THE MEDIASTINAL MASS

Mason: Murray & Nadel's Textbook of Respiratory Medicine, 4th ed.

2005

Anatomy

• The mediastinum is the region between the pleural sacs

• Three compartments:– Anterior– Middle– Posterior

Harrison’s priciples of internal medicine. 17th ed

Pembagian mediastinum

1. Mediastinum superior

2. Mediastinum anterior

3. Mediastinum medial

4. Mediastinum posterior

Mediastinum Superior (1)

Batas atas: • Iga 1 sampai corpus v. Th. 1

(thoracic inlet)

Batas posterior: • V Th. 1-4

Batas bawah: • Angulus ludovici s/d V. Th 4

(plane of sternal angle)

Mediastinum Anterior (2)

Batas atas: • Angulus ludovici s/d V. Th 4 (plane of

sternal angle)

Batas anterior: • Corpus sternalis dan Pr. Xyphoideus

Batas posterior: • Pericardium

Batas bawah: • Diafragma

• The anterior mediastinum – extends from the sternum anteriorly to the

pericardium and brachiocephalic vessels posteriorly

– contains the thymus gland, the anterior mediastinal lymph nodes, and the internal mammary arteries and veins.

Harrison’s priciples of internal medicine. 17th ed

Mediastinum Medial (3)

Batas atas: • Angulus ludovici s/d V. Th 4 (plane

of sternal angle)

Batas anterior: • Perikardium

Batas posterior: • Pericardium

Batas bawah: • Diafragma

Anatomy

• The middle mediastinum – lies between the anterior and posterior mediastina

– contains the heart; the ascending and transverse arches of the aorta; the venae cavae; the brachiocephalic arteries and veins; the phrenic nerves; the trachea, main bronchi, and their contiguous lymph nodes; and the pulmonary arteries and veins.

Harrison’s priciples of internal medicine. 17th ed

Mediastinum Posterior (4)

Batas atas: • Angulus ludovici s/d V. Th 4 (plane

of sternal angle)

Batas anterior: • Perikardium

Batas posterior: • V. Th 5-12

Batas bawah: • Diafragma

Anatomy

• The posterior mediastinum– bounded by the pericardium and trachea anteriorly

and the vertebral column posteriorly

– contains the descending thoracic aorta, esophagus, thoracic duct, azygos and hemiazygos veins, and the posterior group of mediastinal lymph nodes.

Harrison’s priciples of internal medicine. 17th ed

Menurut Klinisi

• Mediastinum anterior:– mediastinum anterior dan medial

diperluas sampai ke mediastinum superior, anterior dari bidang yg mell trakhea.

• Mediastinum medial: – mediastinum posterior, sebagian

mediastinum superior, sebelah posterior dari bidang yang melewati anterior trakhea.

• Mediastinum posterior:– korpus vertebrae beserta ruang

paravertebra, termasuk saraf simpatis (asal dari tumor neurogenik)

DEFINITION

• Specific lesions that present as a mass in the mediastinum may be discovered incidentally or identified during evaluation of thoracic or systemic symptoms

• Mediastinal metastases or tumors invading the mediastinum from other intrathoracic sites are customarily omitted

• Primary lesions of the trachea, heart, or esophagus are not discussed, even though they lie within the mediastinum

CLASSIFICATION AND INCIDENCE

Table 1. Disorders Presenting as a Mass in the Mediastinum

Anterior Mediastinum

Thymic neoplasms

Germ cell tumors

Teratoma

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

Middle Mediastinum

Lymphadenopathy

  Reactive and granulomatous inflammation

  Metastasis

  Angiofollicular lymphoid hyperplasia (Castleman's disease)

Lymphoma

Developmental cysts

  Pericardial cyst

  Foregut duplication cysts

    Bronchogenic cyst

    Enteric cyst

  Others

Vascular enlargements

Diaphragmatic hernia (hiatal)

