Teratomas and Other Germ Cell Tumors of the Mediastinum

Updated: Oct 31, 2017
  • 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 extragonadal location in which germ cell tumors are most commonly 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 are primarily solid in consistency. If the tumors are chiefly cystic in nature, they are referred to as epidermoid or dermoid cysts, terms that should not obscure 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.

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.

Several exciting advances have been made in areas of diagnostic imaging, biologic analysis, and therapy.

Emerging diagnostic modalities, such as positron emission tomography (PET), as well as 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.

Video-assisted thoracoscopic surgery (VATS) is used by thoracic surgeons to treat a number of mediastinal diseases. In addition to biopsy of masses and lymph nodes, it also has been employed for resection of various mediastinal cysts, mediastinal parathyroid adenomas, and localized benign tumors of the posterior mediastinum (eg, ganglioneuromas). VATS thymectomy has been performed as well, though the completeness of thymic resection achievable via this approach has been the subject of some controversy. VATS has also been described for resection of teratomas of the mediastinum.

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Anatomy

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 the locations of specific mediastinal masses are defined. 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, in discussing the location or origin of specific masses or neoplasms, the mediastinum is subdivided into three spaces or compartments, 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
  • The posterior compartment, or posterior mediastinum, comprises the area posterior to the heart and trachea and includes the paravertebral sulci

The vast majority of teratomas and other germ cell tumors arise in the anterior compartment of the mediastinum. The most common tumors found in the anterior mediastinum 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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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 following:

  • Tracheobronchial tree and lungs
  • Esophagus
  • Superior vena cava
  • Pleura
  • Chest wall
  • 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 (β-hCG).

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

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

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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 two of the three 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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Epidemiology

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.

With respect to 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. Whereas mediastinal seminoma almost exclusively is found in males, several histologically verified cases have been described in females.

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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, prognosis generally is excellent. Germ cell tumors included in this group are benign teratomas or dermoid cysts.

Prognosis after treatment of malignant mediastinal tumors depends upon the type of lesion, its biologic behavior, and the extent of the disease present.

Prognosis for malignant germ cell neoplasms is listed below. Nonseminomatous histology, presence of nonpulmonary metastases, primary mediastinal germ cell tumor location, and elevated levels of β-hCG are independent prognostic factors for shorter patient survival.

Seminoma

Primary treatment for seminoma generally is radiotherapy or chemotherapy. A number of series reported cure rates of about 60-65% after primary radiotherapy and as much as an 87% long-term survival after chemotherapy is used as the primary form of treatment. Residual disease is present radiographically in 10-20% of cases after initial systemic treatment has been completed.

Some controversy about the management of this problem exists. Some centers advocate close observation because many residual masses simply are fibrotic changes. However, many take an aggressive approach to radiologic evidence of residual disease and promote surgical resection.

Nonseminomatous mediastinal germ cell tumors

Long-term (>24 months) disease-free survival rates after completion of systemic chemotherapeutic treatment in these patients is about 42%. The best prognosis is for those patients who underwent resection after chemotherapy and normalized or decreased tumor marker levels. [1]

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