25% of primary mediastinal germ cell tumors and about 3% of all mediastinal tumors.
  • While mediastinal seminoma almost exclusively is found in males, several histologically verified cases have been described in females.
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Etiology

Although various theories exist regarding the development of germ cell tumors, the etiology of germ cell tumors of the mediastinum remains unknown. Approximately 20% of nonseminomatous germ cell tumors have Klinefelter syndrome, and they develop tumors 10 years earlier than those without the syndrome.

Germ cell tumors

Germ cell tumors can be benign or malignant. Benign varieties include benign teratoma and teratodermoids. Malignant tumors include seminomas and nonseminomatous germ cell tumors, which are classified further as teratocarcinomas, choriocarcinomas, embryonal carcinomas, and endodermal sinus or yolk sac tumors.

Benign teratoma

Several theories exist regarding the development of benign teratomas. One theory suggests that benign teratomas are derived from cells from the region of the third branchial cleft or pouch. Another states that benign teratomas form from totipotential cells, which are capable of forming tissues from at least 2 of the 3 primitive germ cell layers but reside in an inappropriate anatomic location for the cell types present. The third theory states that these tumors arise from germinal nests of cells located along the urogenital ridge that failed to migrate to the gonads in embryologic development.

Seminomas and nonseminomatous germ cell tumors

Some debate exists regarding the origin of seminomas and nonseminomatous germ cell tumors. According to one theory, these tumors develop from extragonadal or extraembryonic yolk sac germinal cells whose normal migration along the urogenital ridge to the gonad was halted in the mediastinum. A second theory suggests that they originate from somatic cells from the branchial cleft area associated with the developing thymus.

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Pathophysiology

Tumors and cysts of the mediastinum can produce local and systemic symptoms.

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 local symptoms. 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 easily can 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 result secondarily in nearby structures (eg, 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 they also 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, as well as 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, and pleural effusion, as well as 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. Approximately 95% of patients with germ cell tumors of the mediastinum have an elevated tumor marker. Alpha-fetoprotein (AFP) is elevated more often than beta human chorionic gonadotropin (bhCG).

Germ cell tumors

Nonseminomatous germ cell tumors produce high levels of AFP, bhCG, or both. Less than 10% of seminomatous tumors produce bhCG, and those that do produce bhCG produce low levels of this marker. Some systemic manifestations (eg, gynecomastia, precocious puberty) can be caused by bhCG.

Serum lactic dehydrogenase (LDH) usually is elevated in cases of seminoma.

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Presentation

A large percentage of mediastinal tumors and cysts produce no symptoms and are found on an incidental chest radiograph or other imaging study of the thorax performed for an unrelated reason. Symptoms are present in about one third of adult patients with a mediastinal tumor or cyst but are observed more commonly in the pediatric population where nearly two thirds present with some symptoms, usually related to the respiratory tract. In adults, asymptomatic masses are more likely to be benign. Most patients with seminomas are symptomatic, while almost all patients with nonseminomatous germ cell tumors of the mediastinum are symptomatic.

Symptoms associated with the respiratory tract predominate in pediatric patients because airway compression is more likely. This occurs because of the significant amount of malleability of the airway structures and the small size of the chest cavity in infants and children. Symptoms most commonly observed include persistent cough, dyspnea, and stridor. If the location and size of the mass produce partial or complete obstruction, obstructive pneumonia also can occur.

Constitutional symptoms (eg, weight loss, fever, malaise, vague chest pain) commonly occur with malignant tumors in pediatric patients but can be observed in some adults as well.

Symptoms associated with compression of some portion of the respiratory tract can be produced in adults by benign lesions as well, but this occurs much less frequently than in children. However, malignant lesions are more likely to produce signs and symptoms of obstruction and/or compression because they invade or transfix normal mediastinal structures.

Clinical findings commonly associated with malignancy include cough, dyspnea, stridor, and dysphagia, as well as 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 also can produce local and referred pain, as well as various other findings such as hoarseness from recurrent nerve involvement, diaphragmatic paralysis from phrenic nerve involvement, 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. Invasion or extrinsic compression of the superior vena cava can produce superior vena cava syndrome.

With reference to malignant germ cell tumors, about 30% of patients found to have mediastinal seminoma are asymptomatic at the time of discovery. When present, symptoms result from local compression or invasion of nearby structures.

In cases of nonseminomatous germ cell tumors, symptoms of compression or invasion of nearby structures virtually always are present at the time of presentation. Patients with this type of tumor usually appear ill and have local or systemic symptoms from metastatic disease.

Various hematologic malignancies and other syndromes can be observed on occasion with nonseminomatous germ cell tumors of the mediastinum. Interestingly, this association is not found to exist with germ cell tumors of gonadal origin.

Mediastinal tumors that produce bioactive substances will be associated with symptoms produced by those substances, as discussed in the previous section.

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Indications

Treatment selection for a given mediastinal tumor or cyst depends upon the diagnosis of the lesion being investigated. Surgical resection is indicated in a large percentage of cases.

Germ cell tumors

Complete surgical resection is indicated for benign teratomas. A median sternotomy, mini-sternotomy, posterolateral thoracotomy, hemiclamshell thoracotomy with or without neck extension, clamshell, and video-assisted thoracic surgery (VATS) are all described as methods for resection. Additional resection is needed when teratomas are adherent to adjacent structures.

Although diagnosis of seminoma often requires an open biopsy, primary resection of seminoma is indicated only in selected cases. These include (1) cases in which the patient is asymptomatic, (2) where the mass does not extend beyond the margins of the anterior mediastinal compartment, and (3) where no sign of metastatic spread within the mediastinum or elsewhere is present.

Surgical resection is not the primary treatment for malignant nonseminomatous germ cell tumors. Surgical resection is indicated after completion of chemotherapy for a residual mediastinal mass in patients who have negative levels of serum tumor markers. This is performed both for diagnosis of the remaining mass and for prevention of possible future malignant degeneration of any residual abnormal tissue. Some consider resection even if tumor markers remain elevated.

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Relevant Anatomy

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 when defining the location of specific mediastinal masses. 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. Most commonly, the compartments or spaces are defined as the anterior, middle, and posterior when the location or origin of specific masses or neoplasms is discussed.

The anterior compartment 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 vast majority of teratomas and other germ cell tumors arise in this area of the mediastinum.

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Contraindications

Although open biopsy may be required to make a diagnosis, surgical resection is not indicated as primary treatment for mediastinal tumors of germ cell origin, including seminoma or nonseminomatous germ cell malignancies of the mediastinum.

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