Posterior Mediastinum

Neurogenic tumors

  Arising from peripheral nerves

  Arising from sympathetic ganglia

  Arising from paraganglionic tissue

Meningocele

Esophageal lesions

  Carcinoma

  Diverticula

Diaphragmatic hernia (Bochdalek)

Miscellaneous

Courtesy of Dr. Robert Stevens, Wenatchee, WA

        

Table 2-- Relative Frequencies of Mediastinal Masses in Adults and Children

Lesion Adults (%) Children (%)

Thymoma 19 —

Developmental cysts 21 18

Bronchogenic 7 8

Pericardial 7 <1

Enteric 3 8

Other cysts 4 2

Neurogenic tumors 21 40

Lymphoma 13 18

Germ cell tumors 11 11

Endocrine (thyroid, parathyroid, carcinoid) 6 —

Mesenchymal tumors 7 9

Primary carcinoma — —

Other malignancies 3 4

Data from Silverman NA, Sabiston DC: Mediastinal masses. Surg Clin North Am 60:757–777, 1980, and based on their review of reported mediastinal masses in 1950 adults and 437 children.

• Adults vs children: – Thymoma and thyroid masses rarely occur in infants and

children– Neurogenic tumors are less common in adults– The likelihood of malignancy is higher in infants and children

than in adults– In adults, about ¼ of all mediastinal mass lesions are malignant,

whereas in children, the percentage is 40% to 45%

• HIV infection substantially alters the spectrum of mediastinal disease– >> granulomatous inflammation from mycobacterial and other

infections, lymphoma, and other opportunistic processes– multiple diseases may be present simultaneously including

bronchogenic carcinoma

SPECIFIC MEDIASTINAL TUMORS AND CYSTS

LESIONS TYPICALLY IN THE ANTERIOR MEDIASTINUM

1. Thymic Neoplasms

– Thymoma is the most common neoplasm occurring in the anterior mediastinum and has been recognized more often recently because of increased aggressiveness in evaluating patients with myasthenia gravis

– Histologically, composed of lymphocytes and epithelial cells, described according to predominating cell type

– Thymoma's histologic appearance correlates poorly with its biologic behavior clinically are categorized according to their local invasiveness

• Peak incidence: 40 and 60 years, equal gender predilection• These neoplasms are rare in children

• 2/3 patients are asymptomatic at the time of diagnosis• The rest of the patients typically have nonspecific chest pain,

cough, or dyspnea

• Myasthenia gravis is reported in 10% to 50% of patients with thymoma

• How thymoma produces myasthenia gravis is unknown, but autoantibodies to the postsynaptic acetylcholine receptor appear to explain the dysfunction of the neuromuscular junction and are found in the majority of patients with myasthenia

• Ro”: – usually detected near the junction of the heart and great vessels– typically, they are round or oval and their margins smooth or lobulated

• Thymic hyperplasia symmetrical– Thymoma distorts the gland's normal shape and extends to one side

• Thymoma is diagnosed with certainty only by examination of tissue

• CT can reveal gross invasion and MRI can demonstrate the continuity of a mediastinal mass with the thymus, and discern invasion of vascular structures

A, Frontal chest radiograph shows a smoothly marginated mass along the right side of the mediastinum (arrows). The obscuration of a portion of the right atrial border indicates that the mass lies within the anterior mediastinum. B, Axial

magnetic resonance T1-weighted image through the base of the heart shows that the mass (arrows) is slightly hyperintense compared to skeletal muscle and resides within the anterior mediastinum. Note the smooth, well defined

margins of the mass, consistent with encapsulated thymoma. (Courtesy of Michael B. Gotway, MD, Department of Radiology, University of California, San Francisco.)

