Adult Chest Surgery

Chapter 131. Overview 

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. 131-1). Mediastinal masses arise from structures that normally reside in the mediastinum, as well as those that migrate through it during development. It is useful to understand the mediastinal anatomy in terms of its major compartments because of the predisposition of certain lesions to arise at specific sites. The anterior mediastinum extends from 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.

Figure 131-1.

 

The anterior, middle, and posterior mediastinal compartments.

Tumors and cysts occur in the mediastinum across all ages and consist of both benign and malignant entities (see Chaps. 137, 138, and 139). 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 following 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.6,7 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.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, mediastinal pleura, or diaphragm.8,9 Other symptoms and signs may include dysphagia, hoarseness, superior vena cava syndrome (see Chap. 140), pericardial tamponade, Horner's syndrome, and reticular pain owing to extension into vertebral foramina.10

DIAGNOSTIC APPROACH

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 with determination of fat, cystic, or soft tissue components.10,11 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.12 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 superior 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.6,11

In rare instances, radionuclide studies may be useful, as in the case of technetium scans for substernal goiters (see Chap. 133), gallium scans for nonseminomatous germ cell tumors,13 and [131I]meta-iodobenzylguanidine scans for mediastinal pheochromocytomas.14 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.15 Usually this artery originates from the intercostal arteries at T9-L2; however, in 15% of individuals, it originates from the T5-8 levels and is an important surgical consideration in relation to the risk of postoperative paraplegia.16

Tumor Markers

Useful serum tumor markers in the management of germ cell tumors include beta-human chorionic gonadotropin (-hCG) and -fetoprotein (AFP). Eighty percent of patients with nonseminomatous germ cell tumors have elevated AFP, and 30% have elevated -hCG.17 Changes in the titer of the markers roughly parallel the increase or decrease of tumor activity.18 Only 10% of patients with pure seminomas have mildly elevated -hCG; any elevation in AFP level indicates a mixed germ cell tumor and portends a worse prognosis than for pure seminoma.

Another serum marker useful in the preoperative workup of an anterior mediastinal mass or in patients with a newly diagnosed thymoma is anti-acetylcholine receptor antibody because its presence is indicative of myasthenia gravis (MG).19 However, only one-third of patients with a known thymoma have associated MG; half of all patients with thymoma have no symptoms at all.20 Occasionally, neuroendocrine tumors of the thymus 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. Additionally, parathyroid tumors in the mediastinum may be associated with an elevated serum level of calcitonin.

Biopsy

The surgeon's role in mediastinal disease is to provide histologic diagnosis either through surgical excision or through biopsy. Lesions that are small and well defined 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's lymphoma and for malignant germ cell tumors. Such subtyping of malignancies involves analysis by immunohistochemistry and flow cytometry. For these reasons, fine-needle aspiration or core needle biopsy techniques may offer inadequate tissue samples for these applications.21,22

The surgeon has multiple diagnostic techniques that can provide adequate biopsy specimens, including cervical mediastinoscopy, anterior mediastinotomy (Chamberlin procedure), and video-assisted thoracic surgery (VATS).23 In many instances, open biopsy 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.24

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 (P) 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, some groups obtain preoperative supine and upright pulmonary function tests and calculate a tracheal cross-sectional area from a CT scan to delineate patients who are at highest risk for respiratory collapse.25 Shamberger and colleagues 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.26,27

ANTERIOR MEDIASTINAL MASSES

Thymoma

The incidence of thymoma is highest in patients between the ages of 40 and 60 years and is distributed equally between the sexes.28 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's syndrome.29 Evidence of local invasion should be determined by chest CT scan with IV contrast material. A well-circumscribed lesion is likely a benign thymoma, whereas a lesion showing infiltration into surrounding mediastinal structures is likely malignant. Approximately 20–30% of all thymomas are malignant.30,31 Of all thymic tumors, thymic carcinoma and thymic carcinoid have a dismal survival regardless of stage of the disease.32

The mainstay of treatment consists of surgical resection. As a consequence of the concern for tumor shedding resulting from open biopsy, the lesion should be fully excised without prior biopsy if it is small and well defined. Fine-needle aspiration biopsy may not be helpful as a result of the difficulty of distinguishing thymoma histologically from lymphoma.33 Biopsy of a large mass with local infiltration should be performed to ascertain diagnosis before resection is pursued. Operative approaches for resection of thymoma generally include median sternotomy or posterolateral thoracotomy if the pulmonary hilum must be controlled. Total thymectomy with radical resection is performed through a full sternotomy (see Chap. 136) or, for maximal exposure of the mediastinum, through a clamshell incision with bilateral thoracosternotomy.34 It is debatable whether early-stage thymoma may be amenable to thymectomy via VATS (see Chap. 135) or transcervical approach35–39 (see Chap. 134). These techniques have been criticized as potentially incomplete resections because most surgeons agree that all thymic tissue should be resected, including the cervical horns and tissue remnants abutting the pleura and pericardium. 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.

