AUTHOR AND EDITOR INFORMATION

Section 1 of 12  

• Authors and Editors
• Introduction
• Indications
• RELEVANT ANATOMY
• Contraindications
• Workup
• Treatment
• Complications
• Outcome And Prognosis
• Future And Controversies
• Multimedia
• References

INTRODUCTION

Section 2 of 12  

• Authors and Editors
• Introduction
• Indications
• RELEVANT ANATOMY
• Contraindications
• Workup
• Treatment
• Complications
• Outcome And Prognosis
• Future And Controversies
• Multimedia
• References

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.

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.

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.

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.

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.

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.

Clinical

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.

INDICATIONS

Section 3 of 12  

• Authors and Editors
• Introduction
• Indications
• RELEVANT ANATOMY
• Contraindications
• Workup
• Treatment
• Complications
• Outcome And Prognosis
• Future And Controversies
• Multimedia
• References

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, 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.

RELEVANT ANATOMY

Section 4 of 12  

• Authors and Editors
• Introduction
• Indications
• RELEVANT ANATOMY
• Contraindications
• Workup
• Treatment
• Complications
• Outcome And Prognosis
• Future And Controversies
• Multimedia
• References

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.

CONTRAINDICATIONS

Section 5 of 12  

• Authors and Editors
• Introduction
• Indications
• RELEVANT ANATOMY
• Contraindications
• Workup
• Treatment
• Complications
• Outcome And Prognosis
• Future And Controversies
• Multimedia
• References

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.

WORKUP

Section 6 of 12  

• Authors and Editors
• Introduction
• Indications
• RELEVANT ANATOMY
• Contraindications
• Workup
• Treatment
• Complications
• Outcome And Prognosis
• Future And Controversies
• Multimedia
• References

Lab Studies

• Beta human chorionic gonadotropin
• • Elevated levels of beta human chorionic gonadotropin (bhCG) virtually always are found in association with nonseminomatous germ cell tumors. Always obtain this study, as well as alpha-fetoprotein (AFP) levels, in young male patients presenting with an anterior mediastinal mass. Serum levels of bhCG greater than 500 mg/mL are said to be diagnostic for the presence of a nonseminomatous germ cell tumor.
  • Seminomas generally do not produce elevated levels of this substance. Less than 10% of patients with seminoma have an elevated bhCG level, and the measured level is usually much lower than that found with nonseminomatous tumors.
• Alpha-fetoprotein
• • AFP almost always is elevated in individuals with nonseminomatous germ cell tumors. As noted above, always obtain this test in young males found to have an anterior mediastinal mass. As with bhCG, serum levels greater that 500 mg/mL are virtually diagnostic for nonseminomatous germ cell tumors.
  • Elevation of the AFP level is not found in individuals with pure seminoma.
• Tumor rejection antigen 1 (TRA-1-60) is a relatively new tumor marker for embryonal cell carcinoma. This study may be useful in monitoring patients with mediastinal germ cell tumors with an embryonal cell component.
• CD30 is believed to be useful in the monitoring of patients with embryonal cell carcinoma as well.
• Genetic analysis should be performed to determine the presence of chromosomal abnormality isochromosome 12p.

