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

Because a great many organ systems and varieties of tissues are represented within the mediastinum, tumors that occur in this area can represent many different clinical entities and pathologic processes. Lymphomas, primary or ectopic endocrine tumors, and a wide variety of mesenchymal tumors can occur in the mediastinum. An understanding of the embryology and of the anatomic relationships of the normal structures of the mediastinum is essential in the proper determination of the exact nature of a mass or tumor located in this area.

History of the Procedure

Although the entire field of surgery is an ancient one, successful surgical procedures of 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 a 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, Milton was able to perform a tracheostomy and give artificial respiration through it. This support enabled him to explore the mediastinum successfully 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 the monograph 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.

Wakely and Mulvany described intrathoracic goiters in 1940. The authors divided these lesions into 3 subtypes. These were (1) the "small substernal extension" of a goiter primarily located in the neck; (2) the "partial" intrathoracic goiter for which a large portion, although not all of the goiter, is in the thorax; and (3) the "complete" intrathoracic goiter, for which the entire goiter appears to be within the thorax. Their report indicated that 8-9% of goiters had some intrathoracic component. Of these, more than 80% were of the first type, and only approximately 3% were of the third type.

The first described removal of a parathyroid adenoma from the mediastinum occurred in 1932. This was performed on a patient who had undergone 6 previously unsuccessful surgeries for hyperparathyroidism.

Problem

Any discussion of neoplasms or other masses found within 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.

Because a number of mediastinal tumors and other masses are most commonly found in particular mediastinal locations, many authors have artificially subdivided the area for better descriptive localization of specific lesions. Usually, 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.

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

A relatively common mass identified as an anterior mediastinal mass is a substernal extension of a thyroid goiter. This is not, by definition, a tumor that originates within the mediastinum, but is often first identified as a mass lesion within the mediastinum that must be differentiated from other sources and, when symptomatic, must be treated. Even though not a primary tumor of the mediastinum, substernal extension of the cervical thyroid gland is discussed in this article because it is a relatively common problem and is traditionally considered one of the differential diagnoses of an anterior mediastinal mass.

While neoplasms of the middle mediastinum are most commonly of lymphatic origin, neurogenic tumors also occasionally occur in this area. Another significant group of masses identified in this compartment is cystic structures associated with developmental abnormalities of the primitive foregut or the precursors of the pericardium or pleura. They include bronchogenic, esophageal, gastric, and pleuropericardial cysts. Isolated cystic abnormalities of lymphatic origin, such as hygromas or lymphangiomas, can develop within the middle mediastinal compartment but are more often extensions of these abnormalities from cervical lymphatics.

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.

Frequency

A review of collected series reveals that many mediastinal neoplasms and masses vary in incidence and presentation depending on patient age. Also, a number 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, followed by thymic tumors, lymphomas, and germ cell tumors. Foregut and pericardial cysts are the next most frequently occurring abnormality within this group. However, 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 also passed neurogenic tumors in frequency.

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

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.

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.

Although lymphomas can be found in any of the mediastinal compartments, many of them manifest in the anterior compartment. As many as 45% of masses found in the anterior mediastinum of children are lymphomas, and, in adults, they are the second most common anterior mediastinal mass.

True ectopic thyroid tissue, entirely detached from the cervical thyroid gland and having its own (albeit anomalous) blood supply in the mediastinum, is extremely rare. Only a few case reports exist. Most thyroid tissue found in the mediastinum results from an extension of the cervical thyroid gland, usually as a goiter. More than 80% of these extensions lie beneath the manubrium and in a position superior to the arch vessels. The remainder can lie within the middle mediastinum, some in a retrotracheal or even retroesophageal position.

According to various reports, occult malignancy, usually papillary thyroid carcinoma, can be found in resected intrathoracic thyroid tissue. This has been reported in approximately 5% of cases.

Of all parathyroid tumors, only 1-3% are truly mediastinal in location, defined as those inaccessible by standard cervical exploration and requiring median sternotomy for excision.

Mesenchymal tumors represent approximately 6% of all masses found in the mediastinum. More than 50% of these are malignant.

Etiology

Tumors and cysts found in the mediastinum have various causes.

Lymphatic tumors

Several types of lymphomas can be found in the mediastinum. They may be found in the mediastinum as a primary process or as one of a number of involved locations in a systemic process. All forms of lymphoma originate from abnormalities of specific types of lymphocytes. They are generally divided into Hodgkin and non-Hodgkin lymphomas.

The many forms of non-Hodgkin lymphoma are categorized by cell type. The most common types of lymphoma found in the mediastinum include immunoblastic T-cell, immunoblastic B-cell, follicular center cell, and lymphoblastic. The most common form of Hodgkin lymphoma found in the mediastinum is the nodular sclerosing type.

Mesenchymal tumors

Mediastinal neoplasms can arise from several cell types. They may be benign or malignant in activity, although a little more than half are malignant. The most common types of tissues from which they originate include vascular, lymphatic, muscular, fibrous, and adipose tissues. Very uncommon mediastinal tumors from a mesenchymal source include those originating from bony, cartilaginous, synovial, and meningeal tissues.

