Approach to the adult patient with a mediastinal mass

INTRODUCTION — Benign or malignant mediastinal masses can develop from structures that are normally located in the mediastinum or that pass through the mediastinum during development, as well as from metastases of malignancies that arise elsewhere in the body. The approach to a patient with a mediastinal mass will be reviewed here, including planning the diagnostic workup as well as initial therapy. In addition, a brief overview of the most common causes of mediastinal masses is presented. Detailed discussions of specific pathologic processes are presented in separate topic reviews, as noted below.

INITIAL PRESENTATION

Incidental finding on imaging — A mediastinal mass can be an incidental finding in patients who undergo plain chest radiography or advanced imaging studies, such as computed tomography or magnetic resonance imaging. These may have been obtained prior to elective surgery or as part of the evaluation of an unrelated condition.

Findings on the chest radiograph can vary from subtle mediastinal findings (image 1) to the presence of a widened mediastinum or large mass in the mediastinum (image 2).

Symptoms — Symptoms, if present, may be due to direct mass effect of the mediastinal anomaly or to systemic effects of the illness. In general, malignant lesions are more likely to be symptomatic [1-3].

●Mediastinal mass effects – Direct involvement or compression of normal mediastinal structures cause a wide range of symptoms. These can include cough, stridor, hemoptysis, shortness of breath, pain, dysphagia, hoarseness, facial and/or upper extremity swelling due to vascular compression (eg, superior vena cava syndrome), hypotension due to tamponade physiology or cardiac compression, and Horner syndrome due to sympathetic chain involvement.

●Systemic effects – Systemic symptoms such as fever, night sweats, and weight loss can be present in the case of lymphoma or may be due to a variety of paraneoplastic syndromes, such as myasthenia gravis with thymoma.

PRESUMPTIVE CLINICAL DIAGNOSIS — The initial evaluation of a suspected mediastinal mass consists of a thorough history and physical examination, supplemented by laboratory and imaging studies. A combination of these, particularly the location of the mass, often helps narrow the possibilities when a mediastinal mass is detected on imaging. Laboratory studies or blood tumor markers can also help support a specific diagnosis. In some instances, these are enough for a presumptive diagnosis to guide therapy. As an example, the presence of a large anterior mediastinal mass and elevations in certain tumor markers can very reliably establish the diagnosis of some germ cell tumors. In other cases, a tissue biopsy (percutaneous, endobronchial, surgical) may be necessary to confirm a clinical suspicion prior to establishing a therapeutic plan. (See 'Differential diagnosis' below and 'Tissue diagnosis' below and 'Germ cell tumor' below.)

History and physical examination — Clinicians should carry out a comprehensive history and physical examination while focusing on the symptoms and signs that are more often associated with mediastinal masses. The age and sex of the patient are often helpful in formulating a differential diagnosis, as the prevalence of mediastinal mass subtypes may vary drastically across these demographics.

Reviewing the time course of the development of symptoms (see 'Symptoms' above) or the absence of specific symptoms can help narrow the list of potential diagnoses. Mediastinal processes can undergo slow growth over the course of years (eg, thymoma in some patients) or rapid expansion (eg, lymphoma). Mediastinal masses can also be associated with abnormalities in other parts of the body (eg, testicular masses with germ cell tumors); thus, the history should include a thorough review of systems and should not be narrowed to questions related to the mediastinum. Thymomas can be associated with certain paraneoplastic disorders. (See "Clinical presentation and management of thymoma and thymic carcinoma", section on 'Paraneoplastic disorders'.)

Similarly, the physical examination should not be solely focused on areas directly related to the mediastinum. Rather, a complete physical examination is needed, which includes examination of the head, neck, upper extremity, chest, and abdomen but also examination of all areas that could demonstrate lymphadenopathy, as well as a scrotal examination in males.

Laboratory studies — Peripheral blood collection and analysis for tumor markers can support a presumptive diagnosis in some instances of anterior mediastinal masses. Tumor markers are most helpful when thymoma or germ cell tumor is suspected. In general, the following laboratory tests are reasonable to routinely check for patients in whom a diagnosis has not already been established.

●Anti-acetylcholine receptor antibodies – This may be positive in some patients with thymic tumors and indicate or herald the presence of myasthenia gravis. (See 'Thymic mass' below.)

●Alpha-fetoprotein (AFP) – Elevated levels of AFP are found in malignant germ cell tumors; specifically, 60 to 80 percent of nonseminomatous dysembryomas are serum AFP positive. (See 'Germ cell tumor' below.)

●Beta-human chorionic gonadotropin (beta-hCG) – Beta-HCG is associated with seminoma (10 percent) and nonseminomatous (30 to 50 percent) germ cell tumors. (See 'Germ cell tumor' below.)

●Lactate dehydrogenase (LDH) – LDH may be elevated in patients with nonseminomatous dysembryoma, though this laboratory finding is generally not as specific as AFP or beta-hCG. Additionally, LDH may be elevated in patients with lymphoma.

Imaging — Computed tomography (CT) of the chest with intravenous contrast is typically used to evaluate abnormalities seen on plain radiographs. In many cases, no further imaging beyond the CT is needed to evaluate the mediastinal mass.