Imaging Studies

• Chest radiography
• • Posteroanterior (PA) and lateral radiograph of the chest for an unrelated cause are the usual ways in which an asymptomatic mediastinal mass is identified. Chest radiography obviously is the first study that would be performed in an individual with symptoms referable to the thorax. The PA view allows for determination of bilaterality and superior or inferior location, while the lateral chest radiograph determines the specific compartment.
  • The lateral chest radiograph is very helpful in the determination of the involved compartment of the mediastinum. This information, combined with the age, sex, and associated clinical findings, aids the physician in the proper choice of subsequent diagnostic studies.
• CT scan of the chest and mediastinum
• • CT has become a routine part of the diagnostic evaluation of mediastinal tumors, cysts, and other masses.
  • CT is the test of choice for mediastinal masses. This test can greatly assist in determining the exact location of the mediastinal tumor and its relationship to adjacent structures. It also is useful in differentiating masses that originate in the mediastinum from those that encroach upon the mediastinum from the lung or other structures. It also detects pulmonary and mediastinal metastasis and differentiates from mediastinal fatty masses.
  • The CT scan is very useful in differentiating tissue densities. This assists greatly in distinguishing structures that are cystic or vascular from those that are solid.
  • CT scanning can reveal evidence of local invasion of adjacent structures by a mass or the presence of intrathoracic metastases.
• Magnetic resonance imaging
• • MRI is not routinely used to investigate germ cell neoplasms. MRI is more useful than CT to determine mediastinal invasion and involvement of the brachial plexus, diaphragm, or neural foramen, but this information is rarely useful from a clinical perspective.
  • MRI offers direct multiplanar imaging. It can be used when iodinated contrast cannot be administered. It provides increased detail in the subcarinal and aortopulmonary window areas, as well as the inferior aspects of the mediastinum at the level of the diaphragm.
  • MRI is more useful than the CT scan in the evaluation of invasion or extension of tumors, especially tumors closely associated with the heart. MRI is superior to the CT scan for the evaluation of masses located at the thoracic inlet or at the thoracoabdominal level. CT is superior in detecting pulmonary metastasis, spacial relationship to other mediastinal structures, and bony destruction.
• Radionuclide scanning
• Nuclear imaging can be used selectively in the workup of mediastinal masses when specific tumors are suspected. The iodine-131 (I-131) or iodine-123 (I-123) scans are not indicated specifically for the identification of germ cell tumors, but they are used to identify thyroid tissue. They are mentioned here as a tool that can be used to distinguish the nature of an unknown anterior mediastinal mass.
• Because germ cell tumors and abnormalities of the thyroid (eg, ectopic thyroid, substernal extension of cervical thyroid) both present as anterior mediastinal masses, these iodine-tagged radionuclear studies may help to confirm or eliminate thyroid tissue as the diagnosis. These scans especially are useful in the identification of anterior mediastinal masses located at the level of the thoracic inlet, such as the substernal extension of a cervical thyroid goiter.
• Note that these studies must be performed before any tests requiring the administration of iodinated contrast because this material may interfere with thyroid uptake and scanning.
• Echocardiography and ultrasonography: Ultrasonographic methods have been used to differentiate solid from cystic mediastinal masses and to assist in determining a connection between a mass and adjacent structures. These studies are more useful in the evaluation of masses associated with the heart and in vascular abnormalities. In general, given the accuracy and detail provided by CT scan, MRI, and selected radionuclide scans, ultrasound techniques generally are not used as primary tools in the evaluation of mediastinal tumors and cysts.
• Positron emission tomography: Positron emission tomography (PET) has been studied extensively for the evaluation of a number of neoplasms, such as lung, colorectal, breast, lymphoma, and melanoma. Its use in the evaluation of mediastinal tumors is being evaluated. It has been reported to be useful with thymic neuroendocrine tumors.
• Arteriography: Conventional angiography has been used to differentiate mediastinal masses from vascular abnormalities, as well as to exhibit the relationship between known masses and adjacent vascular structures. MRI and magnetic resonance arteriography (MRA) appear to provide satisfactory definition of the masses in this area.

