Mediastinal Cancer

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Continuing Education Activity

The mediastinum is a cavity that separates the lungs from the other structures in the chest. Generally, it is further divided into three main parts: anterior mediastinum, posterior mediastinum, and middle mediastinum. Cancers in the mediastinum can develop from structures that are anatomically located inside the mediastinum or that transverse through the mediastinum during development, and also from metastases or malignancies that originate elsewhere in the body.


  • Summarize the etiology of mediastinal cancers.
  • Explain how the history and physical examination findings usually vary by the type of mediastinal cancer, where it is located, and the aggressiveness of the tumor.
  • Discuss the tests performed most commonly to diagnose and evaluate mediastinal cancers.
  • Review strategies to optimize care coordination among interprofessional team members to improve outcomes for patients affected by cancer of the mediastinum.


The mediastinum is a cavity that separates the lungs from the other structures in the chest. Generally, it is further divided into three main parts: anterior mediastinum, posterior mediastinum, and middle mediastinum. The borders of the mediastinum include the thoracic inlet superiorly, the diaphragm inferiorly, the spine posteriorly, the sternum anteriorly, and the pleural spaces laterally. Structures contained within the mediastinal cavity include the heart, aorta, esophagus, thymus, and trachea.[1][2] The obtrusiveness of cancer and the severity of its signs and symptoms are dependent on its behavior within this visceral network. Cancers in the mediastinum can develop from structures that are anatomically located inside the mediastinum or that transverse through the mediastinum during development, and also from metastases or malignancies that originate elsewhere in the body. 


There are many different types of mediastinal cancers. Their prognosis depends on their behavior, their proclivity to invade or disseminate, and their resistance to treatment.[3] As stated above, the mediastinum can be proportioned into three parts, anterior, middle, and posterior, with each section having its inherent neoplasms.[4][5]

Anterior Mediastinum (bound by the pericardium posteriorly, pleural sacks laterally, and the sternum forward)

Thymic Carcinoma and Thymoma

Thymic carcinomas are rare but highly aggressive, early-metastasizing cancers derived from thymic epithelial cells. They are also the most common cancers of the anterior mediastinum, comprising (collectively with thymomas) about 20% of all mediastinal cancers and 10% of all thymic tumors.[5] They can be further differentiated into squamous cell carcinoma, basaloid carcinoma, mucoepidermoid carcinoma, lymphoepithelial-like carcinoma, sarcomatoid carcinoma, clear-cell carcinoma, adenocarcinoma, NUT (nuclear protein of testis) carcinoma, and undifferentiated carcinoma.[5] Like thymomas, thymic carcinomas occur in the 40 to 60 age range.[6] Thymic carcinomas have a fibrous stroma comixed with areas of necrosis, cystic changes, and calcifications. An initial diagnostic approach involves an evaluation by an MRI or CT though the former is sometimes favored. These scans will delineate the extent of the disease, its invasiveness, and hence its potential for complete resection. PET scanning has a less clear role as false-positive results occur in non-cancerous entities such as fibrosing mediastinitis, thymic hyperplasia, and infections.[7] Thymomas, being well-differentiated, tend to be PET negative, while thymic carcinomas are positive. Mediastinal thymic carcinoma is notably PET-positive; its presence portends a poorer prognosis. 

Thymomas, like carcinomas, are also thought to originate from thymic epithelial cells.[6] The thymomas are thought to have a central role in the initial development of the immune system. The thymus typically regresses by puberty, but the immune foundation it serves is believed to be the reason that thymomas are associated with a plethora of immune-based maladies. Examples include myasthenia gravis, red cell aplasia, polymyositis, systemic lupus erythematosus, Cushing syndrome, syndrome of inappropriate antidiuretic hormone, acquired hypogammaglobulinemia (AKA Good Syndrome), and Thymoma-associated multiorgan autoimmunity (AKA TAMA) which has a presentation akin to graft-versus-host disease (GVHD). Thymomas oft occur in adults, rarely in youths or children. There are no clear risk factors. Asians and African-Americans have a greater incidence. Thymomas behave in a show-growing, indolent fashion but can become invasive. Thymomas may transform into carcinomas, but this may take well over a decade. The National Comprehensive Cancer Network (NCCN) advocates diagnosing thymomas using clinical and X-ray features - avoiding a biopsy when or if possible. This is due to the inherent danger of seeding the tumor within the biopsy tract. In aggregate, upwards of 20% of thymic tumors will require a pretreatment biopsy. A transpleural thymoma biopsy, in particular, should be avoided as it can seed a path within the pleural space, thereby converting what may have been a stage I thymoma into stage IV disease.  