While 30% of patients with thymoma have MG, only approximately 10–15% of patients with MG have an associated thymoma.40,41 The indications for thymectomy in MG patients without evidence of thymic masses is controversial, but those who are medical treatment failures are appropriate candidates. Thymectomy should not be performed in patients on an emergency basis; symptoms are best managed by plasmapheresis and immunosuppression, followed by thymectomy once the symptoms are under control. Thymectomy can be performed through a full sternotomy or through less invasive techniques such as the partial upper sternotomy, transcervical approach, VATS, or a combined transcervical-VATS approach.42 The VATS technique can be approached from either the left or right side, with each side having its benefits of better exposure of key structures (e.g., aortopulmonary window on left, superior vena cava-innominate vein junction on right).43 Studies generally have reported the following results from surgical treatment of MG: a remission in 20–25% of patients, with 10–20% being drug-free; improvement in 30–50%; no change in 10%; and progression in a few percent.19

Complications after thymectomy include the usual postoperative respiratory sequelae, with heightened risk in predisposed MG patients. Thus aggressive pulmonary toilet, early mobilization, adequate pain control, and involvement of the neurologist are of supreme importance to ensure a smooth postoperative recovery. Technical complications include injury to the surrounding structures such as the phrenic nerve, thoracic duct, and left innominate vein. In the case of malignant thymoma, there is a risk of pleural seeding; however, this risk is more relevant in the use of percutaneous biopsy and minimally invasive approaches than in the open incisions described earlier.

Lymphoma

Hodgkin's lymphoma has a peak incidence in the third and fourth decades of life, whereas non-Hodgkin's lymphoma is evenly distributed across the first five decades of life. Most patients with lymphoma in the mediastinum usually have systemic disease, but 10% of patients present with primary mediastinal lymphoma.44 Mediastinal involvement usually manifests as enlarged lymph nodes in the anterior or middle mediastinum; thus patients usually report symptoms related to respiratory compression or pleuropericardial disease. The surgeon's role is limited primarily to obtaining tissue for diagnosis and subtyping the lymphoma. Fine-needle aspiration biopsy is often insufficient for diagnosis, and thus one should proceed to biopsy via the least invasive surgical technique by which adequate tissue can be obtained safely, for example, cervical mediastinoscopy, anterior mediastinotomy, or VATS (see Chap. 132). As in biopsies of all mediastinal masses, frozen sections should be obtained to ensure that the pathologist has sufficient tissue for diagnosis and subsequent studies.

Germ Cell Tumors

Although extragonadal primary germ cell tumors (GCTs) are uncommon, the mediastinum is the most common location in adults (see Chap. 139). In the pediatric population, mediastinal GCTs are equally divided between the sexes. In adults, benign GCTs are equal between the sexes, but more than 90% of malignant GCTs occur in males in their third decade of life.45 In males with a potential mediastinal GCT, it is important to exclude a gonadal primary tumor through physical examination and scrotal ultrasound. All patients should have serum levels of -hCG and AFP measured as part of the initial workup.

Benign teratomas or dermoid cysts are the most common GCTs in both children and adults, with a frequency of about two-thirds of all GCTs.46,47 Fewer than half these lesions are associated with symptoms, and up to 30% have calcifications that are present on chest x-ray. These tumors contain elements derived from all three embryonic germ cell layers and display little tendency toward malignant degeneration. CT scans show well-defined lesions with fatty, cystic, and calcific components. Treatment consists of surgical resection without biopsy.

Among malignant GCTs, seminomas comprise more than half the cases. In addition to the routine chest imaging performed for mediastinal lesions, staging abdominal CT scans and scrotal ultrasounds are essential in GCTs to screen for extrathoracic disease. Serum -hCG and AFP levels are measured and are low in seminomatous GCTs. Only approximately 10% of patients have even mildly elevated -hCG levels, and all patients with pure seminomatous GCT have undetectable AFP levels.27 Because these lesions often infiltrate into surrounding mediastinal structures, open biopsy should be performed to distinguish between seminoma and a mixed tumor. The treatment for pure seminoma is radiation therapy with cisplatin-based chemotherapy. After induction chemotherapy, any residual lesion greater than 3 cm should be resected to ensure the removal of all viable tumor and to determine whether additional adjuvant therapy is necessary.

