Lesions within the mediastinum represent an interesting variety of masses, both malignant and benign, that arise from the diverse organs and tissues which occupy the central thorax. Overall, the incidence of all mediastinal masses is low, especially compared with the frequency of lesions arising within the lung—bronchogenic cancer, etc. Mediastinal malignancies constitute less than 20% of all thoracic tumors.
Mediastinal masses arise from specific structures that reside in relatively constant anatomic arrangement. The distribution and origin of mediastinal masses are summarized.
Distribution of Tumors and Mass Lesions in the Mediastinum
Complete resection is the treatment of choice for all neurogenic tumors. A standard posterolateral thoracotomy offers optimal exposure; however, more limited incisions, including thoracoscopy, can be effective for resection of clinically benign small (< 6 cm) lesions. For lesions that cannot be completely excised, postoperative radiation may decrease local recurrence and symptoms. Incompletely excised or especially large or infiltrative neuroblastomas should receive combination radiation and chemotherapy.
Although classically in adults the majority of mediastinal masses tend to be benign (cysts, neurogenic tumors, etc), recent series have demonstrated a shift toward malignant processes being more prevalent. Whether this represents a true change in tumor incidence or enhanced detection secondary to improved imaging techniques is unclear. Some general rules remain valid, however.
An extensive workup of a mediastinal lesion is not required for diagnosis since surgery is usually required both to establish the diagnosis and provide effective treatment. Standard posteroanterior and especially lateral chest films will often provide much useful information; however, contrast CT scanning has become the diagnostic test of choice. MRI, while helpful for assessing vascular extension, has not proved to be more effective than dynamic CT scanning.
Oblique or overpenetrating x-rays are sometimes helpful. Fluoroscopy may show pulsation or variation of shape or location with change of position and respiration. Tomography may reveal calcification or air-fluid levels. Barium swallow is used to evaluate intrinsic esophageal lesions or esophageal displacement by extrinsic masses. Contrast studies of the intestinal tract may reveal the stomach, colon, or small bowel in a hernia. Myelography can be of crucial importance in neurogenic tumors to explain symptoms or plan operative management. Computerized tomographic reconstructed images (virtual bronchography) may be useful to differentiate lung tumors mimicking a mediastinal mass.
CT angiography help to identify aneurysms or displacement. Pulmonary arteriography may be useful to distinguish mediastinal and pulmonary tumors.
Scintiscan is important in evaluating possible substernal goiter in anterior mediastinal lesions, since goiters can generally be removed by the standard cervical approach. Skin tests and serologic studies may be used in suspected granulomatous disease. Bone marrow examination, hormone assays, and serum tumor markers are important adjuncts.
Bronchoscopy and esophagoscopy are occasionally useful to identify primary lung lesions or lesions of the esophagus. Mediastinoscopy and mediastinal biopsy must be used cautiously in mediastinal tumors that are potentially curable. Excisional biopsy is imperative in lesions (eg, thymomas) that are histologically difficult to evaluate since a curable cancer might be dispersed. Mediastinoscopy is useful for the diagnosis of sarcoidosis, Castleman’s disease, or disseminated lymphoma.
When substernal goiter is excluded, neurogenic tumors constitute 26% of mediastinal masses, cysts 20%, teratodermoids 16,6%, thymomas 12,1%, lymphomas 12%, and all other lesions 12%. About 25% are malignant. In children, the incidence of cancer is about the same, but teratodermoids and vascular tumors are more common.
Symptoms are more frequent in malignant than benign lesions. Fifty percent of patients have respiratory symptoms such as cough, wheezing, dyspnea, and recurrent pneumonias. Hemoptysis and, rarely, expectoration of cyst contents may occur. Chest pain, weight loss, dysphagia are found with equal frequency. Myasthenia (15–20% with thymoma), fever, and superior vena caval obstruction are each found in about 5% of patients.
The following symptoms suggest cancer: hoarseness, Horner’s syndrome, severe pain, superior vena caval obstruction. Malignant tumors, especially lymphomas, may produce chylothorax. Fever may be intermittent in Hodgkin’s disease. Thymoma causes myasthenia, hypogammaglobulinemia, Whipple’s disease, red blood aplasia, and Cushing’s disease. Hypoglycemia is a rare complication of mesotheliomas, teratomas, and fibromas. Hypertension and diarrhea occur with pheochromocytoma and ganglioneuroma. Neurogenic tumors may produce specific neurologic findings from cord pressure or may be associated with hypertrophic osteoarthropathy and peptic ulcer disease.
