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
While 30% of patients with thymoma have MG, only approximately 10% to 15% of patients with MG have an associated thymoma.35,36 The indications for thymectomy in MG patients without evidence of thymic masses are controversial, but the American Academy of Neurology recommends that all patients with nonthymomatous MG should be considered for thymectomy to increase the probability of remission or clinical improvement.37 Thymectomy should not be performed in patients on an emergency basis; symptoms are best managed by plasmapheresis and immunosuppression, followed by thymectomy once the patient is medically optimized. Thymectomy can be performed through a full sternotomy or through less invasive techniques such as the partial upper sternotomy, transcervical approach, VATS, or robotic (see Chapter 159). 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).38 Studies generally have reported the following results from surgical treatment of MG: a remission in 20% to 25% of patients, with 10% to20% being drug-free; improvement in 30% to 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 innominate vein.
Hodgkin lymphoma has a peak incidence in the third and fourth decades of life, whereas non-Hodgkin 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.39 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 for subtyping the lymphoma. FNA 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 Chapter 159). As in biopsies of all mediastinal masses, frozen sections should be obtained to ensure that the pathologist has sufficient lesional tissue for diagnosis and subsequent studies (e.g., flow cytometry, cytogenetics, molecular analysis).
Although extragonadal primary GCTs are uncommon, the mediastinum is the most common location in adults (see Chapter. 163). 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.40–42 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 β-hCG and AFP measured as part of the initial workup.
Benign teratomas or dermoid cysts are the most common GCT in both children and adults, with a frequency of about two-thirds of all GCT43 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 GCT, seminomas comprise more than half the cases. In addition to the routine chest imaging performed for mediastinal lesions, staging abdominal CT scans, scrotal ultrasounds, and PET/CT scans are essential to screen for extrathoracic disease. Serum β-hCG and AFP levels are measured and are low in seminomatous GCTs. Only approximately 10% of patients with GCT have even mildly elevated β-hCG levels, and all patients with pure seminomas have undetectable AFP levels.41 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 β-hCG, AFP, or both, and tumor marker levels parallel the clinical activity of the tumor. 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 response to chemotherapy or for selected patients with relapse in whom the lesion appears to be a solitary recurrence and is technically resectable.16
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.
Approximately 20% of parathyroid glands are ectopic and may be found along the thymic line of descent within the anterior mediastinum. 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. Patients in whom preoperative localization is warranted, parathyroid tissue is best localized by 99mTc sestamibi imaging.44 Selective parathyroid angiography or venous sampling is done only when results from noninvasive imaging are equivocal.
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. On chest CT scan, thyroid goiters have a characteristic multinodular appearance, circumscribed by a smooth surface and containing calcifications and cystic areas.45,46 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 needed (see Chapter 160).