A distinct entity only by their anatomical location, mediastinal tumours comprise a variety of cysts and primary neoplasms. Correct diagnosis and treatment require accurate radiological assessment, an understanding of the natural course of these tumours, and an established plan for evaluation and treatment. Since resection is not always the appropriate form of therapy for this diverse group of tumours, the principal goals of surgical involvement need to be stated clearly. (1) Is complete resection necessary or will biopsy without thoracotomy be more appropriate? (2) What approach should be used to accomplish the surgical procedure? (3) How will radiation therapy or chemotherapy alter the surgical management?

The boundaries of the mediastinum are the thoracic inlet superiorly, the diaphragm inferiorly, and laterally the medial surfaces of the parietal pleura. Three arbitrary compartments within this space have been defined (Fig. 1) 1967. The anterosuperior compartment is bounded by the sternum anteriorly and the anterior surface of the pericardium posteriorly. The middle or visceral compartment encompasses the space occupied by the heart, great vessels, trachea, main bronchi, and oesophagus. The posterior compartment contains the prevertebral space and the paravertebral gutters. A separate superior compartment is occasionally defined as extending between the angle of Louis and the fourth vertebra to the thoracic inlet.

This compartmentation is useful because most lesions occur only or predominantly in one of these regions. Table 1 538 lists the typical location of common mediastinal tumours and cysts. Thymomas, lymphomas, and germ cell tumours are most common in the anterior compartment, cysts predominate in the visceral space, and neurogenic tumours and cysts occur with equal frequency in the posterior compartment. A recent study of 400 consecutive patients found the anterosuperior mediastinum the site of cysts and neoplasms in 54 per cent of patients, the posterior mediastinum in 26 per cent, and the middle compartment in 20 per cent.

Localization is primarily accomplished with radiological tests. In addition to standard chest films, computed tomography (CT) is routinely performed to give precise information about anatomical relationships. CT is used to assess whether the mass is homogenous or consists of multiple enlarged lymph nodes. In planning treatment and operative approach, the answer to two questions is of critical importance and may require additional studies.

CT with bolus injection of contrast may often avoid angiography by excluding aneurysms and vascular tumours. Angiography may be necessary to define arch vessel involvement, the feeding vessel of a paraganglioma, sequestration, or a mediastinal vascular malformation. The origin of the spinal blood supply, the artery of Adamkiewicz, should be angiographically demonstrated in paravertebral tumours involving the lower thoracic spine.

Approximately 10 per cent of all benign nerve sheath tumours cause extradural compression of the spinal cord due to extension of the tumour through the intervertebral foramen into the spinal canal. Because such dumb-bell-shaped tumours require a combined thoracic and neurosurgical approach for safe one-stage resection, preoperative evaluation of tumour extent with CT, linear tomography, myelography, or magnetic resonance imaging (MRI) is important. The three advantages associated with MRI are absence of X-ray exposure, no need for intravenous or intraspinal contrast, and the availability of sagittal cuts through the chest that provide further information about the mass. MRI and ultrasound may help to identify the cystic nature of mediastinal tumours. Venograms are occasionally useful to assess patency of the innominate vein or the superior vena cava. Fluoroscopy of the diaphragm allows functional evaluation of the phrenic nerve.

Various polypeptides, hormones, and enzymes occur in association with mediastinal tumours. For the purpose of this discussion, remarks are restricted to serological markers of non-seminomatous malignant germ cell tumours.

Human chorionic gonadotropin (hCG) is a glycoprotein with a molecular weight of 45000 and consists of &agr;- and &bgr;-subunits. The &bgr;-chain is unique to hCG. In the normal placenta, hCG is produced by the syncytiotrophoblast and maintains the corpus luteum during early pregnancy. The oncological usefulness of &bgr;-hCG as a tumour marker is derived from its association with choriocarcinoma and, less often, embryonal carcinoma, yolk sac tumour, and seminoma.

Alpha-fetoprotein is a glycoprotein with a molecular weight of 64000 that occurs in liver, gastrointestinal tract, and yolk sac of the normal fetus. Alpha-fetoprotein decreases to adult levels by 1 year of age. This tumour marker is increased in the serum of patients with hepatocellular cancer, embryonal carcinomas, and yolk sac tumours.

Immunohistochemical staining and localization of &bgr;-hCG and alpha-fetoprotein in tumour can be employed to diagnose specific germ cell tumours.

Well over 90 per cent of patients with non-seminomatous germ cell tumours are marker-positive for either &bgr;-hCG or alpha-fetoprotein. These two markers not only help in the diagnosis of germ cell tumours, but allow also monitoring of chemo- and radiotherapy. Return of marker levels to normal during chemotherapy before resection is a favourable prognostic factor. Elevated levels are a reliable indicator of viable tumour.