Germ Cell Tumor

The most common location for malignant germ cell tumors are the gonads; however, they can also arise in extragonadal regions. The mediastinum is the most commonly known location for extragonadal germ cell tumors. It has been speculated that they occur in these locations due to the abnormal migration of germ cells during embryogenesis. In adults, 10% to 15% of all mediastinal tumors are germ cell tumors, while approximately 25% of tumors are germ cell tumors in children. Thirty percent to 40% of these germ cell tumors are malignant and mainly found in men. When a mediastinal germ cell tumor is discovered, primary testicular or ovarian germ cell tumors should be excluded because the mediastinum could be a site of metastasis. Germ cell tumors include seminomas (termed dysgerminomas in women), embryonal carcinoma, yolk sac tumor, choriocarcinoma, immature teratoma, and mature teratomas. Other germ cell tumors of the mediastinum include mixed germ cell tumors, germ cell tumors with somatic type solid malignancy, and germ cell tumors with associated hematological malignancy.[8]

Teratomas involve cells from the embryonal cells layers of the ectoderm, mesoderm, and endoderm.[9] They appear over the torso, including the mediastinum when they fail to migrate properly during embryonal development.[10] They remain in the body midline but have a low incidence in the mediastinum, only 8 to 13%. Histologically, teratomas may be mature or immature (having malignant elements).[11] Teratomas tend to occur in patients less than 40 years of age. Benign mediastinal teratomas occur with equal frequency in males and females. Malignant teratomas are more common in males. Over half of patients manifest no signs or symptoms.[9] When symptoms do occur, the most common is dull, aching chest pain.[12] Characteristically, though not frequently, patients may manifest trichophytic or coughing up hair.[12] This is due to a fistula, communication between the teratoma and the tracheobronchial tree. 

Other symptoms may include hemoptysis, fever, and pleural effusion.[10] The presence of a pleural or pericardial effusion is felt to overlay a tumor rupture.[13] Mediastinal (mature) teratomas contain soft tissue in almost all cases, fluid in 88%, fat in 76%, and not infrequently calcifications, ossifications, and teeth. The rapid growth of a teratoma has been ascribed to a number of mechanisms, including hemorrhage, ischemia/necrosis with concurrent inflammation, and damage caused by components of the tumor itself like lipase/amylase (pancreatic), sweat (skin), and digestive juices (intestinal) for example. The presence of an elevated alpha-fetoprotein (AFP) or a beta-human chorionic gonadotropin (BHCG) rules out pure/mature teratomas (and seminomas) and suggests a diagnosis of malignancy such as embryonal cancer, endodermal sinus cancer, or choriocarcinoma.[14] Here the elevated markers make the diagnosis even if a biopsy fails to do so. For benign/mature teratomas, complete surgical resection is the only modality.[11][14] There is no role for adjuvant chemotherapy or radiation. For immature teratomas, complete surgical resection with either adjuvant or neoadjuvant chemotherapy is felt to prolong survival. Delay in treatment allows the mature teratoma to possibly convert to a malignant form. A delay in surgery can complicate the eventual effort to resect and cure. This tumor may become transfixed to surrounding structures, leaving the surgery fraught with risks like rupture, pulmonary atelectasis, infection, and empyema. While tumor size complicates resectability, surgical delay can bring a perioperative demise. 

"Growing teratoma syndrome" (GTS) is a special situation that can occur anywhere within the torso but is particularly problematic within the mediastinum.[15][16][17] Recognizing it demands a shift in treatment. In germ cell tumors, it carries a prevalence in the range of 1.9% to 7.6%. Typically it occurs during the treatment of non-seminomatous germ cell tumors. These tumors would initially respond to their Platinol-based chemotherapy with shrinkage as well as normalization of their markers (alpha-fetoprotein AFP and beta-human chorionic gonadotropin BHCG). LDH, if elevated, might also normalize. However, the tumor may suddenly grow faster during the treatment cycle though the markers remain negative. What is believed to have happened is that the chemotherapy has destroyed the immature malignant cells but allowed the growth of a mature, benign teratomatous component. 

