approach to mediastinal masses - Turner White

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pulmonary Disease Board Review Manual 

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Editorial Purpose 

The Hospital Physician Pulmonary Disease Board 

Review Manual is a peer-reviewed study guide 

for fellows and practicing physicians preparing 

for board examinations in pulmonary disease. 

Each manual reviews a topic essential to current 

practice in the subspecialty of pulmonary 

disease. 

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NOTE FROM THE PUBLISHER: 

This publication has been developed without 

involvement of or review by the American 

Board of Internal Medicine. 

Endorsed by the 

Association for Hospital 

Medical Education 

Approach to Mediastinal 

Masses 

Series Editor and Contributor: 

Gregory C. Kane, MD, FACP, FCCP 

Associate Professor, Division of Pulmonary and Critical Care Medicine 

Program Director, Internal Medicine Residency, Jefferson Medical 

College, Philadelphia, PA 

Contributor: 

Francisco Aecio Almeida, Jr., MD 

Fellow, Division of Pulmonary and Critical Care Medicine, Thomas 

Jefferson University Hospital, Philadelphia, PA 

Table of Contents 

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . .2 

Anatomic Considerations . . . . . . . . . . . . . . . . . . .2 

Approach to Evaluation . . . . . . . . . . . . . . . . . . . .2 

Middle Mediastinal Mass . . . . . . . . . . . . . . . . . . .3 

Anterior Mediastinal Mass . . . . . . . . . . . . . . . . . .6 

Posterior Mediastinal Mass . . . . . . . . . . . . . . . . . .9 

Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . .10 

References . . . . . . . . . . . . . . . . . . . . . . . . . . . . .10 

Cover Illustration by Catherine Twomey 

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pulmonary Disease Volume 12, Part 2

Pulmonary Disease Board Review Manual 

Approach to Mediastinal Masses 

Francisco Aecio Almeida, Jr., MD, and Gregory C. Kane, MD, FACP, FCCP 

INTRODUCTION 

Mediastinal masses affect patients of all ages and can 

be asymptomatic. In fact, only approximately one third 

of mediastinal tumors cause symptoms. 1 Consequently, 

a mediastinal mass is frequently first noted on a routine 

chest radiograph, although the plain radiograph 

is rarely diagnostic. When symptoms develop, patients 

can present with complaints related to compression of 

vital structures (eg, cough or wheezing from bronchial 

compression, dysphagia from esophageal compression, 

superior vena cava syndrome from compression); pain 

from involvement of bone, pleura, or pericardium; diaphragmatic 

paralysis or vocal cord paralysis due to involvement 

of the phrenic nerves or recurrent laryngeal 

nerves, respectively; limb paralysis due to involvement 

of the spinal column; or constitutional complaints. 

Both localized disorders (eg, primary tumors or cysts) 

and systemic diseases, including metastatic neoplasms 

and granulomas, can be responsible for mediastinal 

masses. 

Although several techniques for obtaining tissue 

for the diagnosis of mediastinal masses are available, 

neither guidelines nor a standard of care approach 

to evaluating these masses has been developed. Due 

to the diversity of the structures within the mediastinum, 

the wide variety of histologic types of mediastinal 

masses, and the relative difficulty in gaining access for 

diagnostic examination, masses in the mediastinum 

can present a diagnostic and management challenge. 

In this manual, we review the diagnostic entities to be 

considered and typical diagnostic approaches used in 

patients who present with mediastinal masses. 

ANATOMIC CONSIDERATIONS 

The mediastinum is located in the center of the 

thorax between the 2 pleural cavities, the diaphragm 

and the thoracic inlet. 2 Although various divisions of 

the mediastinum exist, most clinicians use Fraser et al’s 

classification in which the mediastinum as visualized 

on a lateral radiograph is divided into anterior, middle, 


Hospital Physician Board Review Manual 

and posterior compartments (Figure 1). 3 The anterior 

mediastinal compartment is bounded anteriorly 

by the sternum and posteriorly by the pericardium, 

aorta, and brachiocephalic vessels. The compartment 

contains the thymus gland, branches of the internal 

mammary artery and vein, lymph nodes, the inferior 

sternopericardial ligament, and variable amounts of 

fat. 4 The middle mediastinal compartment contains 

the pericardium and its contents, the ascending aorta 

and the aortic arch, the superior and inferior vena cava, 

the brachiocephalic (innominate) arteries and veins, 

the phrenic nerves and cephalad portion of the vagus 

nerves, the trachea and main bronchi and their regional 

lymph nodes, and the pulmonary arteries and veins. 4 

The posterior mediastinal compartment is bounded 

anteriorly by the pericardium and the vertical part of 

the diaphragm, laterally by the mediastinal pleura, and 

posteriorly by the bodies of the thoracic vertebrae. It 

contains the descending thoracic aorta, esophagus, 

thoracic duct, azygos and hemiazygos veins, autonomic 

nerves, fat, and lymph nodes. 4 

When formulating the differential diagnosis of a 

mediastinal mass, the location of the mass should be 

considered because some disorders occur characteristically 

in certain compartments (Table 1). 