Cystic hygroma is a form of lymphangioma that most commonly extends into the mediastinum from the neck. It is most often discovered at (or shortly after) birth and is believed to result from a developmental lymphatic abnormality within the neck.

Ectopic endocrine tumors

Approximately 20% of normal parathyroid glands are located inside the capsule of the thymus or in the anterior mediastinum. Parathyroid adenomas can develop within these ectopic glands in the mediastinum, and approximately 80% are identified within the anterior compartment. Parathyroid carcinoma can occur in an ectopic mediastinal parathyroid gland, but this is very unusual.

Aberrant thyroid tissue or thyroid completely separated from the cervical gland (rarely) can be found in the mediastinum. A distinguishing feature of this tissue is that its blood supply originates within the mediastinum. This feature is unlike the more commonly found substernal thyroid, which is simply an extension of the cervical thyroid gland into the mediastinum and receives its blood supply from the normal thyroid vessels within the neck. Thyroid tumors, benign or malignant, can arise in aberrant mediastinal thyroid tissue.

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 usually more evident in children than in adults. Compression or obstruction of portions of the airway, esophagus, or 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 result secondarily in nearby structures (eg, lungs) as a result of local compression or obstruction.

Because of the close proximity to the trachea and the limited space of the thoracic inlet, patients with intrathoracic extension of a cervical goiter commonly present with symptoms of upper airway compression and can also present with esophageal compression.

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. 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 (SVCS); 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.

Lymphatic tumors

In some cases, Hodgkin lymphoma has been associated with hypercalcemia. The elaboration of other specific bioactive substances has not been associated with Hodgkin and non-Hodgkin lymphoma of the mediastinum. However, many individuals with these diseases have various systemic findings such as weight loss, night sweats, fever, and malaise.

Mesenchymal tumors

Rarely, fibrosarcomas can produce an insulinlike substance.

Ectopic endocrine tissue

Thyroid tumors developing within the mediastinum can produce excess thyroid hormone and associated systemic manifestations.

Mediastinal parathyroid adenomas or carcinomas commonly produce excess parathyroid hormone (PTH).

Clinical

A large percentage of mediastinal tumors and cysts produce no symptoms and are found incidentally during chest radiograph or imaging studies of the thorax performed for other reasons. Symptoms are present in approximately one third of adult patients with a mediastinal tumor or cyst but are more commonly observed in the pediatric population, nearly two thirds of which presents 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 amount of malleability of the airway structures and the small size of the chest cavity in infants and children. Symptoms observed most commonly include persistent cough, dyspnea, and stridor. If the location and size of the mass produce partial or complete obstruction, obstructive pneumonia can also occur. Infectious symptomatology, and even signs of sepsis, can also occur if a mediastinal cyst becomes infected.

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

Symptoms associated with compression of some portion of the respiratory tract can also be produced by benign lesions in adults, but this is much less likely than in children. Intrathoracic extension of a cervical goiter is one noted largely benign abnormality that commonly manifests with upper respiratory symptoms. At least 70% of individuals with intrathoracic goiters have some symptoms of airway compression. Cough, wheezing, stridor, dyspnea, and dysphagia are among the common complaints.

Infectious symptoms or sepsis from infection of a mediastinal cyst can also occur in adults, although, again, this is very unlikely in this age group.

Malignant lesions are more likely to produce signs and symptoms of obstruction and/or compression than benign lesions because they invade or transfix normal mediastinal structures. Clinical findings associated with these malignant properties include cough, dyspnea, stridor, dysphagia, and more dramatic findings (eg, SVCS). Invasion of the chest wall or pleura by a malignant neoplasm can produce persistent pleural effusions and significant local pain. Invasion of nearby nerves within the thorax can also produce local and referred pain and various 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.

Mediastinal tumors that produce bioactive substances are associated with symptoms produced by those substances, as discussed in Systemic pathophysiology above.

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 on the diagnosis of the lesion. Surgical resection is indicated in a large percentage of cases.

Lymphatic tumors

Surgical resection is not indicated as primary treatment for any of the lymphomas involving the mediastinum. However, various surgical procedures, including staging laparotomy, may be required for the sampling of lymph nodes or other tissues so that accurate diagnosis and staging of the lymphatic tumor is achieved.

Specific complications of mediastinal lymphoma, such as pericardial effusion and tamponade or persistent pleural effusion, may require surgical treatment. Occasionally, surgical resection of a residual mediastinal mass is indicated after the completion of chemotherapy and radiotherapy in order to establish the presence or absence of residual tumor and to determine if further chemotherapy is indicated.

Mesenchymal tumors

Surgical excision is indicated for almost all tumors of mesenchymal origin. One noted exception is that of rhabdomyosarcoma, for which a combination for radiation and chemotherapy offers the best survival results.