Unlike their germ cell cohort, benign teratomas have a negative (AFP/BHCG), negative PET scan, and are resistant to both chemotherapy and radiation. With the discovery of GTS, the chemotherapy should be stopped, and the only modality of treatment, complete surgical resection, should be given. GTS has been reported in the retroperitoneum (most common site), lung, forearm, mesentery, liver, pineal gland, and the inguinal/cervical/supraclavicular nodes. The 'benign' teratomatous element grows quickly, and if surgery is delayed, it can overrun and obstruct the surrounding viscera. During this situation, it is also essential to rule out other non-malignant sources of markers such as an elevated AFP in hepatic dysfunction or an elevated BHCG due to marijuana use, or an increased luteinizing hormone. Generally speaking, with surgery, the overall survival can be 90%; incomplete resection brings recurrence. Histologic analysis of the resected specimen shows a benign mature teratoma with a non-germ cell component. In the mediastinum, the treatment data appears relatively poorer. The 5-year overall survival rate is 30% to 45%, with a 4% operative mortality (due primarily to pulmonary problems). Following complete resection, GTS can recur in up to 4% of cases; with incomplete resection, the rate can be as high as 83%. 


Primary mediastinal lymphoma is a relatively uncommon tumor. It is generally observed in senior women and men. The most common types of primary lymphomas which present as a disease in the mediastinum are primary mediastinal large B-cell lymphoma, Nodular Sclerosing Hodgkin's disease, marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT), as well as other the more rare T-lymphoblastic leukemia/lymphoma, anaplastic large cell lymphoma, and other T-/B-/NK-cell entities. Secondary lymphomas of the mediastinum, which originate elsewhere in the body and metastasize to the mediastinum, are more common than primary mediastinal lymphomas.[18] Primary mediastinal lymphoma is a tumor of large B cells with concurrent sclerosis.[19]  It is likely of thymic B cell origin. It is an entity separate from Diffuse Large B-cell Lymphoma. Microscopic analysis may show some resemblance with this lymphoma or with nodular sclerosing Hodgkin's disease. It is found in young adults and is virtually confined to the anterior mediastinum. Treatment initially involves complex chemotherapy with radiation reserved for consolidation.[20] For relapse, intensive chemotherapy followed by an autologous stem cell transplant is the favored approach. Nodular sclerosing Hodgkin's disease frequently presents as an anterior mediastinal mass though rarely obstructive or obtrusive.[21] 

Cervical or supraclavicular adenopathy may be present. Their discovery is most often serendipitous. Chemotherapy carries a good 90%, or more, 5-year survival. PET scanning is used in initial staging and to judge the efficacy of therapy as patients with good responses seen on the PET scan can negate a full course of chemotherapy or the addition of radiation.[22][23] Marginal zone lymphoma of mucosa-associated Lymphoid Tissue (AKA MALT or  "thymic MALT lymphoma")  is a relatively rare lesion of the anterior mediastinum.[24]  It is oft found in Asian adult females and is associated with autoimmune diseases, especially Sjogren syndrome.[25] Its behavior is indolent, and it frequently exists as an encapsulated tumor, often with cystic regions and rarely with adenopathy. The literature advocates an en-bloc surgical resection of the nodes and tumor with adjuvant chemotherapy (e.g., RCHOP) for positive nodal disease.

Middle Mediastinum (bounded by the pericardial and bilateral pleural sacks both anteriorly and posteriorly)

Parathyroid Adenoma

Several tumors can metastasize to the middle mediastinum. Parathyroid adenoma is one. Primary hyperparathyroidism affects up to 0.5% of the population, with increasing incidence after age 50.[26]  While a quarter of the cases have ectopic foci, only about 2% are in the mediastinum - less so in the middle portion. Surgical resection is the treatment of choice, offering cures to upwards of 98%.[27] Treatment failure is due to either an incomplete resection or ectopic foci (as in the middle mediastinum). Because of this difficulty, it is recommended that patients undergo a preoperative evaluation with concurrent Tc99-Sestamibi and Single-Photon Emission (SPECT/CT) scanning that carry an excellent sensitivity for defining ectopic disease.[28] Better preoperative planning is important as middle mediastinal lesions favor a sternotomy approach - different from others.[29] 

