CAUSES OF AN ANTEROSUPERIOR MEDIASTINAL MASS

T: thymus-see primary tumours of the thymus

o rare, they are the most common causes of a neoplasm of the anterosuperior mediastinum
o thymoma (staging)
one-third are benign
two-thirds are malignant
invasive thymoma (most)
thymic carcinoma (rare)
o thymolipoma/thymoliposarcoma
o thymic cyst
congenital (contains thymic tissue in wall)
secondary to thoracotomy
following chemotherapy or radiotherapy for mediastinal tumours
inflammatory
o benign thymic hyperplasia
o thymic carcinoid
o primary thymic lymphoma
T: thyroid-see primary tumours of the thyroid
T: thoracic aorta-see causes of a dilated thoracic aorta
T: terrible lymphoma
o Lymphoma is a malignancy arising from lymphocytes or lymphoblasts. Lymphoma can be restricted to
the lymphatic system or can arise as extranodal disease. This, along with variable aggressiveness
results in a diverse imaging appearance.
o Lymphoma can present as nodal or extra-nodal disease. Hodgkins lymphoma and low-grade NHL
classically present as nodal disease, whereas high-grade NHL can present with complications from mass
effect such as superior vena cava obstruction, cauda equina syndrome, etc. Extra-nodal disease can
affect any organ.

o Lymphoma can often present with B symptoms (fever, night sweats and weight loss).

o Risk factors include:

viral infection, e.g. EBV, HTVL-1, HIV, HCV, HSV

bacterial infection, e.g. Helicobacter pylori
chronic immunosuppression, e.g. post-transplantation
prior chemotherapy (especially alkalising agents) and drug therapy, e.g. digox
T: teratoma and germ cell tumours-see mediastinal germ cell tumours
o Germ cell tumours are one of the causes of anterior mediastinal mass, and any of the germ cell
histologies may be identified. They can therefore be divided histologically into:
o seminoma
o non-seminomatous germ cell tumours (NSGCT)
embryonal cell carcinoma
choriocarcinoma
yolk sac tumour
teratoma: most common
mixed germ cell tumour
 Background
Superior vena cava syndrome (SVCS) is obstruction of blood flow through the superior vena cava (SVC). It is a medical
emergency and most often manifests in patients with a malignant disease process within the thorax. A patient with SVCS
requires immediate diagnostic evaluation and therapy.

William Hunter first described the syndrome in 1757 in a patient with syphilitic aortic aneurysm. [1] In 1954, Schechter reviewed
274 well-documented cases of SVCS reported in the literature; 40% of them were due to syphilitic aneurysms or
tuberculous mediastinitis.[2]

Since the early reports, these infections have gradually decreased as the primary cause of SVC obstruction. Lung cancer,
particularly adenocarcinoma, is now the underlying process in approximately 70% of patients with SVCS.[3, 4, 5] However, as many
as 40% of cases are attributable to nonmalignant causes

Pathophysiology
The SVC is the major drainage vessel for venous blood from the head, neck, upper extremities, and upper thorax. It is located in
the middle mediastinum and is surrounded by relatively rigid structures such as the sternum, trachea, right bronchus, aorta,
pulmonary artery, and the perihilar and paratracheal lymph nodes. It extends from the junction of the right and left innominate
veins to the right atrium, a distance of 6-8 cm. It is a thin-walled, low-pressure, vascular structure. This wall is easily compressed
as it traverses the right side of the mediastinum.[7]

Obstruction of the SVC may be caused by neoplastic invasion of the venous wall associated with intravascular thrombosis or,
more simply, by extrinsic pressure of a tumor mass against the relatively thin-walled SVC. Complete SVC obstruction is the
result of intravascular thrombosis in combination with extrinsic pressure. Incomplete SVC obstruction is more often secondary to
extrinsic pressure without thrombosis. Other causes include compression by intravascular arterial devices. The incidence is on
the rise, in line with the increased use of endovascular devices.[4]

An obstructed SVC initiates collateral venous return to the heart from the upper half of the body through four principal pathways.
The first and most important pathway is the azygous venous system, which includes the azygos vein, the hemiazygos vein, and
the connecting intercostal veins. The second pathway is the internal mammary venous system plus tributaries and secondary
communications to the superior and inferior epigastric veins. The long thoracic venous system, with its connections to the
femoral veins and vertebral veins, provides the third and fourth collateral routes, respectively.

