Pulmonary Medicine

Mediastinal Tumors

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What every physician needs to know

The mediastinum is an anatomic space in the chest located between the two pleural spaces, behind the posterior sternal table, extending superiorly to the thoracic inlet, posteriorly to the anterior longitudinal ligament of the spine and paraspinal sulci, and inferiorly to the diaphragm. Several descriptions of the mediastinal compartments based upon anatomic boundaries are available.

The three-compartment model proposed by Shields defines the anterio compartment and its contents as the thymus, the internal mammary vessels, the extrapericardial aorta and its branches, the great veins, the and lymphatic tissue; the middle (visceral) compartment is defined as as the heart, the intrapericardial great vessels, the pericardium, and the trachea; and the posterior (paraventral sulcus) compartment is defined as the esophagus, the vagus nerves, the thoracic duct, the sympathetic chain, and the azygus venous system.

Classification

Thymoma

There are several clinical and pathologic classification systems for thymomas. The most widely used clinical classification scheme is the Masaoka classification, while histologic classification systems include the Muller-Hermelink and the World Health Organization (WHO) systems. The Masaoka and WHO systems are those used most often.

Masaoka: Clinical classification system

  • Stage I Encapsulated tumor may invade microscopically into, but not through, the capsule

  • Stage II

    • Stage IIa Macroscopic invasion into the thymus or fat or adherent to, but not through, the pleura or pericardium

    • Stage IIb Microscopic trans-capsular invasion

  • Stage III Macroscopic invasion of adjacent organs (pericardium, great vessels, lung)

  • Stage IV

    • Stage IVa Pleural or pericardial dissemination

    • Stage IVb Lymphogenous or hematogenous metastases

Muller-Hermelink subtypes: Pathologic classification system

  • Cortical: Medium to large epithelial cells with abundant lymphocytes (tend to be higher stage)

  • Medullary: Small to medium cells with fewer lymphocytes

  • Mixed: Combination of cortical and medullary subtypes

WHO classification: Pathologic classification system

  • Type A: Spindle cell, medullary

  • Type AB: Mixed

  • Type B

    • Type B1 Lymphocyte-rich, predominantly cortical

    • B2 Cortical

    • B3 Epithelial, well-differentiated thymic carcinoma

Thymic Carcinoma

The thymic carcinoma classification is based upon histologic characteristics that correlate with survival. The two categories of thymic carcinomas are low-grade (squamous, mucoepidermoid, and basaloid, with a median survival of twenty-nine months) and high-grade (sarcomatoid, clear cellm with a median survival of eleven months).

Hodgkins Lymphoma

The four subtypes of Hodgkins lymphoma are nodular sclerosing, lymphocyte-rich, mixed cellularity, and lymphocyte-depleted. Nodular sclerosing, the most common subtype, has a predilection for the thymus. The other subtypes typically spare the thymus and involve other lymph nodes in the mediastinum.

The Ann Arbor Staging System with Cotswold Modifications is the staging system for Hodgkins lymphoma most commonly used today.

  • Stage I: Involvement of one lymph node region or lymphoid structure

  • Stage 2: Two or more lymph node regions on the same side of the diaphragm

  • Stage 3: Lymph nodes on both sides of the diaphragm

  • Stage 4: Involvement of extra-nodal sites

Modifications

A : No symptoms

B: Fever, night sweats, weight loss greater than 10 percent in six months

X: Bulky disease (>1/3 widening of mediastinum or >10 cm diameter of nodal mass)

E: Involvement of a single contiguous, extra-nodal site

Germ cell tumors

Germ cell tumors of the mediastinum are classified into teratomas, seminomas, and non-seminomatous germ cell tumors.

Are you sure your patient has a mediastinal tumor? What should you expect to find?

The initial evaluation of a patient with a mediastinal mass includes a thorough history and physical exam. Most patients with mediastinal masses are asymptomatic, and masses are incidentally found on imaging. When present, symptoms usually result from local compression or invasion of adjacent mediastinal structures. A history of a cough, chest pain or pressure, head and arm swelling (superior vena cava syndrome), and shortness of breath (pleural or pericardial effusion, tracheal involvement) should be ascertained. Inferior vena caval compression can result in the expected sequelae, such as lower extremity swelling. Fevers, night sweats, and weight loss should also be documented.