APPROACH TO EVALUATION 

The diagnosis of mediastinal disorders may be 

approached in 2 phases: noninvasive imaging techniques 

and invasive procedures for tissue sampling. 5 

All patients should have a detailed history and physical 

examination before a major work-up is initiated. Symptoms 

or signs of myasthenia gravis may obviate the need 

for preliminary biopsy, and patients with these findings 

can be referred for excision of the mass. A palpable 

superficial lymph node may suggest a metastatic disease 

or lymphoma, again obviating the need for sampling 

the mediastinal mass. A palpable thyroid may suggest 

mediastinal extension of a cervical goiter. A testicular 

examination should be done in all male patients with 

an anterior mediastinal mass. If there is any doubt 

whether a mass is present, ultrasound evaluation of the 

pulmonary Disease www.turner-white.com 

Volume 12, Part 2

A p p r o a c h t o M e d i a s t i n a l M a s s e s 

scrotum should be performed before invasive tests in 

the chest are performed. 

Most mediastinal abnormalities are first detected 

by standard posteroanterior and lateral chest radiographs. 

5 Whenever a mediastinal mass is detected on 

plain films, a computed tomography (CT) scan of 

the chest is generally indicated. Most patients with a 

mediastinal mass who present to a pulmonologist will 

likely already have had a CT scan of the chest. We recommend 

that a CT scan of the chest with intravenous 

contrast media be obtained in those who have not had 

a scan. Although some centers use intravenous contrast 

routinely to evaluate the mediastinum, it is only required 

for optimal evaluation of the hila. 6 Demonstration 

of the status of the intrathoracic blood vessels is 

the major indication for magnetic resonance imaging 

(MRI) of the mediastinum. 6 Also, MRI provides better 

soft tissue differentiation than CT, and therefore it may 

offer better characterization of cysts and adenomas 

(Table 2). MRI should be considered in patients who 

cannot receive iodinated intravenous contrast. 

In most patients with a mediastinal mass, an invasive 

procedure is required to obtain a diagnostic tissue sample 

(Table 3). Tissue sampling is always necessary in patients 

with suspected lymphoma (which can occur in any 

mediastinal compartment), lymphadenopathy (which 

would suggest metastatic disease or lymphoma), or positive 

serologic tests for α-fetoprotein (AFP) or β-human 

chorionic gonadotropin (β-HCG, which would suggest 

nonseminomatous malignant germ cell tumors). If lymphoma 

is an important differential diagnosis, a definitive 

biopsy (not fine-needle aspiration or core needle biopsy) 

generally should be performed. Patient characteristics 

(eg, performance status, age) must be considered when 

deciding how invasive the biopsy approach will be. If 

fine-needle aspiration and/or core needle biopsy are 

to be attempted, we favor either transbronchial biopsy, 

ideally utilizing endobronchial ultrasound (EBUS), 

or CT-guided biopsy based on proximity. Endoscopic 

ultrasonography-guided biopsy should be considered, 

also based on proximity to the esophagus, in centers 

where there is experience with this procedure. 

middle Mediastinal Mass 

Case Presentation 1 

A 25-year-old woman presents with a complaint of 

heartburn, dysphagia, and mid-chest discomfort of 

3 weeks’ duration. She has not experienced fever, chills, 

Figure 1. Lateral chest radiograph showing the mediastinum 

divided into anterior (A), middle (M), and posterior (P) compartments. 

(Adapted from Park DR, Pierson DJ. Disorders of the 

mediastinum: general principles and diagnostic approach. In: Murray 

JF, Nadel JA, editors. Textbook of respiratory medicine. 3rd ed. 

