Cancer, Mediastinum


Article Author:
Talha Jilani


Article Editor:
Abdul Siddiqui


Editors In Chief:
Evelyn Metz
Julie Sewell
Aditya Arya


Managing Editors:
Orawan Chaigasame
Carrie Smith
Abdul Waheed
Frank Smeeks
Kristina Soman-Faulkner
Benjamin Eovaldi
Radia Jamil
Sobhan Daneshfar
Saad Nazir
William Gossman
Pritesh Sheth
Hassam Zulfiqar
Navid Mahabadi
Steve Bhimji
John Shell
Matthew Varacallo
Ahmad Malik
Mark Pellegrini
James Hughes
Beata Beatty
Hajira Basit
Phillip Hynes


Updated:
3/24/2019 9:21:32 PM

Introduction

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]

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.

Etiology

There are many different types of mediastinal cancers. Their location in the mediastinum can further determine the causes of these cancers. [3]

Anterior Mediastinum

Thymic Carcinoma

Thymic carcinoma is a rare but aggressive, early-metastasizing cancer derived from thymic epithelial cells. It is also the most common cancer of the anterior mediastinum and can be further differentiated into squamous cell carcinoma, basaloid carcinoma, mucoepidermoid carcinoma, lymphoepithelioma-like carcinoma, sarcomatoid carcinoma, clear-cell carcinoma, adenocarcinomas, NUT carcinoma, and undifferentiated carcinoma.[4]

Germ Cell Tumors

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 common known location for extragonadal germ cell tumors. It has been speculated that they occur in these locations due to abnormal migration of germ cells during embryogenesis. In adults, 10% to 15% of all mediastinal tumors are germ cell tumors, while in children, approximately 25% of tumors are germ cell tumors. Thirty percent to 40% of these germ cell tumors are malignant and found mostly 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. Mature teratomas of the testis are considered cancerous, and it can metastasize to the mediastinum. Other germ cell tumors of the mediastinum include mixed germ cell tumor, germ cell tumor with somatic type solid malignancy, and germ cell tumor with associated hematological malignancy.[4]

Lymphoma

Primary mediastinal lymphoma is a relatively uncommon tumor. It is generally observed in senior women and men. The most common types of primary lymphoma which present as a disease in the mediastinum are nodular sclerosing Hodgkin lymphoma (NSHL) and primary mediastinal large B-cell lymphoma. Others include extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma), other mature B-cell lymphomas, T-lymphoblastic lymphoma/leukemia, anaplastic large cell lymphoma, and other rare mature T-cell and NK-cell lymphomas, Hodgkin lymphoma (other types). Secondary lymphomas of the mediastinum, which originate elsewhere in the body and metastasize to the mediastinum are more common than primary mediastinal lymphomas.[5]

Mediastinal Thyroid Mass

Usually benign, these can become cancerous

Posterior Mediastinum

Neurogenic Mediastinal Neoplasms

These are derived from neural cells in any location but are commonly found in the mediastinum. These neurogenic tumors represent more than 60% of the masses found in the posterior mediastinum, are mostly 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), these can rarely become malignant. Ganglion cell neoplasms (neuroblastomas and ganglioneuroblastomas) are malignant tumors that occur mostly in children. Paraganglionic cell neoplasms (pheochromocytomas and paragangliomas).

Middle Mediastinum

Thyroid Cancers

Metastasis from thyroid cancers can spread to the middle mediastinum.

Mediastinal Thyroid Mass

Usually benign, these can occasionally become cancerous.

Metastatic Lung Cancers

Lung cancers can metastasize to the mediastinum either by direct extension or lymph node metastasis.

Esophageal Cancers

Advanced esophageal cancers can present as a mass in the mediastinum.

Epidemiology

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 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.[6]

Histopathology

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

History and Physical

A detailed history and physical should be done. The history and physical examination findings usually vary by the type of mediastinal cancer, where it is located, and aggressiveness of the tumor. 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 should be taken and include a complete review of symptoms followed by a complete physical examination. In general, malignant lesions tend to be symptomatic.

Evaluation

Cancers in the mediastinum have a wide diversity of presentation. [7][8] The location of cancer and its composition are paramount to narrowing the differential diagnosis. The tests performed most commonly to diagnose and evaluate mediastinal cancers include:

Chest X-ray

Chest radiographs (posteroanterior and lateral) are usually the first step in the discovery of 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 as 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. However, radiography is of very limited value in characterizing mediastinal cancers.