Diagnostic Procedures

• Transthoracic needle biopsy
• • In the past, percutaneous biopsy methods were believed too dangerous to use in the evaluation of mediastinal masses, and open surgical biopsy was the diagnostic procedure of choice. Although still controversial, CT-guided fine-needle aspiration (FNA) and core needle biopsy techniques increasingly are used with success at several centers. Differentiation of thymomas, lymphomas, and germ cell tumors can be made in a number of cases when tissue obtained from a core needle biopsy is subjected to special histologic staining methods, including immunohistochemical techniques. In some cases, lymphoma subtypes can be identified as well. Note that expert clinical judgment is necessary in selecting appropriate cases for this diagnostic method. In addition, considerable expertise in tissue processing and analysis is necessary for diagnostic accuracy, which is reported to be 85-95%.
  • FNA has been used occasionally for diagnosis of primary bronchogenic cysts. However, most authorities do not recommend aspiration of a cyst because a sample of the cyst wall, which is required for diagnosis, is not obtained by this method. Also, most cysts will recur after simple aspiration. This technique is not recommended for esophageal cysts. FNA has been described for neurogenic tumors, although because surgical resection is the treatment for these lesions after adequate workup, needle biopsy may be deemed an unnecessary step.
• Cervical mediastinoscopy and substernal extended mediastinoscopy: Cervical mediastinoscopy is a commonly used surgical diagnostic procedure for evaluation of the retrovascular pretracheal area of the mediastinum. This procedure is used most commonly for staging of bronchogenic carcinoma and for evaluation of hilar and paratracheal lymphadenopathy, but it can be modified into what has been termed a substernal extended mediastinoscopy to evaluate the prevascular area of the mediastinum. Thymic masses and any tumors found in the anterior mediastinum (eg, germ cell tumors), as well as lymph nodes of the aortopulmonary window, are accessible for obtaining a biopsy using this approach.
• Anterior mediastinotomy: This parasternal approach to the mediastinum has been used most commonly in situations in which standard cervical mediastinoscopy was believed or found to be inadequate. It classically is performed in the upper left parasternal area for access to the aortopulmonary window and areas of the anterior mediastinum inferior to the aortic arch. Anterior mediastinotomy is being replaced in many centers either by extended cervical mediastinoscopy or by video-assisted thoracic surgical (VATS) techniques.
• Video-assisted thoracoscopy: VATS techniques have been used successfully for biopsy of various mediastinal masses and are used commonly for the sampling of perihilar lymph nodes. VATS is one of the commonly used methods for evaluation of mediastinal lymphoma, but its use also has been extended to the anterior compartment of the mediastinum for biopsy and even resection of some masses.
• Sternotomy and thoracotomy: In spite of the numerous minimally invasive options available for histologic diagnosis of mediastinal tumors and cysts, open surgical access is needed at times. In some cases, standard sternotomy or thoracotomy may be the safest method available to obtain an adequate tissue diagnosis. Additional surgical exposures include the hemiclamshell thoracotomy with or without neck extension, clamshell, and, hemiclamshell with supraclavicular extension.

Histologic Findings

Seminoma

Mediastinal seminoma has an appearance very similar to the type of seminoma that originates within the gonad. These tumors often possess some cystic changes and are associated with prominent reactive lymphoid follicular hyperplasia, granulomatous reaction, and fibrosis. The cellular portion of seminomas is comprised of sheets or lobules of medium-sized round or polygonal cells with clear cytoplasm separated by fine septae. Cellular areas often are infiltrated by lymphocytes. Individual cells have hyperchromatic nucleoli. Mitoses commonly are noted.

Teratoma

Teratomas often are divided into mature, immature, and teratoma with malignant components. Mature teratomas commonly are cystic and possess well-differentiated tissues from the 3 germinal cell layers. They often include cartilage or adipose tissue, glandular epithelium, and squamous epithelium.

Immature teratomas are less common and contain some mature epithelial and connective tissue components as well as immature areas with neuroectodermal and mesenchymal elements. Most of these tumors are well circumscribed by a wall of fibrous tissue, which may have some calcification within it. Cyst contents may include hair and sebaceous material.

Teratomas with additional malignant components have been classified additionally by the type of malignant tissue identified. These include (1) germ cell tumor type, (2) adenocarcinoma or squamous carcinoma, (3) mesenchymal or sarcomatous type, and (4) a combination of any of the previous 3 types.

Choriocarcinoma

Choriocarcinomas are composed of large pleomorphic multinucleated cells with ample eosinophilic cytoplasm known as syncytiocytotrophoblasts and cytotrophoblasts, which are polygonal cells with a clear cytoplasm, round nuclei, and conspicuous nucleoli. Most of these tumors are found to have large amounts of hemorrhage and necrosis.