Neurogenic tumors almost always occur in the posterior mediastinum. Rarely, the vagus or phrenic nerve is involved. The most common variety of tumors (40–65%) arises from the nerve sheath (schwannoma and neurofibroma) and is usually benign. Ten percent of neurogenic tumors are malignant. Malignant tumors occur more frequently in children. Most malignant tumors (neuroblastoma, etc) arise from the nerve cells. Neurogenic tumors may be multiple in type, with widening of the intervertebral foramen. In these cases, MRI is necessary to determine if the mass extends within the spinal canal. Dumbbell tumors have been removed in the past by a two-stage approach, though a single-stage approach is now extensively used.
Pheochromocytomas of the middle mediastinum can be localized using 123I metaiodobenzylguanidine.
Mediastinal Cystic Lesions
Cysts of the mediastinum may arise from the pericardium, bronchi, esophagus, thymus. Pericardial cysts are also called springwater or mesothelial cysts. Seventy-five percent are located near the cardiophrenic angles, and 75% of these are on the right side. Bronchogenic cysts arise close to the main stem bronchus or trachea, often just below the carina. Histologically, they contain elements found in bronchi, such as cartilage. Enterogenous cysts are known by several names, including esophageal cyst, enteric cyst, or duplication of the alimentary tract. They arise along the surface of the esophagus, may be embedded within its wall. They may be lined by squamous epithelium similar to the esophagus or gastric mucosa. Enterogenous cysts are occasionally associated with congenital abnormalities of the vertebrae. About 10% of cysts in the mediastinum are nonspecific, without a recognizable lining.
Germ Cell Tumors
They are common mass lesions of the anterior mediastinum. Historically, they are both solid and cystic, and the more differentiated ones may contain hair or teeth. Microscopically, ectodermal, endodermal, mesodermal elements are present. These tumors occasionally rupture into the pleural space, lung, pericardium, or vascular structures.
Most germ tumors of the mediastinum are metastatic and present with concomitant retroperitoneal disease. Primary cell malignancies are rare, representing less than 5% of all mediastinal germ cell cancers and less than 5% of all primary mediastinal tumors. Men—in particular white males in their twenties and thirties — are most commonly affected.
Because germ cells are pluripotent cells, they can give rise to several histologically distinct malignancies.
Almost all of these tumors (> 90%) produce tumor markers, including -hCG and AFP. LDH—a nonspecific tumor marker — is produced by most bulky mediastinal germ tumors and is often an effective indicator of tumor burden.
Much progress in treating these tumors has been made with combination therapy. Currently, over 50% 5-year survival is achievable for nonseminomatous and over 90% 5-year survival is typical for seminomatous mediastinal germ cancer. Patients should be screened and followed with AFP, -hCG, LDH markers. Surgical resection should be offered after combination chemotherapy has been administered and only after all elevated tumor markers have normalized.
Residual mediastinal masses following chemotherapy and normalization of tumor markers should be resected. At surgery, approximately 40% will be mature teratomas (with the potential for malignant degeneration), 40% necrotic tumors, and 20% residual tumors (requiring postoperative salvage chemotherapy). Rarely is palliative debulking surgery indicated if tumor markers remain elevated after several cycles of chemotherapy. Instead, alternative chemotherapy or investigational therapy should be offered.
Lymphoma is usually associated with disseminated disease metastatic to the mediastinum. It is typically identified in the anterior compartment but can present anywhere through the mediastinum. This is the second most common mass in the anterior mediastinum. Occasionally, lymphosarcoma, Hodgkin’s disease, or reticulum cell sarcoma arises as a primary mediastinal lesion.
Treatment of mediastinal mass lesions
Treatment is tailored to the specific disease process causing the mediastinal mass. In almost all cases, tissue diagnosis is imperative for guiding appropriate therapy. Minimally invasive techniques (FNA or core needle biopsy) or mediastinoscopy and mediastinotomy are appropriate for diagnosis of a mediastinal mass that is secondary to metastatic disease. Mediastinal masses, however, that represent primary malignancies (thymoma, neurogenic tumors, etc) are treated usually with initial surgical resection. Surgical approaches include median sternotomy (anterior masses), posterolateral thoracotomy (posterior and middle mediastinal masses) as well as VATS or bilateral anterior thoracotomy (all mediastinal compartments). Adjuvant chemotherapy is important for malignant germ lesions, malignant neurogenic tumors, and bulky or advanced thymomas. Postoperative radiation therapy decreases local recurrence in higher-stage thymoma and in other incompletely resected lesions. Radiation and chemotherapy constitutes the principal therapy for primary mediastinal lymphoma.
Overall, the outlook for patients with mediastinal masses has improved, with advances in combined chemotherapy and multimodality therapy. Surgical morbidity and mortality remain low (1–4%). Patients with benign mediastinal lesions do significantly better (> 95% cure rates) compared with those who have malignant mediastinal masses (< 50% overall survival).