Thymoma

A thymoma is a thymic epithelial tumor in which the epithelial component exhibits no overt atypia and retains histologic features specific to the normal thymus. Most tumors contain a proportion of epithelial cells and lymphocytes. Although the majority of thymomas are completely encapsulated, 34 percent invade through the capsule and may extend into surrounding structures, including the thymus, pleura, pericardium, and lung. Distant spread can occur to the pleura, the diaphragm, and occasionally the mediastinal lymph nodes. The pleura is the most common site for distant spread and recurrence. Lymphogenous and hematogenous spread is rare.

The majority of patients diagnosed with thymomas are asymptomatic at the time of presentation, although approximately a third of patients with thymomas present with a history of chest pain, cough, or dyspnea attributed to compression of adjacent structures.

Paraneoplastic syndromes, including myasthenia gravis, pure red cell aplasia, hypogammaglobulinemia, systemic lupus erythematosus, SIADH, rheumatoid arthritis, and thyroiditis, are observed in up to 40 percent of patients with thymomas.

Myasthenia gravis (MG), the most common paraneoplastic syndrome, is reported in 30-50 percent of patients with thymomas. MG is an autoimmune neuromuscular disease that is caused by circulating autoantibodies that block atetylcholine receptors at the postsynaptic membrane. Approximately 10-15 percent of patients with a diagnosis of MG will have a thymoma. MG occurs more frequently in women than in men, and symptoms include diplopia, ptosis, weakness, dysphagia, and fatigue. Complete remission of MG following thymectomy occurs in approximately 36 percent of cases; the presence of a thymoma does not affect the remission rate.

Pure red cell aplasia (PRCA) occurs because of a loss of reticulocytes, probably because of IgG antibody-inhibiting red blood cell synthesis that results in a normoblastic, normochromic anemia with an associated absence of reticulocytes. The spindle cell variant of thymoma is commonly seen in PRCA. Anemia improves in a third of patients after thymectomy/thymoma resection.

Hypogammaglobulinemia is an uncommon paraneoplastic syndrome that occurs in less than 5 percent of patients with thymoma. Good's syndrome (thymoma with hypogammaglobulinemia) is a rare cause of combined B and T cell immunodeficiency in adults. In patients with thymoma, the cause and pathogenesis of this syndrome is unknown. Typically, the hypogammaglobulinemia does not respond to thymectomy/thymoma resection, and the long-term prognosis is not favorable.

Thymic Carcinoma

Thymic carcinomas are aggressive epithelial tumors that are associated with a high incidence of local invasion and distant metastases (lung, liver, brain, and bone). Symptoms are more common than they are in thymomas, and patients frequently present with cough, chest pain, and shortness of breath.

Thymic carcinomas, which have a similar appearance to thymomas on CT scan and MRI, spread along pleural and pericardial surfaces, so loss of normal tissue planes is common with these tumors. Malignant cytologic features, including cell atypia, necrosis, and mitotic figures, distinguish this tumor from invasive thymomas.

Hodgkins Lymphoma

Hodgkins lymphoma represents approximately 50-70 percent of mediastinal lymphomas, with an incidence of 2-4 cases per 100,000 people per year. Hodgkins affects the anterior mediastinal compartment more often than non-Hodgkin's lymphoma does (46% vs. 13%), although it is rare for either to be localized to the mediastinum.

Approximately 20-30 percent of patients with Hodgkins lymphoma experience B symptoms (fevers, night sweats, and weight loss), and patients with mediastinal involvement may develop chest pain, cough, and shortness of breath. Involvement of local structures may result in SVC syndrome, resulting in head and upper extremity swelling. Supraclavicular or cervical adenopathy is common in these patients, so a careful head and neck exam is warranted in all patients with a mediastinal mass.