For some tumours, chemotherapy or radiotherapy are the primary modes of treatment. Tissue assessment by fine needle aspiration or mediastinoscopy avoids thoracotomy and reduces any delay of therapy. Specific tumours have characteristic findings on CT (multiple enlarged lymph nodes in lymphoma) or elevated serum tumour markers (non-seminomatous germ cell tumours) that are highly suggestive of the diagnosis. Considerable judgement is required in assessing a homogenous anterior mediastinal mass without obvious lymph node enlargement and negative serum markers. If thymoma is suspected and the tumour appears resectable, no further diagnostic evaluation is necessary prior to resection. Percutaneous aspiration for cytology should be reserved for patients with massive neoplasms suspected to be thymomas, in whom preoperative radiotherapy may make the lesion more amenable to resection.

Percutaneous fine needle aspiration under fluoroscopy or CT guidance provides a cytological aspirate of tumour. The risk to the patient is minimal and consists of the development of pneumothorax and haemorrhage from a vascular tumour. A limited amount of material is available for histological examination, making subtyping of lymphomas difficult. The primary role of mediastinoscopy lies in the evaluation of paratracheal and subcarinal lymphadenopathy. Biopsy examination of presumed mediastinal lymph nodes is performed only after mediastinoscopic needle aspiration to exclude the possibility of a vessel appearing as a lymph node. Anterior mediastinotomy, the Chamberlain procedure, offers access to the aortic window and the anterior mediastinum. The usefulness of thoracoscopy has not been established. This technique may provide access for visual inspection and biopsy examination through the pleural space.

Neoplasms of thymic origin account for approximately one-third to one-half of all tumours in the anterosuperior compartment and occur infrequently outside the mediastinum. Thymic cysts and hyperplasia are occasionally reported in children. Carcinoid tumours, thymic lymphoma, Hodgkin's disease, and thymic carcinoma are rare disorders. Thymomas, by far the most common thymic tumours, originate from thymic epithelial cells and are divided into four subgroups according to the mixture of epithelial cells and lymphocytes: (a) predominantly epithelial, (b) predominantly lymphocytic, (c) mixed lymphoepithelial, and (d) spindle cell variety, a subtype of epithelial thymoma. A recent classification separates cell types as cortical, medullary, or mixed on the basis of immunohistochemistry and light microscopy. While some data suggest improved prognosis for medullary and mixed cell types, the accuracy of this classification in predicting relapse and survival is not established.

Various autoimmune disorders are associated with thymoma. Myasthenia gravis is the syndrome most commonly encountered. Its clinical hallmark is an abnormal fatiguability of voluntary muscle groups due to the presence of circulating antibodies to the acetylcholine receptor at the neuromuscular junction. Symptoms respond to blockage of cholinesterase inactivation of acetylcholine. Medical treatment consists of oral administration of pyridostigmine bromide and, in severe cases, steroids. A thymoma is present in 10 per cent of patients with myasthenia gravis and thymic hyperplasia in 70 to 80 per cent. Conversely, myasthenia gravis is encountered in 30 to 40 per cent of patients with thymoma. Because of improvement in the management and the favourable effects of plasmapheresis in severe myasthenia, the presence of myasthenia in patients with thymoma is no longer considered an adverse factor in survival. Removal of the thymus gland results in a partial or complete remission of myasthenia gravis documented by a reduction or elimination of medication in 60 to 80 per cent of patients.

Thymic lesions are rare in children below age 16; peak incidence is between age 50 and 70. Symptoms are present in approximately half of all patients without neuromuscular syndromes. These are chest pain, cough, dyspnoea, respiratory infections, fever, and occasionally obstruction of the superior vena cava due to a large tumour. In asymptomatic patients, a chest film obtained for other reasons may demonstrate the anterior mediastinal mass.

In most patients, resection should be done without prior biopsy because of the risk of seeding the biopsy tract. Tumours confined to the thymus are best approached by median sternotomy to allow complete resection of the tumour and the gland. Careful preoperative evaluation of pulmonary function in patients with myasthenia gravis is mandatory. Plasmapheresis is used for patients with generalized myasthenia and respiratory weakness. Plasmapheresis is performed 1 week prior to surgery on alternating days for a total of three treatments. The patient should be weaned from steroids if possible and anticholinergic medications are discontinued on the evening before operation. Preoperative radiotherapy (3000 to 4000 Gy) followed by resection 2 or 3 weeks later may be indicated for extremely large tumours or those causing obstruction of the superior vena cava.

Every attempt should be made to excise the tumour and the entire gland with sufficient margin. Both pleural spaces are widely opened to assess extent of tumour, to identify both phrenic nerves, and to recognize any pleural metastasis. One phrenic nerve may be safely sacrificed if encased by tumour. Involved lung is resected in continuity, usually as a wedge with a linear stapler. If the pericardium is involved, it should be resected in continuity with the neoplasm. Involvement of the superior vena cava or its tributaries is removed by lateral resection or graft replacement.