Philadelphia: W.B. Saunders; 2000:2080. Copyright © 2000, with 

permission from Elsevier.) 

night sweats, or significant weight loss. The patient is 

a native of India and immigrated to the United States 

at 11 years of age. She has never smoked. Eight years 

prior to presentation, she had a nonreactive tuberculin 

skin test using purified protein derivative (PPD). Physical 

examination reveals normal vital signs, no palpable 

lymph nodes, and clear lungs on auscultation. 

An initial portable anteroposterior radiograph is 

normal. A barium swallow examination demonstrates 

a focal ulceration of the mid portion of the esophagus 

without perforation. Esophagogastroduodenoscopy 

(EGD) demonstrates an esophageal ulceration with 

fistula formation. A chest CT scan with intravenous contrast 

is obtained to further evaluate for involvement of 

adjacent organs and reveals a 2.3 × 3.4 × 5.0 cm enhancing 

subcarinal mass inseparable from the esophagus 

(Figure 2;see page 6) as well as compression of the right 

pulmonary artery. 

• What diagnoses should be considered when evaluating 

a middle mediastinal mass? 


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Table 1. Differential Diagnosis of Mediastinal Mass by Compartment 

Anterior Mediastinum Middle Mediastinum Posterior Mediastinum 

Thymic diseases: thymoma, thymic carcinoma, thymic 

carcinoid, thymolipoma, non-neoplastic thymic cysts 

Germ cell tumors: seminoma, nonseminomatous germ cell 

tumors (embryonal cell carcinoma, choriocarcinoma) 

Lymphoma: Hodgkin’s disease, non-Hodgkin’s lymphoma 

Thyroid neoplasms 

Parathyroid neoplasms 

Mesenchymal tumors: lipoma, fibroma, lymphangioma, 

hemangioma, mesothelioma, others 

Diaphragmatic hernia (Morgagni) 

Primary carcinoma 

Angiofollicular lymphoid hyperplasia (Castleman’s disease) 

Lymphadenopathy: reactive and granulomatous 

inflammation (eg, tuberculosis or 

fungal diseases, metastasis) 

Lymphoma: Hodgkin’s disease, non- 

Hodgkin’s lymphoma 

Developmental cysts: pericardial cyst, 

foregut duplication cysts (bronchogenic 

cyst, enteric cyst), others 

Vascular enlargements 

Diaphragmatic hernia (hiatal) 

Neurogenic tumors arising from 

peripheral nerves, sympathetic 

ganglia, or paraganglionic tissue 

Meningocele 

Esophageal lesions: carcinoma, 

diverticula 

Diaphragmatic hernia (Bochdalek) 

Miscellaneous 

Adapted from Park DR, Pierson DJ. Disorders of the mediastinum: general principles and diagnostic approach. In: Murray JF, Nadel JA, editors. 

Textbook of respiratory medicine. 3rd ed. Philadelphia: W.B. Saunders; 2000:2081. Copyright © 2000, with permission from Elsevier. 