Some mesenchymal tumors of the mediastinum are so rare that only anecdotal reports of their diagnosis and treatment exist; thus, recommendations for treatment of these tumors cannot be made.

Ectopic endocrine tissue

Surgical excision is indicated for ectopic endocrine tissue within the mediastinum. Nonfunctioning thyroid or parathyroid tissue may not have been identified previously and is often removed incidentally during surgery for another reason. Functioning or malignant endocrine tissues require removal.

Substernal goiter is not true ectopic endocrine tissue, but rather, the direct extension of an abnormal cervical thyroid into the mediastinum. Surgical resection may be indicated, even in asymptomatic cases, because of the risk of sudden airway obstruction and because of the somewhat increased chance of malignancy. Resection can be performed via the standard cervical thyroidectomy incision in almost all cases. On rare occasions, sternotomy is required.

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

When determining 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.

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

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 blood supply of almost all intrathoracic thyroid goiters is derived from the inferior thyroid arteries.

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, and numerous lymph nodes.

The posterior mediastinum comprises the area posterior to the heart and trachea and includes the paravertebral sulci. The posterior mediastinum 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.

CONTRAINDICATIONS

Section 5 of 12  

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

Surgical removal is not indicated as primary treatment for lymphomas and rhabdomyosarcomas.

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

• Serum calcium, phosphorus, and PTH levels
• • Serum chemical findings diagnostic for primary hyperparathyroidism can be observed when parathyroid adenoma or carcinoma develops within ectopic parathyroid glands in the mediastinum. These findings include elevated serum calcium levels associated with a decrease of serum phosphorus. PTH levels are elevated.
  • In cases in which no pathology is found in the neck, extend the evaluation of the cause of primary hyperparathyroidism to the mediastinum.
• Thyroid-stimulating hormone and thyroid function studies: Functioning thyroid adenomas can develop in ectopic mediastinal thyroid tissue and can cause thyroid stimulating hormone suppression and associated elevation of serum triiodothyronine levels.

Imaging Studies

• Chest radiography
• • Posteroanterior (PA) and lateral radiograph of the chest for an unrelated cause is the usual way in which an asymptomatic mediastinal mass is identified. Chest radiography is obviously the first study performed in an individual with symptoms referable to the thorax.
  • Lateral chest radiograph findings are 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 scan is a routine part of the diagnostic evaluation of mediastinal tumors, cysts, and other masses.
  • CT scan findings can greatly assist in determining the exact location of the mediastinal tumor and in determining its relationship to adjacent structures. They are useful also in differentiating those masses that originate in the mediastinum from those that encroach on the mediastinum from the lung or other structures.
  • While not infallible, the CT scan is very useful in helping differentiate tissue densities. This assists greatly in distinguishing cystic or vascular structures from those that are solid.
  • CT scan images can reveal evidence of local invasion of adjacent structures by a mass or the presence of intrathoracic metastases. In the past, CT scan was recommended in the evaluation of all paravertebral masses to help determine the presence of intraspinal extension or invasion. More recently, MRI has proven superior for this purpose.
• Magnetic resonance imaging
• • MRI is useful in both the initial diagnosis of a mediastinal mass and in follow-up evaluation after treatment. It provides superior vascular images and can help better delineate the relationship of an identified mediastinal mass to nearby intrathoracic vascular structures. MRI can help differentiate between a possible mediastinal mass and a vascular abnormality such as an aortic aneurysm.
  • MRI offers direct multiplanar imaging. It can be used when iodinated contrast is contraindicated. MRI provides increased detail in the subcarinal and aortopulmonary window areas and in the inferior aspects of the mediastinum at the level of the diaphragm.
  • MRI is superior to the CT scan images for the evaluation of masses located at the thoracic inlet or at the thoracoabdominal level. MRI is used increasingly for evaluation of residual or recurrent disease after treatment of lymphoma. Although histologic analysis of any residual mass after chemotherapy and radiotherapy remains the standard, MRI evaluation findings of questionable areas are found to correlate well with histologic findings in differentiating residual tumor from fibrosis.
• Radionuclide scanning
• • Nuclear imaging can be used selectively in the workup of mediastinal masses when specific tumors are suggested. Gallium Ga 67 is used commonly in the evaluation of mediastinal lymphoma, both for initial evaluation and for posttherapy follow-up.
  • The iodine I 131 or iodine I 123 scans are very helpful in distinguishing thyroid tissue from other masses. They are often used in identifying an anterior mediastinal mass located at the level of the thoracic inlet as the substernal extension of a cervical thyroid goiter. A radioactive iodine scan also may help identify ectopic thyroid tissue within the mediastinum. These studies must be performed before any tests requiring the administration of iodinated contrast because this material may interfere with thyroid uptake and scanning.
  • Scanning with technetium Tc 99m sestamibi may be useful in the identification of mediastinal parathyroid tissue.
  • The octreotide scan, using indium In 111–labeled pentetreotide, is useful for localizing various neuroendocrine neoplasms, including carcinoid tumors, pheochromocytomas, and paragangliomas. It has also been used at some centers for the evaluation of certain lymphomas.
• Echocardiography and ultrasonography
• • Ultrasonographic methods have been used to help differentiate solid from cystic mediastinal masses and to assist in determining the connection between a mass and adjacent structures.
  • The findings from 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 images, MRI, and selected radionuclide scan findings, ultrasound techniques are generally not used as a primary tool in the evaluation of mediastinal tumors and cysts.
• Positron emission tomography
• • Positron emission tomography (PET) scan findings have been studied extensively for the evaluation of a number of neoplasms such as lung, colorectal, breast, lymphoma, and melanoma. It has become an extremely useful adjunct in the evaluation and staging of these pathologies.
  • The usefulness of this study in the evaluation of mediastinal tumors is being evaluated.
• Arteriography
• • Conventional angiography findings have been used to differentiate mediastinal masses from vascular abnormalities and to exhibit the relationship between known masses and adjacent vascular structures.
  • MRI and magnetic resonance angiography have replaced conventional angiography in most cases.
• Video-assisted thoracoscopy
• • Video-assisted thoracoscopy (VATS) techniques have been used successfully for biopsy of various mediastinal masses and are used routinely for the sampling of perihilar lymph nodes.
  • VATS is one of the more commonly used methods for evaluation of mediastinal lymphoma.
• Sternotomy and thoracotomy
• • In spite of 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.