Pathological staging of thymoma is determined by the extent of invasion (Table 2) 539. Although assessment by the surgeon at the time of operation is usually accurate, invasion of the capsule may not be recognized, and some stage II tumours may thus be understaged.

Survival after complete resection of stage I and II tumours is excellent and exceeds 90 per cent at 5 years. One recent study noted at 10 years a survival of 78 per cent for stage I and 74 per cent for stage II. Survival of patients with stage III disease including incompletely resected tumours is approximately 20 per cent at 10 years. Deaths from thymoma are rare in stage I. Half of all deaths within 10 years are due to thymoma, and almost half of all thymoma-related deaths occur 5 to 10 years after operation. Because of the relatively high incidence of mediastinal recurrence in patients with stage II and III disease (10 per cent), routine postoperative radiotherapy with 5000 Gy is recommended.

Tumours of the lymphatic system constitute almost half of all anterior mediastinal masses in childhood and one-quarter of mediastinal tumours in adults, with a predilection for the fourth decade of life. The mediastinum is rarely the only site of involvement. Both Hodgkin's disease and non-Hodgkin's lymphoma occur with similar frequency. Hodgkin's disease typically spreads from one lymph node region to another in a centripetal fashion. In the mediastinum, the nodular sclerosing cell type, associated with a more favourable prognosis, is more frequently encountered. Diffuse large cell or lymphoblastic lymphomas show a characteristic centrifugal spread and skip lymph node stations. For the diagnosis of both lymphatic tumours, lymph node biopsy is required rather than a cytological aspirate to determine cell type, and mediastinoscopy or a Chamberlain procedure are performed when peripheral lymph nodes are not involved.

While treatment of Hodgkin's disease with a small mediastinal mass may consist of radiotherapy alone, bulky Hodgkin's disease is usually treated with a combination of chemotherapy and irradiation. There is anecdotal evidence that resection of localized Hodgkin's disease confined to the thorax is beneficial. Prognosis, even in advanced stages, is favourable. Non-Hodgkin's lymphomas are currently treated in most institutions with combination chemotherapy. With high-dose chemotherapy, 55 to 85 per cent of patients achieve complete remission. Half of these patients will be disease-free after 2 years.

Germ cell tumours account for approximately 10 per cent of all mediastinal masses. A recent large series noted an equal proportion of benign and malignant teratomas, including seminomas and embryonal germ cell tumours. Germ cell tumours may occur at any age between childhood and fifth decade, but malignant germ cell tumours predominate in men between the age of 20 and 35. Malignant tumours give rise to symptoms including chest pain, cough, dyspnoea, fever, weight loss, or haemoptysis. The evaluation of young men with anterior mediastinal masses, should include determination of alpha-fetoprotein and &bgr;-hCG and exclusion of a testicular or abdominal mass.

Once the diagnosis is confirmed by biopsy examination, treatment with cisplatin-based chemotherapy is instituted for malignant non-seminomatous tumours. Some centres advocate treatment of anterior mediastinal tumours on the basis of positive serum tumour markers alone when biopsy is inconclusive to avoid the delay imposed by thoracotomy in these rapidly growing tumours. Resection is reserved for patients with residual mediastinal tumour after completion of chemotherapy. A 5-year survival rate of 61 per cent for patients responding to chemotherapy and less than 10 per cent for non-responders has been reported.

Patients with serum marker-negative mediastinal seminomas should undergo radiation after careful evaluation for metastatic disease. Small tumours can be resected, followed by postoperative radiotherapy. In the presence of metastatic disease, treatment with cisplatin-based chemotherapy has resulted in complete response and long-term survival in some patients. Approximately 60 per cent of patients with local mediastinal disease are cured. Relapse at distant sites occurs in the remaining patients.

In benign germ cell tumours, resection is usually curative.

Although neurogenic tumours may arise from any neural structure in the mediastinum, they are most commonly found in the paravertebral gutters of the posterior compartment. In this region, between 50 and 80 per cent of all tumours are of neurogenic origin. They derive mainly from two cellular components of neural tissue: autonomic ganglion and nerve sheath. Other tumours, including paragangliomas, phaeochromocytomas, and peripheral neuroectodermal tumours, occur with much less frequency.

They appear almost exclusively in children and adolescents. The three variants of this cell type display a decreasing degree of maturity. Ganglioneuroma is a benign lesion, while ganglioneuroblastoma and neuroblastoma are malignant. Neuroblastoma, the most immature type, occurs most frequently in children under the age of 3. Ganglioneuroblastoma is of intermediate malignancy and is typically seen in the older child. Both tumours share similar radiographical features of bone destruction and calcification. Most patients are symptomatic. Horner's syndrome, chest pain, cough, dyspnoea, dysphagia, and paraplegia due to cord compression may be noted. If tumours elaborate catecholamines, diarrhoea, sweating, and flushing can occur. In contrast, benign ganglioneuromas are usually asymptomatic and rarely produce catecholamines. They characteristically arise in older children or adolescents.