• Thymomas are neoplastic, but most have relatively benign biologic behavior

• Patients whose tumors are fully encapsulated can expect survival equal to that of the general population

• Invasive tumors have a poorer prognosis, with 50% to 77% 5-year and 30% to 55% 10-year survival

• Recurrence after resection occurs in nearly a third of patients

• The presence of a thymoma-associated systemic syndrome has traditionally been regarded as a poor prognostic sign

• Thymomas may respond to hormonal therapy but are usually managed by resection via a median sternotomy approach, or via VATS

• Most authors favor removal of as much tumor mass as possible, even when it invades surrounding tissues

• Adjunctive treatment with postoperative radiotherapy is provided and the addition of preoperative or adjuvant chemotherapy appears promising

• Thymectomy may also improve symptoms in some patients with myasthenia gravis although survival appears to be improved primarily in those without an actual thymoma found at thymectomy

• Other thymic mass lesions include benign conditions such as thymic hyperplasia, thymic cysts, and lipothymoma.

• Thymic carcinoma is a histologically malignant process that invades locally and frequently metastasizes.

• The prognosis depends on the histologic grade and the anatomic stage and is generally poor.

• Resection and combined chemotherapy and radiation therapy are advocated.

• Carcinoid tumors Cushing's syndrome, associated with multiple endocrine adenomatosis.

• The thymus is also a common site for mediastinal Hodgkin's lymphoma

2. Germ Cell Tumors

• 10% to 12% of primary mediastinal masses are derived from germinal tissues

• 4 main groups: – teratoma and teratocarcinoma– Seminoma– embryonal cell carcinoma– Choriocarcinoma

• Arise from remnant multipotent germ cells that have migrated abnormally during embryonic development

Teratoma

• The most common germ cell tumors• Made up of tissues foreign to the area in which they occur (>>

Ectodermal) • >> young adults, men and women are affected with equal

frequency. • Most (80%) are benign• Teratocarcinoma malignant, aggressive, rapidly spreading

neoplasm with a poor prognosis.• 1/3 pts are asymptomatic

– pain, cough, and dyspnea– erodes into a bronchus, hemoptysis or even the expectoration of

differentiated tissue such as hair (trichoptysis) or sebaceous material may occur

– rupture into the pleural space and produce acute respiratory distress or enter the pericardium, causing pericardial tamponade

• CXR: – smooth, rounded, and well circumscribed if they are cystic and

more lobulated and asymmetrical if they are solid. • Soft tissue, fat, and calcification (occasionally, fully

formed teeth and bone) can be identified on CT images

• All teratomas should be resected because of the uncertainty as to whether they are benign and the possibility of further enlargement with impingement on adjacent structures

• In malignant teratoma, adjuvant combination chemotherapy may result in improved survival

Axial computed tomographic image through the base of the heart shows a large right-sided anterior mediastinal mass with heterogeneous attenuation. Elements of calcium, soft tissue, and fat (*) are present. The presence of fat

within an anterior mediastinal mass is characteristic of teratoma. (Courtesy of Michael B. Gotway, MD, Department of Radiology, University of California, San Francisco.)

Seminoma (dysgerminoma)

• >> men, usually in the third decade of life• >> chest pain, dyspnea, cough, hoarseness, or dysphagia, superior

vena cava obstruction can occur• Aggressive malignant tumors, extend locally and metastasize

distantly, usually to skeletal bones• May secrete HCG, but not alpha-fetoprotein• Poor prognosis: age over 35 years; superior vena cava obstruction;

supraclavicular, cervical, or hilar adenopathy; fever• Extremely radiosensitive and may respond dramatically to

chemotherapy even in cases with dissemination• With aggressive cisplatin-based regimens, long-term survival with all

mediastinal seminomas is approximately 80%

Nonseminomatous mediastinal germ cell tumors – may be grouped into embryonal cell carcinoma and choriocarcinoma.

