tumores en el mediastino

8/17/2019 Tumores en El Mediastino

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Fishman's Pulmonary Diseases and Disorders, 5e >

Chapter 82: Benign and Malignant Neoplasms of th

Mediastinum

Bryan M. Burt; Joseph B. Shrager

Introduction

Primary lesions of the mediastinum are less common than lesions that secondarily involve the mediastinum.Overall, the majority of masses discovered in the mediastinum will be found to be metastases from a primarylung cancer. Neoplasms that arise primarily in the mediastinum, however, are often encountered in the clinic

and are represented by a variety of lesions. This chapter first reviews the anatomy of the mediastinum and thenfocuses on the benign and malignant neoplasms that arise within each of the anatomic regions of themediastinum. Covered elsewhere in this textbook (see Chapter 80) are nonneoplastic disorders of themediastinum that include pneumomediastinum, acute mediastinitis, chronic mediastinitis, and other miscellaneous disorders. Likewise, congenital lesions of the mediastinum, such as bronchogenic,enterogenous, neurogenic, thymic, pericardial, and thoracic duct cysts, are also covered elsewhere (see Chapte81).

Anatomy of the Mediastinum

The mediastinum comprises an anatomic space located between the thoracic inlet and the diaphragm, and bordered on the left and right sides by the pleural cavities. This central anatomic location houses or bordersvital structures of almost every major organ system including the heart and great vessels of the circulatorysystem, the esophagus, and major airways of the aerodigestive tract, the thymus of the immune system, andimportant nerves such as the phrenic and vagus nerves. Further, various endocrine organs may project into it,distant malignancies may metastasize to it, and infectious processes can manifest themselves within it.

The mediastinum is compartmentalized based upon the borders of anatomic structures as seen on a lateralchest radiograph (Fig. 82-1). We believe that the most anatomically appropriate and clinically useful model of

the mediastinum is the three-compartment model.1 The three-compartment scheme divides the mediastinuminto anterior, middle, and posterior compartments. Here, the anterior mediastinum extends from the thoracicinlet superiorly to the diaphragm inferiorly and is bounded anteriorly by the posterior table of the sternum, and

posteriorly by the anterior pericardium and the aorta, innominate vein, and brachiocephalic vessels. Thecontent of the anterior compartment includes the thymus, variable amounts of fat and lymphatic tissues, andthe internal mammary arteries and veins. The middle compartment of the mediastinum is bounded anteriorly

by the pericardium and posteriorly by the pericardium and posterior wall of the trachea, extending only as highas the pericardial reflection. The middle mediastinum contains the heart, pericardium, superior and inferior vena cava, ascending and transverse aorta, trachea and mainstem bronchi, and lymphatic tissues. The posterior mediastinum extends from the thoracic inlet to the diaphragm, and in this “three-compartment scheme,” lies

posterior to the posterior pericardium and airway. It includes the descending aorta, thoracic duct, esophagus,vagus nerves, and lymph nodes, as well as structures emerging from the spinal canal such as intercostal nerves

Figure 82-1

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Three-compartment model of the mediastinum. A. Lateral radiograph of the chest. B. Schematic representationof the contents of the three compartments of the mediastinum. C. Cross sections of the thorax at T4 (left) andT8 (right) to show relative positions of mediastinal structures.

One of the main advantages of categorizing the anatomy of the mediastinum is the ability it confers to generatea differential diagnosis for a mediastinal mass based on the structures naturally contained within thecompartment in which it arises (Table 82-1). Such a classification scheme allows a clinician to proceedsystematically to determine the appropriate diagnostic or therapeutic approach depending on the differentialdiagnosis.

Table 82-1 Structures and Primary Neoplasms in the Three-Compartment Model of the Mediastinum

Structures Common Lesions Rare Lesions

Anterior compartment

Thymus Thymomas Thymic carcinoma; benign thymic tumors

Fat and lymphatics Lymphomas Vascular lesions

Internal mammary vessels Germ cell tumors Mesenchymal tumors

Thyroid (occasional) Endocrine tumors (e.g., ectopic parathyroid, goiter)

Castleman’s disease

Middle compartment

Heart Foregut cysts Pleural and pericardial cysts

Pericardium Lymphoma Castleman disease

Aorta

Superior and inferior vena cava


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Trachea and main bronchi

Lymph nodes

Posterior compartment

Descending aorta Nerve sheath tumors Vascular tumors

Esophagus Neurogenic tumors Mesenchymal tumors

Vagus nerves Lymphatic lesions

Thoracic duct Neurenteric cysts

Sympathetic chain

Lymph nodes

Epidemiology and Incidence

The incidence and type of primary mediastinal neoplasms varies with patient age. In combined series totaling3017 mostly adult patients, the incidence of mediastinal masses in decreasing frequency were thymomas andthymic cysts (26.5%), neurogenic tumors (20.2%), germ cell tumors (GCTs) (13.8%), lymphomas (12.7%),foregut cysts (10.3%), and pleuropericardial cysts (6.6%). In children, combined series totaling 718 patientsdemonstrated that neurogenic tumors were most common (41.6%), followed by GCTs (13.5%), foregut cysts

(13.4%), lymphomas (13.4%), angiomas and lymphangiomas (6.1%), and thymic tumors or cysts (4.9%). 2 Ingeneral, the incidence of anterior lesions is higher in adults, and posterior lesions predominate in children.Further, the incidence of malignancy differs among primary mediastinal masses arising in each of the differentcompartments. In one of the largest series, Davis and colleagues demonstrated that among patients withmediastinal masses, malignancy was found in 59% of those in the anterior mediastinum, 29% of those in the

middle mediastinum, and 16% of those in the posterior mediastinum.3

As discussed below, mediastinal masses are often incidentally detected on imaging studies obtained for other reasons. An estimate of the frequency of “incidental” mediastinal masses has been provided by a large lungcancer screening study. In 9263 individuals at high risk for lung cancer who underwent a computedtomography (CT) screening examination, a mediastinal mass was found in 71 patients (0.77%). The majority

of these incidental masses were thymic and most were treated successfully with a conservative approach.4

Signs and Symptoms

Signs and symptoms of mediastinal tumors can vary widely at presentation and usually offer only nonspecificclues to the nature of the underlying disease process. While over 60% of patients do present with symptoms, itis also quite common for an asymptomatic mass to be detected on a routine screening examination. Mostasymptomatic patients with a mediastinal mass will have a benign lesion, while the majority of patients that

present with symptoms have an underlying malignant process. In Davis’ series of 400 patients withmediastinal masses, 83% of the lesions found on routine chest radiographs were benign, whereas 57% of

lesions in symptomatic patients were malignant.3

The presenting symptoms of a mediastinal mass vary widely and are influenced by anatomic location and the presence of malignant invasion or mass effect. Dyspnea or cough may result from airway invasion or abutment, tamponade, or the presence of a pleural effusion. Dysphagia is seen with esophageal compression,and chest pain may represent chest wall or neural invasion or abutment. Invasion of the airway may result inhemoptysis, invasion of the recurrent laryngeal nerve may present as hoarseness, and invasion of the superior vena cava can present with facial swelling and superior vena cava syndrome. Constitutional symptoms such asfever and night sweats are often associated with mediastinal lymphoma, and myasthenic symptoms may besuggestive of thymoma.


