Download sarc, mediast - UMF IASI 2015

CHAPTER 11
SARCOIDOSIS
11.1. ETIOLOGY
Despite advances in the immunology of sarcoidosis, the etiology of this disease remains unknown.
Various studies examining T cell receptor expression on lymphocytes isolated from the lungs of patients
with sarcoidosis support an immunologic reaction to a single agent. Potential antigens that have been
implicated in stimulating this disease include both exogenous agents, such as infections (mycobacteria,
Yersinia enterocolitica, viruses, fungi) and respirable particles (inhaled organic or inorganic antigens), as
well as endogenous agents, such as latent viral or tumor antigens. No evidence, however, indicates that
any of these agents is the cause of sarcoidosis. Sarcoidosis has also been shown to occur in some families
and in some identical twins, suggesting that genetic factors also play a role in expression of this disease.
Sarcoidosis is a multisystem disorder of unknown etiology characterized pathologically by the
presence of epithelioid granulomas.
11.2. PATHOLOGY
The epithelial granuloma is the pathologic hallmark of sarcoidosis. The epithelioid granuloma
contains two zones: a central compact zone consisting of mature mononuclear phagocytes, epithelioid
cells, and giant cells mixed with lymphocytes of the CD4+ type and a peripheral zone consisting of
macrophages, monocytes, fibroblasts, and lymphocytes, which, in addition to the CD4+ type, are also of
the CD8+ type. Morphologically, both the mononuclear phagocytes and the lymphocytes appear
activated. In the lung, granulomas are primarily localized to areas that parallel lymphatic drainage,
including the peribronchial and mediastinal lymph nodes, pleural tissue septa and along blood vessels.
11.3. PATHOGENESIS
Sarcoidosis results from the immunologic persistence of activated monocytes (macrophages) and
activated CD4+ lymphocytes at sites of disease. The activated mononuclear cells can affect the host by
regulating the initiation, maintenance, and resolution of local granuloma formation and by releasing a
variety of mediators that potentially have systemic effects on the host (interleukin 1 [IL-1], tumor
necrosis factor [TNF], interleukin 8 [IL-8]). The precursor to granuloma formation in sarcoidosis is
alveolitis. In the lung this inflammatory process is localized to the interstitium and is reflected in the cells
recovered by bronchoalveolar lavage. In normal people, alveolar macrophages make up greater than 85%
of the cells, whereas lymphocytes constitute less than 15% of the cells, and both lymphocytes and
macrophages are not activated. In contrast, patients with sarcoidosis have greater numbers of both
macrophages and lymphocytes in bronchoalveolar lavage, with lymphocytes constituting a much larger
percentage of the cells. The lymphocytes recovered are predominantly T helper cells. Activated sarcoid
macrophages and lymphocytes may participate in the fibrotic process by releasing mediators that can upregulate fibroblast proliferation and collagen release.
In sarcoidosis, granuloma formation is often confined to specific sites of disease activity. For example,
although both macrophages and T helper lymphocytes are increased in number and activated in the lungs
of patients with sarcoidosis, these same patients often have a reduction in the circulating number of T
helper cells.
11.4. CLINICAL FINDINGS
Worldwide in distribution, sarcoidosis has a predilection for temperate environments. It is common in
Sweden but occurs very infrequently in Africa, Southeast Asia, and the Hawaiian Islands. Sarcoidosis can
occur in any age and race; however, it appears to be found more frequently in younger people (more than
70% of cases in people under 40 years of age), blacks, and within the black race, females.
Sarcoidosis can be asymptomatic; 80% of patients with sarcoidosis in a New York study had no
symptoms. Also, a chest radiographic screening of the population in Denmark detected fourfold more
patients with sarcoidosis than did studies for patients who had symptoms.
Sarcoidosis can affect any organ of the body. The disease can present acutely, subacutely, or
chronically and can affect a single organ, or multiple organs (table 26). The patient's ethnic background
has been demonstrated to influence the mode of presentation, organ involvement, and clinical course in
sarcoidosis. For example, Swedish and Irish women often have Loeffler's syndrome, an acute disorder
manifested by erythema nodosum, polyarthritis, iritis and fever that has a good prognosis. In contrast,
West Indian people have a later onset of disease and multiple organ involvement, including the
respiratory, ocular, and reticuloendothelial systems. It seems that genotype may influence disease
expression. Human leukocyte antigen B8 (HLA-B8), for example, has been associated with erythema
nodosum, arthritis, and early resolution.
