The mediastinum is defined as the space between the lungs. It is bordered by the sternum anteriorly, the thoracic inlet superiorly, the diaphragm inferiorly, and the ribs (Fig. 155-1). Mediastinal masses arise from structures that normally reside in the mediastinum, as well as those that migrate through it during development. The mediastinum is compartmentalized into four major spaces based on anatomic landmarks. The superior mediastinum extends from the thoracic inlet to an imaginary line between the angle of Louis and the fourth thoracic vertebral body. The anterior mediastinum spans the back of the sternum to the front of the ascending aorta and pericardium. The posterior mediastinum is located between the posterior pericardium and the spine; this includes the costovertebral sulci. The middle mediastinum lies between the anterior and posterior mediastinal compartments. These divisions are not precise and become less defined as lesions invade or displace adjacent organs, leading to distorted anatomy. Nevertheless, they provide a framework to classify and understand mediastinal diseases. With knowledge of the patient’s age, location of the lesion, and presence or absence of sentinel signs and symptoms, a reasonable preoperative diagnosis often can be made.

Tumors and cysts occur in the mediastinum across all ages and consist of both benign and malignant entities (see Chapters 161–163). The location of the most frequent mediastinal masses differs by age. In children, the most common lesion is the neurogenic tumor in the posterior mediastinum, which accounts for about half of all mediastinal masses in the pediatric population. By contrast, the most frequent lesion in adults is thymoma in the anterior mediastinum. Posterior mediastinal lesions are less common in adults, whereas thymic lesions are rare in children. The trend is otherwise similar in adults and children, with lymphoma and germ cell tumor as the next most common mediastinal tumors, in order.^1–5

Most mediastinal masses are asymptomatic, but many can be associated with specific symptoms and signs. Symptoms depend on the size of the lesion, whether it is benign or malignant, and the presence or absence of infection. It is generally agreed that malignant lesions are more likely to be symptomatic than benign lesions.^5,6 Approximately 25% of all mediastinal tumors are malignant in both adults and children. Roughly two-thirds of children are symptomatic at presentation, whereas only one-third of adults have symptoms.^7,8 Most symptoms are related to mediastinal structures that have been either compressed or invaded by tumor. These consist of respiratory symptoms such as cough, stridor, hemoptysis, and dyspnea or pain related to invasion of the chest wall, pleura, or diaphragm.^5,8 Other symptoms and signs may include dysphagia, hoarseness, superior vena cava syndrome (see Chapter 164), pericardial tamponade, Horner syndrome, and reticular pain owing to extension into vertebral foramina.⁷

Imaging

Preoperative imaging such as chest x-ray and chest CT scanning with IV contrast material offers insight into the size, location, presence of calcifications, and tissue consistency of the lesion. Determination of fat, cystic, or soft tissue components may be obtained from chest CT and/or MRI scan.^9,10 In the initial workup, it is essential to establish that the lesion is truly mediastinal as opposed to being intraabdominal, as in the case of diaphragmatic hernias, or pseudomediastinal, as in a mass that arises as an anomaly of the vascular system (e.g., an aortic aneurysm). Chest CT scanning also provides essential information regarding the involvement of other organs, such as obstruction of the upper airways, presence of pleural or pericardial effusions or vascular encasement, or extension into the spinal canal.¹¹ It is also important to identify the presence of any pulmonary masses that suggest a primary malignancy or metastatic disease. For the most part, the resolution of helical chest CT scanning makes it unnecessary to pursue further imaging. However, in the case of neurogenic tumors of the posterior mediastinum, MRI can better delineate extension of the mass into the neural foramina and spinal canal. MRI is also used to evaluate processes that involve the great vessels and can obviate the need for IV contrast material administration.^10,11

In rare instances, radionuclide studies may be useful, as in the case of technetium scans for substernal goiters (see Chapter 157), gallium scans for nonseminomatous germ cell tumors,¹² and [¹³¹I]meta-iodobenzylguanidine scans for mediastinal neuroendocrine tumors.¹³ Angiography and myelography are used infrequently today, given the excellent CT and MRI images that are available, but one possible application of angiography is to show the involvement of the artery of Adamkiewicz by neurogenic tumors.¹⁴ Usually this artery originates from the intercostals arteries at T9 to L2; however, in 15% of individuals, it originates from the T5 to T8 levels and is an important surgical consideration in relation to the risk of postoperative paraplegia.¹⁵

PET/CT is not routinely utilized except to rule out the presence of extrathoracic or disseminated disease. In select cases, the degree of FDG uptake on PET can suggest the aggressiveness of the tumor.