Chest CT can confirm the presence of a mediastinal mass, and, on occasion, an abnormality that was thought to be a mediastinal mass is determined to be something else. Chest CT also provides detailed information regarding the mediastinal abnormality, including its location, size, relationship to other structures, and tissue characteristics, including presence of fat, fluid, or calcifications (eg, teratoma). Such detailed information, particularly involvement/invasion or compression of surrounding structures, is critical in planning treatment and preparing a patient for possible resection. (See 'Surgical resection' below.)

Other imaging studies can be useful for diagnostic purposes or treatment planning in select instances. Examples include:

●Chest and/or cardiac gated magnetic resonance (MR) imaging – MR is useful in distinguishing compression versus invasion, particularly in cases of large anterior mediastinal masses where this distinction can be difficult on CT, even when using intravenous contrast. (See 'Anterior mediastinal masses' below.)

●Positron emission tomography (PET) – For a mediastinal mass that is suspected to be a lymphoma, using 18F-fluorodeoxyglucose (FDG) with fused CT may be performed. This modality can be useful to identify a preferred biopsy site. For tumors found to be PET avid on initial study, it can be useful in monitoring response to treatment. However, it is important to note that FDG-PET imaging can be misleading because nonmalignant conditions such as teratoma and thymic cysts have been shown to have FDG accumulation in 14 to 42 percent of cases [4]. In addition, normal thymus has been shown to have a maximum standardized uptake value (SUV) of 2.00 to 2.09, and thymic rebound has also been observed, where patients treated with chemotherapy for another malignancy have been found to have increased PET activity with a mean SUV of 2.89 at a mean interval of 10 months after chemotherapy completion [5]. (See 'Lymphoma' below.)

●Chest or spine MR – These provide a detailed evaluation of posterior mediastinal masses that are adjacent to the spine. MR is better than CT for determining whether a mass extends into the neural foramina or spinal canal, which is important for surgical planning. (See 'Posterior mediastinal masses' below.)

●Technetium scan – For a mediastinal mass that is suspected to be ectopic thyroid tissue or a substernal goiter, a technetium scan be used to confirm this suspicion. (See 'Thymic mass' below.)

●[¹³¹I] meta-iodobenzylguanidine – This study is useful for confirming the presence of a mediastinal pheochromocytoma. (See "Clinical presentation and diagnosis of pheochromocytoma", section on 'Imaging'.)

●Scrotal ultrasound – Abnormalities on scrotal examination are evaluated using ultrasound. Any concerning findings should prompt further urologic evaluation. (See "Nonacute scrotal conditions in adults".)

●⁶⁸Gallium-1,4,7,10-tetraazacyclododecane-N,N',N"N'"-tetraacetic acid-d-Phe1,Tyr3-octreotate (Ga-68 DOTATATE) PET/CT scan – Preliminary data and case reports suggest the utility of Ga-68 DOTATATE PET/CT studies in staging thymic neuroendocrine tumors [6]. (See "Thymic neuroendocrine (carcinoid) tumors", section on 'Somatostatin receptor-based diagnostic imaging'.)

TISSUE DIAGNOSIS — A definitive diagnosis generally requires a tissue sample, which can be obtained either by biopsy prior to treatment or as part of a planned therapeutic resection of the entire mass.

Biopsy — Biopsy of the mediastinal mass is needed to confirm a suspected diagnosis in some but not all cases prior to definitive treatment. Duplication cysts do not require biopsy, if imaging clearly demonstrates a cystic lesion without any soft tissue abnormality that could represent the presence of a neoplasm. Whatever biopsy method is used (percutaneous, endobronchial, surgical), pathology should confirm that adequate diagnostic tissue has been obtained, either by cytological assessment or frozen section. The use of rapid on-site cytological examination (ROSE) has been shown to increase the diagnostic yield of transbronchial biopsies from 65 to 80 percent [7]. If necessary, additional biopsies should be performed while the patient is still sedated or anesthetized so the patient does not have to go through repeated diagnostic procedures.

The decision to biopsy can be difficult when a patient clearly has a resectable anterior mediastinal mass but the clinical scenario does not allow definitive distinction between lymphoma or thymoma. Confirming the diagnosis when lymphoma is suspected with biopsy is preferred. The risk of forgoing biopsy and not obtaining a preresection diagnosis is the possibility that the surgeon will resect a lymphoma that could have been managed with nonsurgical treatment. On the other hand, biopsy (percutaneous, endobronchial, surgical) of an encapsulated thymoma can cause tumor seeding. Although this situation is likely rare, multiple case reports have demonstrated needle tract and chest wall seeding after thymoma biopsy [8,9], and seeding of either the mediastinal space, the pleura, or the needle tract can create a situation where surgery is no longer curative without adjuvant radiation. An even more disastrous situation is when tissue biopsy causes seeding of the pleural cavity, which changes a curable situation into one in which the patient remains at risk for pleural recurrence throughout his/her lifetime: such possibilities should be discussed with the interventional radiologist and all efforts should be to avoid a transpleural route when performing these percutaneous biopsies. Guidance regarding the decision between biopsy and surgical resection is discussed below. (See 'Surgical resection' below.)

