The Mediastinum

The Mediastinum

1. Anatomy
A. Compartments
1) Mediastinal borders: thoracic inlet (superior), diaphragm (inferior), sternum (anterior), spine (posterior), pleura (lateral)
2) Anterosuperior compartment is anterior to pericardium
3) Contents include thymus and great vessels
4) Middle, or visceral, compartment is between anterior and posterior pericardial reflections
5) Contents include heart, phrenic nerves, tracheal bifurcation, major bronchi, lymph nodes
6) Posterior, or paravertebral, compartment is posterior to posterior pericardial reflection
7) Contents include esophagus, vagus nerves, sympathetic chains, thoracic duct, descending aorta, and azygos/hemiazygos

2. Mediastinal Conditions
A. Mediastinal Emphysema
1) Introduction of air from esophagus, tracheobronchial tree, neck, or abdomen
2) Causes include penetrating or blunt trauma, or spontaneous mediastinal emphysema
3) Presents as substernal chest pain, crepitation, and pericardial crunching sound
4) May result in tamponade
5) Treat underlying cause; may require chest tube placement for pneumothorax
B. Mediastinitis
1) Occurs in about 1% of patients after median sternotomy
2) Risk factors include prolonged surgery or CPB, re-exploration, wound dehiscence, shock, and use of bilateral internal mammary artery grafts in patients who are older or have diabetes
3) Presents as fever, elevated WBC, and tachycardia
4) Best treatment results with wound debridement and tissue flaps
C. Mediastinal Hemorrhage
1) Caused by trauma, aortic dissection, aneurysm rupture, or surgical procedures
2) May result in mediastinal tamponade, which is more insidious than pericardial tamponade
3) Meticulous hemostasis and adequate chest tube drainage will prevent this syndrome
4) Spontaneous mediastinal hemorrhage can result from mediastinal masses, altered coagulation status, and severe hypertension
D. Superior Vena Cava Obstruction
1) Acute and chronic syndromes occur
2) See CTSN lecture on SVC Syndrome

MEDIASTINAL TUMORS

1. Location

1) Lesions are predictable to some degree predictable
2) Most common tumors are neurogenic (20%), thymomas (20%), primary cysts (20%), lymphomas (13%), and germ-cell tumors (10%)
3) Most are located in anterosuperior compartment (54%), followed by posterior (26%) and middle (20%) tumors

Tumors and Cysts by Location
Anterior Middle Posterior
Thymoma Enterogenous cyst Neurogenic origin
Germ cell tumor Mesothelial cyst Neurenteric cyst
Lymphoma Lymphoma Lymphoma
Hemangioma Thoracic duct cyst
Parathyroid adenoma Granuloma
Thymic cyst Hamartoma
Lipoma
Aberrant thyroid
Lymphangioma

4) A significant portion (25-40%) of mediastinal tumors are malignant
5) Anterosuperior tumors are more likely to be malignant, as are tumors of patients between the ages of 10 and 40
6) Neurogenic tumors and non-Hodgkin's lymphomas are the most common tumors in children

2. Clinical Presentation

1) About two-thirds of patients will have symptoms at the time of diagnosis
2) The absence of symptoms is a reasonably good indicator that a diagnosed tumor is benign
3) Most common symptoms include chest pain, cough, and fever
4) Signs of mechanical compression or invasion of mediastinal structures are more common with malignant tumors
5) Paraneoplastic syndromes are not uncommon and include Cushing's syndrome, thyrotoxicosis, hypertension, hypercalcemia, hypoglycemia, diarrhea, and gynecomastia

3. Diagnosis
A. CXR will localize the tumor and give information on calcification and relative density of the tumor
B. CT scanning identifies chest wall invasion, multiple masses, and extension into spinal column
C. MRI is more accurate for vascular involvement and intracardiac pathology
D. Echocardiography is useful for patients with middle compartment tumors to localize between intracardiac and pericardial tumors
E. Guided needle biopsy can make a diagnosis of malignancy in 80-90% of patients
F. Mediastinoscopy/mediastinotomy may be necessary to make a diagnosis and establish resectability