Laboratory Tests

Useful serum tumor markers in the management of germ cell tumors (GCTs) include beta-human chorionic gonadotropin (β–hCG) and α-fetoprotein (AFP). Eighty percent of patients with nonseminomatous GCTs have elevated AFP, and 30% have elevated β-BCG.¹⁶ Changes in the titer of the markers roughly parallel the increase or decrease of tumor activity.¹⁷ Only 10% of patients with pure seminomas have mildly elevated β-hCG; any elevation in AFP level indicates a mixed germ cell tumor and portends a worse prognosis than for pure seminoma. In addition, elevated AFP levels are nearly diagnostic for nonseminomatous germ cell tumor and obviate the need for tissue biopsy.

Another serum marker useful in the preoperative workup of an anterior mediastinal mass or in patients with a newly diagnosed thymoma is antiacetylcholine receptor antibody because its presence is indicative of myasthenia gravis (MG).¹⁸ However, only one-third of patients with a known thymoma have associated MG; half of all patients with thymoma have no symptoms at all.¹⁹ Occasionally, neuroendocrine tumors of the anterior mediastinum secrete corticotropin-releasing hormone, and very rarely, neurogenic tumors cause hypoglycemia by secreting insulin. Neuroblastomas may be hormonally active and can be detected with measurement of catecholamines or their breakdown products, that is, vanillylmandelic acid and metanephrines, in the urine. Thus, like pheochromocytomas, neuroblastomas may be associated with diarrhea, cramping, and hypertension. Workup of thyroid goiters includes thyroid function tests, and parathyroid tumors in the mediastinum may be associated with an elevated serum level of calcitonin. Elevated serum LDH may be associated with lymphoma and is used as a prognostic marker for progression of this disease.²⁰

Biopsy

The surgeon’s role in mediastinal disease is to provide histopathologic diagnosis either through surgical excision or through biopsy. Lesions that are small and well circumscribed may be resected without preoperative biopsy, but larger tumors that show evidence of local invasion or that are suspicious for diseases to be treated by nonsurgical means should undergo biopsy.

In the case of lesions that are treated via medical therapy, it is especially important to biopsy adequate tissue not only for diagnosis but also for subclassification, as is the case for non-Hodgkin lymphoma and for malignant germ cell tumors. Subtyping of malignancies involves analysis by immunohistochemistry and flow cytometry. In the initial workup, it is reasonable to consider obtaining a fine-needle aspiration (FNA) by the least-invasive approach: CT-guided transthoracic approach or by endoscopic ultrasound-guided biopsy (either via transbronchial or transesophageal route). However, because of the limited tissue yield, in addition to sampling error and cellular heterogeneity within the lesion, FNA may provide inadequate tissue samples to achieve definitive diagnosis.^21,22 Additional tissue may be obtained by core-needle biopsy or surgical biopsy.

The surgeon has multiple diagnostic techniques that can provide adequate biopsy specimens, including cervical mediastinoscopy, anterior mediastinotomy (Chamberlain procedure), transcervical approach, and video-assisted thoracic surgery (VATS). In many instances, surgical biopsy (e.g., via VATS) has the added benefit of allowing excision of the mass, if so indicated. In the age of minimally invasive techniques, it is rare to perform median sternotomy or thoracotomy for diagnosis alone. With regard to biopsy approaches, biopsy incisions must be planned with consideration for future surgical resection. Similarly, one should be cautious to avoid spilling tumor cells into the pleural spaces because this may prevent subsequent curative resection of the lesion.^21,22