Diagnostic Procedures

• Transthoracic needle biopsy
• • In the past, percutaneous biopsy methods were considered too dangerous to be used in the evaluation of mediastinal masses, and open surgical biopsy was the diagnostic procedure of choice. Although still controversial, increased success using CT-guided fine-needle aspiration (FNA) and core needle biopsy techniques is reported at several centers.
  • Differentiation between 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 also be identified. 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.
  • FNA has been used occasionally to aid in the diagnosis of primary bronchogenic cysts. However, most authorities do not recommend aspiration of a cyst because a sample of the cyst wall, required for diagnosis, is not obtained by this method. Also, most cysts 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 in the evaluation of the retrovascular pretracheal area of the mediastinum. It is used most commonly for staging of bronchogenic carcinoma and for evaluation of hilar and paratracheal lymphadenopathy.
  • It can be modified into what has been termed a substernal extended mediastinoscopy to evaluate the prevascular area of the mediastinum. The thymus and any tumors or cysts found in this area and in lymph nodes of the aortopulmonary window are accessible for biopsy using this approach.
• Anterior mediastinotomy
• • This parasternal approach to the mediastinum is used most commonly in situations in which standard cervical mediastinoscopy is considered, or has been found to be, inadequate.
  • The classic approach is to perform it in the upper left parasternal area in order to gain 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 VATS techniques.
• Posterior mediastinotomy
• • This is a rarely used procedure for biopsy of some of the posteriorly situated lymph nodes or a mass in the paravertebral sulcus. Posterior mediastinotomy is performed most commonly on the right side in a paravertebral location immediately lateral to the paravertebral muscles.
  • As with the anterior mediastinotomy, small segments of several ribs in the area may be excised for extrapleural access to the ipsilateral paravertebral sulcus. The mediastinoscope may also be used for lymph node biopsy with this approach.
  • It is rarely used for mediastinal tumors and cysts because these are more appropriately managed by either standard thoracotomy or VATS techniques.

Histologic Findings

Lymphoma

Hodgkin disease and non-Hodgkin lymphoma are the 2 main subclassifications of this large area.

Hodgkin disease

According to the Rye classification, Hodgkin lymphoma is divided into the histopathologic types of (1) nodular sclerosing, (2) lymphocyte predominant, (3) mixed cellularity, and (4) lymphocyte depleted.

A characteristic feature of all forms of Hodgkin lymphoma is the presence of Reed-Sternberg cells. These are large cells with acidophilic cytoplasm that usually have binucleated or have bilobed nuclei with large, prominent, deeply eosinophilic nucleoli.

The nodular sclerosing variety is generally composed of broad bands of collagenous material, which appear to subdivide the tumor into nodular components. Cellular components include Reed-Sternberg cells, lymphocytes, neutrophils, plasma cells, eosinophils, and histiocytes. Some variants of the nodular sclerosing type have been described.

Lymphocyte-predominant Hodgkin disease displays L and H cells, which are lymphocytic and histiocytic cells that possess lobulated nuclei and pale cytoplasm. These are found within a predominant framework of small lymphocytes. Epithelioid histiocytes are very evident, while Reed-Sternberg cells are present but infrequent.

The mixed cellularity type of Hodgkin disease has a diffusely cellular appearance composed of plasma cells, histiocytes, eosinophils, and lymphocytes. Reed-Sternberg cells are common, and fibrosis in this form is minimal. The lymphocyte-depleted form of Hodgkin disease is very similar in appearance to large cell non-Hodgkin disease. Immunophenotyping is a necessary addition to histopathologic analysis for proper classification of Hodgkin disease.