The goal of surgical therapy is complete resection. In the benign ganglioneuromas, this goal is easily accomplished, and the prognosis after resection is excellent. In the majority of neuroblastomas and some ganglioneuroblastomas, complete resection is often not possible. Postoperative radiotherapy to the tumour bed and adjuvant chemotherapy are added when resection is incomplete. Most neuroblastomas are advanced at the time of diagnosis and overall long-term survival is less than 30 per cent. The prognosis of thoracic neuroblastomas is better in younger patients under the age of 2 years, where it approaches 90 per cent. Survival rates in older children are less favourable.

Posterior mediastinal neurogenic tumours that extend into and through the intervertebral neural foramen have been termed ‘dumb-bell’ tumours (Fig. 2) 1968,1969. They should be resected in a single stage by a combined thoracic and neurosurgical approach. A staged operation that leaves part of the tumour in the spinal canal may result in uncontrolled bleeding and paraplegia. The operative approach for resection is depicted in Fig. 3 1970. After careful mobilization of the intrathoracic mass, a laminectomy is performed and the tumour is resected. If the dura is opened during the course of the operation, it is closed and covered with a pleural flap. The resection is done with direct visualization of the spinal cord to minimize the risk of neurological injury.

Less than 10 per cent of nerve sheath tumours are malignant. They occur predominantly in young adults. Women predominate. Of the two types of tumour, neurilemoma and neurofibroma, the former is the more common. Neurofibromas (schwannomas) are encapsulated and may present themselves with multiple lesions, particularly when associated with von Recklinghausen disease. Involvement of the intervertebral foramen is found more frequently than in autonomic ganglion tumours. Symptoms occur infrequently and may indicate a malignant variant. Treatment consists of enucleation of benign tumours and resection of non-encapsulated or malignant tumours with appropriate margin. Prognosis of the benign lesion is excellent, while few patients with malignant tumours survive beyond 1 year.

About one-quarter of all mediastinal masses are cysts. There are two types of foregut cysts: bronchogenic cysts, which arise from the tracheobronchial tree, and enteric duplication cysts, which are derived from the oesophagus. These two constitute the majority of intrathoracic cysts. Mesothelial cysts are of pericardial or pleural origin. The rare neuroenteric and gastroenteric cysts result from an embryological defect in development. Both are associated with abnormalities of the spinal column, and gastroenteric cysts may communicate with the infradiaphragmatic gastrointestinal tract.

Mediastinal cysts come to surgical attention either as an incidental finding on radiological studies of the chest or when they cause symptoms. In children, symptoms are typically due to mass effect in the small thorax, which can result in dyspnoea, stridor, respiratory distress, or dysphagia. Cysts can cause complications at any age because of infection, haemorrhage into the cyst, erosion into adjacent structures, or, in rare instances, malignant degeneration. Surgical resection is therefore indicated even in asymptomatic patients.

Davis RD Jr, Oldham HN Jr, Sabiston DC Jr. Primary cysts and neoplasms of the mediastinum: recent changes in clinical presentation, methods of diagnosis, management, and results. Ann Thoracic Surg 1987; 44: 229–37.

Gordon LI, Kies MS. Diagnosis and treatment of mediastinal lymphomas. In: Shields TW, ed. Mediastinal surgery. Philadelphia: Lea and Febiger, 1991: 198–204

Grillo HC, Ojemann RG, Scannell JG, Zervas NT. Combined approach to ‘dumbbell’ intrathoracic and intraspinal neurogenic tumours. Ann Thoracic Surg 1983; 36: 402–7.Mullen B, Richardson JD. Primary anterior mediastinal tumours in children and adults. Ann Thoracic Surg 1986; 42: 338–45.

Shields TW, Reynolds M. Neurogenic tumours of the thorax. Surg Clin N Am 1988; 68: 645–68.

Trastek VF. Management of mediastinal tumours. Ann Thoracic Surg 1987; 44: 227–8.

Wilkins EW Jr. Mediastinal tumour. In: Grillo HC, et al., eds. Current therapy in cardiothoracic surgery. Philadelphia: BC Decker, 1989: 122–5.

Wilkins EW Jr, Grillo HC, Scannell JG, Moncure AC, Mathisen DJ. Role of staging in prognosis and management of thymoma. Ann Thoracic Surg 1991; 51: 888–92.

Wright CD, et al. Primary mediastinal nonseminomatous germ cell tumour. Results of a multimodality approach. J Thoracic Cardiovasc Surg 1990; 99: 210–7.