Posterior Mediastinum (bounded by the pericardium anteriorly, diaphragm inferiorly, and the transverse thoracic plane superiorly)

Neurogenic Mediastinal Neoplasms

These neurogenic tumors represent more than 60% of the masses found in the posterior mediastinum, are primarily found in children, and can reach a large size before becoming symptomatic. Approximately 30% of neurogenic neoplasms are malignant. They present with a large variety of both clinical and pathological features that are classified by the origin of the cell type. These are the most common cause of neurogenic mediastinal cancers and are classified as nerve sheath neoplasms (Schwannomas and neurofibromas) and ganglion cell neoplasms (neuroblastomas and ganglioneuroblastomas). 

Schwannomas are nerve sheath tumors. They compose half of the mediastinal neurogenic tumors though only 9% of all Schwannomas occupy the mediastinum.[30][31][32] They are mostly benign and slow-growing though malignant transformation can occur, typically in patients with Neurofibromatosis. The treatment of benign tumors involves surgical resection, oft using VATS (Video-assisted Throacosopy). For malignant lesions, surgery is followed by adjuvant radiation. Chemotherapy is of no use. Neurofibromatosis lesions of the mediastinum that occur in conjunction with the vagus nerve are almost always found with von Recklinghausen disease.[33] Histologically, these are typical of a plexiform pattern which makes surgical excision (the treatment of choice) more difficult. Neuroblastomas can arise from the sympathetic ganglia near the thoracic spine.[34][35] It is the most common tumor in the pediatric age group, with most patients less than two years of age. Treatment requires surgical resection with adjuvant chemo(radio)therapy. Ganglioneuroblastoma is a tumor of the adrenal gland or the sympathetic nervous system.[36][37] It is most common in young children, particularly 1 to 2 years of age. Early diagnosis and surgery are recommended as a 2-year survival of 92% is quoted in the literature. Recurrences tend to occur in adults and youths - the older the patient, the poorer the outcome.   


Mediastinal cancers are usually rare. Typically, they are diagnosed in patients aged 30 to 50 years but can develop at any age from any tissue that is located or passes through the mediastinum. Children usually present with cancers in the posterior mediastinum, while adults typically present with cancers in the anterior mediastinum. There is a similar incidence in men and women, but it can vary with the type of cancer present.[38]


There are various mediastinal cancers, and the histopathology depends upon the origin of the cancer.

History and Physical

A detailed history and physical should be performed. The history and physical examination findings usually vary by the type of mediastinal cancer, its location, and the tumor's aggressiveness. Some people present with no symptoms, and cancers are typically found during imaging of the chest which is performed for other reasons. If symptoms are present, they are often a result of cancer compressing the surrounding structures or symptoms from a paraneoplastic syndrome. These symptoms may include a cough, shortness of breath, chest pain, fever, chills, night sweat, coughing, hoarseness, unexplained weight loss, lymphadenopathy, coughing up blood, wheezing, or stridor. Mediastinal masses could also be associated with abnormalities in other parts of the body (such as testicular masses with germ cell tumors). Thus, a thorough history is necessary and includes a complete review of symptoms followed by a comprehensive physical examination. In general, malignant lesions tend to be symptomatic.


Cancers in the mediastinum have a wide diversity of presentations.[39][40] The location of cancer and its composition are paramount to narrowing the differential diagnosis. The old medical adage of "least aggressive to most invasive" applies well here. Dependent upon the situation, a biopsy can be precarious. For certain disorders, a biopsy may not be appropriate. The tests performed most commonly to diagnose and evaluate mediastinal cancers include the following.

Chest X-ray

Chest radiographs (posteroanterior and lateral) are usually the first step in discovering a mediastinal mass and can help localize the mass is in the anterior, posterior, or medial mediastinum to help with the differentials. The mass could be an incidental finding on an asymptomatic patient who has had a chest X-ray before elective surgery or an evaluation of an unrelated condition. It can also be done as an evaluation in patients who present with symptoms due to the mediastinal mass or paraneoplastic syndromes. In general, malignant lesions tend to be symptomatic. When a mass protrudes into the mediastinum, the normal structures (e.g., aorta) lose their roentgenographic signatures, their "silhouette sign."[7] However, radiography is of very limited value in characterizing mediastinal cancers.