Non-Hodgkin lymphoma

While many types of non-Hodgkin lymphoma have been described, those types particular to the mediastinum are (1) large cell lymphoma, (2) anaplastic large cell lymphoma, (3) mucosa-associated lymphoid tissue lymphoma, (4) lymphoblastic lymphoma, and (5) other lymphomas.

The mediastinal form of large cell lymphoma has some features that appear to distinguish it from large cell lymphomas at other locations. Intermediate- to large-sized lymphoid cells are found in the presence of significant sclerosis. Bands of sclerosis may be seen surrounding groups of the tumor cells. The nuclei of tumor cells are commonly multilobulated, and cytoplasm can be acidophilic or clear. While the lymphoid cells are large in this tumor, they are actually smaller than those of large cell lymphomas in other areas. Some authors have termed this tumor B-cell lymphoma.

Anaplastic large cell lymphomas are generally found in a cutaneous or systemic form, but primary mediastinal involvement has been described. The tumors have highly atypical lymphoid cells with evenly dispersed chromatin, large nucleoli, and significant amounts of mitotic figures. Cells have distinct borders, and nuclei are often pleomorphic and multilobated, simulating Reed-Sternberg cells.

Mucosa-associated lymphoid tissue lymphoma (ie, MALToma) tumors are rare in the mediastinum and are often associated with autoimmune vascular disease. They are composed of monotonous sheets of small lymphoid cells.

Lymphoblastic lymphoma is closely associated with acute lymphoblastic leukemia. Lymphoblastic lymphoma is characterized by a diffuse infiltrate of immature lymphoid cells, having nuclei with evenly dispersed chromatin and indistinct nucleoli. Fibrosis is sparse and necrosis is common in these tumors. Numerous mitotic figures are present.

Other lymphomas include mantle cell lymphoma, which is otherwise known as lymphocytic lymphoma of intermediate differentiation. Mediastinal lymphadenopathy due to this form has been identified. These tumors are composed of small- to intermediate-sized lymphoid cells with somewhat irregular nuclei. Their architecture is not distinct, but it is somewhat nodular in appearance. The tumor cells have commonly been noted to occupy the border zone surrounding the reactive germinal centers of lymph nodes. Differentiating these tumors from lymphoblastic lymphoma may be challenging in some cases. Immunohistologic studies are usually needed.

Ectopic endocrine tissue

Thyroid and parathyroid tissue found in the mediastinum is histologically identical to that found in the neck. This is true for both benign and malignant lesions.

Mesenchymal tumors

The many mesenchymal tumors that can occur in the mediastinum are rare and are histologically identical to their counterparts occurring in other areas of the body.

Staging

• Well-established staging systems exist for several tumors that occur within the mediastinum. Most noted are those for thymoma, lymphoma, and neuroblastoma.
• No specific staging systems are described for the many other types of tumors that occur, most likely because of their rarity.
• 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
• Once the diagnosis of mediastinal lymphoma is made, additional studies are performed to determine the extent of disease present, ie, to stage the patient. The staging workup at present generally consists of CT scan with contrast, radionuclide studies, and lymphangiographic studies. Bilateral bone marrow biopsies are also recommended. Because incorrect staging can occur when imaging studies are the only study performed, many authorities still recommend the addition of staging laparotomy.

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.

Lymphoma

Hodgkin disease of the mediastinum is treated primarily by radiation or a combination of radiation and chemotherapy. Mediastinal Hodgkin disease in the very early stages (stage PS IA) may be treated with radiation therapy only. Disease at unfavorable stages I or II benefits more from a combination of radiation and chemotherapy. Stage III and IV disease is treated with chemotherapy. Most chemotherapy for Hodgkin disease is performed using a regimen of doxorubicin, vinblastine, bleomycin, and dacarbazine (ABVD) alone or a regimen in which ABVD is alternated with nitrogen mustard, vincristine, procarbazine, and prednisone (MOPP). An alternative method suggested by some authors is a combination of low radiation doses (3500 cGy) plus chemotherapeutic agents that do not include alkylating agents. This is suggested as a regimen that may lessen the undesirable late effects of the more traditional chemotherapy protocols.

Non-Hodgkin lymphoma

Non-Hodgkin lymphoma of the mediastinum is treated with the same chemotherapy regimens as prescribed for the disease found in other areas of the body.

Lymphoblastic lymphoma

Treatment of this aggressive lymphoma is most often performed with high doses of cyclophosphamide, doxorubicin, vincristine, and methotrexate followed by leucovorin rescue. Specific treatment of the central nervous system is performed in these regimens because a high level of disease involvement occurs in this area.

Mesenchymal tumors

In most cases, surgical resection, if possible, is the treatment of choice. Radiation therapy has been used postoperatively with some benefit in cases of malignant fibrous histiocytoma. It has also been used in rhabdomyosarcoma, with uncertain results.