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Anterior Mediastinal Neoplasms

Neoplasms of the anterior mediastinum are discussed below.

Evaluation of the Anterior Mediastinal Mass

In a patient with an anterior mediastinal mass, it is often possible to make a strong provisional diagnosis based

upon clinical evaluation and imaging data.

5

Whereas specific workup for common anterior mediastinal masslesions is described in the following sections, some general principles are reviewed here.

History and Examination

In an individual younger than 40 years, lymphoma is the most likely diagnosis and the presence of International Working Formulation (IWF) group B symptoms or palpable lymphadenopathy further increasesthe level of suspicion. In contrast to lymphoma, thymic neoplasms are very uncommon before the fourthdecade of life. The presence of a paraneoplastic syndrome associated with an anterior mediastinal massessentially clinches the diagnosis of thymoma. The majority of GCTs (benign or malignant) are diagnosed inthe second or third decade of life. Whereas patients with a thymoma often have an indolent presentation,

patients with a lymphoma or a malignant GCT often have a rapid onset of symptoms. Workup must includeexamination of the testes to rule out a testicular primary GCT.

Serum Studies

Autoantibodies to the acetylcholine receptor (anti-AChR) should be measured as their presence is virtuallydiagnostic of myasthenia gravis, even if the patient is without obvious symptoms. Characteristic serum tumor markers such as beta-human chorionic gonadotropin (β-HCG) and alpha-fetoprotein (AFP) are elaborated by

most malignant GCTs but not by benign GCTs.6 Elevated serum LDH is suggestive of lymphoma. Evidence ohypo- or hyperthyroidism, as measured by thyroid-stimulating hormone (TSH) and thyroid hormones (T3 andT4), suggests mediastinal goiter, though goiter is not invariably associated with abnormal hormone production

Imaging Studies

CT provides valuable data about the anatomic location of the tumor, its physical characteristics (fatty, solid, or cystic) and degree of invasiveness. Occasionally, magnetic resonance imaging (MRI) provides usefuladditional information concerning obliteration of normal tissue planes and vascular invasion. Althoughimaging is most often not diagnostic of the specific type of tumor, some imaging features can be

pathognomonic. For example, the finding of a well-encapsulated lesion in the anterior mediastinum containingseveral tissue elements – calcium, fat, fluid – is essentially diagnostic of a mature teratoma.

Need for Biopsy

The decision whether to perform a biopsy of an anterior mediastinal mass is not simple. Routine biopsy shouldnot be endorsed, not only because of the unnecessary morbidity and costs associated with the procedure, butalso because of the potential risk of tumor spread. Well-encapsulated lesions believed not to be lymphoma areoften resected for both diagnosis and treatment, without a preceding biopsy. Conversely, for locally invasive orfrankly unresectable anterior mediastinal masses, a biopsy should often be performed as such lesions mayrepresent lymphoma, aggressive thymomas that could benefit from neoadjuvant treatment, malignant GCTs, orother rare diseases.

Once a clinical diagnosis of thymoma is made, the goal is to proceed directly to resection without preliminary


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biopsy, as these tumors have a predilection for local recurrence once the thymic capsule has been violated.When palpable peripheral nodes are present, the diagnosis of lymphoma is often most easily obtained byexcision of one of them. Patients with suspected lymphoma and an isolated anterior mediastinal mass shouldundergo either a CT-guided core needle biopsy or a Chamberlain procedure (anterior mediastinotomy) for diagnosis, depending upon the pathologist’s level of comfort in classifying lymphoma on the basis of specimensize at one’s institution. Resection of lymphoma is not indicated and can almost always be avoided by

performing a diagnostic biopsy when lymphoma is suspected. Surgical extirpation is the mainstay of treatmentfor mature GCTs, and biopsy is not indicated for these lesions if they have the characteristic imagingcharacteristics. Malignant GCTs, on the other hand, are treated primarily with chemotherapy, radiotherapy, or

both. In situations where these lesions are suspected but tumor markers (AFP and β-HCG) are not markedlyelevated, biopsy should be performed.

Thymoma

Clinical assessment and management of thymoma are discussed below.

Presentation

The age distribution of patients with a thymoma is represented by a broad peak between approximately 35 and

70 years with a median age of about 54 years.7 The ratio of men to women with this disease is about equal.Approximately one-third of patients with a thymoma will not report significant symptoms and an additionalone-third will report symptoms of cough, dyspnea, or chest pain reflective of compression or invasion of adjacent structures. Patients may also present with symptoms of an associated paraneoplastic syndrome. Fortyto 45% of patients with a thymoma will present with myasthenia gravis and, conversely, 5% to 15% of patients

with myasthenia gravis will be found to have a thymoma.8,9 Notably, myasthenia gravis can develop sometime after diagnosis of thymoma, and occasionally following resection, highlighting the necessity of completeresection of both the thymoma and the entire thymus gland. Thymomas may also be associated with pure redcell aplasia, agammaglobulinemia, systemic lupus erythematosus, and other autoimmune disorders.

Diagnosis

A clinical diagnosis of thymoma is often sufficient to proceed to resection without biopsy. The presence of a paraneoplastic syndrome associated with an anterior mediastinal mass essentially clinches the diagnosis of thymoma. Autoantibodies to the acetylcholine (Ach) receptor should be measured, and their presence isvirtually diagnostic of myasthenia gravis and also clinches the diagnosis of thymoma. Interestingly, Achreceptor antibodies are demonstrated in approximately 60% of patients who have thymoma without neurologic

symptoms.10 It is not necessary to obtain a preoperative tissue biopsy for a small, resectable anterior mediastinal tumor whose radiographic features are typical of thymoma in an asymptomatic patient. Althoughthere are no pathognomonic imaging features that differentiate thymoma from several other mediastinaltumors, in a patient without B-symptoms to suggest lymphoma, the diagnosis of thymoma is strongly

suggested by a CT scan demonstrating a well-circumscribed, solid anterior mediastinal mass without the low-density areas that would suggest the cystic and fatty components of a teratoma (Fig. 82-2). Most thymomas aresolid tumors, but up to a third may have components that are necrotic, hemorrhagic, or cystic. Several smallstudies have investigated the utility of PET in evaluation of thymoma and have suggested that FDG uptake isgreater in thymoma than in thymic hyperplasia, and that thymic carcinomas demonstrate the highest FDG

avidity.11 However, PET is not required to stage a thymoma preoperatively when it appearsnoninvasive/nonmalignant on CT.