Differential Diagnosis 

Lymphomas 

The differential diagnosis of a middle mediastinal 

mass is summarized in Table 1. Lymphoma is one of 

the most common mediastinal tumors, representing 

10% to 15% of all mediastinal masses, 7,8 and presents 

more frequently as a generalized disease, although it 

may manifest as a primary mediastinal disease. 9–11 In 

patients with peripheral lymphoma and mediastinal 

involvement, 50% to 70% have Hodgkin’s disease 

(HD) and 15% to 25% have non-Hodgkin’s lymphoma 

(NHL). 9,12 Subtypes of HD include nodular sclerosis 

(the most common subtype), 10 mixed cellularity, 

lymphocyte depletion, lymphocyte-rich classical, and 

nodular lymphocyte predominant. Nodular sclerosis 

HD has a predilection for the anterior mediastinum, 

especially the thymus. 9,10,13 Only 20% to 30% of patients 

with HD present with fever, night sweats, and/or weight 

loss. 14 Although HD may present with cough, wheezing, 

chest pain, and/or dysphagia due to invasion of or 

mass effect on mediastinal structures, up to 55% of patients 

may be asymptomatic, and these masses may be 

incidentally noted on radiographs obtained for other 

reasons. 10 Large B-cell lymphoma and lymphoblastic 

lymphoma (variants of NHL) also have a predilection 

for the anterior mediastinum and are the most common 

primary mediastinal NHL. 9,12 

Tuberculosis and Other Granulomatous Disorders 

Tuberculous lymphadenitis is another important consideration 

in this patient. Tuberculosis (TB) is responsible 

for up to 43% of all of peripheral lymphadenopathy 

in the developing world. 15 In the United States, 5.4% 


of all TB cases are extrapulmonary, and 31% of these 

are lymphatic. 16 In developed countries, 70% to 85% of 

patients with TB lymphadenitis are immigrants. The cervical 

region is most frequently involved, but mediastinal 

involvement occurs in approximately 27% of cases. 17 Although 

some suggest that an isolated chronic nontender 

lymphadenopathy in a young adult without systemic 

symptoms is the most common presentation of tuberculous 

lymphadenitis, 18 a series of 61 patients found that 

all patients had night sweats, weight loss, and weakness. 17 

In this same series, except for one HIV-positive patient, 

all patients had a positive PPD test. Most HIV-negative 

patients with tuberculous lymphadenitis have an unremarkable 

chest radiograph. 17,19 Tuberculous mediastinal 

lymphadenopathy presenting with dysphagia 20 or esophageal 

perforation 21 has been reported. 

In patients with granulomatous mediastinitis secondary 

to histoplasmosis, symptoms that include chest 

pain, cough, hemoptysis, and dyspnea may be caused 

by compression of the airways, superior vena cava, or 

pulmonary vessels. 22 Involvement of the esophagus may 

result in dysphagia, odynophagia, or chest pain but 

only occasionally leads to the development of bronchoesophageal 

or tracheoesophageal fistulas. 23,24 

Developmental Cysts 

Mediastinal cysts account for 18% of mediastinal 

masses. 25 Foregut duplication cysts, which are frequently 

the reference for bronchogenic and enteric cysts, are 

typically found near the large airways, often just posterior 

to the carina. 5 Bronchogenic cysts affect adults in 

their mid-thirties (mean age, 36 years), while enteric 

cysts are relatively uncommon in adults but are the 



Table 2. Comparison of Computed Tomography and Magnetic Resonance Imaging in the Evaluation of Mediastinal Masses 

CT Superior MRI Superior CT and MRI Equivalent 

Spatial resolution 

Detection of calcification 

Detection of bony destruction 

Detection of lung nodules 

Evaluation of lung parenchyma 

Single study screening for lung, liver, and 

adrenal metastases 

Multiplanar imaging capability 

No intravenous contrast needed 

Potential for cardiac gating 

Identification of complex fluid collections 

Soft tissue differentiation: tumor versus fibrosis, tumor 

versus postobstructive pneumonitis 

Evaluation of brachial plexus, neural foramina, diaphragm, 

bone marrow, mediastinal tissue invasion 

Detection of pure fluid collections 

Detection of chest wall invasion 

Evaluation of vascular obstruction 

(contrast CT) 

Adapted from Moore EH. Radiologic evaluation of mediastinal masses. Chest Surg Clin N Am 1992;2:9. Copyright © 1992, with permission from 

Elsevier. 

CT = computed tomography; MRI = magnetic resonance imaging. 

most common cysts found in infants and children. 5 Two 

thirds of patients with developmental cysts eventually 

develop local symptoms. 25 Bronchogenic cysts generally 

present as a well-circumscribed mass without significant 

compressive effects and with variable CT density of its 

contents and a smooth, thin wall 27 ; therefore, it is an 

unlikely diagnosis for this patient. 

• What diagnostic testing is appropriate in this patient? 

DIAGNOSTIC TESTING 

Lymphoma is one of the leading differential diagnoses 

in this case, and fine-needle aspiration or core 

needle biopsy do not consistently provide sufficient 

tissue for histologic, immunologic, and molecular biologic 

assessment of this disease. 28 Therefore, a surgical 

approach is appropriate for this patient. 

Table 3. Techniques for Obtaining Mediastinal Tissue 

Surgical excision 

Video-assisted thoracoscopic surgery 

Thoracotomy 

Anterior mediastinotomy (Chamberlain’s procedure): for lesions in 

left hila or aortopulmonary window 

Mediastinoscopy 

Needle aspiration and core biopsy 

Transbronchial via a fiberoptic bronchoscope 

Percutaneous (computed tomography or ultrasonography guided) 

Endoscopic ultrasonography guided 

CASE 1: Further evaluation 

A biopsy via cervical mediastinoscopy is performed, 

and the specimen demonstrates granulomatous inflammation 

with foci of caseation (Figure 3 and Figure 4). 

Special stains for fungus and mycobacterium are negative. 

Following this procedure, a PPD tuberculosis test 

is placed and is reactive (22 mm). A presumptive diagnosis 

of tuberculous lymphadenitis is made. 

• Could this mass have been approached in a different 

way? 