For a posterior mediastinal mass, a preresection biopsy is pursued if a diagnosis has not been established by clinical presentation and imaging, the mass involves structures considered not resectable, or the mass appears resectable but the resection would be extensive and require complex reconstruction. These are most often neurogenic tumors or sarcomas, which can generally be sampled using computed tomography (CT)-guided biopsy. Those patients who are appropriate candidates for upfront surgical resection are discussed below. (See 'Surgical resection' below.)

Occasionally, an adequate tissue diagnosis is elusive in spite of adequate attempts at biopsy. As an example, in nodular sclerosing Hodgkin lymphoma, the abnormal tissue can be dominated by fibrosis with a paucity of the cells that are needed to firmly establish the diagnosis. In these situations, a reasonable approach is to obtain a positron emission tomography (PET) scan and proceed with a biopsy of the most metabolically active area on PET by whatever approach allows the best access to that area. If the biopsy is still not completely diagnostic, further treatment must proceed based on the most likely diagnosis considering clinical, imaging, and pathologic characteristics.

Percutaneous — Both anterior and posterior mediastinal masses can often be biopsied under CT guidance [10,11]. The diagnostic yield of percutaneous biopsy of mediastinal masses is 74 to 77 percent, with a rate of up to 100 percent for thymic neoplasms, but a nondiagnostic result occurs in 75 percent of patients ultimately found to have lymphoma [12,13].

Core needle biopsies rather than fine needle aspiration (FNA) should be obtained whenever possible as FNA often will not allow differentiation among the possible diagnoses. One study has shown that core biopsy had a diagnostic yield of 77 percent, compared with a diagnostic yield of only 60 percent for FNA [12]. A larger-bore core needle biopsy is often required to obtain sufficient tissue to diagnose a mediastinal lymphoma as FNA can be inadequate when tissue is needed for immunohistochemistry and flow cytometry analysis to subtype malignancies such as lymphoma.

Endobronchial — Endobronchial biopsy (EBUS) is reasonable to consider when the mediastinal mass is located immediately adjacent to an airway. Lesions in these locations are often difficult to access percutaneously even with radiographic imaging guidance due to the proximity of major vascular structures. Using EBUS to guide biopsy can significantly increase the potential yield of this diagnostic procedure. (See "Flexible bronchoscopy in adults: Associated diagnostic and therapeutic procedures", section on 'Transbronchial biopsy'.)

Endoscopic — Endoscopic ultrasound via the esophagus may allow for FNA of certain periesophageal posterior mediastinal masses. However, transesophageal FNA of cystic lesions must be considered very carefully (ie, foregut duplication cysts) given the theoretical risk of infecting the cyst fluid.

Surgical — When percutaneous or endobronchial biopsy is not possible or cannot provide adequate tissue to definitively establish a diagnosis, surgical biopsy may be necessary.

As an example, when lymphoma is considered a possibility based on the clinical scenario, excisional biopsy of a small mass, if possible, or incisional biopsy of a large mass is preferred, although in select cases large core needle biopsies may be adequate. (See "Clinical presentation and diagnosis of classic Hodgkin lymphoma in adults", section on 'Evaluation' and "Clinical presentation and initial evaluation of non-Hodgkin lymphoma", section on 'Type of biopsy'.).

Surgical options for obtaining a tissue sample are described below. Assessment of the adequacy of the biopsy samples should be carried out with frozen section. Minimally invasive approaches (eg, mediastinoscopy, video-assisted thoracoscopy) can be tried prior to resorting to open surgical approaches.

●Anterior mediastinotomy (ie, Chamberlain procedure (figure 1)) may be appropriate for lesions that are substernal. Anterior lesions typically displace normal structures away from the planned biopsy site, which allows a biopsy to be performed without entering the pleural space, which reduces the risk of postoperative pneumothorax, pleural effusion, need for a chest tube, and pleural seeding of thymomas. An anterior mediastinotomy will almost always yield a sufficient tissue to provide a diagnosis and usually can be done as an outpatient or same-day surgical procedure. (See "Surgical evaluation of mediastinal lymphadenopathy", section on 'Anterior mediastinotomy'.)

●Cervical mediastinoscopy (figure 2) is an option for lesions in the middle mediastinum. A mediastinoscope is inserted through a small incision just above the sternal notch and directed into the mediastinum. This approach is effective at obtaining tissue from mediastinal masses that are adjacent to the airway. Lesions in the paratracheal and subcarinal spaces can be safely sampled with this approach. (See "Surgical evaluation of mediastinal lymphadenopathy", section on 'Mediastinoscopy'.)

An extended mediastinoscopy that explores other areas adjacent the great vessels in the middle mediastinum can also be useful but requires an additional level of expertise. Most surgeons opt for another biopsy approach if a standard cervical mediastinoscopy does not provide safe access to the tissue in question.