Figure 82-2


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Thymoma. Axial section from a CT scan demonstrates a 4-cm mass abutting the thoracic aorta without anyevidence of invasion (arrows).

Once a diagnosis of thymoma is suggested, the goal is to proceed directly to resection without preliminary biopsy, as these tumors have a predilection for local recurrence once the capsule has been violated. Adefinitive tissue diagnosis is needed primarily when a presumed thymoma is so advanced that it would be besttreated either nonoperatively or with neoadjuvant chemotherapy or chemoradiotherapy, or in instances wherethere is a strong possibility of lymphoma. If required, the pathologic diagnosis of thymoma can usually be

achieved by image-guided core needle biopsy, or if that fails, through open surgical biopsy. The success rate ofneedle biopsy in establishing the diagnosis of thymoma is approximately 60% and the success rate of surgical

biopsy is approximately 90%.12 In our opinion, video-assisted thoracoscopic surgical (VATS) biopsy of ananterior mediastinal mass in which thymoma is in the differential should be assiduously avoided, due to thegreat potential of spread into the pleural space. If core needle biopsy fails and a diagnosis is required, aChamberlain procedure (anterior mediastinotomy) should be performed.

All patients with suspected thymoma should be evaluated for myasthenia gravis. This evaluation usually begins with a careful assessment for the presence of ocular, bulbar, and limb muscle weakness. The diagnosisof myasthenia gravis in a patient with a characteristic history and physical examination requires two positiveconfirmatory tests among pharmacologic (Tensilon test), serologic (anti-AChR antibodies), and

electrodiagnostic (EMG) studies. If there is any suggestion of myasthenia gravis on initial presentation, the patient should undergo preoperative evaluation by a neurologist. Medical optimization prior to surgery usingsome combination of cholinesterase inhibitors, intravenous immunoglobulin, plasmapheresis, and occasionallysteroids, can help avoid respiratory failure in the perioperative period. Other paraneoplastic syndromes are alsoassociated with thymoma, including hypogammaglobulinemia in 10% of patients, and pure red cell aplasia in5% of patients.

Staging

The most widely utilized classification scheme for thymoma was proposed by Masaoka in 1981 and is based


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on the local invasiveness of the tumor (Table 82-2).13 The Masaoka classification system has prognostic

value14 and permits stratification for adjuvant therapy. One difficulty with this system is that it is based uponthe findings at the time of surgical resection, thus precluding its use for triaging some patients to neoadjuvanttherapy.

Table 82-2 Staging of Thymic Malignancies

Stage Description 10-y Survival (%)

I Encapsulated tumors without gross or microscopic invasion 90 (75–100)

II Transcapsular invasion 75 (42–100)

IIA Microscopic invasion

IIB Macroscopic invasion

III Macroscopic invasion of surrounding tissues (lung, pericardium, vena cava, or aorta) 56 (26–84)

IVA Disseminated disease within the chest 38 (22–47)

IVB Distant metastases Unknown

Source: Data from Detterbeck FC. Evaluation and treatment of stage I and II thymoma. J Thorac Oncol.2010;5(10 Suppl 4):S318–S322.

Thymomas are also classified histologically. A thymoma is composed of a mixture of thymic epithelial cellswith bland features as well as lymphocytes in various stages of development. The neoplastic cell of origin is

believed to be the thymic epithelial cell and not the lymphocyte,15 and thymomas appear histologically benigneven when they are invasive. In 1985, Müller-Hermelink proposed a novel histologic classification system toseparate all thymomas into categories of cortical, medullary, or mixed, based on the histologic appearance of

the thymic epithelial cells.16 Cortical thymomas are composed of large, round, or polygonal epithelial cellsand medullary thymomas contain smaller, spindle cell–shaped epithelial cells with irregular nuclei. Thishistologic classification system was found to reliably predict tumor behavior and prognosis, with medullarythymomas behaving in an essentially benign fashion and cortical thymomas more frequently demonstrating

evidence of invasive and malignant disease.17 Later studies have demonstrated that both the Masaoka staging

and Müller-Hermelink grading systems are strong and independent prognostic indicators of both overall aswell as disease-free survival.14,18,19

More recently, the World Health Organization (WHO) proposed a histologic classification system (resemblingthe Müller-Hermelink system) that has become the histologic grading system of choice in the current era and i

useful to distinguish between thymoma, thymic carcinoma, and thymic carcinoids (Table 82-3).20 It is nowaccepted that the Masaoka staging criteria used in combination with the WHO grading criteria provide the

most accurate prognostic information for survival and recurrence in thymoma.21,22

Table 82-3 World Health Organization (WHO) Histologic Classification System

Type Description

A Tumor in which foci having features of type A thymoma are admixed with foci rich in lymphocytes

B1 Tumor resembles normal functional thymus; combines large expanses having an appearance practically

indistinguishable from that of normal thymic cortex with areas resembling thymic medulla

B2

Tumor in which neoplastic epithelial component appears as scattered plump cells with vesicular nucleiand distinct nucleoli among a heavy population of lymphocytes; perivascular spaces are common andsometimes very prominent; a perivascular arrangement of tumor cells resulting in a palisading effectmay be seen

B3Thymoma predominantly composed of epithelial cells having a round or polygonal shape and exhibitingno or mild atypia; they are admixed with a mild component of lymphocytes, resulting in a sheet-likegrowth of the neoplastic epithelial cells


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C

Thymic tumor exhibiting clear-cut cytologic atypia and a set of cytoarchitectural features no longer specific to the thymus, but rather analogous to those seen in carcinomas of the other organs; type Cthymomas lack immature lymphocytes; whatever lymphocytes may be present are mature and usuallyadmixed with plasma cells

Treatment

Surgical resection is the mainstay of treatment of Masaoka stage I–III thymoma while the treatment of stage

IVa thymoma is controversial. Resection of even a small, stage I thymoma without myasthenia gravis shouldinclude removal of the entire thymus en bloc along with the tumor because (1) myasthenia gravis can

potentially develop postoperatively (and total thymectomy is an appropriate treatment for myasthenia gravis),and (2) a second focus of tumor within the thymus is occasionally found. The gold standard surgical approachto thymoma remains median sternotomy but minimally invasive approaches including VATS and robotictechniques are likely equally effective for smaller tumors in experienced hands. Certainly if there is suspicionof invasion into adjacent structures, sternotomy is the preferred approach as it is critical that the involved

portions of these structures are resected en bloc with the thymus gland and tumor. This can require resection oflung, pericardium, innominate vein, superior vena cava, phrenic nerve, and even aorta.