Fatigue, weakness, malaise, weight loss, anorexia, fever and sweats are some of the most common
symptoms at presentation in sarcoidosis.
Sarcoidosis can determine intrathoracic and extrathoracic involvement. Generally regarded as benign,
sarcoidosis can also involve a number of vital structures, including those in the respiratory, cardiac,
endocrine, ophthalmologic, and central nervous systems, with potential life-threatening implications.
Table 26 - Organ system involvement in sarcoidosis
Organ system
Thoracic
Pulmonary
Hilar nodes
Parenchima
Cardiac
Extrathoracic
Erythema nodosum
Hypercalcemia
Hypercalciuria
Gastrointestinal
Musculoskeletal
Nervous system
Ophtalmologic
Liver
Lymph nodes
Upper respiratory
Clinical incidence
90-95%
75%
50%
5-10%
11.4.1.
INTRATHORACIC
SARCOIDOSIS
•
The
respiratory system
is
the
most
frequently involved
15-20%
organ system. Up to
2-5%
90% of patients with
20-50%
sarcoidosis
have
1-2%
pulmonary
10-20%
involvement
at
3-5%
some time during
20-50%
the course of their
20%
disease. Of these,
20%
60% may develop
5-15%
symptoms of cough,
wheezing,
or
dyspnea.
Intrathoracic lymph nodes are enlarged in 75-90% of patients. The hilar nodes are usually involved and
less frequently the mediastinal nodes. Chest radiographs are grouped into the following stages:
- stage 0, normal;
- stage I, bilateral hilar adenopathy (figure 55);
- stage II, bilateral hilar adenopathy with diffuse parenchymal infiltrates;
- stage III, diffuse parenchymal infiltrates without bilateral hilar adenopathy.
Progressive pulmonary sarcoidosis occurs in up to 20% of patients. The resultant physiologic
abnormalities are those seen in most restrictive diseases. Some patients may also have an added
obstructive component resulting from endobronchial disease. Exercise testing may be useful in
delineating the pulmonary or extrapulmonary (cardiac disease, anemia, myopathy) cause of dyspnea in
patients with sarcoidosis. Briefly, although pulmonary function tests do not always correlate with the
symptoms and radiographic stage of sarcoidosis, they appear to be a sensitive way to follow the course of
disease. The upper airway can also be involved with sarcoidosis, including the nasopharynx, larynx,
vocal cords, paranasal sinuses, and nasal bones.
Figure 55 - Stage I sarcoidosis
This radipograph shows bilateral hilar node enlargement. The “tongue” of normal lung between the hilar
node enlargement and the cardiac outline is often observed in sarcoidosis.
The stages demonstrated on chest radiographs can not anticipate the progression of the underlying
disease, but can predict the resolution of infiltrates (table 27).
Table 27 - Radiographic stage of sarcoidosis and prognosis
Stage
Resolution
Progression
I
II
III
54%
31%
4%
7%
13%
10%
• Cardiac sarcoidosis, although infrequent, is important because it can be potentially lethal and a
major source of symptoms, including dyspnea and cough, without clinical evidence of disease elsewhere.
Similar to that of the lung, granulomatous involvement of the heart is patchy. The degree of cardiac
compromise depends not only on the extent but also on the location of the disease. Granulomas localized
to the conduction system potentially can result in heart block or arrhythmias. Likewise, extensive
myocardial involvement may cause a restrictive and dilated cardiomyopathy. The mortality from cardiac
sarcoidosis approaches 20% to 30%. Severe pulmonary disease also causes secondary cor pulmonale. In
addition to direct cardiac involvement, the heart's electrical system also may be altered by hypercalcemia.
11.4.2. EXTRATHORACIC SARCOIDOSIS
• The mechanism for both the hypercalcemia and the hypercalciuria in sarcoidosis is an increase
in 1,25-dihydroxycholecalciferol concentration which results in an increase in intestinal calcium
absorption. In addition, chronic renal insufficiency from nephrolithiasis and nephrocalcinosis may be the
result of a persistent hypercalcemia.