Embryonal carcinoma

The architecture of embryonal carcinoma varies from solid to trabecular. The cells are highly atypical and have a moderate amount of cytoplasm, large nuclei, conspicuous nucleoli, and numerous mitotic figures. Histologic architecture can vary greatly within a single specimen from very primitive, undifferentiated cells to an organized, glandular configuration.

Yolk sac or endodermal sinus tumors

Yolk sac or endodermal sinus tumors have the most variable histology and include (1) the endodermal sinus type, which has a labyrinthine or festoon pattern and contains Schiller-Duval bodies; (2) glandular-alveolar; (3) microcystic; (4) myxomatous; (5) papillary; (6) polyvesicular-vitelline; (7) hepatoid; (8) solid; (9) clear-cell; (10) endometrioid; (11) parietal; (12) sarcomatoid; (13) macrocystic; and (14) intestinal, which manifest a pattern with villouslike projections lined by tumor cells.

The most common type identified in some large series is the reticular type, which has strands or cords of cells within a myxoid matrix. Schiller-Duval bodies, which are glomeruloid in appearance, as well as intracellular and extracellular hyaline globules, often are observed. Several of these histologic patterns can be found within the same tumor.

Staging

Well-established staging systems exist for several tumors that occur within the mediastinum. Most noted are those for thymoma, lymphoma, and neuroblastoma. These are listed below.

A well-defined staging system exists for germ cell tumors arising in gonadal structures; however, because of their infrequency, no specific staging systems have yet been described for primary germ cell tumors of the mediastinum. The staging system for germ cell tumors of the gonads, both seminomatous and nonseminomatous, is determined by the primary tumor, regional lymph node, remote metastases (TNM) classifications, as well as an additional category, S, signifying the serum tumor marker status of the individual. This staging system will be provided below.