Stage I thymomas are treated adequately with complete resection alone. Although in the past adjuvant

radiotherapy was frequently administered to patients with stage II thymoma, accumulated data suggest thatadjuvant radiotherapy is of little additional benefit following complete resection.23 – 25 Thymoma is aradiosensitive tumor however, and for patients who have incomplete resection, postoperative radiotherapy isrecommended. For patients with advanced disease (stage III or IV thymoma), chemotherapy is recommendedand is often followed by radiation for patients with incompletely resected disease. For thymoma that is initiallyconsidered unresectable, induction chemotherapy followed by surgical resection can result in favorable rates of

overall and disease-free survival.26,27 Further, surgical resection plays an important role in the management of

recurrences and complete resection of a recurrence can result in improved overall survival.28

Outcome

Although thymomas are generally indolent tumors, they should be considered a malignant neoplasm as theyhave the ability to metastasize to the pleura, pericardium, and (less commonly) distant sites. One studyreported that 4% of 207 patients evaluated for surgical resection of a thymoma had lymph node or distantmetastases at presentation, and another 16% developed nodal or distant metastases at some point in their

course.29 Others have shown that distant metastases can occur with any stage or histology.30,31 Detterbeck reviewed overall survival in compiled surgical series of at least 100 patients (2437 patients total) anddemonstrated favorable 10-year survival rates of approximately 90% and 70% for stage I and II, and 55% and

35% for stage III and IVa thymoma, respectively.12 Completeness of resection is the most important predictor of recurrence and survival; significantly better survival is demonstrated when resection is complete in all largestudies examining this issue.

Locoregional recurrence is far more common than distant recurrence, and about half of all local recurrencesinvolve the pleural space or the lung. The average recurrence rate for stage I tumors is 3% but increases to

11% and 30% for stage II and III tumors, respectively.7 The relatively indolent nature of a thymoma isreflected by an average time to recurrence of 5 years, with rare recurrences seen as far out as 20 years. The

presence of myasthenia gravis is no longer considered a negative prognostic factor, as it was in older studies,and over 30% of patients with myasthenia and thymoma ultimately achieve a complete remission of the

myasthenia following thymectomy.32 Similarly, approximately one-third of patients with associated red cellaplasia experience improvement following thymectomy. In contrast, hypogammaglobulinemia associated withthymoma generally does not respond to thymectomy.


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Thymic Carcinoma

Clinical assessment and management of thymic carcinoma are discussed below.

Presentation

Thymic carcinomas (WHO type C) are highly aggressive neoplasms of thymic epithelial origin and are verydifferent from thymomas (WHO types A, AB, and B). Thymic carcinomas are rare, constituting approximately

10% of all thymic neoplasms.28 They can occur at any age but are most frequently observed in persons between 30 and 60 years of age. The majority of patients with thymic carcinoma present with symptoms of local invasion or compression such as cough, chest pain, or superior vena cava syndrome. Pericardial and/or

pleural effusions are often seen. Thymic carcinoma is typically not associated with myasthenia gravis. Unlikethymomas, thymic carcinomas frequently metastasize to lymph nodes and distant sites. Eighty percent of

patients have local invasion of contiguous mediastinal structures at the time of presentation, and 40% of cases

have metastatic spread to bones, lung, pleura, liver, or lymph nodes.33 Over half of the patients will present

with locally advanced, although potentially resectable, disease.34,35

Diagnosis

Thymic carcinomas can be distinguished from thymomas based on their malignant histologic features anddifferent immunohistochemical and genetic characteristics. Imaging studies often reveal an invasive

presentation, and for this reason, percutaneous needle biopsy should generally be undertaken.

Staging

The Masaoka staging system and WHO histologic classification system are used to stage thymic carcinoma. Inthe WHO system, thymic carcinomas are type C lesions. These tumors are distinct from thymoma and shouldnot be considered in the same light as a thymoma with local invasion. Histologically, thymic carcinomacontains a number of different cell types, but they are unified by their unequivocal malignant appearance onlight microscopy. Division of patients into those with low-grade histology and those with high-grade histologyhas prognostic significance. The median survival for patients with low-grade histology (squamous,mucoepidermoid, and basiloid thymic carcinomas) is 29 months, as compared to 11 months for patients with

high-grade histology (sarcomatoid and clear cell thymic carcinoma).36

Treatment

While there is no standard-of-care approach to patients with thymic carcinoma, a multidisciplinary strategy isrecommended. The prevailing practice is that patients with stage I–III and some IVa patients should be treated

with some combination of surgical resection plus chemotherapy and/or radiotherapy.37 Although thymic

carcinomas generally respond poorly to chemotherapy, carboplatin and paclitaxel are recommended becausethis combination has shown the highest response rates in clinical trials. For the rare thymic carcinoma patientswith clearly resectable disease, surgery is considered the primary therapeutic modality. For those with diseasethought to be initially unresectable or disease that appears clearly to be invading one or more surroundingorgans or major vascular structures, neoadjuvant chemotherapy and/or radiation may improve operability and

permit subsequent resection.36,38,39

Outcome

The prognosis for patients with thymic carcinoma is much worse than for patients with thymoma, with 5-year


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overall survival rates for thymic carcinomas in the range of 30% to 50%.35,40,41 A more recentclinicopathologic study of 65 cases of primary thymic carcinoma, however, reported a more favorable 5-year survival rate of 66%. In this study, 63% of the patients received additional therapy in the form of

chemotherapy or radiation.34 Similar to thymoma, patients with completely resected thymic carcinomas havelonger overall and progression-free survival rates than those who undergo incomplete resection or areunresectable. In a recent series of 60 patients with thymic carcinoma (40 treated surgically), completelyresected lesions and early Masaoka stages are the most important factors associated with successful diseasecontrol and long-term survival. Five-year survival of 85% was obtained after complete resection, compared

with 29% in those with incomplete resection.42 In another series of 16 patients, a multimodality approach thatincluded surgery resulted in complete resection in 88% of the patients and a mean survival of 4.2 years for the

entire group.43

Other Thymic Neoplasms

Clinical assessment and management of a variety of other thymic neoplasms are considered below.

Thymic Hyperplasia

Thymic hyperplasia is a term used to describe either a histologically normal thymus that is enlarged for the patient’s age, or a thymus that histologically shows cellular hyperplasia, which is also generally associatedwith gross enlargement of the gland. This condition can present as a spectrum of disease ranging fromrespiratory compromise due to impingement on the airway (almost always in the pediatric population) to themore common situation of an incidental finding on an unrelated imaging study. Many of the thymus glandsremoved from patients with myasthenia gravis demonstrate “true thymic hyperplasia” (cellular hyperplasia),and this is thought to contribute to the pathogenesis of myasthenia gravis. In addition to myasthenia gravis,thymic hyperplasia can be seen following severe or chronic illness, the so-called “thymic rebound.” Steroiduse will also generally lead to substantial thymic hyperplasia. Practically speaking, when a diffusely enlargedthymus without a discrete mass is discovered in an otherwise asymptomatic patient, this can be followed

expectantly, as these glands have a negligible incidence of harboring significant thymic disease.44

Thymolipoma

Thymolipomas are distinguished from simple mediastinal lipomas by their location within the thymic capsule.