• Ocular sarcoidosis, often clinically asymptomatic, can result in blindness. The most common
structure involved is the anterior uveal tract. Involvement of any of the ocular structures, however, has
been described. Although a careful eye history (altered visual acuity, watering, redness, photophobia) and
examination are important, sarcoid eye disease is often asymptomatic and can only be detected by slitlamp examination.
• Sarcoidosis can involve any portion of the nervous system, including the cranial nerves (most often
VII), the peripheral nerves, the skeletal muscle, the basal meninges, and the central nervous system in the
form of inflammation or mass lesions. Lesions are more frequently localized at the base of the brain and,
if localized to the hypothalamic/ pituitary region, may result in diabetes insipidus or galactorrhea
/amenorrhea. Seizures are a marker of severe central nervous system disease. Cerebrospinal fluid is
typically lymphocytic with an elevated protein concentration.
• In sarcoidosis, the liver may be enlarged, but severe hepatic dysfunction with esophagogastric
variceal formation is unusual. Splenic enlargement may result in pancytopenia.
• Skin manifestations from sarcoidosis can be the result of direct granulomatous involvement of the
tissue (lupus pernio, skin plaques, cutaneous nodules) or the result of a vasculitic response. The latter is
the mechanism responsible for erythema nodosum in these patients. Lupus pernio is a chronic violaceous
lesion of the face that, in contrast to erythema nodosum, has been associated with multiple organ
involvement, laryngeal sarcoidosis, and a poor prognosis.
• Sarcoidosis can also affect the skeletal, gastrointestinal and urinary systems. Involvement of the
parotid or lacrimal glands in combination with uveitis and fever has been termed uveoparotid fever or
Heerfordt's syndrome.
• Peripheral lymphadenopathy is common, involving the cervical, axillary, epitrochlear and inguinal
nodes. These nodes are nonadherent and have a firm, rubbery texture; palpation causes no pain and the
nodes do not ulcerate.
11.5. LABORATORY FINDINGS
 Blood tests in sarcoidosis show lymphocytopenia, increased erythrocyte sedimentation rate,
hyperglobulinemia and high level of angiotensin-converting enzyme; hypercalcemia is rare. Angiotensinconverting enzyme (ACE) levels are elevated in 40-80% of patients with active sarcoidosis (its synthesis
is controlled by T lymphocytes). This finding is neither sensitive nor specific enough to have diagnostic
significance..
 The chest x-ray is abnormal in almost all cases, showing bilateral hilar adenopathy, associated or
not with diffuse parenchymal changes (reticulonodular infiltrates). The three radiographic patterns of
sarcoidosis – already described in the previous chapter – are not consecutive stages of the disease and do
not represent evolutive criteria for sarcoidosis. Focal infiltrates, acinar shadows, nodules, and, rarely,
cavitation may be seen. Pleural effusion is noted in fewer than 10% of patients.
 The lung function tests show restriction, with decreased lung volumes and normal forced expiratory
volume in one second (FEV1), typical aspect for interstitial lung disease. The diffusing capacity is also
decreased.
 Endoscopy with transbronchial biopsy and bronchoalveolar lavage is the procedure of choice in
patients with suspected pulmonary involvement. Bronchoalveolar lavage fluid in sarcoidosis is usually
characterized by an increase in lymphocytes and a high CD4/CD8 cell ratio.
 Skin test anergy (including tuberculin skin test) is present in 70% of patients with sarcoidosis.
11.6. DIAGNOSIS
The diagnosis of sarcoidosis is made on the basis of the history, radiographic and pathologic findings.
It generally requires histologic demonstration of noncaseating granulomas in biopsies from a patient with
other typical associated manifestations. Other granulomatous diseases (especially tuberculosis) must be
ruled out. If indicated, biopsy of easily accessible sites, like palpable lymph nodes, skin lesions, or
salivary glands, is likely to provide positive findings. Transbronchial lung biopsy has a high rate of
positive findings, especially in patients with radiographic evidence of parenchymal involvement. Biopsy
is essential whenever clinical and radiographic findings suggest the possibility of an alternative diagnosis
such as lymphoma.