• Masaoka postsurgical staging system for thymomas
• • Stage I: Grossly, the tumor is completely encapsulated. Microscopically, no invasion of the capsule is observed.
  • Stage II
    • IIA: Grossly, invasion is observed into the surrounding fatty tissues or mediastinal pleura.
    • IIB: Microscopically, tumor invasion is observed extending into the capsule.
  • Stage III: Gross evidence of invasion into an adjacent organ or structure (eg, pericardium, lung, great vessels [including vena cava]) is present.
  • Stage IV
    • IVA: Tumor dissemination is observed in pleura or pericardium.
    • IVB: Evidence of hematogenous or lymphogenous metastases is present.
• The other staging method, put forth by Marino and Muller-Hermelink, is based upon the cell type found within a given thymoma. Thymomas are classified as either cortical, medullary, or mixed. Some combination of these systems most likely may be the most accurate method of staging.
• Lymphomas found in the mediastinum are staged according to the Ann Arbor staging system.
• • Stage I - Involvement of 1 lymph node region on either side of the diaphragm
  • Stage II - Involvement of 2 or more lymph node regions on the same side of the diaphragm
  • Stage III - Involvement of 2 or more lymph node regions on both sides of the diaphragm
  • Stage IV - Disseminated organ involvement
• The International Neuroblastoma Staging System (INSS) is used widely for the staging of neuroblastoma and essentially has replaced other staging systems. The staging system for neuroblastomas is as follows:
• • Stage I: Tumor is localized and confined to its area of origin. Complete gross excision can be performed (residual microscopic disease may or may not be present). Ipsilateral and contralateral lymph nodes removed at surgery are microscopically negative.
  • Stage 2A: Incomplete gross excision of unilateral tumor occurs. Ipsilateral and contralateral lymph nodes removed at surgery are microscopically negative.
  • Stage 2B: Complete or incomplete gross excision of a unilateral tumor with positive ipsilateral lymph nodes occurs. Identifiable contralateral lymph nodes are microscopically negative.
  • Stage 3: Tumor is found to infiltrate across the midline with or without regional lymph node involvement or the tumor is unilateral (but contralateral lymph node involvement is found) or the tumor is midline with bilateral lymph node involvement.
  • Stage 4: Tumor dissemination to bone, bone marrow, distant lymph nodes, liver, and other organs (except as defined for stage 4S) occurs.
  • Stage 4S: Localized primary tumor as defined by stage 1 or 2 is present but with disseminated disease to liver, less than 10% of bone marrow, skin, or all and is diagnosed in a patient as a newborn to younger than age 1 year.
• While a staging system for germ cell tumors originating in nongonadal sites has not been determined, one does exist for germ cell tumors that originate in the gonads. To illustrate this, the TNM classification used to stage primary testicular malignancies is delineated here. This staging system, however, is not used for primary mediastinal germ cell tumors.
• • Primary tumor (pT)
    • pTX - Primary tumor cannot be evaluated.
    • pT0 - No evidence of primary tumor (scar noted histologically in testis without evidence of tumor cells)
    • pTis - Carcinoma in situ (tumor confined to intratubular areas)
    • pT1 - Tumor confined to testis and epididymis with possible invasion of tunica albuginea but not tunica vaginalis; no evidence of vascular or lymphatic invasion
    • pT2 - Tumor confined to testis and epididymis with extension through tunica albuginea and involving tunica vaginalis or with evidence of vascular or lymphatic invasion
    • pT3 - Tumor invasion of spermatic cord with or without evidence of vascular or lymphatic invasion
    • pT4 - Tumor invasion of scrotum with or without vascular or lymphatic invasion
  • Regional lymph nodes (N)
    • NX - Regional lymph nodes cannot be evaluated.
    • N0 - No metastasis to regional lymph nodes
    • N1 - Metastasis with a lymph node mass of 2 cm or less in greatest dimension or metastases to more than 1 lymph node with none being more than 2 cm in greatest dimension
    • N2 - Metastasis with lymph node mass greater than 2 cm but less than 5 cm in greatest dimension or metastasis to more than 1 lymph node with any 1 mass greater than 2 cm but less than 5 cm in greatest dimension
    • N3 - Lymph node metastasis with greatest dimension being more than 5 cm
  • Distant metastasis (M)
    • MX - Distant metastasis cannot be assessed.
    • M0 - No distant metastasis
    • M1 - Distant metastasis
    • M1a - Nonregional nodal or pulmonary metastasis
    • M1b - Distant metastasis to areas other than nonregional lymph nodes or lungs
  • Serum tumor markers (S)
    • SX - Serum markers not available or not performed
    • S0 - Serum marker levels within normal limits
    • S1 - LDH greater than 1.5 times upper times of normal level and human chorionic gonadotropin (hCG), in mIU/mL, greater than 5000 and AFP (ng/mL) greater than 1000
    • S2 - LDH 1.5-10 times upper limits of normal level or hCG (mIU/mL) 5000-50,000 or AFP (ng/mL) 1000-10,000
    • S3 - LDH greater than 10 times upper limits of normal level or hCG (mIU/mL) greater than 50,000 or AFP (ng/mL) greater than 10,000
  • Table 1. Staging for Primary Gonadal Malignancies Based on TNM Classification

    Stage	T	N	M	S
    Stage 0	pTis	N0	M0	S0
    Stage I	pT1-4	N0	M0	SX
    Stage IA	pT1	N0	M0	S0
    Stage IB	pT2 pT3 pT4	N0 N0 N0	M0 M0 M0	S0 S0 S0
    Stage IS	Any pT/Tx	N0	M0	S1-3
    Stage II	Any pT/Tx	N1-3	M0	SX
    Stage IIA	Any pT/Tx Any pT/Tx	N1 N1	M0 M0	S0 S1
    Stage IIB	Any pT/Tx Any pt/Tx	N2 N2	M0 M0	S0 S1
    Stage IIC	Any pT/Tx Any pT/Tx	N3	M0 M0	S0 S1
    Stage III	Any pT/Tx	Any N	M1	SX
    Stage IIIA	Any pT/Tx Any pT/Tx	Any N Any N	M1a M1a	S0 S1
    Stage IIIB	Any pT/Tx Any pT/Tx	N1-3 any N	M0 M1a	S2 S2
    Stage IIIC	Any pT/Tx Any pT/Tx Any pT/Tx	N1-3 Any N Any N	M0 M1a M1b	S3 S3 Any S