CT Scan of the Chest

To evaluate masses seen on chest X-rays, a CT scan of the chest is usually performed with intravenous (IV) contrast, which can often show its exact location, whether the mass is well-circumscribed, or if it infiltrates the surrounding structures. In many cases, no further workup is necessary for diagnosis. Characterization of the mass on the CT scan is based on specific attenuation of water, air, fat, calcium, soft tissue, and vascular structures. High-resolution multiplanar reformation images demonstrate the detailed anatomical relationship of cancer's precise location, morphology, and relationship to the adjacent structures.

MRI of the Chest

MRI is indicated when CT finding is equivocal. Recently, special applications of MRI have been developed to identify precisely the tissular components of mediastinal masses. Excellent soft-tissue contrast makes MRI an ideal tool to evaluate cancers of the mediastinum. Chemical-shift MRI has helped differentiate normal thymus and thymic hyperplasia from thymic cancers and lymphoma. Diffusion-weighted MRI (DWI) is another special application that unveils minute biophysical and metabolic differences between tissues and structures. The mean apparent diffusion coefficient for malignant mediastinal entities could be substantially lower than for benign diseases.

Mediastinoscopy with Biopsy

This test collects cells from the mediastinum to determine the type of mass present for a definitive diagnosis. It is done under general anesthesia. A small incision is made under the sternum, and a small tissue sample is removed to analyze if cancer is present. This test will help the physician determine the type of cancer present with very high sensitivity and specificity. Establishing the diagnosis of lymphoma generally requires a core biopsy for flow cytometry.

Endobronchial ultrasound (EBUS) and Endoscopic ultrasound (EUS)

Endobronchial ultrasound has become the diagnostic procedure of choice for most mediastinal pathologies. Most of the mediastinal lymph node stations, including stations 2, 4, 7, 10, and 11, can be accessed with the help of an EBUS and combined with EUS, even other stations like 7, 8, and 9 can be accessed. EBUS can be done under conscious sedation or general anesthesia. It is usually a single-day, outpatient procedure with minimal complications. It is safer than mediastinoscopy, with almost similar diagnostic efficacy.

Laboratory Studies

Basic Laboratory tests such as complete blood count (CBC) and basic metabolic panel (BMP) can help in the differential diagnosis of lymphomas. In the instances of mediastinal masses, tumor markers can help support a presumptive diagnosis. These include:

  • Beta-hCG (associated with germ cell tumors and seminoma)
  • LDH (may be elevated in patients with lymphoma)
  • AFP (associated with malignant germ cell tumors): Mediastinal non-seminomatous germ cell tumors are more likely to result in distinct elevations of serum AFP and less likely in elevations of beta-hCG compared to gonadal or retroperitoneal non-seminomatous germ cell tumors. Malignant germ cell tumors are closely related to serum tumor markers, especially AFP and beta-hCG. The measurement of these serum tumor markers is important in the diagnosis, management, and follow-up of these patients.

Testicular Ultrasound

In suspected cases of metastasis to the mediastinum from primary testicular germ cell tumors, palpation of the testicles is insufficient, and ultrasonography of the testicles should be performed in all patients.

Treatment / Management

The treatment for mediastinal cancers depends primarily on the type of cancer, its location, aggressiveness, and symptoms it may be causing. Treatments of the most common mediastinal cancers are discussed below.[41][42][43]

Thymic Cancers

Treatment of thymic cancers usually requires surgery, followed by radiation or chemotherapy. Pulmonary function studies and a cardiac evaluation should be done in any patient where surgery is being contemplated on the thymus. This is to determine if the patient has enough cardiopulmonary reserve for the surgery.[6] Surgery is the initial treatment in patients who present with tumors invading readily resectable structures like the mediastinal pleura, pericardium, or adjacent lung. A resected specimen will then be sent for histopathologic examination for staging and to determine if postoperative radiotherapy or chemotherapy are required. The ability to completely resect the thymic carcinoma is dependent on the degree of invasion and/or adherence to surrounding structures. The pericardium and surrounding lung parenchyma are sometimes removed to achieve complete resection with histologically negative margins.