Patients with suspected myocardial or central nervous system sarcoidosis have a potentially lifethreatening disease that requires specific therapy. Gallium-67 scanning may be helpful in selecting the
tissue to biopsy. The Kveim test has been used to confirm the diagnosis of sarcoidosis; the 4- to 6-week
delay before test interpretation, the 20% false-negative rate, the number of false-positive results, and the
lack of a commercially available reagent make this test impractical for routine use. Angiotensin
converting enzyme (ACE) is elevated in up to 80% of patients with sarcoidosis because of the ongoing
production of the enzyme by epithelioid cells in the granulomas; it is not specific for sarcoidosis and can
be elevated in a variety of disorders. ACE serum levels usually fall with clinical improvement.
11.7. DIFFERENTIAL DIAGNOSIS
Sarcoidosis has to be differentiated from other lung diseases manifested by similar radiographic
elements: hilar and mediastinal lymph nodes enlargement and parenchimal reticulonodular pattern
(diffuse fibrosis). In the differential diagnosis of sarcoidosis the following diseases will be considered:
Infectious diseases – Bacteria  Mycobacteria - M. tuberculosis
- Atypical mycobacteria
 Brucella
 Francisella tularensis
 Yersinia enterocolitica
- Fungi
 Histoplasma capsulatum
 Coccidioidis immitis
Noninfectious diseases
 hypersensitivity pneumonitis
 inorganic dusts - talc, beryllium
 drugs – methotrexate
 neoplasms – lymphoma, mediastinal tumors
 Wegener`s granulomatosis
11.8. PROGNOSIS
Pulmonary sarcoidosis is usually a self-limited condition, with about 50% of patients showing some
improvement and 25% remaining unchanged. The reversible lesion in the lung is the alveolitis, whereas
the fibrosis is irreversible. About 20% of patients with lung involvement suffer irreversible lung
impairment, characterized by progressive fibrosis, bronchiectasis and cavitation. Pneumothorax,
hemoptysis, mycetoma formation in lung cavities and respiratory failure often complicate this advanced
stage of sarcoidosis. Myocardial sarcoidosis occurs in about 5% of patients, sometimes leading to
cardiomyopathy, cardiac arrhythmias and conduction disturbances. Up to 10% of patients may die from
sarcoidosis. In general, patients with multiple organ involvement, a slower onset of disease, and a more
advanced stage on chest radiography have a worse prognosis. The prognosis is best for patients with hilar
adenopathy alone.
11.9. TREATMENT
 Individualizing therapeutic regimens is particularly important in patients with sarcoidosis because
the disease has a heterogeneous presentation and course. Most patients, because of the disease's selflimited nature, do not require therapy but rather simple observation. Anti-inflammatory therapy is
indicated for individuals who have either severe or progressive disease. To determine if progressive
disease is present, individuals initially with apparently benign disease should be followed at least at 6month intervals to observe for evidence of progressive disease. Serial pulmonary function testing is
particularly useful in this regard.
 Some patients must be treated immediately. These patients usually have critical organ involvement
(cardiac disease, central nervous system disease, ocular disease, persistent hypercalcemia or
hypercalciuria) or disfiguring skin lesions. Many patients with pulmonary disease need to be treated
immediately if progressive pulmonary functional impairment is already evident. Glucocorticoids are
currently the principal anti-inflammatory agents used: prednisone (1 mg/kg/day) for 4 to 6 weeks, with a
rapid tapering (0.25 mg/kg/day) for 3 months more. The prednisone is then tapered to an alternate-day
regimen to reduce systemic side effects or to as low a dosage as the patient tolerates. If disease progresses
despite prednisone therapy, disease recurs after tapering the prednisone, or severe glucocorticoid-related
side effects occur, we institute alternative anti-inflammatory therapy with alternative anti-inflammatory
agents: methotrexate, cyclophosphamide or cyclosporine.
CHAPTER 14
MEDIASTINAL SYNDROMES
14.1. ANATOMY AND PHYSIOLOGY
The mediastinum comprises the part of the thorax that lies between the lungs. The mediastinum is
bounded superiorly by the thoracic inlet, anteriorly by the sternum, laterally by the parietal pleura,
inferiorly by the diaphragm, and posteriorly by the spine and ribs. Within the mediastinum lie the heart
and central vessels, the major airways, the esophagus, phrenic nerves, vagus nerves, sympathetic
trunks, lymph nodes, and the main channel of the lymphatic system. All these structures can be affected
primarily or secondarily by diseases involving the mediastinum.