Histologically, these neoplasms composed of mature adipocytes as well as normal thymic components.45

Thymolipomas, like thymomas, can be associated with thymic paraneoplastic syndromes such as red cellaplasia, hypogammaglobulinemia, and aplastic anemia. These lesions can grow to significant size and result incompressive and obstructive symptoms. The treatment of thyolipomas is surgical excision.

Thymic Carcinoid

Thymic carcinoids are very rare neoplasms of the thymus that are classified as neuroendocrine carcinomas.They have a strong association with endocrinopathies such as multiple endocrine neoplasia type I. Unlike othecarcinoids, they rarely present with carcinoid syndrome, but many do secrete ACTH resulting in Cushingsyndrome. Thymic carcinoids tend to be very aggressive tumors. Upon presentation, the majority of thymic

carcinoids are locally invasive and approximately half of all patients will have metastatic disease.46 Surgery isthe therapy of choice for resectable neuroendocrine carcinomas of the thymus and should include aggressivelocal resection. The prognosis is poor despite aggressive therapy, and most patients present with local

recurrence or metastases within 5 years of surgery and will die within 10 years.47


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Germ Cell Tumors

GCTs comprise a group of neoplasms that arise from gonadal tissue. The anterior mediastinum is the mostcommon location for occurrence of extragonadal GCTs. GCTs account for 15% of all anterior mediastinalmasses in adults (85% of which are benign mature GCTs) and 25% of anterior mediastinal masses in children

(essentially all of which are benign).48 GCTs typically occur in young adults in the second to fourth decades olife with no gender predilection.

While previously thought to be metastatic from a gonadal primary, it is now accepted that these neoplasms are primary mediastinal tumors. The precise origin of the germ cells that form these tumors in sites heterotopic tothe gonads is still not completely clear, but this may result from aberrant migration of germ cells duringembryonic development or as a part of normal embryogenesis. Because primordial germ cells areundifferentiated cells from which a variety of different tumors can arise, there have been numerousoverlapping and sometimes confusing classification and grading systems proposed for these tumors. Evenmore confusing for classifying GCTs is that it is common to see two or more GCT histologies arising fromwithin a single mass. Based on the need for standard classification, investigators from the Armed ForcesInstitute of Pathology developed a reproducible histologic classification system (Table 82-4) and clinical

staging system (Table 82-5) based on review of more than 300 cases.49

Table 82-4 Classification of Mediastinal Germ Cell Tumors (GCTs)Mature teratoma

Immature teratoma

Teratomas with malignant component:Type I: with an associated GCT (seminoma, etc.) Type II: with another epithelial malignancy (squamous, adenocarcinoma, etc.) Type III: with sarcomatous component(rhabdomyosarcoma, osteosarcoma, etc.) Type IV: a combination of any of the above

Seminoma

Yolk sac tumor (endodermal sinus tumor)

Embryonal carcinoma

Choriocarcinoma

Combined GCT without teratomatous component

Table 82-5 Clinical Staging of Mediastinal Germ Tumors

Stage Characteristics

I Well-circumscribed tumor with or without focal adhesions to the pleura or pericardium but without -

microscopic evidence of invasion into adjacent structures

II Tumor confined to the mediastinum with macroscopic and/or microscopic evidence of infiltration into

adjacent structures (pleura, pericardium, great vessels)

III Tumor with metastases

IIIA With metastases to intrathoracic organs (lymph nodes, lung, etc.)

IIIB With extrathoracic metastases

Mediastinal GCTs are composed of benign and malignant neoplasms that for descriptive purposes can besimplified into three categories. Benign mediastinal GCTs are composed primarily of benign mediastinalteratomas, which account for 60% of all mediastinal GCTs. Malignant tumors are divided into seminomatousGCTs, which account for 40% of malignant mediastinal GCTs, and nonseminomatous GCTs (NSGCTs) whichaccount for 60% of malignant mediastinal germ tumors. NSGCTs include embryonal cell carcinomas,choriocarcinomas, yolk sac tumors, and malignant teratomas.

Mediastinal Teratomas


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Teratomas are defined by the presence of tissue from more than one of the three primitive germ cell layers.Mature (benign) teratomas are composed of well-differentiated elements such as fat, muscle, and cartilage(mesoderm); hair, skin, and teeth (ectoderm); and intestinal tissue (endoderm). Mature teratomas can besymptomatic or asymptomatic upon presentation. Symptoms include chest pain, dyspnea, cough, or fever (if they become infected). Occasionally the tumor may erode into an airway and a patient may cough up hair (trichophytosis) or oily sebum that is pathognomonic of a benign mediastinal teratoma.

CT with contrast is the diagnostic procedure of choice and usually demonstrates a thick-walled cystic mass.Calcification is often present and when intermixed with areas of fat and/or fluid density, the diagnosis is made

with a high degree of certainty.50 Benign teratomas can also be primarily solid, and in these cases thediagnosis is more challenging. Tumor markers such as β-HCG and AFP should be measured and will not beelevated in benign teratoma. Needle biopsy of a mass that is highly suspected to be a benign teratoma based onimaging is not necessary. Such a patient should go directly to surgical resection.

The treatment for benign GCTs is total resection before the development of complications. Even benignteratomas are frequently adherent to adjacent structures such as lung, blood vessels, and pericardium; en blocresection of involved structures is sometimes required. Radiation and chemotherapy play no therapeutic role,unless concurrent malignant disease is present. Outcome after resection of a benign teratoma is excellent, on

the order of 93% 10-year survival.51 Occasionally, teratomas will contain less well-differentiated tissues and

behave more aggressively, resembling malignant teratomas (see below).

