Tumor Mediastinum

NEOPLASMS OF MEDIASTINUM THEODORE D. LIWONGAN

1. ANATOMY

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 borders vital structures of almost every

major organ system including the heart and great vessels of the circulatory system,

the esophagus, and major airways of the aerodigestive tract, the thymus of the

immune system, and important 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.

2. EPIDEMIOLOGY AND INCIDENCE

The incidence and type of primary mediastinal neoplasms varies with patient age. In

combined series totaling 3017 mostly adult patients, the incidence of mediastinal

masses in decreasing frequency were thymomas and thymic 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 patients demonstrated 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 In general, 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 different compartments. In one of the largest series,

Davis and colleagues demonstrated that among patients with mediastinal 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.

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 lung cancer screening study. In 9263 individuals at

high risk for lung cancer who underwent a computed tomography (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.

3. DIAGNOSIS

Mediastinal masses rarely cause chest pain. Most attract attention by compression

of normal structures or are found incidentally on chest X-ray. Signs suggesting

mediastinal tumors are dyspnea from retrosternal goiter, hoarseness, and brassy

cough from compression of the recurrent laryngeal nerve, Horner syndrome (unilateral

ptosis, miosis, and anhidrosis) from involvement of the superior cervical ganglion,

edema of the arms and neck with cyanosis from obstruction of the SVC, and chylous

pleural effusion. Lymph nodes are enlarged in Hodgkin disease, non-Hodgkin lymphoma,

carcinoma, germ cell tumors, or tuberculosis. Other locations of neoplastic tissue

are retrosternal goiter, thymoma, and teratoma (dermoid cyst). When a dermoid forms

a tracheal fistula, it may produce trichoptysis, coughing up of hair.

4. ANTERIOR MEDIASTINUM TUMORS 4.1. THYMOMA

4.1.1. PATHOLOGY

Thymomas are neoplasms of thymic epithelial cells. They almost always

occur in adult life and most (80%) are benign.

Most thymomas are in the anterosuperior mediastinum, although a few

may occur elsewhere where thymic tissue is present, such as the neck, middle

and posterior mediastinum and pulmonary hilus. Benign

thymomas are irregularly shaped masses that vary from

a few centimeters to 15 cm or more. They are

encapsulated, firm and gray to yellow tumors that are

divided into lobules by fibrous septa. Large thymomas

may have foci of hemorrhage, necrosis and cystic

degeneration. Sometimes, the entire thymoma is cystic and multiple sections

are required to identify the true nature of the lesion.

Thymomas contain a mixture of neoplastic epithelial cells and

nontumorous lymphocytes. The proportions of these elements vary from case to

case, and even among different lobules. The epithelial cells are plump or

spindle shaped, with vesicular nuclei. In cases in which epithelial cells

predominate, they may show organoid differentiation, including perivascular

spaces with lymphocytes and macrophages, tumor cell rosettes and whorls

suggesting abortive Hassall corpuscles.

MALIGNANT THYMOMAS INVADE LOCALLY AND MAY METASTASIZE. One fourth of

thymomas are not encapsulated and show malignant features.

Type I malignant thymoma is the most common cancer of the thymus, and

is virtually indistinguishable histologically from encapsulated, benign

thymomas. However, it penetrates the capsule, implants on pleural or

pericardial surfaces and metastasizes to lymph nodes, lung, liver and bone.

Type II malignant thymoma is a very uncommon invasive tumor, also

called thymic carcinoma. Its morphology is highly variable and it resembles

squamous carcinomas, lymphoepithelioma-like carcinomas (identical to those

in the oropharynx), sarcomatoid variants (carcinosarcoma) and other rare

patterns. These variants share a distinct epithelial appearance and a

mediastinal tumor that lacks this feature is probably not thymic carcinoma.

4.1.2. CLINICAL PRESENTATION AND DIFFERENTIAL DIAGNOSIS

Carcinoid tumors, lipomas, and thymic cysts also may

produce radiographic masses. After combination

chemotherapy for another malignancy, teenagers and

young adults may develop a rebound thymic

hyperplasia in the first few months after treatment.

Granulomatous inflammatory diseases (tuberculosis,

sarcoidosis) can produce thymic enlargement.

Thymomas are most common in the fifth and sixth

decades, are uncommon in children, and are

distributed evenly between men and women.

About 40–50% of patients are asymptomatic; masses are detected

incidentally on routine chest radiographs. When symptomatic, patients

may have cough, chest pain, dyspnea, fever, wheezing, fatigue, weight

loss, night sweats, or anorexia. Occasionally, thymomas may obstruct the

superior vena cava. Pericardial effusion may be present. About 40% of

patients with thymoma have another systemic autoimmune illness related

to the thymoma. About 30% of patients with thymoma have myasthenia gravis,

5–8% have pure red cell aplasia, and ~5% have hypogammaglobulinemia.