Classically the mediastinum is divided into three compartments: anterior, middle and posterior
mediastinum. The contents of each compartment are listed below (table 29).
Table 29 - Contents of mediastinal compartments
Anterior or anteroposterior
Thymus gland
Aortic arch and major branches
Innominate veins
Lymphatic and areolar tissue
Thyroid gland (occasionally)
Upper trachea and upper esophagus
Middle
Heart
Pericardium
Trachea
Hilum of each lung
Tracheobronchial lymph nodes
Phrenic nerves
Posterior
Esophagus
Vagus nerves
Sympathetic nerve chains
Thoracic duct
Descending aorta
Azygos and hemiazygos venous systems
Paravertebral lymph nodes
 The differential diagnosis of an anterior mediastinal mass includes thymoma, teratoma (figure 59),
thyroid lesions, lymphoma and mesenchymal tumors (lipoma, fibroma).
Figure 59 - Anterior mediastinal tumour: dermoid cyst.
A smooth, clearly defined opacity is superposed on the shadow of the left hilum
 The differential diagnosis of a middle mediastinal mass includes lymphadenopathy, pulmonary
artery enlargement, aneurysm of the aorta, developmental cyst (bronchogenic, pleuropericardial),
dilated azygous vein and foramen of Morgagni hernia.
 The differential diagnosis of a posterior mediastinal mass includes hiatus hernia, neurogenic tumor
(neurofibroma, neurosarcoma, ganglioneuroma, pheochromocytoma) meningocele, esophageal tumor,
foramen of Bochdalek hernia.
14.2. CLINICAL FINDINGS
Symptoms and signs of mediastinal masses are nonspecific and are usually caused by the effects
of the mass on surrounding structures. In adults, almost 50% of mediastinal masses are
asymptomatic. In children, mediastinal lesions are more likely to cause symptoms and findings.
About 50% of symptomatic mediastinal masses prove to be malignant, whereas about 90% of
asymptomatic masses are benign.
 The most frequent symptoms are chest pain, cough, dyspnea, hoarseness, recurrent respiratory
infection, and dysphagia, all usually resulting from compression by a mediastinal lesion or invasion of
adjacent structures.
 Less frequent local symptoms include superior vena caval obstruction, vocal cord paralysis, Claude
Bernard - Horner syndrome and spinal cord compression.
 The presence of cough, hemoptysis, or stridor with a mediastinal mass suggests malignancy;
hemoptysis is particularly suggestive of a bronchogenic carcinoma. Inspiratory stridor may occur with
narrowing of the extrathoracic trachea or bilateral vocal cord paralysis and is a threatening sign. Usually,
tumors grow to a large size before pain develops, but retrosternal pain suggests malignancy or
inflammatory disease. Dyspnea may be caused by compression of the major airways, involvement of the
phrenic nerve paralyzing diaphragmatic function, or a concomitant pleural effusion (table 30).
Table 30 - Symptoms of mediastinal masses
Cough
Hemoptysis
Stridor
Dyspnea, especially with phrenic nerve palsy
Hoarseness (vocal cord paralysis)
Superior vena caval obstruction
Pain (usually retrosternal)
Dysphagia
Pleural effusion, including chylothorax
Spinal cord compression
Pericarditis and pericardial tamponade
Horner's syndrome
 Some patients have systemic symptoms resulting from endocrine secretion by the tumor, such as
manifestations of hyperthyroidism caused by intrathoracic thyroid adenoma, hypercalcemia secondary
to parathyroid adenoma, and systemic hypertension in association with neurogenic tumor. Myasthenia
gravis occurs with thymoma, and fever occurs with Hodgkin's disease (table 31).
Table 31 - Systemic syndromes associated with mediastinal tumors
Tumor
Syndrome
Thymoma
Myasthenia gravis, red cell aplasia,
hypogammaglobulinemia, Cushing's syndrome
Gynecomastia
Thyrotoxicosis
Fever of undetermined origin, hypercalcemia
Osteoarthropathy
Hypertension
Hypertension, diarrhea
Hypercalcemia
Germ cell tumor
Substernal goiter
Lymphoma (Hodgkin's disease)
Neurofibroma
Pheochromocytoma
Ganglioneuroma
Parathyroid adenoma
14.2.1. SUPERIOR VENA CAVAL OBSTRUCTION
Obstruction of the superior vena cava produces a characteristic syndrome that often appears
abruptly with headache, swelling, and venous engorgement of the face, chest and arms. Patients with
superior vena caval obstruction have distended, nonpulsatile jugular veins and often prominent upper
thoracic collateral venous circulation. Obstruction below the junction of the azygos vein usually
produces greater obstructive symptoms and results in extensive collateral routes through the abdominal
wall to enter the drainage system of the inferior vena cava. Conjunctival edema and even chemosis can
occur when obstruction has been rapid in onset.