Chemotherapy has been used in some cases of liposarcoma preoperatively to downsize a previously inoperable tumor. It has also been attempted in angiosarcoma, with uncertain benefit. Chemotherapy, with or without radiotherapy, is the recommended treatment for cases of localized mediastinal rhabdomyosarcoma and is shown to improve the disease-free survival rate. In the remaining mesenchymal tumors of the mediastinum, chemotherapeutic treatment has either proven ineffective or not been studied.

Ectopic endocrine tumors of the mediastinum

Surgical resection is the treatment of choice for parathyroid adenomas and carcinomas of the mediastinum.

Treat thyroid neoplasms with surgical resection. Other treatment modalities used for unresectable mediastinal tumor are identical to those used for metastatic thyroid disease from the cervically located gland.

Surgical therapy

Surgical resection is the treatment of choice for most neoplasms that occur in the mediastinum.

In cases of benign neoplasms, complete excision of the lesion itself is generally sufficient. All benign neoplasms that are encapsulated should be resected without violation of the capsule.

Resect intrathoracic thyroid goiters.

When surgical resection of malignant neoplasms of the mediastinum is the primary treatment, perform en bloc resection of the tumor whenever possible.

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. For safe management of the airway distorted or narrowed by a mediastinal mass, consider detailed preoperative assessment of the airway and ensure adequate visualization and readily available supplementary equipment (eg, flexible bronchoscope). Placement of a double-lumen endotracheal tube to provide single-lung ventilation is usually 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 easy availability of necessary blood products (all of paramount importance) before surgery is begun.

Involvement of associated intrathoracic structures by tumor may mandate their resection. Pulmonary resection; excision of nervous structures such as the phrenic, vagus, or sympathetic chain; or even resection of major vascular structures (eg, superior vena cava) may be required. Importantly, 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.

Several mediastinal tumors can produce important effects that should be taken into account before any type of operative procedure, even simple biopsy, is entertained.

Superior vena cava syndrome

SVCS can occur in association with several 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 preoperative patient, treatment with bedrest, elevation of the head, and oxygen administration can be helpful. Salt restriction and diuretics are not generally indicated. Use corticosteroids only for the treatment of associated laryngeal edema or in the presence of brain metastases producing increased intracranial pressure.

Take care in the placement of intravenous lines because venous inflow to the heart from the supracardiac great veins will be greatly altered. 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. Do not place intravenous lines in the neck because jugular venous pressure may be markedly elevated and accidental extravasation of blood from these sites may lead to airway compromise.

Perform intubation 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 because this produces increased intracerebral venous pressure. Consider this during transport; positioning of the patient must be taken into account.

Intraoperative details

As with all thoracic surgery, position the patient properly for the indicated procedure. Tumors or cysts located in the anterior mediastinum are generally 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.

Postoperative details

Care of patients after resection or biopsy of mediastinal tumors 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. Manage patients who require ventilatory support for a longer time, 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. Several methods to assist with pulmonary toilet are available.

Pain control 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 can also be used, and, with proper choice of analgesic agents, they provide good pain relief. Patient-controlled analgesia is another widely used method and is preferred to traditional intramuscular or intravenous administration of narcotics and other agents. It is not as efficient as epidural analgesia for pain control. 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 do 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. Patients are monitored 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 mL in 24 hours, 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 monitored for a short time (ie, 3-6 mo) postoperatively while wound healing and progression of patient activity is being monitored.

Because of the heterogeneity and the small numbers of malignant tumors found in the mediastinum, no single specific method has been described for the follow-up care of patients who undergo intended curative resection of a malignant neoplasm.

Treatment of mediastinal lymphomas is with chemotherapy and/or radiotherapy. Follow-up care is conducted according to standard lymphoma protocols.

Other malignant mediastinal neoplasms can be observed at appropriate intervals using chest radiographs and CT scans according to the physician's discretion.

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 prevention of these complications.

Wound infections after sternotomy or thoracotomy are rare. The chest wall has an excellent blood supply, and, with few exceptions, healing occurs readily. In addition, existing intrathoracic infection is generally not a factor during resection of any of the noted mediastinal tumors, and these operations are considered clean procedures. The exception to this may 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 sternal dehiscence occurs without the presence of infection, perform a simple washout, debridement, and rewiring. If infection is present, perform aggressive debridement of devascularized bone and cartilage and 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 and atelectasis on the affected side. Individuals with marginal pulmonary status from underlying pulmonary disease or those with neuromuscular abnormalities causing weakness of the muscles of respiration can experience significant respiratory difficulties from this complication.

Injury to a vagus nerve can also 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 stomach and 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 is generally excellent. This group of tumors includes such neoplasms as thymolipomas; benign mesenchymal tumors such as fibromas, angiomas, and lymphangiomas; ectopic benign thyroid tissue, including intrathoracic extension of a cervical goiter; and parathyroid adenomas.

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

Mediastinal lymphomas

Excellent survival rates are reported with appropriate chemotherapeutic treatment of Hodgkin disease. According to some reports, even patients with stage IV disease can have disease-free survival for more than 10 years in as many as 70% of cases.