Despite these collateral pathways, venous pressure is almost always elevated in the upper compartment if obstruction of the
SVC is present. Venous pressure as high as 200-500 cm H2 O has been recorded in patients with severe SVCS.

Etiology
More than 80% of cases of SVCS are caused by malignant mediastinal tumors.[8, 9, 10] Bronchogenic carcinomas account for 75-
80% of all these cases, with most of these being small-cell carcinomas.[3] Non-Hodgkin lymphoma (especially the large-cell type)
account for 10-15%. Causes of SVCS appear similar to the relative incidence of primary lung and mediastinal tumors. Rare
malignant diagnoses include Hodgkin disease, metastatic cancers,[11] primary leiomyosarcomas of the mediastinal vessels, and
plasmocytomas.[12, 13, 14]

Nonmalignant conditions that can cause SVCS include the following:

Mediastinal fibrosis
Vascular diseases, such as aortic aneurysm, vasculitis, and arteriovenous fistulas
Infections, such as histoplasmosis, tuberculosis, syphilis, and actinomycosis
Benign mediastinal tumors such as teratoma, cystic hygroma, thymoma, and dermoid cyst
Cardiac causes, such as pericarditis and atrial myxoma
Thrombosis related to the presence of central vein catheters

Age-, sex-, and race-related demographics

Malignant causes of SVCS are predominantly observed in individuals aged 40-60 years. Benign causes account for most of the
cases diagnosed in individuals aged 30-40 years. Obstruction of the SVC in the pediatric age group is rare and has a different
etiologic spectrum.

Malignant causes of SVCS are most commonly observed in males because of the high incidence of lung cancer in this
population. In contrast, cases related to benign causes show no sex-related differences in frequency.

The frequency of SVCS in different races depends largely on the frequency of lung cancer and lymphomas in these populations.
 History
Early in the clinical course of superior vena cava syndrome (SVCS), partial obstruction of the superior vena cava (SVC) may be
asymptomatic, but more often, minor symptoms and signs are overlooked.

As the syndrome advances toward total SVC obstruction, the classic symptoms and signs become more obvious. Dyspnea is
the most common symptom, observed in 63% of patients with SVCS.[7, 20] Other symptoms include facial swelling, head
fullness, cough, arm swelling, chest pain, dysphagia, orthopnea, distorted vision, hoarseness, stridor, headache, nasal
stuffiness, nausea, pleural effusions, and light-headedness

Physical Examination
The characteristic physical findings of SVCS include venous distention of the neck and chest wall, facial edema, upper extremity
edema, mental changes, plethora, cyanosis, papilledema, stupor, and even coma. Bending forward or lying down may
aggravate the symptoms and signs.

Following are frequent symptoms:

Dyspnea[3]
Headache[3]
Facial edema[3]
Venous distention in the neck and distended veins in the upper chest and arms[3]
Upper limb edema[3]
Lightheadedness[2]
Cough[2]
Edema of the neck, called the collar of Stokes[4]

Pemberton's sign- Pemberton's sign was named after Dr. Hugh Pemberton, who characterized it in 1946.[1]

The Pemberton maneuver is a physical examination tool used to demonstrate the presence of latent pressure in the
thoracic inlet.[2] The maneuver is achieved by having the patient elevate both arms until they touch the sides of the
face. A positive Pemberton's sign is marked by the presence of facial congestion and cyanosis, as well as
respiratory distress after approximately one minute

Complications
Complications of SVCS may include the following:

Laryngeal edema
Cerebral edema
Decreased cardiac output with hypotension
Pulmonary embolism (when an associated thrombus is present)
Differential Diagnoses
Bacterial Pneumonia

Cardiac Tamponade

Chronic Obstructive Pulmonary Disease (COPD)

Fungal Pneumonia

Imaging in Acute Respiratory Distress Syndrome

Mediastinitis

Syphilis

Thoracic Aortic Aneurysm

 Tuberculosis

Viral Pneumonia Imaging

Imaging Studies
Patients presenting with overt superior vena cava syndrome (SVCS) may be diagnosed by means of physical examination
alone. However, subtle presentations necessitate diagnostic imaging.