Causes
In patients with a history of smoking, especially middle-aged males, the diagnosis is almost always
bronchogenic carcinoma. Attempts to confirm the diagnosis histologically must be undertaken with care
because of the risks of bleeding. Sputum cytology may be helpful. If cytology is negative, bronchoscopy
must be performed. Evidence of disease elsewhere, such as in lymph nodes, should be sought because
scalene lymph node biopsy or mediastinoscopy may be accompanied by bleeding. However, fine-needle
aspiration of supraclavicular nodes or of a mediastinal mass is safe in these patients.
In younger patients, in patients with bilateral hilar masses, or in those with lymphoma
elsewhere, it is important to establish a histologic diagnosis because therapy depends on it. In such
patients, more material for histology is necessary than can be obtained by fine-needle aspiration, and
tissue from extrathoracic sites should be sought.
Treatment
Once the diagnosis of caval obstruction has been established, treatment is determined by the
nature of the primary disease. Symptomatic therapy includes diuretics and corticosteroids.
Emergency treatment with chemotherapy or radiotherapy is often indicated for this condition.
Whatever form of therapy is used, relief of obstructive symptoms is usually satisfactory because
collateral vessels develop, even in the absence of resolution of the caval obstruction. Surgical relief of
caval obstruction in patients with nonmalignant disease has been tried with occasional success, but
generally surgical procedures offer little therapeutic help.
14.2.2. HOARSENESS
Hoarseness associated with a mediastinal mass usually results from paralysis of the left recurrent
laryngeal nerve. This paralysis is most often associated with malignancy but is occasionally caused by an
aortic aneurysm.
14.2.3. CLAUDE BERNARD - HORNER SYNDROME
Tumors of the anterior mediastinum may produce involvement of the cervical or thoracic
sympathetic ganglia, resulting in Claude Bernard-Horner syndrome (unilateral palpebral ptosis,
enophthalmos, constricted pupil, warmth and dryness of the face on the affected side). The most
common cause of Horner's syndrome is bronchogenic carcinoma.
14.3. LABORATORY FINDINGS
Diagnostic studies have the purpose of localizing the lesion, determining its site of origin, and
obtaining a tissue diagnosis. The investigation of mediastinal lesions should follow a sequence from
simpler, inexpensive techniques to complex, expensive and less comfortable techniques.
 Since localization is of major importance, radiographic techniques play a crucial role. A good chest
film, particularly the lateral view, is the initial diagnostic test, providing information on the size and
location of the mass.
 Computed tomography (CT) is most valuable because masses of different density can be identified,
fatty tissue and cysts can be differentiated. With the use of contrast materials, vascular lesions can be
distinguished from nonvascular structures. CT is used to assess mediastinal lymphadenopathy and is
particularly valuable in the posterior mediastinum.
 A barium contrast study of the esophagus may distinguish intrinsic pathology from extrinsic
compression or may demonstrate a fistula.
 Magnetic resonance imaging (MRI) may be used to complement a CT scan. Its advantages include
distinction between vessels and masses, no need for contrast media, and better delineation of hilar
structures. MRI also allows imaging in multiple planes, whereas CT permits only axial imaging.
 angiography, Doppler sonography, venography of brachiocephalic veins and the superior vena
cava for suspected vascular lesions.
 thyroid scintigraphy is used in diagnosing thyroid tumors.
 Nonvascular masses usually require a histologic diagnosis; several techniques are available for
obtaining tissue. In the appropriate setting, not only may bronchoscopy and esophagoscopy reveal
compression, but a biopsy may also be obtained. Transthoracic fine-needle aspiration for cytology is also
a useful technique.