4. Thymoma
A. Features
1) Represents 20% of all mediastinal masses in adults
2) Peak incidence is in 3rd to 5th decades of life; rare in children
3) About half are of mixed cell type, followed by epithelial (28%) and lymphocytic (20%) types
4) Between 15 and 65% of thymomas are benign
5) Frequently associated with paraneoplastic syndrome, most commonly myasthenia gravis
6) Myasthenia gravis is diagnosed in 30-50% of patients with a thymoma, and 15% of myasthenia patients will have a thymoma
7) Autoimmune reaction directed against the postsynaptic nicotinic receptors results in skeletal muscle fatigability and weakness, especially in axial muscles
B. Operative Technique
1) Remove all anterior mediastinal tissue and any invasive disease, including involved lung, pleura, pericardium, and SVC/innominate vein
2) Thymic blood supply arises from the internal mammary arteries
3) Patients with stage IIa or higher disease should receive postoperative radiation
4) Chemotherapy is indicated for stage III or IV disease
5) Debulking may be appropriate for stage IV disease, although there is no evidence for increased survival · At 5 years after resection, 25-30% of patients will have complete resolution of myasthenia symptoms and 30-50% will be improved
6) Prognosis is dependent on stage of tumor, not on presence of myasthenia gravis

5. Thymic Carcinoid
A. Most occur in males and about two-thirds are symptomatic
B. Originate from Kulchitsky cells in the thymus, but are not associated with myasthenia gravis or the carcinoid syndrome
C. May cause other paraneoplastic syndromes, however, most commonly Cushing's syndrome (33%)
D. Presence of such syndromes is a very poor prognostic factor
E. Up to 75% will develop local recurrence or metastases
F. Low overall cure rate and mean survival is 3 years

6. Lymphoma
A. Between 40 and 70% of lymphoma patients will have mediastinal involvement during their disease course
B. Only 5-10% of lymphoma patients will have isolated mediastinal disease, and are usually symptomatic
C. Characteristic Hodgkin's lymphoma symptoms are chest pain after alcohol consumption and cyclic Pel-Ebstein fevers
D. Nodular sclerosing and lymphocyte predominance forms of Hodgkin's lymphoma are the most common to cause mediastinal involvement
E. Up to 40% of patients with lymphoblastic non-Hodgkin's lymphoma will have mediastinal disease
F. Surgery is indicated if fine-needle aspiration is inconclusive or to evaluate residual mass after chemotherapy
G. Surgical options include cervical mediastinoscopy, parasternal mediastinotomy, and thoracoscopy

7. Germ Cell Tumors
A. Comprise 15-25% of anterior mediastinal masses
B. Most common in children and young adults
C. Includes teratomas, teratocarcinomas, seminomas, embryonal cell carcinomas, choriocarcinomas, and endodermal cell or yolk-sac tumors
D. Identical to germ cell tumors originating in the gonads, but are not metastatic lesions from primary gonadal tumors
E. About 60% are benign and 40% are malignant
F. Predominantly Benign Tumors
1) Teratomas are complex, multiple tissue element tumors
2) Symptoms are related to mechanical effects
3) Simplest form is the dermoid cyst, which consists of mostly dermal and epidermal tissue
4) More complex teratomas may have well-differentiated bone, cartilage, nerve, or glandular tissue
5) Malignant tumors are differentiated upon histologic identification of embryonic tissue
G. Malignant Tumors
1) Male predominance and most patients are symptomatic
2) 40% are seminomas and 60% are nonseminomas (embryonal cell, choriocarcinoma, yolk-sac, and teratocarcinoma)
Seminomas Non-seminomas
AFP/B-HCG rare 90%
Associated syndromes none Klinefelter's, trisomy 8, 5q deletion
Radiosensitivity High Insensitive
Metastatic behavior Remain intrathoracic Frequently disseminated
Treatment Radiation Cis-platinum chemotherapy
Remission Over 80% CR in 55-60%, PR in 30-35%
5-year survival 50-80% 50-60%
Remission CR=complete PR=partial