Retrospectively, a tuberculin skin test could have 

been performed before any invasive procedures were 

performed, especially if the patient’s immigration status 

had been taken into account. Most HIV-seronegative 

patients (this patient eventually tested negative for HIV 

infection) with tuberculous lymphadenitis are PPD positive. 

17–19 If this path had been chosen, one might have 

considered doing a bronchoscopy with transbronchial 

needle biopsy and aspiration before a mediastinoscopy 

because most patients with tuberculous lymphadenitis 

can be diagnosed with these procedures. 17,29,30 Also, 

isolation of Mycobacterium tuberculosis is not necessary to 

make a diagnosis of tuberculous lymphadenitis because 

less than 50% of patients with this disorder have positive 

cultures. 17 However, M. tuberculosis grew in this patient’s 

tissue culture after 4 weeks. In centers where pulmonologists 

feel comfortable doing transbronchial needle 

biopsy and aspiration, this path likely would have been 

taken. EBUS has the capability of visualizing the layers 

of the bronchial mucosa and can differentiate with 

reliability neighboring tumors or masses, lymph nodes, 

and vascular structures. 31 In addition, EBUS-guided 

lymph node sampling has been shown to be superior to 

standard aspiration in all locations except the subcarinal 

region. 32 EBUS-guided transbronchial fine-needle 

aspiration should be used where available to sample 

masses near to the tracheobronchial tree. In this case, 




Figure 2. Computed tomography scan of case patient 1 showing 

a subcarinal mass that is inseparable from the esophagus (solid 

arrow). The mass also demonstrates irregular enhancement with a 

central area of probable necrosis (dashed arrow). 

Figure 4. Photomicrograph of a specimen of the subcarinal 

mediastinal mass from case patient 1. A large area of necrosis is 

surrounded by a granulomatous chronic inflammatory infiltrate. 

Note the prominent giant cell (arrow) (hematoxylin and eosinstained, 

20×). 

A 34-year-old African-American man with mild hypertension 

presents to the emergency department with acuteonset 

chest pain that began several hours prior to presentation. 

He has no cough, dyspnea, fever, chills, night 

sweats, or weight loss. He is a lifelong nonsmoker. Physical 

examination reveals normal vital signs, no palpable 

lymph nodes, and clear lungs on auscultation. 

An initial chest radiograph is normal. A CT angiogram 

of the chest does not demonstrate pulmonary 

embolism but does show a large anterior mediastinal 

mass (Figure 5). 


an anterior mediastinal mass? 

Figure 3. Photomicrograph of a specimen of the subcarinal mediastinal 

mass from case patient 1. A single granuloma demonstrates 

central necrosis with surrounding palisaded epithelioid macrophages 

(hematoxylin and eosin-stained, 20×). 

EBUS was probably not appropriate due to the subcarinal 

location of the mass. Alternatively, endoscopic 

ultrasound-guided fine-needle aspiration biopsy has 

shown promise in the diagnosis of mediastinal lesions 

located near the esophagus. 33,34 

anterior mediastinal mass 



DIFFERENTIAL DIAGNOSIS 

Thymic Neoplasms 

The differential diagnosis of an anterior mediastinal 

mass is summarized in Table 1. Thymic tumors are the 

most common primary tumors of the anterior mediastinum, 

constituting 30% to 50% of all the masses in 

this location; thymomas are responsible for most of 

these. 8,35–37 Most patients are adults older than 40 years, 

with equal sex predilection. 35,36 Approximately 50% of 

patients with thymoma are asymptomatic at the time 

of diagnosis. 38,39 At diagnosis, symptoms due to tumorrelated 

syndromes or, more commonly, myasthenia 

gravis are present in up to one half of patients. 40,41 

Conversely, only 15% of patients with myasthenia gravis 

have a thymoma. 42 All patients suspected to have thymoma, 

even if they are asymptomatic, should have a 

serum antiacetylcholine (Ach) receptor antibody level 

examined to exclude myasthenia gravis. 43,44 

Most thymomas arise in the upper anterior mediastinum 

but may project into the adjacent middle or 




the large anterior mediastinal mass (straight arrow) and adenopathy 

(curved arrow). 