 Mediastinoscopy is performed through an incision just above the sternal notch and is a valuable
procedure for obtaining adequate amounts of tissue for specific diagnosis. Only lesions in the upper
anterior mediastinum can be explored by this technique. Lesions beyond the reach of the
mediastinoscope can be approached by anterior mediastinotomy.
14.4. SPECIFIC DISEASES
14.4.1. TUMORS
The location of mediastinal tumors is important in diagnosis because of the predilection of
mediastinal lesions to arise in specific compartments (table 32).
Anterior mediastinal tumors
 Thymoma is the most common tumor originating in the anterior mediastinum. Benign and
malignant thymomas are distinguished by their invasive features rather than by their microscopic
appearance. About 30% of thymic tumors are malignant and invade locally rather than by
hematogeneous spread. Approximately 70% of thymomas are associated with systemic symptoms, of
which the most common is myasthenia gravis, associated with up to 50% of thymomas; conversely, 10%
to 15% of patients with myasthenia have a thymoma. The treatment of choice for a thymoma is surgical
removal. A patient with myasthenia has a significant chance of improvement. Malignant thymomas may
respond to radiation therapy, occasionally used in conjunction with surgery.
 Germ cell tumors of the mediastinum occur in adolescents or young adults and are classified into
benign teratomas, malignant teratomas and seminomas. About 20% of these tumors are malignant and
occur more frequently in males. The cystic teratomas, or dermoids, are usually benign, whereas almost
one third of solid tumors are malignant. Benign teratomas may be identified because calcification, hair,
or teeth are found within the cyst. Benign teratomas are usually easily resected, but complete removal
of malignant teratomas may be impossible. Seminoma is the most common form of malignant germ cell
tumor to affect the mediastinum primarily and the anterior compartment exclusively. Treatment of
patients with seminoma should include surgical extirpation and radiation therapy
Table 32 - Classification of mediastinal masses
Anterior or anterosuperior
Thymoma
Germ cell tumor
Lymphoma
Substernal goiter
Enlarged fat pad or lipoma
Aneurysm of ascending aorta
Parathyroid adenoma
Middle
Bronchogenic carcinoma
Bronchogenic cyst
Lymphoma
Metastatic tumor
Systemic granuloma (sarcoid, histoplasmosis, tuberculosis)
Pericardial cyst
Posterior
Neurogenic tumor
Bronchogenic cyst
Enteric cyst
Aneurysm of descending aorta
Diaphragmatic hernia
Paravertebral abscess
Meningocele
Achalasia
 Substernal goiters are an important cause of anterior mediastinal masses. The routine chest film is
occasionally diagnostic, with evidence of displacement and/or compression of the trachea, a smooth
outline, and some calcification within the mass. CT is often most helpful, demonstrating continuity of
the mass with the cervical thyroid and confirming calcification. Surgical excision is the treatment of
choice.
 Aneurysms of the ascending aorta, now usually arteriosclerotic in origin, usually present as
anterior mediastinal masses. Angiography is often required to define the full extent of the aneurysm and
assess the feasibility of surgery.
 Patients with spontaneous or iatrogenic Cushing's syndrome often have radiographic evidence of
fullness of the anterior mediastinum, best visualized on the lateral chest film, caused by an enlarged
mediastinal fat pad and no therapy is indicated. CT is particularly useful in identifying fatty tissue in
these patients or when a lipoma is present.
 Lymphomas may present as anterior mediastinal masses (figure 60). Diagnosis must be confirmed
histologically.
 Fibromas, hemangiomas and lymphangiomas are rare, benign masses that require surgical
excision to confirm the diagnosis.
Figure 60 - Anterior mediastinal tumour: lymphoma
Middle mediastinal tumors
 Lymph node enlargement is a common cause of a mass in the middle mediastinum, most often
caused by malignancies, either lymphoma or metastatic carcinoma (figure 61). Small cell carcinoma of
the lung may also present as a middle mediastinal mass, with a central bronchial tumor and mediastinal
lymph node involvement.
Figure 61 - Mediastinal metastatic tumour
The left hilum is enlarged by a round mass which was proved to be a metastases from a stomach
tumour.
Benign disorders involving mediastinal
coccidioidomycosis, and primary tuberculosis.
nodes
include
sarcoidosis,
histoplasmosis,
 Congenital cysts account for about 20% of mediastinal masses. Most are discovered incidentally
on routine chest radiographs in asymptomatic individuals and are confirmed to be cystic on a CT scan.