TREATMENT

Section 7 of 12  

• Authors and Editors
• Introduction
• Indications
• RELEVANT ANATOMY
• Contraindications
• Workup
• Treatment
• Complications
• Outcome And Prognosis
• Future And Controversies
• Multimedia
• References

Medical therapy

While most tumors and cysts of the mediastinum are treated surgically, medical therapy is the primary form of treatment in several diseases.

Germ cell tumors

Seminomas

Radiation therapy is the primary treatment for seminoma. A dose range of 3000-4500 cGy is recommended. Chemotherapy often is used in patients older than 35 years or those with features of advanced disease. Cisplatin-based chemotherapy regimens are found very effective in seminoma. Some evidence suggests that chemotherapy should become the primary form of treatment for seminoma and that radiotherapy should be used for the treatment of locoregional areas of involvement. Surgery has almost no indication in seminoma except for purposes of diagnosis. Patients should receive radiotherapy even if complete resection appears to have been achieved.

Nonseminomatous germ cell tumors of the mediastinum

Benign teratomas of the mediastinum are the only mediastinal nonseminomatous germ cell tumors for which surgical resection is indicated as primary treatment.

A number of cisplatin-based chemotherapeutic protocols are used as primary treatment of malignant mediastinal nonseminomatous germ cell tumors. Initial regimens last 3-4 months with re-staging performed after completion of treatment. Recurrence develops in about 20% of cases, and salvage chemotherapy regimens are used in these patients. Surgical resection of residual disease within the chest may be required primarily for diagnosis after initial chemotherapy treatment. As many as 75% of patients requiring resection have benign teratoma, nonviable tumor, or fibrosis found.

Surgical therapy

Surgical resection is the treatment of choice for most neoplasms that occur in the mediastinum, except for malignant germ cell neoplasms.

The most common mediastinal tumors for which nonsurgical forms of therapy are considered the primary treatment are seminomas, malignant nonseminomatous germ cell tumors, lymphoma, and advanced-stage neuroblastoma in children.

In cases of benign neoplasms, complete excision of the lesion itself generally is sufficient. Benign teratomas are tumors for which surgical excision is adequate therapy. All benign neoplasms that are encapsulated should be resected without violation of the capsule. VATS techniques have been introduced in teratoma resection with promising results.

Surgical resection is advised in nonseminomatous malignant germ cell tumors of the mediastinum when radiographic studies show residual mediastinal disease present after appropriate chemotherapeutic treatment has been administered. Residual masses are observed in 10-20% of cases after treatment. Resection of residual masses in these cases is performed to determine the presence or absence of residual malignancy. If the former is the case, additional chemotherapeutic treatment may or may not be considered.

In cases of seminoma, some controversy exists regarding resection of residual posttreatment masses. Some authors state that no surgical intervention is needed and that radiographic follow-up is the appropriate course of action. Others state that residual masses greater than a specified size should be resected.

Preoperative details

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. Consider detailed preoperative assessment of the airway, as well as adequate visualization and readily available supplementary equipment (eg, flexible bronchoscope), for safe management of the airway distorted or narrowed by a mediastinal mass. Placement of a double-lumen endotracheal tube to provide single-lung ventilation usually is 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 necessary blood products (all of paramount importance) before the operation 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. The surgeon must be prepared for this, and the patient must be informed preoperatively that such resection may be required because this may have additional impact on recovery and perioperative risk.

Although uncommon in cases of germ cell tumors for which surgical resection is the indicated treatment, several mediastinal tumors can produce important effects that should be taken into account preoperatively.