CT Scan of the Chest

To evaluate masses seen on chest x-rays, 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 needed 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, as well as its 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 been helpful in differentiating normal thymus and thymic hyperplasia from thymic cancers and lymphoma. Diffusion-weighted MRI (DWI), another special application that unveils minute biophysical and metabolic differences between tissues and structures. According to Gumustas et al., the mean apparent diffusion coefficient for malignant mediastinal entities could be substantially lower than that for the 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 sample of tissue 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 of the mediastinal pathologies. Most of the mediastinal lymph node stations including station 2, 4, 7, 10, and 11 can be accessed with the help of an EBUS. 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 found to be 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 nonseminomatous 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 nonseminomatous germ cell tumors. This was demonstrated by Bokemeyer et al. Malignant germ cell tumors are closely related to serum tumor markers, especially AFP and beta-hCG and measurement of these serum tumor markers is important in 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 not sufficient, 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. [9][10][11]

Thymic Cancers

Treatment of thymic cancers usually requires surgery, followed by radiation or chemotherapy. 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. Sometimes to achieve complete resection with histologically negative margins, the pericardium and surrounding lung parenchyma are also removed. Types of surgery which 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 who have extensive pleural/pericardial metastases, unreconstructable great vessel invasion, heart, tracheal involvement, or distant metastases. Although there are no clinical trials providing evidence of the benefit of surveillance after treatment, monitoring with thoracic imaging is warranted given early intervention may be more effective. The National Comprehensive Cancer Network recommends a CT scan every 6 months for 2 years, then annually for 5 years. The prognosis for patients with thymic carcinoma depends on the stage of disease, complete resectability, and histologic type.[12]

Lymphomas

Treatment depends on the type of lymphoma, its stage, and metastases. Most lymphomas are generally treated with chemotherapy followed by radiation.[13]

  • Diffuse large B-cell lymphoma (DLBCL) are known to grow quickly. Most often, the treatment of choice is chemotherapy with a combination of 4 drugs: cyclophosphamide, doxorubicin, vincristine, and prednisone (known as CHOP), and the monoclonal antibody rituximab. This combination, also called R-CHOP, is commonly given in cycles separated by 3 weeks. Because this regimen includes the drug doxorubicin, which could damage the heart, it is not suitable for patients who have heart problems, and the use of other chemotherapy regimens is recommended.
  • Primary mediastinal B-cell lymphoma originates in the mediastinum and is essentially managed like the early-stage of diffuse large B-cell lymphoma. The primary treatment is around 6 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 there is no active lymphoma is observed on the PET/CT scan, the patient may be observed without further intervention. However, if the PET/CT scan shows a possible active lymphoma in the mediastinum, radiation may be needed. 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. The most common 4-drug combination used in the United States is 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 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. 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, and this 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 get rid of 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 nonseminomatous 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 nonseminomatous primary mediastinal germ cell tumor have a worse prognosis of survival compared to men with mediastinal seminoma. After chemotherapy, patients may undergo a salvage surgery to remove the remaining tumor. The optimal strategy for long-term survival in patients who present with mediastinal nonseminomatous germ cell tumors remains to be defined. A study in Indiana University described 31 patients with mediastinal nonseminomatous 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 nonseminomatous germ cell tumors (NSGCTs), who were 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
  • Tuberculosis
  • Aneurysm
  • Bronchogenic cyst
  • Lymphoma
  • Seminoma
  • Pheochromocytoma
  • Nonseminoma

Prognosis

The prognosis depends on the cause and response to treatment.

Complications

Respiratory compromise

Tracheomalacia

Consultations

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 that is 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

There are many lesions that can occur in the mediastinum and making a diagnosis can be challenging. A multidisciplinary approach consisting of a primary care physician assistant, nurse practitioner, primary care physician, oncologist, radiologist, thoracic surgeon, anesthesiologist, and intensivist is recommended. Placing these individuals under general anesthesia also has the potential to 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.

Nurses should educate the patient and the family on the different types of 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 the early complications. [14][15](Level V)

Outcomes

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 removal of important tissues like the phrenic nerve and innominate vein. Only via a multidisciplinary approach and communication with the different specialist can the morbidity of surgery and treatment be decreased.[16][17][18] (Level V)


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Cancer, Mediastinum - Questions

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Cancer, Mediastinum - References

References

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