• HCG, alpha-fetoprotein, or carcinoembryonic antigen gynecomastia, in 50% of patients

• Klinefelter's syndrome and with hematologic malignancy

• >> men in the third and fourth decades• usually symptomatic

• cisplatin-based treatment regimens have markedly improved the outcome, with over 50% of patients achieving long-term survival

• may respond to aggressive chemotherapy and salvage regimens involving bone marrow transplantation

3. Lymphoma

• Lymphoma is a common cause of a mediastinal mass in both adults and children, 10% and 20% of cases in most series

• Hodgkin's lymphomas: – occurs bimodally in adolescents and young adults and in those over 50– 50% to 60% of patients with Hodgkin's disease have mediastinal lymph node involvement at

the time of diagnosis,

• Non-Hodgkin's lymphomas:– occur most commonly in older adults– Non-Hodgkin's lymphomas involve the mediastinum in only 20% of cases

• Lymphoma is especially common as a thoracic complication in HIV-infected patients. • HIV-associated lymphomas are usually immunoblastic, although Hodgkin's disease

also is more common in patients with HIV infection than in the general population.

• Incidental discovery of a mass on a chest radiograph is a common presentation of lymphoma, although many patients have systemic symptoms or more localized complaints such as cough and chest pain.

• Tracheal compromise and superior vena cava obstruction are common, as are pericardial and pleural involvement, and Hodgkin's disease often involves the hilar nodes and lung parenchyma.

• Resection is not a necessary part of therapy, but anterior thoracotomy or mediastinoscopy is usually required to confirm the diagnosis if adenopathy is not evident outside the mediastinum.

• The prognosis of Hodgkin's and other lymphomas has improved strikingly in the last 2 decades as more effective and less toxic combinations of radiotherapy and chemotherapy have evolved, and effective salvage regimens, including bone marrow transplantation, have been developed to treat relapsed disease.

4. Thyroid Lesions

• Ectopic thyroid glands account for fewer than 10% of mediastinal masses in surgical series

• Asymptomatic, hoarseness, cough, or swelling of the face and arms may occur

• Intrathoracic thyroid tissue is easily recognized by radioactive iodine scanning

• Most mediastinal goiters, being of cervical origin, can be resected by a transcervical approach, without need for sternotomy.

5. Parathyroid Lesions

• 10% of cases of hyperparathyroidism• Mediastinum is the most common site for ectopic

parathyroid adenomas in surgically resistant hyperparathyroidism

• Half of ectopic parathyroid adenomas lie in the anterior mediastinum, usually near the thymus

• Parathyroid cysts may enlarge sufficiently to appear as a mass on the chest radiograph and to produce symptoms

• CT, ultrasound, or MRI

• Technetium-99m sestamibi scans are highly accurate in the detection of aberrant parathyroid tissue

• No differences in meaningful perioperative or ultimate outcomes of patients who did and did not undergo preoperative localization studies

• Parathyroid adenomas are cured by complete resection, and resection via VATS is increasingly advocated

6. Mesenchymal Tumors

• lipomas, fibromas, mesotheliomas, and lymphangiomas, plus several other rare tumors

• arise from connective tissue, fat, smooth muscle, striated muscle, blood vessels, or lymphatic channels

• Unless the lesion is very large, the presence of symptoms usually means that the lesion is malignant

Lipoma • >> mesenchymal tumor of the mediastinum and is most

often anterior• encapsulated or unencapsulated

The chest radiograph of a 31-year-old man showing an abnormality at the right cardiophrenic angle noted as an incidental finding. B, Computed tomogram demonstrates a well-circumscribed homogenous fat-density mass

characteristic of mediastinal lipoma extending into the right hemithorax (arrow).

LESIONS TYPICALLY IN THE MIDDLE MEDIASTINUM

1. Enlargement of Lymph Nodes

• Numerous classifications exist for the mediastinal lymph nodes, a comprehensive example of which is the 11-region scheme of the American Thoracic Society.

• Nodes in the subcarinal, paratracheal, and hilar areas tend to be larger than those elsewhere, but most authors consider a short axis diameter of 1.0 cm to be the upper limit of normal size.

Simplified schematic diagram depicting mediastinal lymph node groups. (From McLoud TC, Meyer JE: Mediastinal metastases. Radiol Clin North Am 20:453–468, 1982.)