Figure 6. Photomicrograph of a sample from the anterior mediastinal 

mass in case patient 2. Prominent fibrous bands surround 

nodules of lymphoid tissue, a pattern characteristic of nodular 

sclerosis Hodgkin’s disease (hematoxylin and eosin-stained, 20×). 

posterior mediastinum. 6 They vary in size from very 

small to larger than 20 cm in diameter. Thymomas are 

typically found just anterior to the aortic root, 36 above 

the right ventricular outflow tract and the main pulmonary 

artery, and project into one side of the midline. 6 

Thymomas are usually well-defined, with spherical or 

lobulated borders. 45 Only the larger tumors are visible 

on plain radiograph. 6 On CT, encapsulated thymomas 

can appear as a homogeneous or heterogeneous softtissue 

mass, depending on the presence of hemorrhage, 

necrosis, or cyst formation. 45 It is not possible to 

distinguish encapsulated from invasive thymomas until 

mediastinal invasion has occurred. 6 Other thymic neoplasms 

include thymic carcinoma, thymic carcinoid, 

and thymolipoma; the last 2 are very rare. Thymic 

carcinomas often manifest as large, poorly defined, 

infiltrative anterior mediastinal masses that can exhibit 

cystic changes like thymomas. 46 However, these carcinomas 

frequently metastasize to regional lymph nodes 

and distant sites. 47,48 

Germ Cell Tumors 

The anterior mediastinum is the most common 

extragonadal primary site of mediastinal germ cell tumors. 

49,50 These tumors account for 15% of anterior 

mediastinal tumors in adults aged 20 to 40 years and 

for 24% of tumors in children. 7,50,51 Teratomas are the 

most common mediastinal germ cell tumors, 49,50 and 

they contain varying amounts of tissues derived from 

at least 2 of the 3 primitive germ layers: ectoderm 

(skin, hair, sweat glands, sebaceous material, or toothlike 

structures), endoderm (respiratory or intestinal 

Figure 7. A higher-power photomicrograph of a sample from 

the anterior mediastinal mass in case patient 2. A binucleated 

Reed-Sternberg cell (arrow) with prominent eosinophilic nucleoli 

is surrounded by reactive lymphocytes (hematoxylin and eosinstained, 

60×). 

epithelium, or pancreatic tissue), and mesoderm (fat, 

cartilage, bone, or smooth muscle). 50,52,53 Most teratomas 

are mature, without evidence of poorly differentiated or 

immature elements, and have little or no malignant potential. 

50 Patients are usually asymptomatic. 52 Although 

rare, expectoration of hair (trichoptysis) or sebaceous 

debris is a pathognomonic sign of ruptured mediastinal 

teratoma. 52,54 Rupture of the teratoma into the bronchi, 

pleura, pericardium, or lung can be precipitated by digestive 

enzymes secreted by intestinal mucosa or pancreatic 

tissue in the tumor. 49,52,54 On chest radiograph, these 

tumors are rounded to lobulated, well-circumscribed 




anterior mediastinal masses that often protrude into one 

lung field. 52 On CT, mediastinal mature teratoma typically 

manifests as a heterogeneous anterior mediastinal 

mass with soft-tissue, fluid, fat, or calcium attenuation, 

or any combination of these findings. Fluid-containing 

cystic areas, fat, and calcification occur frequently. The 

findings of fat and fluid levels produced by high lipid 

content in the cyst fluid are diagnostic for teratoma but 

are rare. 55,56 

Although primary mediastinal seminomas are uncommon, 

representing only 2% to 4% of all mediastinal 

masses, they account for 25% to 50% of malignant 

mediastinal germ cell tumors of single histology. 57–59 

Most patients are in their third and fourth decades, and 

about 30% are asymptomatic at the time of initial diagnosis. 

58 On radiologic imaging, seminomas manifest as 

a bulky lobulated homogeneous anterior mediastinal 

mass, 57 infrequently invading adjacent structures. 49,60 

Choriocarcinomas, embryonal carcinomas, endodermal 

sinus tumors, teratocarcinomas, and malignant 

teratomas are commonly grouped together as malignant 

germ cell tumors that are not pure seminomas. 

These rare malignant tumors are found in the anterior 

mediastinum, often in association with the thymus, and 

typically cause symptoms in young men. 49,61 Radiologically, 

these are large, irregular masses, frequently with 

significant heterogeneous areas of low attenuation 

due to necrosis, hemorrhage, and/or cyst formation. 60 

Pleural and pericardial effusions are commonly present. 