Superior vena cava syndrome

Superior vena cava syndrome (SVCS) can occur in association with various thoracic neoplasms. While bronchial carcinoma represents the most common cause of this problem, lymphoma, germ cell malignancies, thymic neoplasms, and a host of the less common mediastinal malignancies can produce it.

If this syndrome is noted to be acute in a patient preoperatively, treatment with bed rest, elevation of the head, and oxygen administration can be helpful. Salt restriction and diuretics generally are not indicated. Use corticosteroids only for treatment of associated laryngeal edema or in the presence of brain metastases that produce increased intracranial pressure.

Placement of intravenous lines should be planned carefully because venous inflow to the heart from the supracardiac great veins will be altered greatly. Many clinicians place intravenous lines in sites below the level of the heart to assure direct, rapid flow of medications and fluids to the heart. Intravenous lines in the neck should not be placed because jugular venous pressure may be elevated markedly, and accidental extravasation of blood from these sites may lead to airway compromise.

Intubation should be performed with care in individuals with SVCS because trauma to the airway may lead to disruption of small venous structures in the wall of the trachea. Normally, bleeding from these tiny vessels is self-limiting; however, in patients with SVCS, venous pressure is elevated, and bleeding may be more pronounced. Individuals with SVCS may not be able to lie comfortably in a supine position for an extended period of time because this produces increased intracerebral venous pressure. Consider this factor during transport and positioning of the patient.

Chronic SVCS can be treated with resection and interposition graft reconstruction if the patient is symptomatic.

Intraoperative details

As with all thoracic surgery, positioning the patient properly for the indicated procedure is of paramount importance. Tumors or cysts located in the anterior mediastinum generally are approached through a median sternotomy. This approach would be 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 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. VATS techniques have been introduced in teratoma resection with promising results in several centers. Additional exposure includes a hemiclamshell thoracotomy with or without neck extension, which may be preferred for tumors in the anterior mediastinum with extensive involvement of the hemithorax. A neck extension or supraclavicular extension can be incorporated with involvement that extends into the neck or subclavian vessels, respectively. A clamshell incision can also be used for tumors that extend into both hemithoraces. A tumor may extend to adjacent structures, and resection of the thymus, pericardium, lung, phrenic nerve, innominate vein, and superior vena cava can be appropriate.

Postoperative details

Care of patients after resection or biopsy of a mediastinal tumor 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 their cases 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 also is a critical factor in postoperative management after thoracic surgery. Adequate cough effort and ventilatory excursion cannot be maintained without satisfactory pain control. Administration of analgesic agents by thoracic epidural catheter is an excellent and highly effective method of pain management. Lumbar epidural catheters also can 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. It is not as efficient for pain control as epidural analgesia.

A continuous infusion of 0.25% bupivacaine at 4 mL/h through the ON-Q elastomeric infusion pump is also a safe and effective adjunct in postoperative pain management after thoracotomy. The use of the ON-Q Post-Op Pain Relief System (I-Flow Corporation, Lake Forest, Calif) 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 will 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. Patient recovery is followed with daily chest radiographs that are evaluated for residual undrained collections, complete pulmonary expansion, lobar atelectasis and infiltrates, and other abnormalities. When drainage from the chest tubes is less than 50-100 cc in a 24-hour period, 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.

Follow-up

Patients who undergo resection of benign neoplasms or mediastinal cysts can be observed for a short time (ie, 3-6 mo) postoperatively while wound healing and progression of patient activity is monitored.

Due to 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.

Specific serum markers are very useful in posttreatment surveillance of patients with nonseminomatous germ cell tumors. These studies include alpha-fetoprotein (AFP), beta human chorionic gonadotropin (bhCG), and LDH levels. If serum levels are found to be elevated at some point after treatment, additional imaging studies, such as CT or PET scan of the chest, should be performed to evaluate the patient for recurrent disease. Because nearly all relapses occur within 2 years after therapy, monthly surveillance consisting of physical examination, chest radiograph, and assay of serum markers is recommended for the first year posttreatment. Surveillance is recommended every 2 months for the second year.