Thymoma with hypogammaglobulinemia also is called Good’s syndrome.

Among patients with myasthenia gravis, ~10–15% have a thymoma. Thymoma

more rarely may be associated with polymyositis, systemic lupus

erythematosus, thyroiditis, Sjögren’s syndrome, ulcerative colitis,

pernicious anemia, Addison’s disease, stiff person syndrome,

scleroderma, and panhypopituitarism. In one series, 70% of patients with

thymoma were found to have another systemic illness.

MYASTHENIA GRAVIS: Fifteen percent of patients with myasthenia gravis

have thymomas. Conversely, 1/3 to ½ of patients with thymomas develop

myasthenia gravis. This coincident occurrence of thymomas and myasthenia

gravis is more common in men older than age 50.

When thymoma is associated with myasthenic symptoms,the epithelial cells

are plump, rather than spindly. Antigens related to the nicotinic

acetylcholine receptor also occur in thymomas. Thymic hyperplasia is

almost always present in the nontumorous thymic tissue, and lymphoid

follicles may even be present in the thymoma itself.

4.1.3. DIAGNOSIS

Once a mediastinal mass is detected, a surgical procedure is required

for definitive diagnosis. An initial mediastinoscopy or limited

thoracotomy can be undertaken to get sufficient tissue to make an

accurate diagnosis. Fine-needle aspiration is poor at distinguishing

between lymphomas and thymomas but is more reliable in diagnosing germ

cell tumors and metastatic carcinoma. Thymomas and lymphomas require

sufficient tissue to examine the tumor architecture to assure an accurate

diagnosis and obtain prognostic information.

Once a diagnosis of thymoma is defined, subsequent staging generally

occurs at surgery. However, chest computed tomography (CT) scans can

assess local invasiveness in some instances. Magnetic resonance imaging

(MRI) has a defined role in the staging of posterior mediastinal tumors,

but it is not clear that it adds important information to the CT scan

in anterior mediastinal tumors. Somatostatin receptor imaging with

indium-labeled somatostatin analogues may be of value. If invasion is

not distinguished by noninvasive testing, an effort to resect the entire

tumor should be undertaken. If invasion is present, neoadjuvant

chemotherapy may be warranted before surgery.

4.1.4. STAGING

The staging system for thymoma was developed by Masaoka and colleagues.

It is an anatomic system in which the stage is increased on the basis

of the degree of invasiveness. The 5-year survival of patients in the

various stages is as follows: stage I, 96%; stage II, 86%; stage III,

69%; and stage IV, 50%. The French Study Group on Thymic Tumors (GETT)

has proposed modifications to the Masaoka scheme based on the degree of

surgical removal because the extent of surgery has been noted to be a

prognostic indicator. In their system, stage I tumors are divided into

A and B on the basis of whether the surgeon suspects adhesions to adjacent

structures; stage III tumors are divided into A and B based on whether

disease was subtotally resected or only biopsied. The concurrence between

the two systems is high.

Stage Diagnostic Criteria

I Macroscopically and microscopically completely encapsulated; no invasion through capsule

II

IIA Microscopic invasion outside the capsule

IIB Macroscopic invasion into surrounding fat or grossly adherent to pleura or pericardium

III

IIIA Macroscopic invasion into neighboring organs, pericardium, or pleura but not great vessels

IIIB Macroscopic invasion into neighboring organs that includes great vessels

IV

IVA Pleural or pericardial dissemination

IVB Lymphatic or hematogenous metastases

Stage Distribution, % 5-Year Survival, % 10-Year Survival, %

I 36 95–100 86–100

II 26 70–100 50–100

III 22 68–89 47–60

IV 10 47–69 0–11

4.2. GERM CELL TUMOR (TERATOMA)

Thymic germ cell tumors account for 20% of mediastinal tumors. It is

felt that they arise from cells left behind when germ cells migrate

during embryogenesis. The histologies of mediastinal germ cell tumors

are like those in the gonads. Mature cystic teratomas are most common.

Seminomas, embryonal carcinomas, endodermal sinus tumors,

teratocarcinomas, immature teratomas and choriocarcinomas all occur.

Mixed germ cell histologies are common. Mediastinal germ cell tumors may

on occasion show somatic-type malignant components of sarcoma, carcinoma

or hematologic malignancies. Save for mature cystic teratoma, which

affects both sexes equally, the other tumors occur mostly in males.

Thymic seminomas arise only in men. Prognosis is like that for comparable

gonadal tumors, although mediastinal nonseminomatous germ cell tumors

are more aggressive. Other lesions include benign and malignant stromal

tumors. Thymolipomas are benign, well-circumscribed masses of mature

adipose tissue and unremarkable thymic parenchyma. Thymic stromal

sarcomas are low-grade malignant mesenchymal tumors with variable

morphology, but frequently of a liposarcomatous nature. Nonneoplastic

masses include thymic, mesothelial and enteric-type cysts.