• Most often due to three general categories of disease process: – Lymphoma– metastatic cancer– granulomatous inflammation (granulomatous mediastinitis)

• Castleman's disease or angiofollicular lymphoid hyperplasia

• Mediastinal adenopathy is common in HIV-infected patients and is usually infection related, although lymphoma, Kaposi's sarcoma, and other processes may be responsible

• Can be detected accurately by CT and MRI, but imaging studies cannot reliably distinguish between benign and malignant causes of node enlargement

2. Development Cysts

• 10% to 20% of all mediastinal masses in both adults and children• pericardial, bronchogenic, or enteric on the basis of their lining

tissues• Bronchogenic and enteric cysts are often referred to as foregut

duplication cysts because of their origin from aberrant portions of the ventral and dorsal foregut, respectively.

• Pericardial cysts – 1/3 of cystic masses in adults, but are much less common in children– pericardium, diaphragm, or anterior chest wall in the right cardiophrenic

angle. – pericardial cysts may enlarge to cause right ventricular outflow

obstruction, or rupture and hemorrhage to cause pericardial tamponade, or sudden cardiac death

• Bronchogenic cysts – near the large airways, often just posterior to the carina,

although they may be attached to the esophagus or even inside the pericardium

– contains cartilage and respiratory epithelium– Most are discovered incidentally and cause no symptoms

– communicate with the tracheobronchial tree and become infected; enlarge to cause airway obstruction (especially in infants), pulmonary artery compression, or hemodynamic collapse; or rupture with disastrous consequences.

• Enteric or enterogenous cysts

– similar in location and appearance to bronchogenic cysts, but have digestive tract epithelium

– relatively uncommon in adults, but are the most common cysts found in infants and children,~ spinal extension and malformations of the vertebral column (called "neurenteric" cysts)

– can occasionally be multiple and associated with duplications of other portions of the gastrointestinal tract.

• CT or ultrasonography, confirmed by aspiration cytology

• MRI is valuable in cases of suspected spinal extension

• Most authorities favor resection because of diagnostic uncertainties and the potential for development of complications

• Alternatives to thoracotomy include therapeutic aspiration, and thoracoscopic or mediastinoscopic excision.

3. Vascular Masses and Enlargements

• poststenotic aortic dilation, aneurysms or tortuosity of the aorta and great vessels, aortic coarctation, innominate vein and superior vena cava aneurysms, persistent left vena cava, azygous and hemiazygos vein enlargement, anomalous pulmonary venous return, pulmonary venous varix, and cardiophrenic angle varices associated with portal hypertension

• Angiography has been the traditional means of diagnosing mediastinal masses of vascular origin

• CT imaging with intravenous contrast injection permits more convenient detection in most cases today

• MRI shows great promise in enabling definitive diagnosis without radiation or contrast exposure

• However, both CT and MRI can be misleading if the vascular lumen is obscured

4. Diaphragmatic Hernia

• The protrusion of omental fat or other abdominal contents through the diaphragm may occur via several potential routes, and mediastinal mass lesions in any compartment can be the result.

• A hernia through the foramen of Morgagni produces a cardiophrenic angle mass, usually on the right side.

• Bochdalek's hernia, in the posterior mediastinum, generally appears on the left side, presumably because the liver prevents herniation on the right.

• Herniation of fat around the esophagus is believed to precede hiatal hernia formation, and either may appear as a mediastinal mass.

LESIONS TYPICALLY IN THE POSTERIOR MEDIASTINUM

1. Neurogenic Tumors

• Neoplasms arising from neural tissues constitute the largest single group of mediastinal masses, accounting for about 20% of adult cases and twice that proportion in children

• They are classified according to specific tissue of origin into those arising from peripheral nerves, from sympathetic ganglia, and from paraganglionic (chemoreceptor) tissue

• As a group, neurogenic tumors usually appear radiographically as a unilateral paravertebral mass.

• Most are benign and asymptomatic in adults, but in children more than half are malignant and symptomatic.