49,60 

Lymphomas 

Patients with HD typically present with cervical or 

supraclavicular lymphadenopathy. 9 Patients with HD 

who present with mediastinal involvement are usually 

younger than those who present without mediastinal 

disease (29 years versus 38 years). 62 Most patients with 

HD who have an abnormal chest radiograph have bilateral 

asymmetric nodal disease. 63 The prevascular and 

paratracheal nodes are the most commonly affected 

nodes, 64 and only 15% of patients with intrathoracic 

HD have enlargement of a single lymph node group. 13 

Bulky nodal mediastinal disease can be caused by both 

HD and NHL. 9,65 NHL involves the anterior mediastinum 

less frequently than HD. 14 Also, NHL has a greater 

tendency to noncontiguously spread to the middle and 

posterior mediastinum. 13,66 

Goiter 

Despite the frequency of goiter, mediastinal goiter 

represents only 10% of mediastinal masses in surgical 

series. 2 Cervical goiters may descend into the thorax in 


5% to 24% of cases, 2,67 generally into the left anterior 

superior mediastinum. 68 Primary intrathoracic thyroid 

mass, either benign or malignant, developing from heterotopic 

tissue is extremely unusual. 2,69,70 In a study of patients 

with a substernal goiter, the most common symptoms 

were cervical mass (69%), dysphagia (33%), and 

dyspnea (28%); 13% of patients were asymptomatic. 71 

Most patients with a substernal goiter have a palpable 

cervical mass (goiter) on examination. Radiologically, 

mediastinal goiter is an encapsulated, lobulated, heterogeneous 

tumor. 72 The diagnostic radiologic feature is the 

clear continuity with the cervical thyroid gland. 68 

Parathyroid Adenoma 

Only 10% of parathyroid adenomas are ectopic, and 

almost half occur in the anterior mediastinum, 73,74 usually 

near or within the thymus. 75 They are encapsulated 

and rounded, usually measuring less than 3 cm, and on 

CT they may resemble a lymph node. 73,74 

• Considering the above differential diagnoses, how 

should this mass be approached? 

Diagnostic testing 

As in case 1, this patient’s mediastinal disease was not 

detected on the chest radiograph. The CT scan, however, 

clearly demonstrated the presence of the mass in the 

anterior mediastinum. Based on the differential diagnosis, 

malignancy appears to be of greatest concern. Indeed, 

anterior mediastinal masses are more likely to be 

malignant than masses found in the other mediastinal 

compartments. In one series of 400 patients with cysts 

and neoplasms of the mediastinum, 59% of anterior 

masses were malignant, versus 29% and 16% of middle 

and posterior mediastinal masses, respectively. 8 This 

patient’s current CT excludes mature teratoma, mediastinal 

goiter, and parathyroid adenoma with confidence. 

The causes of anterior mediastinal masses presented in 

Table 1 but not discussed above are very rare; thus, the 

leading differential diagnoses at this point should be 

lymphoma, thymoma, and germ cell tumors. 

Serologic evaluation for Ach receptor antibodies, 

AFP, and β-HCG should be performed to exclude 

myasthenia gravis and nonseminomatous malignant 

germ cell tumors. 75 However, lack of myasthenia gravis 

does not rule out thymoma. Also, this patient’s mass is 

located just anterior to the aortic root, the most common 

location of thymomas. Complete surgical resection 

is the mainstay of therapy for thymomas. 76,77 Often, 

patients with primary mediastinal masses and cysts 

undergo surgical resection. 78 Further studies are not 

needed for most isolated symptomatic masses likely to 



be benign (ie, lesions that appear as cysts) and masses 

likely to be thymomas (resectable and nonmetastatic). 

These patients should undergo surgical resection. 

However, the presence of lymphadenopathy, which suggests 

lymphoma and/or metastatic disease, or positive 

AFP or β-HCG serologic test results, precludes surgical 

excision, and limited biopsy specimens should be obtained. 

76 As lymphoma appears to be the leading differential 

diagnoses, a surgical biopsy is the procedure 

of choice in this patient. 

Case 2: Diagnosis 

Testing reveals normal levels of Ach receptor antibodies 

and AFP, and a test for β-HCG is negative. A thoracic 

surgeon performs a cervical mediastinotomy with biopsy 

of the superomedial aspect of the mass. A diagnosis of 

HD, nodular sclerosis type, is established based on histologic 

examination of the sample (Figure 6 and Figure 7; 

see page 7). 

posterior mediastinal mass 


A 60-year-old man with known neurofibromatosis 2 

presents with a 3-day history of dysphagia. He also has 

a chronic left facial palsy with dysarthric speech due to 

excision of a left acoustic neuroma 28 years prior. His 

physical examination is essentially normal, except for 

left facial palsy. A chest radiograph obtained as part of 

his work-up demonstrates a prominent superior mediastinum. 