4.3. LIMFOMA MALIGNUM

Lymphomas are malignant proliferations of lymphocytes. B-cell, T-cell and

NK-cell lymphomas may be immature (derived from precursor cells; lymphoblasts)

or mature (derived from mature effector cells). The latter are more common.

While all lymphomas are malignant, they show a wide spectrum of clinical

behavior: some follow an indolent clinical course (and may not even require

treatment), while others are very aggressive (and can cause death in a short

time, if untreated). Lymphomas mostly affect lymph nodes, but any tissue

or organ may be involved (e.g., GI tract, thyroid, liver, skin, lungs, brain).

If lymphoma cells are present in the peripheral blood and/or bone marrow,

the tumor is “leukemic” or “peripheralized.” Beyond the broad categories

of B-cell, T-cell and NKcell types, lymphomas are further classified by

their postulated cells of origin, normal cellular counterparts,

immunophenotypes, molecular/genetic alterations, clinical features and

morphology. Further, Hodgkin lymphomas (HLs) are classified separately from

non-Hodgkin lymphomas (NHLs). The WHO classification of lymphoid tumors takes

all of these parameters into account and is currently used by pathologists

and clinicians alike.

5. POSTERIOR MEDIASTINUM TUMORS (NEUROGENIC TUMORS)

5.1. NEURILEMOMA (SCHWANNOMA)

5.2. NEUROFIBROMA

5.3. NEUROSARCOMA

6. THERAPY

6.1. SURGICAL

6.2. RADIOTHERAPY

6.3. CHEMOTHERAPY

6.4. RADIOCHEMOTHERAPY

Treatment for mediastinal tumors depends on the type of tumor and symptoms:

Thymic cancers are treated with surgery. It may be followed by radiation

or chemotherapy, depending on the stage of the tumor and the success of

the surgery.

Germ cell tumors are usually treated with chemotherapy.

For lymphomas, chemotherapy is the treatment of choice, and is possibly

followed by radiation.

For neurogenic tumors of the posterior mediastinum, surgery is the main

treatment.

ATTACHMENT

1. Mediastinum

1.1. Superior

1.1.1. Glandular Plane

1.1.1.1. Thymus

1.1.2. Venous Plane

1.1.2.1. Left brachiocephalic vein

1.1.2.2. Right brachiocephalic vein

1.1.2.3. Superior vena cava

1.1.2.4. Arch of the azygos vein

1.1.3. Arterial-Nervous Plane

1.1.3.1. Aortic arch and its branches

1.1.3.1.1. Brachiocephalic artery

1.1.3.1.2. Left common carotid artery

1.1.3.1.3. Left subclavian artery

1.1.3.2. Nerves include the:

1.1.3.2.1. Left and right vagus nerves

1.1.3.2.2. Left and right phrenic nerves

1.1.4. Visceral Plane

1.1.4.1. Trachea

1.1.4.2. Esophagus

1.1.4.3. Left recurrent laryngeal nerve

1.1.5. Lymphatic Plane

1.1.5.1. Thoracic duct

1.2. Inferior

1.2.1. Anterior

1.2.1.1. Loose areolar tissue

1.2.1.2. Lymphatic vessels which ascend from the convex surface of the

liver

1.2.1.3. Two or three anterior mediastinal lymph nodes

1.2.1.4. The small mediastinal branches of the internal thoracic artery

1.2.1.5. Thymus (involuted in adults)

1.2.2. Media

1.2.2.1. Pericardium

1.2.2.2. Heart

1.2.3. Posterior

1.2.3.1. Artery

1.2.3.1.1. Thoracic part of the descending aorta

1.2.3.2. Veins

1.2.3.2.1. Azygos vein

1.2.3.2.2. The hemiazygos vein and the accessory hemiazygos vein

1.2.3.3. Nerves

1.2.3.3.1. Vagus nerve

1.2.3.3.2. Splanchnic nerves

1.2.3.3.3. Sympathetic chain

1.2.3.4. Esophagus

1.2.3.5. Thoracic duct

1.2.3.6. Some lymph glands

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

(teratoma) 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

Trachea and main bronchi

Lymph nodes

Posterior compartment

Descending aorta Nerve sheath tumors Vascular tumors

Structures Common Lesions Rare Lesions

Esophagus Neurogenic tumors Mesenchymal tumors

Vagus nerves Lymphatic lesions

Thoracic duct Neurenteric cysts

Sympathetic chain

Lymph nodes

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http://www.wesnorman.com/thoraxlesson5.htm

https://www.nlm.nih.gov/medlineplus/ency/article/001086.htm