Large cell lymphomas, including anaplastic varieties, are reported to have a more than 50% 3-year survival rate after chemotherapy, radiation therapy, or both.

MALTomas are rare indolent tumors for which long-term survival is good, even in the absence of chemotherapy.

Mantle cell tumors are rare but usually manifest with widespread disease. Median survival is approximately 4 years.

Malignant mesenchymal tumors

The prognosis for liposarcoma depends on several factors. Completely resected pseudoencapsulated tumors have a better prognosis compared to those that are nonencapsulated and invasive. Cell type and cell differentiation also play a role. Myxoid liposarcoma has a poorer prognosis. In one small series, approximately 30% of patients died of their disease after a mean period of less than 3 years.

Angiosarcomas of the mediastinum are rare but have a very poor prognosis, especially when they originate in the heart or great vessels.

Fibrosarcomas have a uniformly poor prognosis, and most patients die from their disease within a few years.

Primary leiomyosarcoma of the mediastinum has been described. In one reported series of 10 patients who underwent resection, 2 were alive and well at 4 and 6 years. Four of the others died of their disease or developed recurrence.

Rhabdomyosarcoma has the best long-term survival of all mesenchymal tumors because effective chemotherapeutic regimens have been identified. According to 1 report, 10-year actuarial survival rates range from 52-83% depending on the stage of disease at presentation and the existence of hematogenous metastases. Survival is much worse if the latter is present.

Mediastinal parathyroid carcinoma

Prognosis is generally good if complete resection can be accomplished.

Intrathoracic goiter with occult malignancy

Prognosis is generally good if complete resection of the gland can be accomplished.

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

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

Emerging diagnostic modalities, such as PET scans, and other radionuclide studies may be able to assist in the diagnosis of specific neoplasms and in posttherapy surveillance for recurrent disease.

Angiographic techniques using localized intra-arterial injection of hypertonic contrast and embolization techniques have been used in several centers to obliterate mediastinal parathyroid adenomas. At present, this technology is used in patients who are considered a poor risk for surgery; however, with increased experience and skill, these methods may become useful in the treatment of many such lesions.

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 VATS technology has entered the armamentarium of the thoracic surgeon with respect to the treatment of a number of mediastinal diseases. This modality is already used commonly for biopsy of masses and lymph nodes. It has also 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 remains to be seen.

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:  Lymphomas, endocrine, mesenchymal, and other rare tumors of the mediastinum. Posteroanterior chest radiograph of a 30-year-old man found to have Hodgkin disease of the mediastinum. Arrows indicate areas of prominent lymphadenopathy associated with his disease.
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Media type:  X-RAY

Media file 2:  Lymphomas, endocrine, mesenchymal, and other rare tumors of the mediastinum. Lateral chest radiograph of a 30-year-old man found to have Hodgkin disease of the mediastinum (same patient as in Image 1). Arrow indicates area of fullness in the anterior mediastinum, probably related to the presence of prominent lymphadenopathy.
	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