●Video-assisted thoracoscopy and video-assisted thoracoscopic surgery (VATS) (figure 3) can be performed from either side of the chest. This approach can be associated with more postoperative pain compared with other minimally invasive procedures; however, the excellent anatomic view also allows biopsy of tissue anywhere in the mediastinum, even immediately adjacent structures such as the aorta, other great vessels, or the heart. VATS can be performed on an outpatient basis, but most surgeons insert a chest tube and admit patients overnight. VATS biopsy is generally performed only if another method has failed to achieve diagnosis. (See "Surgical evaluation of mediastinal lymphadenopathy", section on 'Thoracoscopy' and "Overview of minimally invasive thoracic surgery".)

Surgical resection — The most appropriate surgical approach for resection of a mediastinal mass depends upon the patient, the location and size of the lesion, the presumptive diagnosis, and the preference and experience of the surgeon performing the resection. Options for surgical resection include minimally invasive approaches (VATS through the chest or via subxyphoid approach, robotic assisted, transcervical resection) or traditional open approaches (thoracotomy, median sternotomy, thoracosternotomy [clamshell], hemi-thoracosternotomy [hemi-clamshell] incisions). (See "Overview of minimally invasive thoracic surgery" and "Thymectomy", section on 'Incisions and surgical approach'.)

We suggest proceeding with resection without biopsy in situations where the only imaging abnormality is the mediastinal mass, systemic symptoms typical of lymphoma are not present, and the mediastinal mass is clearly resectable without any suggestion of invasion of local structures on imaging. This strategy may lead to some situations where a patient undergoes resection of a mediastinal lymphoma, but we feel this risk is outweighed by avoiding the more likely situation of potentially worsening the prognosis of a patient with thymoma if the biopsy causes pleural seeding that ultimately causes recurrence. (See 'Biopsy' above.)

Anatomic evaluation and surgical planning — Unnecessary morbidity can be avoided if involvement of unresectable structures is identified prior to surgery. In addition, anatomic information can help determine if resection is suited to a minimally invasive approach. The surgeon and anesthesiologist should always review the risks of the procedure, particularly with induction of anesthesia. The surgeon should be physically present in the operating room during this critical period. (See 'Imaging' above.)

When resection is planned, the relationship between the mediastinal mass and the superior vena cava and airway must be explicitly examined and reviewed with the anesthesia team prior to the procedure. If there is any possibility that superior vena cava compression or occlusion could impair delivery of critical intravenous (IV) infusions to the heart via upper extremity or neck veins, then lower extremity venous access must be obtained either centrally via a femoral line or peripherally via a large bore lower extremity peripheral IV line. (See "Malignancy-related superior vena cava syndrome" and "Anesthesia for patients with an anterior mediastinal mass", section on 'Vascular access'.)

Induction of anesthesia and establishing an airway can be hazardous when a mediastinal mass is present. Awake fiberoptic intubation with the patient sitting up at an incline is often the safest approach in cases where there are any concerns. Mediastinal masses, particularly anterior masses (image 3), can distort the trachea to such an extent that an endotracheal tube cannot be safely passed without direct vision. Induction of anesthesia can also result in severe hypotension and a loss of airway and inability to ventilate the patient if the airway and superior vena cava collapses under compression from the mass when the patient is relaxed, a situation that may not be recoverable even with cervical tracheostomy. Thus, some surgeons advocate having a rigid bronchoscope immediately available. The mechanical structure of the rigid bronchoscope will allow the airway to be intubated in the distal trachea past the compression, effectively stenting the airway open and allowing jet ventilation through the rigid bronchoscope. (See "Anesthesia for patients with an anterior mediastinal mass", section on 'Airway management'.)

The possibility of having extracorporeal support immediately available should be considered in cases where loss of airway or hemodynamic stability is considered a significant risk. This preparation includes having a perfusionist present in the room with a cardiopulmonary bypass (CPB) circuit or an extracorporeal membrane oxygenation (ECMO) circuit prepared. In these cases, access lines should be placed in the patient's femoral vein and artery prior to administration of any anesthesia. These lines can be quickly converted to the needed CPB or ECMO cannulas in the case of an airway disaster. This precaution can be life-saving, although it is costly and potentially difficult to coordinate. Planning a procedure with ECMO support requires careful, multidisciplinary collaboration and may not be available at all centers. (See "Anesthesia for patients with an anterior mediastinal mass", section on 'Planned cardiopulmonary bypass' and "Extracorporeal life support in adults in the intensive care unit: Overview".)

Surgical approach — The specific surgical approach (open or minimally invasive) depends upon the location and size of the lesion. In general, lesions that can be approached by thoracotomy can also be approached with VATS. Both of these methods involve approaching and resecting the mediastinal mass from one side of the chest. However, the enhanced field of view provided by the thoracoscope with a minimally invasive approach (VATS, robotic-assisted thoracoscopic surgery [RATS]) allows this approach to be used for some anterior mediastinal masses that cross the midline, such as a thymoma.