• Clinical manifestations include chest pain from nerve or bone erosion, dyspnea secondary to tracheal compression, and neurologic deficits resulting from spinal cord compression by intraspinal tumor extension.

• In addition, many neurogenic tumors are hormonally active.

Table 71.6   -- Neurogenic Tumors of the Mediastinum

Neoplasms Arising from Peripheral Nerves

Neurofibroma

Neurilemoma (Schwannoma)

Neurosarcoma

Neoplasms Arising from Sympathetic Ganglia

Ganglioneuroma

Ganglioneuroblastoma

Neuroblastoma

Sympathicoblastoma

Neoplasms Arising from Paraganglionic Tissue

Pheochromocytoma

Paraganglioma (Chemodectoma)

• Tumors arising from peripheral nerves include neurofibromas, neurilemomas or schwannomas, and neurosarcomas.

• Neurofibromas – contain both nerve sheath cells and nerve elements

and are the most common tumor of this group. – incompletely encapsulated and may grow quite large,

producing symptoms by nerve compression or space occupation

– Mediastinal neurofibroma may be one manifestation of von Recklinghausen's disease (neurofibromatosis)

• Neurilemoma, or schwannoma– third to fifth decade of life– neurilemoma usually causes no symptoms

and appears as a well-circumscribed, homogeneous density on chest radiograph

– It is always completely encapsulated and does not invade surrounding tissues

– Treatment of both neurilemoma and solitary neurofibroma is resection.

Series of imaging studies of a 64-year-old asymptomatic man with a surgically proved neurilemoma, or schwannoma. A, Posteroanterior chest radiograph showing an incidental finding of a discrete mass behind the right clavicular head (arrow). B, Computed tomogram showing homogeneous,

well-circumscribed appearance and posterior location adjacent to the vertebral column. C, Magnetic resonance image showing extension of the tumor into the neural foramen (arrow).

• Malignant tumors of nerve sheath origin are also known as malignant neurofibroma, malignant schwannoma, or neurogenic fibrosarcoma.

• These tumors behave aggressively, with both local invasion and distant metastasis.

• Half occur in patients with neurofibromatosis. • Treatment requires wide excision and usually

adjuvant radiation.

GENERAL APPROACH TO DIAGNOSTIC INVESTIGATION

EVALUATION OF A PRIMARY MEDIASTINAL MASS

Diagnostic Approach to the Primary Mediastinal Mass

History

Symptoms of local effects or complications

Systemic syndromes as clues to diagnosis (see Table 71.2 )

Physical Examination

Physiologic compromise

Extrathoracic manifestations as clues to diagnosis (see Table 71.2 )

Potential extrathoracic biopsy sites

General condition and candidacy for surgery

Chest Radiography and Computed Tomography

Anatomic location (see Table 71.4 )

Appearance (size, shape, density, invasion)

Characteristic features (see Table 71.3 )

Special Imaging Studies

Thyroid scan (suspected goiter, abnormal thyroid function tests)

Gallium-67 scan (suspected sarcoidosis)

Somatostatin receptor scintigraphy (suspected thymoma)

Technetium-99m scan (suspected parathyroid adenoma)

Positron emission tomography (suspected lung cancer)

Laboratory Studies

Complete blood count

Routine chemistries (hypercalcemia, hypoglycemia)

Thyroid function tests (suspected goiter)

Anti-acetylcholine receptor antibody (myasthenic symptoms or mass contiguous with thymus)

Alpha-fetoprotein and β-human chorionic gonadotropin (suspected germ cell tumor)

Catecholamine levels (suspected neurogenic tumor)

Tissue Biopsy

Transbronchial needle biopsy (especially if bronchoscopy is already indicated)

Transthoracic or transesophageal needle biopsy (for accessible lesions when primary resection is not feasible)

Mediastinoscopy or mediastinotomy (for accessible lesions, if less invasive approaches are unsuccessful)

Primary Surgical Resection

Appropriate diagnostic approach when ultimate goal is resection and no evidence precludes therapeutic resection

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