• Bangerter M, Kotzerke J, Griesshammer M, et al. Positron emission tomography with 18-fluorodeoxyglucose in the staging and follow-up of lymphoma in the chest. Acta Oncol. 1999;38(6):799-804. [Medline].
• Chnaris A, Barbetakis N, Efstathiou A. Primary mediastinal hemangiopericytoma. World J Surg Oncol. 2006;4:23.
• Demmy TL, Krasna MJ, Detterbeck FC, et al. Multicenter VATS experience with mediastinal tumors. Ann Thorac Surg. Jul 1998;66(1):187-92. [Medline].
• Geibel A, Kasper W, Keck A, et al. Diagnosis, localization and evaluation of malignancy of heart and mediastinal tumors by conventional and transesophageal echocardiography. Acta Cardiol. 1996;51(5):395-408. [Medline].
• Giron J, Fajadet P, Sans N, et al. Diagnostic approach to mediastinal masses. Eur J Radiol. Mar 1998;27(1):21-42. [Medline].
• Gordon LI, Kies MS. Diagnosis and Treatment of Mediastinal Lymphomas. In: Shields TW, LoCicero J III, Ponn RB, eds. General Thoracic Surgery. Vol 2. 5th ed. Philadelphia, Pa: Williams & Wilkins; 2000:. 2267-74.
• Greif J, Staroselsky AN, Gernjac M, et al. Percutaneous core needle biopsy in the diagnosis of mediastinal tumors. Lung Cancer. Sep 1999;25(3):169-73. [Medline].
• Iyer RB, Whitman GJ, Sahin AA. Parathyroid adenoma of the mediastinum. AJR Am J Roentgenol. Jul 1999;173(1):94. [Medline].
• Kaga K, Nishiumi N, Iwasaki M, Inoue H. Thoracoscopic diagnosis and treatment of mediastinal masses. Usefulness of the Two Windows Method. J Cardiovasc Surg (Torino). Feb 1999;40(1):157-60. [Medline].
• Kolonic SO, Dzebro S, Kusec R. Primary mediastinal large B-cell lymphoma: a single-center study of clinicopathologic characteristics. Int J Hematol. May 2006;83(4):331-6.
• Koltin D, Uziel Y, Schneidermann D. A case of Jatropha multifida poisoning resembling organophosphate intoxication. Clin Toxicol (Phila). 2006;44(3):337-8.
• Kornstein MJ. Biological Markers and Pathology of Mediastinal Lymphomas. In: Shields TW, LoCicero J III, Ponn RB, eds. General Thoracic Surgery. Vol 2. 5th ed. Philadelphia, Pa: Williams & Wilkins; 2000:. 2257-66.
• Laurent F, Latrabe V, Lecesne R, et al. Mediastinal masses: diagnostic approach. Eur Radiol. 1998;8(7):1148-59. [Medline].
• Lee HY, Goo JM, Lee HJ. The value of computed tomography for predicting empyema-associated malignancy. J Comput Assist Tomogr. May-Jun 2006;30(3):453-9.
• Luketich JD, Ginsberg RJ. The current management of patients with mediastinal tumors. Adv Surg. 1996;30:311-32. [Medline].
• Meade RH. Surgery of the Mediastinum. In: A History of Thoracic Surgery. Springfield, Ill: Charles C. Thomas; 1961:. 257-71.
• Mikhaeel NG. Use of FDG-PET to monitor response to chemotherapy and radiotherapy in patients with lymphomas. Eur J Nucl Med Mol Imaging. Jun 9 2006.
• Protopapas Z, Westcott JL. Transthoracic hilar and mediastinal biopsy. J Thorac Imaging. Oct 1997;12(4):250-8. [Medline].
• Richards ML, Bondeson AG, Thompson NW. Mediastinal Parathyroid Adenomas and Carcinomas. In: Shields TW, LoCicero J III, Ponn RB, eds. General Thoracic Surgery. Vol 2. 5th ed. Philadelphia, Pa: Williams & Wilkins; 2000:. 2383-90.
• Rieger R, Schrenk P, Woisetschlager R, Wayand W. Videothoracoscopy for the management of mediastinal mass lesions. Surg Endosc. Jul 1996;10(7):715-7. [Medline].
• Sahni V, Sunandan S, Agarwal SK. Rare thoracic mass lesion--myofibrobastoma. Indian J Cancer. Jul-Sep 2005;42(3):161-4.
• Savage KJ. Primary mediastinal large B-cell lymphoma. Oncologist. May 2006;11(5):488-95.
• Serna DL, Aryan HE, Chang KJ, et al. An early comparison between endoscopic ultrasound-guided fine-needle aspiration and mediastinoscopy for diagnosis of mediastinal malignancy. Am Surg. Oct 1998;64(10):1014-8. [Medline].
• Shields TW. Overview of Primary Mediastinal Tumors and Cysts. In: Shields TW, LoCicero J III, Ponn RB, eds. General Thoracic Surgery. Vol 2. 5th ed. Philadelphia, Pa: Williams & Wilkins; 2000:. 2105-9.
• Shields TW, Robinson PG. Mesenchymal Tumors of the Mediastinum. In: Shields TW, LoCicero J III, Ponn RB, eds. General Thoracic Surgery. Vol 2. 5th ed. Philadelphia, Pa: Williams & Wilkins; 2000:. 2357-81.
• Shields TW. Lesions Masquerading as Primary Mediastinal Tumors or Cysts. In: Shields TW, LoCicero J III, Ponn RB, eds. General Thoracic Surgery. Vol 2. 5th ed. Philadelphia, Pa: Williams & Wilkins; 2000:. 2115-34.
• Stein H, Hummel M. Histopathology in the light of molecular profiling. Ann Oncol. May 2006;17 Suppl 4:iv5-iv7.
• Strollo DC, Rosado de Christenson ML, Jett JR. Primary mediastinal tumors. Part I: tumors of the anterior mediastinum. Chest. Aug 1997;112(2):511-22. [Medline].
• Strollo DC, Rosado-de-Christenson ML, Jett JR. Primary mediastinal tumors: part II. Tumors of the middle and posterior mediastinum. Chest. Nov 5 1997;112(5):1344-57. [Medline].
• Suster S. Primary large-cell lymphomas of the mediastinum. Semin Diagn Pathol. Feb 1999;16(1):51-64. [Medline].
• Virgo KS, Johnson FE, Naunheim KS. Follow-up of patients with thoracic malignancies. Surg Oncol Clin N Am. Apr 1999;8(2):355-69. [Medline].
• Wakely PE. Cytopathology-histopathology of the mediastinum II. Mesenchymal, neural, and neuroendocrine neoplasms. Ann Diagn Pathol. Feb 2005;9(1):24-32.
• Whooley BP, Urschel JD, Antkowiak JG, Takita H. Primary tumors of the mediastinum. J Surg Oncol. Feb 1999;70(2):95-9. [Medline].

Article Last Updated: Jun 28, 2006