Malignant Seminomatous Germ Cell Tumors

Malignant GCTs, both seminomatous and nonseminomatous, are almost exclusively diseases of men.Seminoma usually presents in men during the third or fourth decade of life as a large anterior mediastinalmass, although it rarely occurs in the middle and posterior mediastinum. Most patients are symptomatic upon

presentation; symptoms are variable and most commonly include chest pain and dyspnea.52

Careful bimanual examination and ultrasound of the testicles should be performed to rule out a testicular primary tumor, and a thorough staging workup should be performed including CT scan of the abdomen along

with the chest. Measurement of serum tumor markers is critical to the diagnosis and follow-up of patients withmediastinal seminomas. Patients with mediastinal seminomas will demonstrate mild elevation of β-HCG

(


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Sixty to 70% of patients with mediastinal seminoma will present with metastatic disease, primarily tointrathoracic organs, although distant metastases can also be found. The treatment of primary mediastinalseminomatous tumors has evolved over the past 20 years from a primarily surgical approach to a chieflynonsurgical approach. It has become clear that the first line of treatment in all cases of mediastinal seminomashould be chemotherapy, and 5-year survival rates upward 90% are achieved with cisplatin-based

chemotherapy regimens.54,55 As is the case with testicular seminomas, pure mediastinal germ cell seminomasare radiosensitive. Whereas radiotherapy alone may achieve complete remission in only about 65% of

patients,56 the addition of radiotherapy to chemotherapy appears to enhance the benefit of chemotherapyalone. The role of surgical resection in this disease remains controversial. Surgery is generally reserved for

patients with residual mediastinal masses following chemotherapy and radiation when residual active diseaseis a concern (e.g., with persistently elevated or rising markers, or increasing FDG avidity on PET). The

benefits of surgical resection in this setting would be to document if there is residual malignant seminomatoustumor (as opposed to necrotic debris) and to completely resect it; in addition, occasional patients are identifiedwho have a previously unrecognized nonseminomatous malignant component of the tumor.

Nonseminomatous Germ Cell Tumors

NSGCTs are malignant tumors that are seen almost exclusively in men and there is a particular propensity for men with Klinefelter syndrome to develop these tumors. A variety of nonseminomatous histologies have been

categorized and their incidence is best gathered from the largest series of 229 cases.49 NSGCTs are composedof teratocarcinoma (41%), endodermal sinus (yolk sac) tumor (35%), choriocarcinoma (7%), embryonalcarcinoma (6%), and mixed histologies (11%). Further, non–germ cell components including sarcoma or epithelial carcinoma were found in 58% of teratocarcinomas.

Mediastinal NSGCTs are characterized by rapid local growth and early distant metastases, and patients often present with advanced disease. Most patients will have symptoms caused by compression or invasion of adjacent structures, and constitutional symptoms including weight loss, fever, and weakness are more commonin patients with NSGCT compared with pure seminoma. Like seminoma, sites of metastases in NSGCT


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include the lung, pleura, lymph nodes, and liver; 85% to 95% of patients with an NSGCT will have at least one

site of metastases.57,58

Workup should include CT of the chest and abdomen and measurement of serum tumor markers. Chest CTwill typically reveal a large, irregular anterior mediastinal mass with poorly defined margins and multipleareas of necrosis and hemorrhage (Fig. 82-4). Unlike seminoma, over 90% of patients with NSGCT will havean elevation of either β-HCG (30%–35% of patients) or AFP (80% of patients), and an AFP level greater than

500 ng/mL is essentially diagnostic of NSGCT.53,59 NSGCTs, especially those with yolk sac histology, are

associated with a variety of hematologic malignancies including leukemia, and these occur independently of the chemotherapy used to treat the tumor.60

Figure 82-4

Nonseminomatous germ cell tumor. A 19-year-old male presented with a 1-month history of fever, heavinessin the chest, and cough. Examination revealed a tall, thin male with dystrophic testes (habitus consistent withKlinefelter syndrome). Serum AFP was 32,000 and β-HCG was 25,000. A. PA radiograph of the chest revealsa large mediastinal mass projecting into the right hemithorax. B. Axial section from a CT at the level of thediaphragm demonstrates an inhomogeneous mass; diaphragmatic invasion could not be assessed. C. Sagittalview of an MRI demonstrates that the mass is contained above the diaphragm. Biopsy revealed embryonal cellcarcinoma.

As most patients present with bulky or metastatic disease, surgical resection is not the first line of treatment.Historically, patients with NSGCT had an exceedingly poor prognosis, but this has dramatically improved withthe implementation of intensive cisplatin-based chemotherapy protocols. A summary of studies of patients


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treated with first-line cisplatin-based combination chemotherapy regimens showed an overall long-term

survival rate of 42%.61 After completion of chemotherapy, patients should be restaged with a CT of the chestand abdomen and serum tumor markers should be remeasured. The majority of patients will be found to haveresidual masses or radiographic abnormalities after completing chemotherapy. Regardless of whether tumor markers are elevated or not, these patients should undergo surgical resection of residual masses if technically

feasible because salvage chemotherapy is usually ineffective,62 and surgical resection is curative in a

substantial portion of patients.63 In addition, occasional patients will be found to have a previouslyunrecognized mature (benign) teratoma component, which can only be cured by resection.

Lymphoma

Both Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) can present as anterior mediastinalmasses. HL accounts for approximately 50% to 70% of mediastinal lymphomas. The three most commontypes of lymphoma found in the mediastinum are nodular sclerosing HL, large cell lymphoma, and

lymphoblastic lymphoma.64 In general, these are systemic diseases that also involve the mediastinum,although some patients do present with disease limited to the mediastinum alone. Due to the generallywidespread nature of these diseases, treatment is centered on systemic chemotherapy and radiation is the

primary modality used for local control. Surgery is not typically utilized as a therapeutic option but may be

required to make a histologic diagnosis.

Hodgkin Lymphoma

HL has a bimodal age distribution with its incidence peaking in young adulthood and again after 50 years of age. HL is divided into four subtypes: nodular sclerosing (most common), lymphocyte-rich, mixed cellularity,and lymphocyte-depleted. Most patients present with asymptomatic lymphadenopathy, but up to 25% of

patients will experience B symptoms consisting of fever, night sweats, and weight loss.65 Over half of all patients with HL will have involvement of the mediastinum, almost always in the anterior mediastinum or involving paratracheal lymph nodes (Fig. 82-5). Suspicion for HL warrants a tissue biopsy and the presence ofReed–Sternberg cells is pathognomonic. Because the tumors tend to be quite fibrotic, with only scattered

malignant cells, surgical biopsy is often required to establish a diagnosis—either by cervical mediastinoscopy(for paratracheal nodes) or by anterior mediastinotomy (for anterior mediastinal masses). PET generallydemonstrates high FDG avidity in lymphomas, and therefore PET/CT may be useful in guiding sites for

biopsy. The Ann Arbor staging system (Table 82-6) is still widely used for staging HL and invasive staging(laparotomy and splenectomy) has fallen out of favor.

Figure 82-5

Hodgkin Disease. Axial section from a CT shows a bulky mediastinal mass and pleural effusion.