Chest radiography
Chest radiography may reveal a widened mediastinum or a mass in the right side of the chest. Only 16% of the patients studied
by Parish et al in 1981 had normal findings on chest radiography.[15]

Computed tomography
Computed tomography (CT) has the advantage of providing more accurate information on the location of the obstruction and
may guide attempts at biopsy by mediastinoscopy, bronchoscopy, or percutaneous fine-needle aspiration.[7] It also provides
information on other critical structures, such as the bronchi and the vocal cords.

A CT scan of the chest is the initial test of choice to determine whether an obstruction is due to external compression or due to
thrombosis. The additional information is necessary because the involvement of these structures requires prompt action for relief
of pressure. (See the images below.)

SPECT

Gallium single-proton emission CT (SPECT) may be of value in select cases.

Magnetic resonance imaging

Magnetic resonance imaging (MRI) has not yet been sufficiently investigated in this setting, but it appears promising. It has
several potential advantages over CT, in that it provides images in several planes of view, allows direct visualization of blood
flow, and does not require iodinated contrast material (an especially important characteristic when stenting is anticipated). [16]

MRI is an acceptable alternative for patients with renal failure or those with contrast allergies. Potential disadvantages include
increased scanning time with attendant problems in patient compliance and increased cost.

Venography
Invasive contrast venography is the most conclusive diagnostic tool (see the image below). It precisely defines the etiology of
obstruction. It is especially important if surgical management is being considered for the obstructed vena cava.

Radionuclide technetium-99m venography is an alternative minimally invasive method of imaging the venous system.
Although images obtained by this method are not as well defined as those achieved with contrast venography, they
demonstrate potency and flow patterns.[22]

Procedures
Most patients with SVCS present before the primary diagnosis is established. Controversy often arises in the treatment of these
patients with regard to the need for pathologic confirmation of malignancy before the start of therapy. Treatment without an
established diagnosis should be initiated only in patients with rapidly progressive symptoms or those in whom multiple attempts
to obtain a tissue diagnosis have been unsuccessful.

Fortunately, relatively noninvasive measures establish the diagnosis in a high percentage of patients with SVCS. Sputum
cytologic results are diagnostic in 68% of the cases, whereas biopsy of a palpable supraclavicular node is positive in
87%.[23] Bronchoscopy has a 60% success rate, whereas thoracotomy is 100% successful.[23] Open biopsy is rarely needed for
diagnosis. Dosios et al showed that cervical mediastinoscopy and anterior mediastinoscopy are effective in establishing a
histologic diagnosis.

Medical Care
In the management of superior vena cava syndrome (SVCS), the goals are to relieve symptoms and to attempt cure of the
primary malignant process. Only a small percentage of patients with rapid-onset obstruction of the superior vena cava (SVC) are
at risk for life-threatening complications.[13]

Patients with clinical SVCS often gain significant symptomatic improvement from conservative treatment measures, including
elevation of the head of the bed and supplemental oxygen.[23] Emergency treatment is indicated when brain edema, decreased
cardiac output, or upper airway edema is present. Corticosteroids and diuretics are often used to relieve laryngeal or cerebral
edema, although documentation of their efficacy is questionable.

Radiotherapy has been advocated as a standard treatment for most patients with SVCS. It is used as the initial treatment if a
histologic diagnosis cannot be established and the clinical status of the patient is deteriorating; however, reviews suggest that
SVC obstruction alone rarely represents an absolute emergency that necessitates treatment without a specific diagnosis. [3, 25]

The fractionation schedule for radiotherapy usually includes two to four large initial fractions of 3-4 Gy, followed by daily delivery
of conventional fractions of 1.5-2 Gy, up to a total dose of 30-50 Gy. The radiation dose depends on tumor size and
radioresponsiveness. The radiation portal should include a 2-cm margin around the tumor.

During irradiation, patients improve clinically before objective signs of tumor shrinkage are evident on chest radiography.
Radiation therapy palliates SVC obstruction in 70% of patients with lung carcinoma and in more than 95% of those with
lymphoma.