The particular approach to resection used for any tumor is primarily determined by the size, location, and nature of the tumor along with the surgeon's experience and expertise. A minimally invasive approach is generally reserved for tumors less than 4 to 5 centimeters in size, although there are no definitive size criteria that preclude an attempt. The key to using a minimally invasive approach is to be able to provide a safe procedure that does not compromise the long-term oncologic effectiveness of the procedure. Many surgeons will not use a minimally invasive approach for patients who have received preoperative treatment with either chemotherapy or radiation therapy because of the potential risks associated with inflammation or fibrosis or for a lesion that appears to have infiltrated into surrounding structures. Nevertheless, surgeons with expertise in minimally invasive techniques may choose this approach depending on their overall assessment of the clinical situation. Starting with thoracoscopic exploration may spare a patient the morbidity of a large incision if the tumor proves to be unresectable (eg, unexpected pleural metastases, extension into the heart or the aorta).

A chest incision is sometimes necessary to assess resectability of a mediastinal tumor, and some patients may receive a chest incision for diagnostic purposes only.

●Large anterior mediastinal masses that cross the midline require sternotomy for exposure; however, a median sternotomy will generally not provide adequate exposure for an anterior mediastinal mass that extends below the level of the pulmonary hilum on either side.

●If the mass extends into the chest on one side only, a hemi-clamshell incision (figure 4) will provide the necessary exposure to achieve a complete resection.

●If the mass extends below the pulmonary hila on both sides, a full clamshell incision (figure 5) is usually necessary.

●Whenever the goal of the operation includes total thymectomy, as is the case in the setting of myasthenia gravis, it is always important to track the cervical limbs of the thymus into the neck. Complete thymic resection can be achieved with appropriate patient positioning and sternal retraction using a cervical (figure 6) approach. In skilled hands, a cervical approach is, arguably, the preferred approach for thymectomy as a treatment for nonthymomatous myasthenia gravis, but it is controversial for the resection of small masses. Thymomas, in particular, have a reputation for seeding if the capsule is violated, and any concern that this might occur should serve as a reason to use a median sternotomy or minimally invasive thoracoscopic approach. (See "Thymectomy", section on 'Incisions and surgical approach'.)

●A thoracotomy incision is a standard approach for middle and posterior mediastinal masses. A thoracotomy can also be a reasonable approach for an anterior mediastinal mass if the mass is completely contained within one side of the chest and does not cross the midline.

DIFFERENTIAL DIAGNOSIS

Mediastinal compartments — The mediastinum is defined as "the space between the lungs." The borders of the mediastinum are the thoracic inlet superiorly, the diaphragm inferiorly, the sternum anteriorly, the spine posteriorly, and the pleural spaces laterally.

The mediastinum is divided into compartments, and this is useful in developing a differential diagnosis when an abnormality is detected (table 1) as well as when planning techniques for biopsy or resection. With the three-compartment model, the anterior, middle, and posterior compartments are relatively easy to define with radiographic studies (figure 7) [14]. (See 'Imaging' above.)

●The anterior compartment lies between the posterior surface of the sternum and the anterior aspect of the great vessels and pericardium. The anterior compartment contains the thymus, internal mammary arteries, lymph nodes, connective tissue, and fat. The most common lesions occurring in the anterior mediastinum are often referred to as the "terrible Ts": thymoma, teratoma/germ cell tumor, (terrible) lymphoma, and thyroid tissue. (See 'Anterior mediastinal masses' below.)

●The middle compartment extends from the pericardium anteriorly to the ventral surface of the thoracic spine posteriorly and contains the pericardium, heart, great vessels, airway, and esophagus. The most common cause of a mass in the middle mediastinum is lymphadenopathy, which can be secondary to lymphoma, sarcoid, or metastatic lung cancer. (See 'Middle mediastinal masses' below.)

●The posterior compartment includes the spine and includes the costovertebral sulci. The posterior compartment contains the proximal intercostals, neurovascular bundles, spinal ganglia, the sympathetic chain, lymphatic tissue, and connective tissue. Neurogenic tumors represent the majority of posterior mediastinal masses. (See 'Posterior mediastinal masses' below.)

Anterior mediastinal masses — The anterior mediastinum is the most common location where mediastinal masses occur in adults (table 1). The most commonly found anterior mediastinal masses are often referred to as "the terrible Ts": thymoma, teratoma/germ cell tumor, (terrible) lymphoma, and thyroid tissue.

Thymic mass — Thymic lesions account for approximately one-half of all anterior mediastinal masses and can include a range of benign and malignant histologies (table 2). The relationship of the thymus to other mediastinal structures is shown in the figure (figure 8).

Thymoma and thymic carcinoma — Thymomas occur in patients of all ages, with a peak incidence between ages 40 to 60 years. The sex distribution is approximately equal. Thymomas are associated with a variety of paraneoplastic syndromes, the most common being myasthenia gravis. These are discussed elsewhere. (See "Clinical presentation and management of thymoma and thymic carcinoma".)

Some patients who are diagnosed with myasthenia gravis will be found to have a thymic mass on imaging. Patients with a thymic mass who have not been evaluated for myasthenia gravis should be tested for anti-acetylcholine receptor antibodies. (See "Diagnosis of myasthenia gravis", section on 'Classification by antibody status'.)