Mediastinal nonseminomatous GCT portends a worse prognosis, with 80% of patients having at least one site of metastasis at the time of diagnosis.Ninety percent of patients have an elevation in either -hCG, AFP, or both, and tumor marker levels parallel the clinical activity of the tumor.17 Despite the presence of elevated tumor markers in the serum, open biopsy must be done to ascertain diagnosis. Treatment consists of cisplatin-based chemotherapy and radiation treatment. Surgical resection is reserved for patients with localized residual tumor after successful chemotherapy or for selected patients with relapse in whom the lesion appears to be a solitary recurrence and is technically resectable.

Thymic Cysts

Thymic cysts are derived from pharyngeal pouches and are universally benign. Usually asymptomatic, they often can grow quite large, compressing nearby structures. Although fluid can be readily visualized by chest CT scan and MRI, cystic components can be present in thymomas and teratomas as well. Excision is curative and excludes other diagnoses.

Parathyroid Adenomas

Approximately 20% of parathyroid glands are ectopic and may be found along the thymic line of descent within the anterior mediastinum.48 Parathyroid adenomas or hyperplastic glands are hypervascular oval masses seen on chest CT scan with variable contrast enhancement. Ectopic inferior parathyroid glands are the most variable in location and usually are found within the anterior mediastinum; ectopic superior parathyroid glands sometimes may be located in the posterior compartment. In patients in whom preoperative localization is warranted, parathyroid tissue is best localized by 99mTc-sestamibi imaging.49 Selective parathyroid angiography or venous sampling is done only when results from noninvasive imaging are equivocal.

Thyroid Goiters

Most intrathoracic thyroid goiters are continuous with the cervical gland; only 2% of goiters are primary substernal tumors with vascular supply derived from the chest.50 On chest CT scan, thyroid goiters have a characteristic multinodular appearance, circumscribed by a smooth surface and containing calcifications and cystic areas.12 Although usually involving the anterior mediastinum, up to 10% of intrathoracic goiters may be located within the posterior mediastinum. Although these usually can be surgically resected via a low cervical collar incision, the incision can be extended to a partial upper sternotomy if needed51 (see Chap. 133).

MIDDLE MEDIASTINAL MASSES

The most common masses of the middle mediastinum remain enlarged lymph nodes around the tracheobronchial tree, for which the differential diagnosis includes lymphoma, sarcoidosis, metastatic disease from the lung, or inflammatory foci resulting from tuberculosis or histoplasmosis or primary masses within the organs of the middle mediastinum, such as lung or esophageal cancer, which are covered elsewhere in this text. Surgical biopsy of enlarged lymph nodes is warranted for diagnosis. Nodes located in the aortopulmonary window are accessible for biopsy via an anterior mediastinoscopy, whereas pretracheal, subcarinal, and tracheobronchial nodes can be accessed by cervical mediastinoscopy (see Chap. 132). More distal mediastinal nodes, including perihilar nodes, can be biopsied via a VATS approach, although access is limited to one side of the mediastinum at any given time.

Cystic masses comprise approximately 20% of all mediastinal masses. Although cysts can occur at any location within the mediastinum, they are most commonly of foregut origin and thus begin in the middle mediastinum. Bronchogenic and esophageal duplication cysts are malformations that are jointly considered enterogenous cysts. When these lesions have associated vertebral malformations, they are called neuroenteric cysts.

Bronchogenic cysts are the most common mediastinal cyst and usually lie in a subcarinal position. Two-thirds of patients present with symptoms related to compression of adjacent structures or obstruction of distal lung with subsequent infection.52 Given their predisposition to infection and potential for malignant degeneration, bronchogenic cysts are best managed with surgical resection via VATS or thoracotomy.53

Esophageal cysts are lined with some form of gastrointestinal epithelium, either stratified squamous epithelium or gastric mucosa. Sixty percent are found in the lower third of the esophagus and are twice as likely to be located in the right chest rather than the left.54 They may be found within or adjacent to the esophagus and thus can be found in both the middle and posterior mediastinal compartments. Rarely, they may communicate with the esophageal lumen, and thus a communication or dimpling sometimes can be visualized on esophagoscopy. Like bronchogenic cysts, they have a tendency to become infected; moreover, if they are lined with acid-secreting gastric mucosa, they have the potential to ulcerate and bleed spontaneously. These cysts may be symptomatic by virtue of their enlarging size, causing dysphagia, chest pain, and cardiac arrhythmias. Treatment consists of surgical resection with closure of any esophageal connection.55

Neuroenteric cysts are rare and are always associated with vertebral anomalies, most commonly spina bifida. The vertebral anomalies occur cephalad to the cyst and include fused or hemivertebrae. Patients may present with respiratory or neurologic signs and symptoms. If there is any evidence of intraspinal extension, the resection will require a joint effort with a neurosurgeon.