- Pericardial cysts are the most common congenital cysts of the mediastinum. They are usually
solitary and are seen in the right cardiophrenic angle. CT and ultrasonography are useful in the
diagnosis. Surgical excision is usually performed.
- Bronchogenic cysts occur in the lung or mediastinum. In the adult they are usually asymptomatic,
whereas in children they may cause tracheobronchial compression with cough, stridor, wheezing,
dyspnea and occasionally atelectasis. Cysts sometimes become infected and produce a mediastinal
abscess. Surgical removal of the cyst is indicated.
Posterior mediastinal tumors
Neurogenic tumors, the most common posterior mediastinal tumors, include all benign and
malignant masses arising from the intercostal nerves, sympathetic ganglia, and chemoreceptor cells. In
adults, most are asymptomatic and benign, whereas in children, 50% are symptomatic and malignant.
The neural tumors are differentiated in neurofibroma, ganglioneuroma, neuroblastoma,
pheochromocytoma. Radiographically, neurogenic tumors are rounded, homogeneous and well
circumscribed and are seen in the paravertebral sulcus. About one third of these neural tumors become
malignant; therefore all should be excised.
14.4.2. PNEUMOMEDIASTINUM
Pneumomediastinum is the presence of gas in the interstices of the mediastinum. It can occur
spontaneously, from trauma, or from dissection of air from the neck or retroperitoneal space.
 Spontaneous pneumomediastinum In the absence of an obvious cause, pneumomediastinum is
said to be spontaneous. Air leaks from alveoli into the interstitium of the lung and then into the
perivascular sheaths, the hilar regions, and subsequently the mediastinum. The condition may be
precipitated by a sudden rise in intrathoracic pressure during coughing or after a Valsalva maneuver.
In adults, this condition can occur in young, otherwise healthy individuals, or it may be associated
with asthma, pneumonia, bronchitis, emphysema or pulmonary fibrosis and it may be a complication of
positive-pressure ventilator therapy. The air may spread from the mediastinum to the subcutaneous
tissues of the neck or axilla, producing subcutaneous emphysema; and it may leak into the pleural space,
producing pneumothorax.
Patients with spontaneous pneumomediastinum may be asymptomatic or have retrosternal chest
pain and dyspnea. The diagnosis is usually made by radiography. A thin line of air is seen along the
border of the mediastinum; sometimes this line of air is more clearly seen on the lateral chest film.
Most patients with spontaneous pneumomediastinum do not require specific therapy but, if
occasionally severe symptoms develop, decompression is indicated by either needle aspiration or
mediastinotomy.
 Traumatic pneumomediastinum is most commonly caused by the rupture of esophagus, which
can occur during an episode of severe vomiting or rarely, after esophageal instrumentation. Rupture of
the esophagus is usually associated with severe, chest pain and may be complicated by acute
mediastinitis.
Traumatic pneumomediastinum can also occur after penetrating wounds of the chest or after
fracture of the trachea or main bronchus after a trauma to the chest. Traumatic pneumomediastinum
requires thoracotomy, with repair of the esophagus or tracheobronchial tree.
14.4.3. MEDIASTINITIS
 Acute mediastinitis is usually the result of introduction of germs into the mediastinum after
perforation of the esophagus. The diagnosis should be suspected when substernal pain, fever and
radiographic evidence of mediastinal air develop after a bout of vomiting or instrumentation. This
setting represents an emergency requiring antibiotic therapy directed at gram-positive, gram-negative,
and anaerobic organisms as well as early surgical drainage and repair.
 Chronic mediastinitis is a condition of unknown cause that produces fibrosis in the mediastinum,
with compression and restriction of vascular structures entering and leaving the mediastinum. It was
previously thought that tuberculosis was the chief cause of chronic fibrosing mediastinitis, but other
granulomatous diseases, particularly histoplasmosis, may also cause this syndrome. The initial infection
may precede the chronic condition by months or years. Symptoms are nonspecific and include chest
pain, superior vena caval obstruction and bronchial obstruction with distal infection and cough.
Full evaluation of the patient includes bronchoscopy and ventilation-perfusion lung scans, in
addition to skin testing for tuberculosis. Treatment is very limited once vascular obstruction has
developed.