The most appropriate approach to biopsy depends on the appearance of the abnormality, but fine needle aspiration should not be used, because distinguishing a thymoma from lymphoma can be difficult histologically [12].

Preoperative biopsy is not necessary if the lesion is well circumscribed and the patient does not have systemic symptoms that suggest another diagnosis.

If the mass infiltrates surrounding structures or the patient has systemic symptoms or other findings that suggest an alternative diagnosis, biopsy should precede definitive resection as it may influence treatment significantly (ie, preoperative chemotherapy, ability to participate in a clinical trial). Masses that appear to infiltrate surrounding structures are more likely to be malignant, which occurs in 15 percent of thymomas.

It should be emphasized that the clinical scenario described here with an apparent locally invasive tumor is different than that described above where the dangers of tumor seeding with biopsy were discussed in the setting of a mass that was deemed easily surgically resectable. (See 'Biopsy' above.)

Preresection biopsy is much more important in a situation where imaging suggests complete resection could either be difficult or not even possible based on local involvement and the diagnosis is not clearly suggested by the clinical presentation and imaging. (See "Clinical presentation and management of thymoma and thymic carcinoma", section on 'General approach'.)

Other thymic masses — Thymic cysts are benign and only require resection if they are compressing other structures or to exclude other diagnoses if imaging does not definitively establish that the lesion is purely cystic or if there is any question of a solid component that could be a neoplasm. Similarly, thymic hyperplasia does not require resection if paraneoplastic symptoms are not present.

Relatively rarely, a thymic mass will turn out to be ectopic parathyroid tissue. Twenty percent of parathyroid adenomas are ectopic and located in the anterior mediastinum. Technetium 99 sestamibi imaging can be used for localization. These tumors may require resection if patients have symptoms of hyperparathyroidism. (See "Primary hyperparathyroidism: Clinical manifestations" and "Preoperative localization for parathyroid surgery in patients with primary hyperparathyroidism".)

Germ cell tumor — The mediastinum is the most common location for extragonadal germ cell tumors in adults. Germ cell tumors can be either benign (teratomas, dermoid cysts) or malignant (seminomas, nonseminomatous germ cell tumors). Seminomas are more common than nonseminomatous germ cell tumors. All patients with a mediastinal mass that could be a germ cell tumor should have alpha-fetoprotein (AFP), lactate dehydrogenase (LDH), and beta-human chorionic gonadotropin (beta-hCG) measured prior to any therapy. For males that present with a mediastinal mass that is suspected or proven to be a germ cell tumor, ultrasound should be performed to exclude a gonadal primary tumor. (See 'Imaging' above.)

Teratoma — Benign teratomas comprise two-thirds of all mediastinal germ cell tumors and have an equal sex distribution (image 4). While most are benign, teratomas have the potential for malignant degeneration and can be very aggressive; the prognosis of malignant teratomas is generally very poor (image 5).

Teratomas are often found incidentally but can cause pain or other symptoms due to compression of adjacent structures. There have been reports of paraneoplastic encephalitis due to anti-N-methyl-D-aspartate receptor antibodies in patients with benign ovarian or mediastinal teratomas [15,16]. Alpha-fetoprotein is normal with teratoma. Teratomas can contain elements of fat, fluid, and bone, and, if the imaging is convincing that teratoma is the most likely diagnosis, biopsy is not necessary. The treatment is surgical resection. (See "Extragonadal germ cell tumors involving the mediastinum and retroperitoneum", section on 'Mature teratomas'.)

Malignant germ cell tumor — Patients require physical examination, including testicular examination and scrotal ultrasound to ensure that the mediastinal findings do not represent metastatic disease from a primary testicular tumor. Ninety percent of malignant mediastinal germ cell tumors in adults occur in males and are most frequent in the third decade of life. In addition to the initial chest computed tomography (CT) scan (image 6), these patients require an abdominal CT scan for staging purposes. (See "Extragonadal germ cell tumors involving the mediastinum and retroperitoneum".)

●Seminoma – Seminomas are slightly more common than nonseminomatous germ cell tumors (image 7). AFP is normal in "pure" seminomas. Beta-hCG is mildly elevated in 10 percent of patients with seminomas. Management of seminomas involves chemotherapy with or without radiation therapy. Surgical excision may be indicated if residual mass is present after therapy but is generally determined between collaboration of the surgeon and medical oncologist and driven by the appearance of the tumor both before and after therapy [17].

●Nonseminomatous germ cell tumor – Nonseminomatous germ cell tumors have components of yolk sac carcinoma, embryonal cell carcinoma, and/or choriocarcinoma, and 80 percent have a metastasis at the time of diagnosis. Ninety percent of nonseminomatous germ cell tumors have elevated AFP and/or beta-hCG. Initial management of nonseminomatous germ cell tumors involves platinum-based chemotherapy. For patients in whom tumor markers normalize, surgical resection is indicated for any residual mass, which could represent either teratoma or residual tumor. If tumor markers do not normalize, patients should undergo additional salvage chemotherapy.