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Table 82-6 Ann Arbor Staging System with Cotswolds Modification For Hodgkin Disease

Stage Characteristics

I Involvement of one lymph node region or lymphoid structure

II Two or more lymph node regions on the same side of the diaphragm

III Lymph nodes on both sides of the diaphragm

IV Involvement of extranodal sites

ModificationsA No symptoms

B Fever, night sweats, weight loss >10% in 6 mo

X Bulky disease (greater than 1/3 widening of the mediastinum or >10 cm diameter of nodal

mass

E Involvement of single, contiguous, or extranodal site

Treatment approaches to HL are separated into those for early-stage disease (stage I and II) and advanced stagedisease (stage III and IV). Modern treatment protocols most often involve chemotherapy regimens combinedwith limited (involved field) radiation. Patients with advanced stage disease as well as patients with Bsymptoms are treated with chemotherapy regimens such as ABVD (adriamycin, bleomycin, vinblastine,dacarbazine). Radiation is sometimes additionally employed in cases of bulky disease and patients who relapsemay benefit from a hematopoietic stem cell transplant. Cure rates are greater than 90% for stage I and II HL,

30% to 90% for stage IIIA, 60% to 70% for stage IIIB, and 50% to 60% for stage IV. 64,65

Non-Hodgkin Lymphomas

NHL is a heterogeneous group of systemic diseases that are categorized into many classes and grades.Mediastinal tumor burden in NHL is more likely to be part of the generalized disease process than the mainfocus of disease, and only 20% of patients with NHL will have involvement of the mediastinum at the time of

presentation. This disease is not limited to the anterior mediastinum and can occur in the middle and posterior

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mediastinal compartments. Of patients with primarily mediastinal disease, the majority will have either lymphoblastic lymphoma or large B-cell lymphoma. The mean age of presentation for these patients is

between 28 and 35 years.

Lymphoblastic lymphomas are highly aggressive tumors, and invasive symptoms including cough, wheezing,dyspnea, and manifestations of superior vena cava syndrome, cardiac tamponade, or tracheal obstruction arecommon. The central nervous system, skin, and gonads may be involved and bone marrow involvement with

blasts is relatively common.64 Primary mediastinal B-cell lymphoma is composed histologically of large cells

with expression of the B-cell–associated antigen CD20; immunohistochemistry and/or flow cytometry arecritical to the diagnosis. Presentation with symptoms related to invasion or obstruction of adjacent structures iscommon, but there is less involvement of extrathoracic sites and bone marrow than in lymphoblasticlymphoma. Staging of NHL is also performed according to the Ann Arbor staging system, and CT scan of thechest, abdomen, and pelvis is the initial and often only necessary imaging (Fig. 82-6).

Figure 82-6

Non-Hodgkin lymphoma. Axial section from a CT demonstrates a large middle and posterior mediastinal masswith distant metastasis to a rib in the contralateral chest. This skip involvement is typical of non-Hodgkinlymphoma.

Treatment regimens for mediastinal NHL are dependent upon stage and histologic subtype. Due to its propensity to involve the bone marrow, lymphoblastic lymphoma commonly employs a treatment regimensimilar to that for acute lymphoblastic leukemia, often including intrathecal chemotherapy and bone marrowtransplantation. Patients with primary mediastinal B-cell lymphoma can be treated with conventionalchemotherapy regimens, but high-dose chemotherapy and “involved field” radiotherapy are sometimesemployed. In general, relapses in NHL are common and the long-term prognosis is worse than for HL.

Other Anterior Mediastinal Neoplasms


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Other anterior mediastinal neoplasms include substernal thyroid and parathyroid adenoma.

Substernal Thyroid

Substernal and ectopic thyroid tissue can present as an anterior mediastinal mass and may involve the middlemediastinum, if the thyroid tissue descends more caudally into the paratracheal space. In the majority of cases,the substernal thyroid is a euthyroid goiter and an enlarged thyroid gland will be palpable in the neck. We havefound that a noncontrast CT is the single most useful test in differentiating substernal thyroid from other

mediastinal masses. Because of its iodine content, substernal thyroid tissue shows enhancement on anoncontrast CT scan and this usually confirms the diagnosis. Surgical resection is recommended, as needle

biopsy cannot rule out malignancy in such a large lesion and substernal goiters will often cause symptoms of airway compression as they continue to grow. Nearly all substernal goiters can be removed by cervicalincision.

Parathyroid Adenoma

The anterior mediastinum is the most common location for an ectopic parathyroid tumor. Often, ectopic parathyroid glands will present as persistent primary hyperparathyroidism after an unsuccessful neck exploration. Before proceeding with mediastinal exploration, localizing studies such as Technetium-99m-

sestamibi scintigraphy and CT are recommended. MRI may be useful to reveal a well-defined mass, however they are usually small (


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of these lesions are benign, slow-growing tumors. Most commonly, they appear as encapsulated and well-marginated masses found in the costovertebral sulci where they arise from intercostal nerve rami. Lessfrequently they can be found in the middle mediastinal compartment when they occur as tumors of the vagusor phrenic nerves. CT typically reveals a solitary, smoothly rounded mass in the upper half of either

paravertebral sulcus abutting the vertebra (Fig. 82-7). An MRI should be employed to rule out intraspinalextension, if there is any possibility of this on CT. Upon presentation, most patients are asymptomatic,although neurologic symptoms from intercostal nerve involvement or intraforaminal extension can be

present.68 Thus, many of these are identified as incidental findings on scans performed for other reasons. Over

one-third of patients with neurofibromas will have neurofibromatosis (von Recklinghausen disease), and these patients tend to present at an earlier age and may have café au lait spots suggesting the diagnosis.68,69

Figure 82-7

Schwannoma. A 67-year-old man who had undergone a total thyroidectomy 20 years earlier presented withchronic cough. A. PA chest radiograph demonstrates a superior mediastinal mass projecting into the righthemithorax. B. Axial section from a CT demonstrates this neurogenic tumor high in thoracic inlet.

Surgical resection is the definitive treatment for these benign nerve sheath tumors, commonly performed via

VATS with favorable results.70,71 There may be a role for chemotherapy and radiation when completeresection is not possible. Excellent long-term survival is obtained with complete surgical excision of the

tumors and recurrence is uncommon.66,70 However, additional neurofibromas or schwannomas may develop

in patients with neurofibromatosis. Ten percent of these tumors extend through the intervertebral foramen andcreate a “dumbbell” appearance on imaging studies. For these lesions, combined thoracic and neurosurgical en

bloc resection can be achieved with low morbidity.72 Typically this is accomplished with a posterior laminectomy followed by an anterior thoracoscopic approach.

Malignant nerve sheath tumors are essentially spindle cell sarcomas of the mediastinum and include malignanschwannoma, neurofibrosarcoma, and malignant neurofibroma. These tumors are rare, affect men and womenequally in the third to fifth decades of life, and are closely associated with neurofibromatosis. Malignantschwannomas remain one of the most poorly characterized of all soft tissue sarcomas. In general, patients withmalignant schwannomas present with large invasive tumors and have a poor prognosis. Complete surgicalresection is rarely possible, and even when accomplished, local recurrence is common. Neurofibrosarcoma

likely evolves from the malignant degeneration of a neurofibroma. Unlike benign nerve sheath tumors, patient


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with neurofibrosarcoma generally have symptoms of pain and nerve impingement.73 On CT imaging, thesetumors often appear as round masses with central areas of necrosis and hemorrhage. Radical surgical excision

provides the only hope of cure; however, the 5-year overall survival rates are low (16% in patients with

neurofibromatosis) and no survival benefit is gained by adjuvant chemotherapy.73,74 Chemotherapy andradiotherapy are options for unresectable tumors.