In patients with SVCS secondary to nonsmall-cell carcinoma of the lung, radiotherapy is the primary treatment. The likelihood
of patients benefiting from such therapy is high, but the overall prognosis of these patients is poor.[26]

Chemotherapy may be preferable to radiation for patients with chemosensitive tumors.[26] In 1983, Maddox et al reported on 56
patients with small-cell lung cancer who presented with SVCS. Correction of SVCS was obtained in 9 (56%) of 16 patients
treated with radiation therapy alone, in 23 (100%) of 23 given chemotherapy, and in 5 (83%) of 6 who received combined
therapy.[27]

The most extensive experience with management of SVCS secondary to non-Hodgkin lymphoma is reported from the M.D.
Anderson Cancer Center. Patients were treated with chemotherapy alone, chemotherapy combined with radiation therapy, or
radiation therapy alone.[28] All patients achieved complete relief of SVCS symptoms within 2 weeks of the institution of any type of
treatment. No treatment modality appeared to be superior in achieving clinical improvement.

When SVCS is due to thrombus around a central venous catheter, patients may be treated with thrombolytics (eg, streptokinase,
urokinase, or recombinant tissue-type plasminogen activator) or anticoagulants (eg, heparin or oral anticoagulants). Removal of
the catheter, if possible, is another option, and it should be combined with anticoagulation to prevent embolization. [7, 17] . These
agents are most effective when patients are treated within 5 days after the onset of symptoms.

In a 1988 report, Adelstein et al discussed prophylaxis against embolic events in the presence of SVC obstruction in the
management of 25 patients with malignant SVCS.[29] Ten patients were retrospectively reviewed after having been diagnosed
clinically without venography and treated without anticoagulation. Five thromboembolic complications occurred, two of which
proved fatal.

Fifteen patients were prospectively evaluated by means of angiography and then treated with anticoagulants. [29] Angiographic
evidence of intraluminal subclavian vein or SVC thrombosis was found in five of these patients, and no thromboembolic
complications occurred. Of the 20 patients who were ultimately given anticoagulation therapy, two had fatal intracranial
hemorrhages. The authors suggested that randomized prospective trials would be needed to determine the roles of venography
and anticoagulation in the management of SVCS.

Admit the patient to the hospital if symptoms of SVCS are moderate to severe or if a patient requires the administration of
thrombolytic therapy or anticoagulation. Transfer may be required for further diagnostic evaluation and surgical intervention.

Oxygen supplementation may be provided if needed. Antiemetics may be provided as needed to prevent nausea and vomiting. If
a patient has been started on steroids, the steroids should be tapered slowly, depending on the patient's condition.

Surgical Care
Surgical bypass
Surgical bypass of the SVC may be a useful way to palliate symptoms in carefully selected patients with SVCS. Indications for
proceeding with such procedures are not fully clear. For the most part, these are patients with advanced intrathoracic disease
amenable only to palliative therapy (ie, after failure of radiation therapy and chemotherapy). Patients with benign disease appear
to be the best candidates for bypass.[30, 31]

Stenting
The principal options for endovascular therapy today are stenting, percutaneous transluminal angioplasty (PTA), thrombolysis,
or some combination thereof. In most patients with SVCS, stenting of the SVC provides rapid symptomatic relief within few days
(see the images below).
Corticosteroids
Class Summary
These agents reduce swelling in patients with cerebral or laryngeal edema.

Dexamethasone (Decadron, Dexasone)

Important therapeutic agent in a number of malignant diseases. Exerts biologic action predominately by binding to glucocorticoid
receptor. For symptomatic management in tumor-associated edema.

Thrombolytics
Class Summary
The potential benefits of thrombolytics for the treatment of pulmonary embolism include fast dissolution of physiologically
compromising pulmonary emboli, quickened recovery, prevention of recurrent thrombus formation, and rapid restoration of
hemodynamic disturbances. For deep vein thrombosis, lysis of the thrombus can prevent pulmonary embolism and permanent
pathologic changes, such as venous valvular dysfunction and postphlebitic syndrome.

Urokinase (Abbokinase)

Converts plasminogen to plasmin, which degrades fibrin clots, fibrinogen, and other plasma proteins.

Anticoagulants
Class Summary
In superior vena cava syndrome (SVCS), these agents are used mainly to prevent pulmonary embolism from superior vena cava
(SVC) thrombus.

Heparin

Inhibits thrombosis by inactivating activated factor X and inhibiting conversion of prothrombin to thrombin.

Warfarin (Coumadin)

Inhibits synthesis of vitamin Kdependent coagulation factors (factors II, VII, IX, X).