3) Initial surgical intervention typically only for diagnosis due to high radiosensitivity of seminomas and frequent metastatic disease in non-seminomas
4) Surgical resection after induction of chemotherapy may have a role in non-seminomatous tumors

8. Endocrine Tumors
A. Intrathoracic Thryoid
1) 80% are substernal extensions of a cervical goiter
2) True intrathoracic thyroid (derives blood supply from thoracic vessels) comprises only 1% of all mediastinal tumors
3) More common in women and in the 6th to 7th decades, most are adenomas
4) Usually presents with tracheal or esophageal compression; thyrotoxicosis is uncommon
5) I-131 scanning should be done to identify presence of functioning cervical thyroid tissue before resecting these tumors
6) Resect substernal extensions through a cervical incision and true intrathoracic lesions through the chest
B. Parathyroid
1) Most are adenomas and are found by the superior pole of the thymus due to common embryogenesis from the third branchial cleft
2) Symptoms are usually due to hyperparathyroid syndrome
3) Parathyroid cysts are not usually hormonally active

9. Primary Cysts
A. Bronchogenic Cysts
1) Most common primary cysts in the mediastinum (5%)
2) Arise from ventral foregut and are usually located in the subcarinal or right paratracheal region/a>
3) Two-thirds are asymptomatic; symptoms include tracheobronchial or esophageal compression and infection from tracheobronchial communication
4) Complete excision is recommended, even if asymptomatic, to prevent late complications
B. Esophageal/Enteric Cysts
1) Comprise 3-5% of mediastinal tumors
2) More common in children and tend to occur in the lower third of the esophagus
3) Dysphagia is the most common symptom
4) CT scanning is essential in patients with vertebral anomalies to evaluate for possible spinal cord involvement (neuroenteric cyst)
5) Avoid endoscopic biopsy, as this may cause cyst perforation and infection
6) Complete excision is indicated; a thoracoscopic approach can be used for uninfected cysts
C. Pleuropericardial Cysts
1) Uncommon, classically occur at the pericardiophrenic angles, 70-80% on the right side
2) Usually asymptomatic and may communicate with the pericardium
3) Guided needle aspiration is the initial therapy of choice
4) Surgical excision is indicated if the cyst recurs or if the diagnosis is in doubt

10. Neurogenic Tumors
A. Etiology and Diagnosis · Most posterior mediastinal masses are of neurogenic origin
1) 95% of these tumors in adults are benign and are usually asymptomatic
2) In children, most neurogenic tumors are malignant
3) Classified according to cell origin; most arise from intercostal nerve or sympathetic chain
Intercostal nerve Sympathetic ganglia Paraganglia cells
Neurofibroma Ganglioma Paraganglioma
Neurilemoma Ganglioneuroblastoma (pheochromocytoma)
Neurofibrosarcoma Neuroblastoma

4) Neurilemomas are the most common and originate from Schwann's cells
5) These are encapsulated tumors which stain with S-100 protein immunostain
6) Two primary types: Antoni A (organized pallisading pattern) and Antoni B (loose reticular pattern)
7) Neurofibromas originate from peripheral nerve
8) Form a pseudocapsule and have more variability with the S-100 stain
9) Both types of tumors are associated with von Recklinghausen's disease, although more commonly neurofibromas
10) Chest CT is sufficient for diagnosis of most of these tumors, and MRI should be used when an intraspinal component is present

B. Operative Indications
1) Benign tumors (neurofibroma, neurilemoma, ganglioneuroma) can be effectively treated with local excision
2) Combined thoracic and neurosurgical approach is indicated for tumors with intraspinal extension
3) Recurrence is rare for benign tumors
4) Local recurrence is common for malignant tumors and overall prognosis is poor