Lymphoma — Patients who present with mediastinal lymphomas may present with systemic symptoms such as fevers, weight loss, or night sweats but can also present with symptoms such as chest pain, dyspnea, wheezing, stridor, hoarseness, dysphagia, or superior vena cava syndrome due to compression of mediastinal structures.

The most common types of lymphoma presenting with disease in the mediastinum are nodular sclerosing Hodgkin lymphoma and primary mediastinal B-cell lymphoma (image 8). (See "Approach to the adult survivor of classic Hodgkin lymphoma" and "Primary mediastinal large B cell lymphoma".)

Establishing the diagnosis of lymphoma generally requires a core biopsy for flow cytometry. Fine needle aspirates often do not provide sufficient tissue to determine structural composition to definitively diagnose all subtypes of lymphoma. Definitive histologic diagnosis of nodular sclerosing Hodgkin lymphoma can sometimes be difficult. Although surgical resection is not typically considered part of the treatment regimen for lymphoma, surgeons may occasionally be asked to resect an isolated mediastinal mass proven to be lymphoma if the patient is thought to have prohibitive risks of complications with chemotherapy or radiation therapy or if the diagnosis remains in question based on a needle biopsy. In addition, and as discussed above, surgeons may occasionally resect an isolated mediastinal mass that was clinically thought to be a thymoma but, after resection, is confirmed to be lymphoma. (See 'Tissue diagnosis' above.)

Enlarged/ectopic thyroid — Intrathoracic thyroid tissue typically causes symptoms of shortness of breath or dysphagia (image 9). The intrathoracic mass is usually continuous with the thyroid gland in the neck; only 2 percent of cases are separate from the cervical thyroid. (See "Clinical presentation and evaluation of goiter in adults", section on 'Obstructive symptoms'.)

Resection can be achieved via transcervical thyroidectomy in 95 percent of cases. Less commonly, intrathoracic mobilization via video-assisted thoracoscopic surgery or with a partial or full sternal split is required for resection. Mediastinal masses, such as a large goiter, can cause significant airway deviation and/or narrowing. Careful anesthetic and operative planning are required to ensure safe resection. (See 'Anatomic evaluation and surgical planning' above and "Treatment of benign obstructive or substernal goiter".)

Middle mediastinal masses

Lymphadenopathy — Lymphadenopathy is the most common lesion presenting as a mass in the middle compartment of the mediastinum (image 10). The most common causes include lymphoma, sarcoid, and metastatic lung cancer. Mediastinoscopy, endobronchial ultrasound, and endoscopic ultrasound via the esophagus are very useful techniques to biopsy lymphadenopathy in this region. (See 'Biopsy' above and "Surgical evaluation of mediastinal lymphadenopathy".)

Benign cystic tumor — Cystic masses comprise approximately 20 percent of middle mediastinal masses (image 11).

●Bronchogenic cysts are the most common cystic lesion and are felt to be secondary to abnormal lung budding during development. Bronchogenic cysts are more common in men. These lesions are sometimes identified because patients have symptoms of substernal pain, cough, recurrent infection symptoms, or dyspnea and are typically located in the right paratracheal region and in the subcarinal location. (See "Congenital anomalies of the intrathoracic airways and tracheoesophageal fistula", section on 'Bronchogenic cyst'.)

●Enteric cysts are the third most common benign esophageal mass, after leiomyomas and polyps, and are usually asymptomatic. Three criteria are required to establish their diagnosis: esophageal attachment, the presence of two layers of muscularis propria, and epithelium characteristic of the gastrointestinal tract. (See "Benign lesions of the esophagus", section on 'Cystic lesions'.)

●Pericardial cysts occur with an incidence of 1 in 100,000 patients. Seventy percent arise in the right cardiophrenic angle. Symptoms can include shortness of breath, right heart failure secondary to compression, infection, and bleeding.

In general, bronchogenic and enteric cysts are resected to establish a definitive diagnosis and to decrease the risk of infection or malignant degeneration. Asymptomatic pericardial cysts can be observed, but resection may be needed if the diagnosis is not completely established by imaging. Simple drainage is generally not recommended, because these cysts typically recur without complete resection.

Cardiovascular aneurysm or anomaly — A variety of cardiovascular pathologies (eg, thoracic aortic aneurysm, pulmonary artery aneurysm, vascular rings) can present as a mediastinal abnormality. In asymptomatic patients, these are often noted initially as a widened mediastinum on chest radiographs (image 12). Symptoms referable to vascular structures may be related to compression of surrounding structures, which may be similar to those of other mediastinal masses or due to complications, such as vascular dissection or rupture, which would rarely be confused with other etiologies. Cardiovascular pathologies are generally easily identified on intravenous contrast-enhanced chest CT. (See "Clinical manifestations and diagnosis of thoracic aortic aneurysm".)

Esophageal tumor — Advanced esophageal tumors may be identified on imaging as a mediastinal mass; however, the location and symptoms such as dysphagia, weight loss, and occult blood loss are not likely to be confused with lymphadenopathy or other middle mediastinal masses. (See "Epidemiology and pathobiology of esophageal cancer".)