Sympathetic Ganglion Tumors

Tumors of the sympathetic ganglia likely represent malignant degeneration of the nerve cell rather than thenerve sheath. These tumors are represented by the spectrum of ganglioneuroma, ganglioneuroblastoma, andneuroblastoma. Mature tumors such as ganglioneuroma occur in older children (median age of ∼7 years) and

tend to behave in a benign fashion, whereas immature tumors such as neuroblastoma tend to occur in younger

patients (median age under 2 years) and behave aggressively.75

Ganglioneuromas are the most benign type of sympathetic ganglion tumor. They are typically diagnosed in thesecond or third decade of life and are the most common neurogenic tumors occurring in childhood. Most

patients with ganglioneuroma are asymptomatic upon presentation, although larger tumors may result insymptoms such as cough, dyspnea, dysphagia, chest pain, and Horner syndrome, and symptoms related to thesecretion of catecholamines have been reported. Ganglioneuromas are generally large, well-circumscribed, andencapsulated tumors located in the paravertebral sulci. Surgical resection is a highly successful treatment for

ganglioneuromas.76

Ganglioneuroblastoma is a tumor that demonstrates histologic elements similar to the well-differentiatedganglion cells seen in a ganglioneuroma as well as less-differentiated neuroblastoma-like features, and thedegree of malignant behavior is related to the extent of the latter. Presentation is in the first decade of life and

both sexes are equally affected. Approximately half of patients will present with symptoms. Most children present with a solitary mass that is amenable to complete surgical resection. The treatment of ganglioneuroblastoma is primarily surgical although chemotherapy is indicated in intermediate and high-risk groups. Overall these tumors are associated with relatively high 5-year survival rates, reported to be 88% in

one large series.

77

Neuroblastomas are the most malignant of the sympathetic ganglion tumors. These highly aggressive andreadily metastasizing tumors are found almost exclusively in children, with 95% occurring in patients less than

5 years old.78 Most patients present with symptoms that include chest pain, dyspnea, myelopathy from spinal

canal involvement, and symptoms of excess catecholamine production. Distant metastases are common. 79 OnCT, mediastinal neuroblastomas appear as elongated paraspinous masses often impinging on adjacent

structures and causing bony destruction. Eighty percent of tumors demonstrate calcification.80 MRI is usefulfor determining nodal, chest wall, and intraspinal involvement. The International Neuroblastoma StagingSystem (INSS) is the most commonly used staging system for this disease. It includes factors such as tumor

size, lymph node metastases, and extent of unresectable disease and can be used to predict survival.81

Amplification of the oncogene N-myc has additionally been shown to correlate with worse prognosis.82 Thetreatment of neuroblastoma depends primarily on stage. For patients with stage I disease, resection alone is

usually curative.83,84 For patients with partially resectable stage II and III diseases, surgical resection isfollowed by postoperative multiagent chemotherapy. Patients with stage IV disease are generally treated withchemotherapy and radiation, and the role of surgery is more controversial.

Neoplasms Arising in Parasympathetic Ganglion

Paragangliomas are rare tumors that arise from specialized neural crest cells associated with autonomicganglia, called paraganglia. Paragangliomas can be categorized into two groups based upon association with


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either the parasympathetic system or the sympathetic system. Parasympathetic paragangliomas do not secretecatecholamines and are termed chemodectomas. Chemodectomas may arise from mediastinal chemoreceptorsincluding the aortopulmonary glomulus or anywhere along the vagus nerve and are chromaffin-negativetumors. Tumors connected with the sympathetic nervous system are divided into functional paragangliomasand nonfunctional paragangliomas based on their ability to secrete catecholamines. These tumors have been

previously referred to as extra-adrenal pheochromocytomas.

Both genders are equally affected by mediastinal paragangliomas, usually in the third or fourth decade of life.The clinical presentation includes symptoms of local mass effect as well as varying degrees of hypertensionand hypermetabolism secondary to the production of epinephrine and norepinephrine. Excess plasma andurinary levels of catecholamines can often be detected. Preoperative localization is essential. CT, MRI, and

echocardiography can be useful for anatomic imaging and functional imaging studies such as 131I-metaiodobenzylguanidine (MIBG) scintigraphy can be used to localize lesions not seen on other scans.Treatment requires surgical excision, and presurgical conditioning with alpha and then beta blockade is usuallynecessary for functional lesions to prevent severe hypertension intraoperatively.

Other Mediastinal Tumors

Additional neoplasms of the mediastinum include those seen in Castleman’s Disease and a variety of

mesenchymal tumors.

Castleman’s Disease

Castleman’s disease is a rare lymphoproliferative disorder that can involve enlargement of one (unicentricCastleman’s disease) or multiple (multicentric Castleman’s disease) lymph nodes. Most adults with unicentricdisease are asymptomatic. The mediastinum is the most common location of unicentric disease and lesions

most frequently occur in the anterior and middle compartments.85,86 Multicentric Castleman’s disease ischaracterized by peripheral lymphadenopathy and hepatosplenomegaly; a subset of patients also demonstratemediastinal and intra-abdominal adenopathy. Human herpesvirus 8 infection has been implicated in the

pathogenesis of multicentric but not unicentric disease.

Castleman’s disease is categorized into two histologic types (hyaline vascular and plasma cell), but it appearsthat centricity rather than histology is more important in predicting long-term outcome in this disease.Complete surgical resection should be performed in unicentric disease and is associated with greater than 95%

overall survival and greater than 80% disease-free survival at 5 years.86 Multicentric Castleman’s disease can be rapidly progressive and often fatal and the role of surgery other than to obtain tissue to establish a diagnosisis uncertain.

Mesenchymal Tumors

Mesenchymal tumors constitute approximately 6% of all tumors that occur in the mediastinum.3 More thanhalf of these lesions turn out to be malignant. A large variety of categories exist for mesenchymal tumors of the mediastinum and their spectrum runs the entire gamut of soft tissue tumors, including but not limited toadipocytic tumors (lipoma, lipomatosis, liposarcoma), vascular tumors (hemangioma, lymphangioma),fibroblastic tumors (fibrous tumors), smooth muscle tumors (leiomyoma, leiomyosarcoma), skeletal muscletumors (rhabdomyoma, rhabdomyosarcoma), and chondroosseous tumors (chondrosarcoma, osteosarcoma).Their management is similar to extrathoracic soft tissue tumors, with resection indicated if possible.

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