A CT scan of the chest shows multiple masses 

involving the posterior and middle mediastinum (Figure 

8). 


a posterior mediastinal mass? 

Neurogenic tumors 

Neurogenic tumors represent approximately 20% of 

all adult mediastinal neoplasms and are the most common 

cause of a posterior mediastinal mass. 7,8,79 These 

tumors occur mainly in the posterior mediastinum, and 

they account for three quarters of primary posterior 

mediastinal neoplasms. 80 

Peripheral Nerve Tumors 

Schwannomas are the most common mediastinal 

neurogenic tumors, being responsible for 50% of mediastinal 

neurogenic tumors in adults. 8,81 Mediastinal 

benign schwannoma originates from Schwann cells; 


2 well-circumscribed spherical masses (arrows) in the posterior 

mediastinum. 

both schwannoma and solitary neurofibroma affect 

patients of both sexes predominantly in their third and 

fourth decade of life. 82 Most patients are asymptomatic, 

83,84 and 30% to 45% of neurofibromas occur in 

patients with neurofibromatosis. 7,81 On imaging studies, 

neurofibromas and schwannomas are generally wellcircumscribed 

homogeneous or heterogeneous, spherical, 

lobulated paraspinous masses. 2,85,86 

Malignant Tumor of Nerve Sheath Origin 

These are rare spindle cell sarcomas that typically 

arise from a simple or plexiform neurofibroma (welldefined, 

nonencapsulated tumor that usually infiltrates 

along an entire nerve trunk or plexus), 86 and approximately 

50% occur in patients with neurofibromatosis. 87 

These tumors are typically seen on CT as spherical welldemarcated 

posterior mediastinal masses. 88 

Sympathetic ganglia tumors 

These tumors include ganglioneuroma, ganglioneuroblastoma, 

and neuroblastoma. They are rare tumors 

occurring mainly in children and are beyond the scope 

of this discussion. 

Lateral thoracic meningocele 

Also known as intrathoracic meningocele, lateral 

thoracic meningocele is a protrusion of the spinal 

meninges through an intervertebral foramen, which is 

usually asymptomatic. 6 Sixty to 75% of affected patients 

have neurofibromatosis. 6,85 On chest radiography, lateral 

thoracic meningocele manifests as a well-defined 

paravertebral mass, usually associated with osseous 

abnormalities such as pressure erosion of the posterior 

10 Hospital Physician Board Review Manual www.turner-white.com


vertebral body, widening of neural foramina, and kyphoscoliosis. 

6,89 The lesions typically measure 2 to 3 cm. 

On CT and MRI, continuity between the cerebrospinal 

fluid in the meningocele and that contained in the thecal 

sac as well as water attenuation or signal characteristics 

consistent with fluid can be demonstrated. 89 The 

other causes of posterior mediastinal masses shown in 

Table 1 are quite rare. 

• Are additional studies needed to diagnose this posterior 

mediastinal mass? 

Multiple neurogenic tumors or a single plexiform 

neurofibroma is pathognomonic of neurofibromatosis. 

90 Considering the established diagnosis of neurofibromatosis, 

this posterior mediastinal mass as well as 

the other intrathoracic masses most likely represent 

neurofibromas, and tissue diagnosis is not necessary. 

Asymptomatic schwannomas and neurofibromas do 

not need to be treated. If symptomatic, the treatment 

of choice is complete surgical resection, either thoracoscopically 

91 or via thoracotomy. In this patient, it 

must be determined whether any of these intrathoracic 

tumors is responsible for his dysphagia. 

CASE 3: DIAGNOSTIC TESTING 

MRI of brain and neck demonstrates multiple masslike 

lesions at the cerebellar pontine angle, jugular fossa, 

and left occipital areas, among others. It is felt that his 

posterior mediastinal mass is not responsible for his symptoms. 

The patient undergoes neurosurgical evaluation. 

CONCLUSION 

There are multiple causes of mediastinal masses, but 

the differential diagnosis can be narrowed based upon 

the compartment of presentation and the appearance 

of the mass on CT scan. When tissue diagnosis is required, 

selection from among the various biopsy procedures 

is based upon patient characteristics, the nature 

of the lesion, and its location. 

acknowledgment 

The authors thank John Farber, MD, for his review 

of pathology slides, and Dinesh Sharma, MD, for his 

review of radiographs. 

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