Anesthetic Considerations

Preoperatively, it is important to discuss anesthetic considerations unique to mediastinal masses, particularly those in anterior and sometimes middle mediastinal locations. In addition to avoiding neuromuscular blocking agents in patients with MG, or hypertension in those with pheochromocytoma, one must realize that patients with large mediastinal masses may have both restrictive and obstructive pulmonary physiology. Large mediastinal masses may displace lung volume and thus result in restrictive impairment. More important, patients with significant extrinsic compression of the airway may have sudden respiratory collapse on induction of general anesthesia. This is attributed to the loss of respiratory drive and the conversion from spontaneous (negative-pressure) to assisted (positive-pressure) ventilation, which maximizes the loss in pressure differential (ΔP) across the point of airway obstruction. In this case, ventilation of the distal airways may not be achieved. Such patients require awake intubation, possibly in the upright position. To avoid general anesthesia, one should consider acquiring tissue diagnosis through less invasive means, if possible (e.g., aspiration of pleural effusion or image-guided percutaneous biopsy), or through an approach under local anesthesia (e.g., suprasternal or anterior mediastinotomy). Although there is no single predictor of anesthetic risk in patients with mediastinal masses, it is advisable to obtain preoperative supine and upright pulmonary function tests and to calculate a tracheal cross-sectional area from a CT scan to delineate patients who are at highest risk for respiratory collapse.²³ Shamberger et al. suggest that those with a peak expiratory flow rate greater than 50% predicted or tracheal area greater than 50% normal can undergo general anesthesia safely.^24,25

Thymic Tumors

The incidence of thymoma is highest in patients between the ages of 40 and 60 years and is distributed equally between the sexes.²⁶ In addition to the high association with MG, up to 10% of those with thymoma have other paraneoplastic syndromes, including red blood cell aplasia, hypogammaglobulinemia, inappropriate antidiuretic hormone secretion, systemic lupus erythematosus, or Cushing syndrome.²⁷ Suggestion of local invasion may be determined by chest CT scan with IV contrast. A well-circumscribed lesion is likely a thymoma, whereas a lesion showing infiltration into surrounding mediastinal structures such as lung or great vessels is likely malignant. Thymomas are classified according to histopathologic (2004 WHO classification) or clinicopathologic criteria (Masaoka staging system).^28,29

All thymomas are considered to have malignant potential in so far as they may demonstrate local invasiveness and propensity to local recurrence after treatment. Of all thymic tumors, thymic carcinoma and thymic carcinoid have a dismal survival regardless of stage of the disease.²⁹

The mainstay of treatment consists of complete surgical resection. Preoperative biopsy of small and well-circumscribed thymic masses is not required, especially if the index of suspicion for lymphoma is low based on the patient’s clinical presentation. Biopsy of a large mass with local infiltration should be performed to ascertain diagnosis before resection is pursued, especially if induction chemotherapy and/or radiation is planned.³⁰ Operative approaches for extended thymectomy generally include median sternotomy (see Chapter 160) with possible extension to thoracosternotomy (hemiclamshell incision) if the pulmonary hilum must be controlled. Maximal exposure of the mediastinum is achieved through a clamshell incision with bilateral thoracosternotomy. According to individual surgeon experience and preference, small thymomas without invasion of surrounding structures may be resected via minimally invasive approach: VATS (see Chapter 159), robotic-assisted, or transcervical approach (see Chapter 158).^31–33

The goal of surgery is extended thymectomy with resection of thymus and surrounding adipose tissue, extending from the thyroid gland down to the diaphragm. If surrounding structures (such as phrenic nerve, lung, pericardium, great vessels) are involved, they should be resected en bloc with the thymectomy specimen. If there is residual tumor after resection, adjuvant radiation therapy is recommended; cisplatin-based chemotherapy is used in the case of widespread disease. Recurrent local disease after resection may be considered for reoperation. Recent guidelines issued by the International Thymic Malignancy Interest Group (ITMIG) emphasize that the surgeon should specifically orient the resected specimen to delineate margins and discourse with the pathologist, whose report of close or positive margins will determine adjuvant treatment.³⁴