During follow-up for seminoma, the patient is observed for at least a 2-year period. Observation consists of a monthly physical examination, LDH monitoring, and chest radiograph. If radiographic observation of a residual mediastinal mass is observed, a CT scan is performed every 3 months for the first year and then at 6-month intervals for the second year.

COMPLICATIONS

Section 8 of 12  

• Authors and Editors
• Introduction
• Indications
• RELEVANT ANATOMY
• Contraindications
• Workup
• Treatment
• Complications
• Outcome And Prognosis
• Future And Controversies
• Multimedia
• References

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. As noted previously, 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 possesses excellent blood supply and, with few exceptions, healing occurs readily. Also, existing intrathoracic infection generally is not a factor during resection of any of the noted mediastinal tumors, and these operations are considered clean procedures. The exception to this might 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, aggressive debridement of devascularized bone and cartilage should be performed, as well as 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, as well as atelectasis, on the affected side. Diaphragmatic plication should be considered to prevent lower lobe atelectasis.

Young children or individuals with marginal pulmonary status from underlying pulmonary disease or those with neuromuscular abnormalities causing weakness of the muscles of respiration (eg, myasthenia gravis) can experience significant respiratory difficulties from this complication.

Injury to a vagus nerve also can 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

Section 9 of 12  

• Authors and Editors
• Introduction
• Indications
• RELEVANT ANATOMY
• Contraindications
• Workup
• Treatment
• Complications
• Outcome And Prognosis
• Future And Controversies
• Multimedia
• References

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 biological 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 beta human chorionic gonadotropin (bhCG) 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 (longer than 24 mo) disease-free survival rates after completion of systemic chemotherapeutic treatment in these patients is about 42%.

FUTURE AND CONTROVERSIES

Section 10 of 12  

• Authors and Editors
• Introduction
• Indications
• RELEVANT ANATOMY
• Contraindications
• Workup
• Treatment
• Complications
• Outcome And Prognosis
• Future And Controversies
• Multimedia
• References

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

Emerging diagnostic modalities, such as 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 biological 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 video-assisted thoracic surgical (VATS) technology has entered the armamentarium of the thoracic surgeon with respect to the treatment of a number of mediastinal diseases. This modality already is used commonly for obtaining biopsy of masses and lymph nodes. It also has been described for resection of various mediastinal cysts, mediastinal parathyroid adenomas, and localized benign tumors of the posterior mediastinum such as ganglioneuromas. At several centers, thymectomy has been performed using this technology. The completeness of thymic resection able to be achieved by this approach is the subject of some controversy. VATS technology has also been reported in resecting teratomas of the mediastinum.

MULTIMEDIA

Section 11 of 12  

• Authors and Editors
• Introduction
• Indications
• RELEVANT ANATOMY
• Contraindications
• Workup
• Treatment
• Complications
• Outcome And Prognosis
• Future And Controversies
• Multimedia
• References

Media file 1:  A 25-year-old man is found to have an asymptomatic anterior mediastinal mass on a routine chest radiograph. This posteroanterior (PA) view shows the edges of the mass extending beyond the normal heart border. At surgery, the mass was found to be a benign teratoma.
	View Full Size Image
Media type:  X-RAY

Media file 2:  Later chest radiograph (see Picture 1) of a 25-year-old man with an asymptomatic anterior mediastinal mass The arrow indicates the area the mass occupies in the anterior mediastinum. This was found to be a benign teratoma.
	View Full Size Image
Media type:  X-RAY

REFERENCES

Section 12 of 12

• Authors and Editors
• Introduction
• Indications
• RELEVANT ANATOMY
• Contraindications
• Workup
• Treatment
• Complications
• Outcome And Prognosis
• Future And Controversies
• Multimedia
• References

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Article Last Updated: Nov 1, 2006