Types of surgery that are being performed include thoracoscopy (minimally invasive), mediastinoscopy (minimally invasive), and thoracotomy (performed by making an incision in the chest). In patients for whom complete resection is not feasible as the initial treatment, for example, those with cancer invasion into the innominate vein, phrenic nerve, heart, or great vessels, therapy involving preoperative chemotherapy and postoperative radiotherapy is indicated. If neoadjuvant chemotherapy allows for a partial or complete response, these cancers are considered potentially resectable, and patients should be reevaluated following therapy. If complete resection cannot be accomplished with surgery, these patients should undergo maximum debulking followed by radiotherapy postoperatively if technically feasible. This may control the residual disease.

For unresectable cancers, systemic therapy, radiotherapy, or chemoradiotherapy may be recommended in patients with extensive pleural/pericardial metastases, non-reconstructable great vessel invasion, heart, tracheal involvement, or distant metastases. Although there are no clinical trials that provide evidence of the benefit of surveillance after treatment, monitoring with thoracic imaging is warranted, given early intervention may be more effective.[44] As of the date of this writing, the National Comprehensive Cancer Network (AKA NCCN) generally recommends a surveillance chest CT with contrast every six months for two years, then yearly for five years in thymic cancer (10 years for thymoma). Thymomas/thymic cancers having extrathoracic metastases are treated using chemotherapy. Locally advanced, the unresectable disease is treated with chemoradiation. Recurrences are approached based on resectability. Surgically-operable lesions receive neoadjuvant chemotherapy and possible adjuvant radiation. As always with neoadjuvant therapy, the purpose is to reduce the lesion and improve resectability. Unresectable recurrences receive radiation and possibly chemotherapy. 


For benign teratomas, complete surgical resection brings a cure. Incomplete resection leads to local recurrence.[16] Immature teratoma or admixtures with other cancers necessitates neoadjuvant or adjuvant therapy as the circumstance dictates.[13] As stated previously, an elevated marker, such as AFP or BHCG, denotes a malignancy even if the biopsy fails to confirm it. 


Treatment depends on the type of lymphoma, its stage, and metastases. Most lymphomas are generally treated with chemotherapy followed by radiation.[45]           

  • Primary mediastinal B-cell lymphoma originates in the mediastinum and is essentially managed like the early stage of diffuse large B-cell lymphoma (DLBCL). The primary treatment is around six courses of CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) plus rituximab (R-CHOP). This could be followed by radiation to the mediastinum in suitable patients. A PET/CT scan is usually done after the chemotherapy to see if there are any lymphoma remnants in the chest. If no active lymphoma is observed on the PET/CT scan, the patient may be observed without further intervention. However, radiation may be necessary if the PET/CT scan shows a possible active lymphoma in the mediastinum. Often, a biopsy of the chest tumor is ordered by the physician to affirm that the lymphoma is still present before starting radiation.
  • Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) is rare cancer. It can be treated with radiation therapy to the stomach, rituximab, chemotherapy, chemotherapy plus rituximab, or the targeted drug ibrutinib. Chlorambucil or fludarabine could be used for single-agent chemotherapy or combinations such as CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) or the combination CVP (cyclophosphamide, vincristine, prednisone) could be used. Hodgkin lymphoma treatment usually starts with chemotherapy.
  • Nodular sclerosing Hodgkin's disease utilizes the most common 4-drug combination in the United States: AVCD: adriamycin (doxorubicin), bleomycin, vinblastine, dacarbazine (DITC), which is given in cycles. Radiation therapy is often given after chemotherapy. 

Neurogenic Tumors

Surgery is the preferred treatment for malignant neurogenic tumors. Procedures include a post-lateral thoracotomy which can give the surgeon good exposure to the tumor, and, more recently, video-assisted thoracic surgery (VATS). VATS is a minimally invasive procedure that inserts a thoracoscope and surgical instruments through small incisions in the chest. This procedure decreases the access trauma and gives a good view, especially for smaller posterior mediastinal neurogenic tumors, but it is not ideal for giant mediastinal neurogenic tumors because of their huge volume. For dumbbell neurogenic tumors, sufficient preoperative evaluation is required of the intraspinal part of the tumor to prevent uncontrollable hemorrhage during surgery. The cooperation of a thoracic surgeon with a neurosurgeon is recommended for this procedure. For malignant mediastinal neurogenic tumors, the five-year survival rate is low and complete resection is rarely possible. There is frequent use of radiation in conjunction with chemotherapy before surgery to decrease the size of the tumor or after to treat the margin of the resection bed.