Pericardial cysts are mediastinal masses that are commonly found at the anterior cardiophrenic angle, right greater than left. The cysts are filled with clear serous fluid and may be serially aspirated. If the lesions show radiographic change over time or produce symptoms, resection is indicated.11 They are otherwise not known to undergo malignant degeneration.

POSTERIOR MEDIASTINAL MASSES

Neurogenic tumors comprise 60% of posterior mediastinal tumors and are the most common etiology of masses in this compartment56,57 (see Chap. 138). They are classified according to the neural cell of origin and may arise from the intercostal nerve sheath, the sympathetic ganglia, or the paraganglionic cells. Neuroblastomas and ganglioneuroblastomas, which arise from sympathetic ganglia, are the most common in children and are malignant. Ganglioneuromas, which also arise from the sympathetic ganglia, are the most common in young adults and are benign.Tumors of the nerve sheath, schwannomas and neurofibromas, account for 90% of adult neurogenic tumors and are benign; they have a peak incidence in the third and fourth decades.28,58 Overall, fewer than 5% of neurogenic tumors are malignant.51 Most are asymptomatic, although malignant forms are associated with symptoms related to compression of surrounding structures, radiculopathy from involvement of nerve roots, and erosion into bone. Additionally, neuroblastomas, paragangliomas, and pheochromocytomas can be hormonally active and may be detected by the measurement of serum catecholamines or urine vanillylmandelic acid.

Tumors arising from paraganglionic cells of the sympathetic nervous system include pheochromocytomas and nonchromaffin paragangliomas. Although these tumors can occur within each of the mediastinal compartments, they are commonly thought of as posterior mediastinal tumors. Both types may be functional and secrete hormones. Malignancy is determined by the degree of local invasiveness or the presence of distant metastasis. Paragangliomas, also known as chemodectomas, are hypervascular soft tissue masses found in the aortopulmonary window or in the costovertebral sulci. The differential diagnosis for such highly vascularized masses includes Castleman's disease and hemangiomas.6

Approximately 10% of pheochromocytomas are extraadrenal. As described previously, [131I]meta-iodobenzyl-guanidine scans are used to localize pheochromocytomas to the mediastinum if initial chest CT scan and MRI are unrevealing. It is important to screen patients with pheochromocytomas for the presence of familial syndromes, such as multiple endocrine neoplasia type II, von Hippel-Lindau disease, and neurofibromatosis type I.59Careful preoperative blood pressure control using alpha blockade followed by beta blockade is required to prevent hypertensive crises.60

Approximately 10–20% of posterior mediastinal neurogenic tumors have a spinal canal component.61 These tumors are called dumbbell tumors and consist of a larger posterior mediastinal component with a smaller intraspinal component connected by a narrow foraminal segment. Of patients with dumbbell tumors, 60–80% have neurologic symptoms.23 It is important to have joint preoperative planning for resection by the neurosurgical and thoracic surgical teams because resection of the intrathoracic component alone can lead to tumor hemorrhage or necrosis of the intraspinal component with subsequent spinal cord compression or can result in a dural injury with leakage of cerebrospinal fluid and subsequent meningitis.

OTHER MEDIASTINAL MASSES

Castleman's Disease

Castleman's disease is also known as angiofollicular lymph node hyperplasia and is characterized by a solitary nodal mass within the mediastinum that significantly enhances on chest CT scan after contrast material injection. Castleman's disease may occur in any compartment of the mediastinum and may be confused on needle-guided biopsy with other lymphoproliferative disorders such as lymphoma or thymoma. Although usually asymptomatic, it can be associated with cough and dyspnea and is treated by curative resection.62

Mesenchymal Tumors

Mesenchymal tumors include lipomas, hemangiomas, lymphangiomas, fibromas, and their malignant counterparts. Although these may occur in any compartment of the mediastinum, they are found mostly in the anterior mediastinum and should be resected because the presence of malignant degeneration cannot be determined preoperatively.

SUMMARY

Mediastinal masses include a wide variety of diseases and etiologies. A differential diagnosis for a given mediastinal mass is based primarily on patient age, symptoms, and mediastinal location. Most masses require biopsy via anterior/cervical mediastinoscopy or VATS to establish a tissue diagnosis, although lesions classic for thymoma, small localized masses, and posterior mediastinal masses may undergo complete surgical excision for both diagnostic and curative intent. "Secretory" mediastinal masses, such as MG, pheochromocytomas, and thymomas, pose specific perioperative risks and concerns, as do large mediastinal masses that impair the airway. It is critical that the thoracic surgeon be aware of the various mediastinal entities and concerns unique to their treatment.

EDITOR'S COMMENT

Imaging is important for suggesting not only the likely diagnosis, but also the best surgical approach. Mastery of mediastinal imaging is essential for surgeons operating in or around the mediastinum.

–SJM

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