Posterior mediastinal masses

Neurogenic tumors — Neurogenic tumors represent more than 60 percent of posterior mediastinal masses. These lesions are classified based upon their neural cell of origin. (See "Peripheral nerve tumors".)

●Schwannomas (image 13) and neurofibromas are benign lesions that arise from the intercostal nerve sheath and make up 90 percent of adult neurogenic tumors.

●Neuroblastomas and ganglioneuroblastomas are malignant tumors that occur most commonly in children and originate from the sympathetic ganglia.

●Ganglioneuromas are benign lesions that arise from the sympathetic ganglia and are most common in young adults. Lesions that arise from paraganglionic cells include pheochromocytomas and paragangliomas.

Some neurogenic tumors are "dumbbell shaped" and arise near intervertebral foramen and have a posterior mediastinal and intraspinal component. Magnetic resonance imaging is generally required to investigate any intraspinal component, which adds significant complexity to resection of "dumbbell" lesions. Thoughtful planning of resection of dumbbell tumors mandates preoperative evaluation by both a spinal surgeon and a thoracic surgeon. Resection often proceeds in a two-step fashion, first using a posterior approach by the spine surgeon, followed by resection of the intrathoracic mass.

Meningocele — A spinal meningocele is a herniation of the meninges through a vertebral column defect or through a foramina. These are most commonly located posteriorly and in the lumbosacral region. Although rare, an anterior spinal meningocele will appear to be a posterior mediastinal mass on imaging. Because these abnormalities are cerebrospinal fluid-filled sacs, they may appear as cystic structures in communication with the vertebral column on imaging. (See "Closed spinal dysraphism: Clinical manifestations, diagnosis, and management".)

Thoracic spine lesions — Masses or lesions of the thoracic spine that extend either anteriorly or laterally can be seen as posterior mediastinal masses. Cross-sectional imaging will generally establish the etiology as arising from the vertebral column. (See "Spinal cord tumors".)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Thymomas and thymic carcinomas".)

SUMMARY AND RECOMMENDATIONS

●Mediastinal mass – Mediastinal masses comprise a wide variety of benign and malignant lesions (table 1) and may be identified incidentally on imaging performed for unrelated reasons (eg, preoperative) or for the evaluation of symptoms related to the mass. Local symptoms may be due to direct involvement or compression of normal mediastinal structures. Systemic symptoms can be due to the tumor or an associated paraneoplastic syndrome. (See 'Initial presentation' above.)

●Imaging – Computed tomography (CT) of the chest can confirm the presence of a mediastinal mass identified on plain radiography or other imaging and also provides detailed information regarding its location (anterior, middle, posterior mediastinum), size, relationship to other structures, and tissue characteristics. The location in the mediastinum (figure 7) and appearance of the mediastinal mass on imaging studies will often narrow the possibilities in the differential diagnosis. The presence of certain tumor markers can provide additional support in suggesting or ruling out specific diagnoses. (See 'Imaging' above and 'Differential diagnosis' above.)

●Tissue Diagnosis – Patient management relies on an accurate definitive diagnosis, which requires an adequate tissue sample. This may be obtained either by biopsy (percutaneous, endobronchial, surgical) or as part of a planned therapeutic resection. Core needle biopsy rather than fine needle aspiration should be obtained whenever possible to better differentiate histologically among the possible diagnoses. Pathology should confirm that adequate tissue has been obtained, and, if necessary, additional biopsies should be obtained while the patient is still sedated or anesthetized. In some situations, surgical resection without prior biopsy is indicated to avoid potential tumor seeding that can occur with biopsy procedures. (See 'Biopsy' above.)

•Anterior mediastinal mass – For patients in whom the only imaging abnormality is an anterior mediastinal mass, systemic symptoms typical of lymphoma are not present, and the mass is clearly resectable without any suggestion of invasion of local structures on imaging, we proceed with resection rather than obtaining preresection biopsy. This approach reduces the likelihood of worsening the prognosis of thymoma, at the potential increased risk of unnecessarily resecting a lymphoma.

•Posterior mediastinal mass – For posterior mediastinal masses, a biopsy is obtained if the clinical presentation and imaging has not strongly suggested a diagnosis, the mass involves structures considered not resectable, or the mass appears resectable, but the resection would be extensive and require complex reconstruction. (See 'Tissue diagnosis' above.)

●Surgical resection – Options for surgical resection include minimally invasive approaches (eg, video-assisted thoracoscopic surgery [VATS], robotic-assisted thoracoscopic surgery [RATS], transcervical resection) or traditional open approaches (eg, thoracotomy, median sternotomy, thoracosternotomy [clamshell], hemi-thoracosternotomy [hemi-clamshell] incisions). Prior to surgery, advanced imaging studies should be reviewed to plan the surgical and anesthetic approach. Lower extremity central venous access may be needed if the tumor involves the superior vena cava. In addition, alternatives for securing the airway at the time of anesthetic induction may be necessary (fiberoptic bronchoscopy, rigid bronchoscopy) and should be planned for in advance. (See 'Surgical resection' above.)

ACKNOWLEDGMENT — The editorial staff at UpToDate acknowledge William E Cohn, MD, who contributed to an earlier version of this topic review.