Mediastinal Germ Cell Tumors

Management of mediastinal germ cell tumors varies with the type of tumor present. It may include chemotherapy, surgery, radiotherapy, or a combination of these treatments.

  • Mediastinal seminoma or dysgerminoma: Treatment essentially depends on the size of the tumor. For smaller sizes, patients usually undergo radiotherapy, which can eradicate the tumor. For larger tumors, the treatment of choice is chemotherapy. This is most commonly a combination of bleomycin, etoposide, and cisplatin (BEP). Radiation has a higher rate of recurrence compared to chemotherapy. If these treatments fail to eliminate all the tumor mass and the remaining area is smaller than 3 cm, patients are likely to be monitored periodically by the physician to see if the tumor grows again. If the residual tumor is greater than 3 cm after treatment, the physician can opt for routine monitoring or further surgery to remove the tumor.
  • Mediastinal non-seminomatous germ cell tumors: Chemotherapy is the first-line treatment for primary mediastinal non-seminomatous germ cell tumors. A combination of drugs is traditionally used, the most common being BEP (bleomycin, etoposide, and cisplatin), and standard therapy consists of 4 courses of BEP. Men with non-seminomatous primary mediastinal germ cell tumors have a worse prognosis of survival compared to men with mediastinal seminoma. After chemotherapy, patients may undergo salvage surgery to remove the remaining tumor. The optimal strategy for long-term survival in patients who present with mediastinal non-seminomatous germ cell tumors remains to be defined. A study at Indiana University described 31 patients with mediastinal non-seminomatous germ cell tumors who received cisplatin, bleomycin, and either vinblastine (20 patients) or etoposide (11 patients) followed by surgical resection; 15 patients (48%) achieved long-term disease-free survival. A retrospective study of 64 patients with mediastinal non-seminomatous germ cell tumors (NSGCTs), treated in France from 1983 through 1990, estimated a 2-year overall survival rate of 53%. More recently, a 5-year overall survival rate of 45% was reported in an international analysis of 141 patients with mediastinal NSGCT from 11 cancer centers, treated from 1975 through 1996 in the United States and Europe. Treatment variables that may determine survival outcomes include the duration the patient received chemotherapy, the use of additional anti-cancer drugs such as anthracyclines, alkylating agents, and when the surgery was performed. 

Differential Diagnosis

Retrosternal goiter/intrathoracic goiter; primary intrathoracic goiter behaves differently from the more common secondary subtype.[46][47] The secondary form is an extension of the thyroid into the retrosternal space. The primary form is separate from the cervical thyroid, with their blood supply coming from intrathoracic sources. It may compress the trachea, which, if prolonged, can lead to a postoperative tracheomalacia that could require a tracheostomy. The treatment of choice is surgical resection. 

Tuberculosis: TB can exist as a unique entity called "mediastinal tuberculous lymphadenitis."[48] It is found almost always in children and Asian/Black developing nations. The basic problem is not in the lungs so much as the inflammatory granulomatous disease in the hilar and mediastinal lymph nodes. These nodes can enlarge and erode into the surrounding viscera. They may mimic other maladies, especially in the posterior mediastinum. They can cause fibrosing mediastinitis, constrictive pericarditis, and tubercular neuritis. 

Aneurysm: Vascular anomalies can distort the overview, giving the radiologic appearance of an underlying mass.[49] In type IV Ehler-Danlos syndrome, there is a dysmorphism in the vascular wall predisposing to aneurysms, dissection, rupture, or fistulae. For symptomatic cases, surgical resection is advocated. 

Bronchogenic cyst; These cysts occur primarily in the middle mediastinum and occur secondarily to the abnormal budding of the tracheobronchial tree during fetal development.[50][51][52] Most cases are asymptomatic or may have a cough at most. Symptomatic patients are resected. Asymptomatic adults may have a conservative "watch-and-wait" approach. However, some advocate resection in young asymptomatic people to avoid late problems such as infection, hemorrhage, and neoplastic transformation.

Pleuropericardial cysts: these are congenital anomalies with a propensity for development in the middle mediastinum.[53][54][55] Some cysts may be acquired after cardiothoracic surgery. Most cysts are asymptomatic and are not prone to malignant transformation. Aspiration can lead to infection; it is recommended not to do so. Most cases resolve spontaneously, but if symptoms do occur like chest pain or dyspnea, surgery is to be performed. Pleuropericardial cysts can run the risk of hemorrhage,l atrial fibrillation, and cardiac tamponade. Asymptomatic patients can be treated conservatively with close follow-up. 


The prognosis depends on the cause and response to treatment.


Respiratory compromise; mediastinal masses can cause airway obstruction leading to respiratory distress, also known as 'critical mediastinal mass syndrome.[56][57][58][59] When biopsy or surgery requires general anesthesia, these patients are at risk for tracheobronchial airway collapse. Muscle relaxants, sedatives, and paralytic agents are said to be avoided. Countermeasures include using extrinsic positive end-expiratory pressure as a "pneumatic splint" to maintain airway patency. Some have advocated cardiopulmonary bypass or ECMO (extracorporeal membrane oxygenation).

Tracheomalacia; This is a condition where the trachea manifests excessive expiratory collapse due to damaged tracheal (wall) elastic fibers.[60][61][62] During expiration, the trachea narrows and shortens, but with wall damage, there is wall collapse and airway obstruction. It can occur due to chronic external tracheal compression from cancers, but it is also seen with non-malignant causes such as cysts, abscesses, aortic aneurysms, chronic obstructive pulmonary disease (COPD), and polychondritis. Diagnosis is made by bronchoscopy. Conservative initial management with interventions like CPAP (continuous positive airway pressure) should be attempted. Surgical intervention, as circumstances dictate, could involve tracheobronchoplasty, tracheostomy. or stenting.   


  • Thoracic surgeon
  • Oncologist

Pearls and Other Issues

  • Cancers in the mediastinum can develop from structures that are anatomically located inside the mediastinum or that transverse through the mediastinum during development, and also from metastases or malignancies that originate elsewhere in the body.
  • Mediastinal cancers are usually rare. Typically, they are diagnosed in patients aged 30 to 50 years but can develop at any age from any tissue located or passes through the mediastinum.
  • Children usually present with cancers in the posterior mediastinum, while adults usually present with cancers in the anterior mediastinum.
  • There is a similar incidence in men and women, but it can vary with the type of cancer present.

Enhancing Healthcare Team Outcomes

Many lesions can occur in the mediastinum, and diagnosis can be challenging. An interprofessional approach including a primary care clinician (MD, DO, NP, or PA), oncologist, radiologist, thoracic surgeon, anesthesiologist, and intensivist is recommended. Placing these individuals under general anesthesia also can cause respiratory obstruction and cardiovascular collapse because of the mass effect on the trachea. Anyone looking after patients with a mediastinal mass should follow the recommendations on diagnosis, treatment, and post-treatment care.

Specialty trained nurses should educate the patient and the family on the lesions and their post-treatment care. Some lesions like lymphoma may be treated with radiation, whereas most other lesions require surgery and/or chemotherapy. In the postoperative period, these patients need pain control, incentive spirometry, and ambulation to prevent early complications. The perianesthesia, critical care, and medical-surgical nurses should monitor the patient and inform the team about major changes or issues. Pharmacists should evaluate medication choices and drug interactions and educate the patients when appropriate.[63][64] [Level 5]


The outcomes for most localized lesions of the mediastinum in children and adults are good. However, if the lesions are large and invade local tissues, surgery may require the removal of important tissues like the phrenic nerve and innominate vein. Only via an intradisciplinary approach and communication with the different specialists can the morbidity of surgery and treatment be decreased.[65][66][67] [Level 5]

(Click Image to Enlarge)
Superior mediastinum, anterior mediastinum, middle mediastinum, posterior mediastinum, Superior compartment, Inferior compartment,
Superior mediastinum, anterior mediastinum, middle mediastinum, posterior mediastinum, Superior compartment, Inferior compartment,
Contributed Illustration by Bryan Parker
Article Details

Article Author

Talha N. Jilani

Article Author

Robert B. Killeen

Article Editor:

Abdul H. Siddiqui


8/21/2022 10:56:21 AM

PubMed Link:

Mediastinal Cancer



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