Non-Hodgkins Lymphoma

Non-Hodgkins lymphoma (NHL) represents 15-25 percent of mediastinal lymphomas. Two variants of NHL, lymphoblastic lymphoma and large B-cell lymphoma, have a predilection for the anterior mediastinum. Lymphoblastic lymphoma arises from thymic lymphocyes and is highly aggressive. Bone marrow involvement in this variant is common and may distinguish it from a primary mediastinal B-cell lymphoma.

Clinical presentation of patients with non-Hodgkins lymphoma varies according to the location of the tumor and its rate of growth in the mediastinum. Large, infiltrating tumors may lead to respiratory difficulties from tracheal invasion, SVC syndrome from vascular invasion/compression, and chest pain from chest wall involvement.

Thymolipoma

Thymolipomas are rare, slow-growing tumors seen in adults, with males and females affected equally. Histologically, these tumors contain mature adipocytes and normal thymic cells. The tumors have been associated with thymic paraneoplastic syndromes, including red cell aplasia, hypogammaglobulinemia, and aplastic anemia.

Thymic cyst

Two types of cysts occur in the thymus: Congenital thymic cysts, which are derived from remnants of thymopharyngeal duct and tend to be unilocular, can occur anywhere along the course of the embryonic thymic gland, from the angle of the mandible to the mediastinum. Acquired thymic cysts are associated with inflammation or an inflammatory neoplasm (e.g., Hodgkins lymphoma) and tend to be multilocular.

Thymic neuroendocrine tumors

Thymic neuroendocrine tumors include the thymic carcinoid tumor and small-cell carcinoma of the thymus. A distinguishing feature of thymic neuroendocrine tumors is the presence of APUD (amine precursor uptake and decarboxylation) cells.

Histologically, carcinoid tumors of the thymus appear similar to carcinoids found in other sites in the body. They may be associated with Cushing's syndrome (a third of cases) and multiple endocrine neoplasia. The classic carcinoid syndrome is rarely associated with thymic carcinoid tumors. Approximately half of thymic carcinoids are hormonally active, usually secreting ACTH with associated Cushing's syndrome. An elevated ACTH level is a poor prognostic indicator in these tumors. The small-cell variant is uncommon and has a poor prognosis.

Thymic carcinoid tumors typically present as a large, lobulated mass in the anterior mediastinum that may have areas of necrosis and hemorrhage. Regional lymph node and distant metastases occur in up to 73 percent of patients.

Germ cell tumors

Primary mediastinal germ cell tumors arise from primitive germ cells that failed to migrate during embryonic development. They represent 15 percent of anterior mediastinal masses and are found primarily in young adults. Histologically, they appear identical to primary gonadal tumors. Although they arise primarily in the mediastinum, a mediastinal mass in a young adult should prompt an evaluation for a primary gonadal tumor.

Mature teratomas are the most common primary mediastinal germ cell tumor (60-70% of mediastinal germ cell tumors). These tumors contain tissue from at least two of the three germ cell layers. Although they do not usually cause symptoms, they may occasionally compress local structures, resulting in chest pain, cough, or shortness of breath, and rupture of tumor precipitated by the presence of digestive enzymes has been reported. Mature teratomas are histologically well defined and benign, but rare cases of malignant transformation of mature teratomas have been reported. Immature teratomas contain fetal tissue, and although they have a good prognosis in children, they can recur or metastasize in adults.

Primary mediastinal seminomas represent 25-50 percent of malignant mediastinal germ cell tumors. Symptoms are common and often include dyspnea, cough, substernal pain, weakness, weight loss, and gynecomastia. Approximately 10 percent of patients present with SVC syndrome. Confirmation of the primary nature of these tumors requires that there be no retroperitoneal or testicular disease present.

Several types of non-seminomatous mediastinal germ cell tumors (NSGCTs) have been identified, including embryonal cell carcinomas, endodermal sinus carcinomas, yolk sac tumors, choriocarcinomas, and mixed germ cell tumors. Symptoms, including chest pain, cough, fever, hemoptysis, and weight loss, are present at the time of presentation in 85 percent of patients primarily because of the large size of these tumors. NSGCTs are associated with a high rate of hematologic neoplasia not related to tumor treatment.

Substernal goiter

Mediastinal goiters represent 5-10 percent of all resected mediastinal masses. Although the majority of intrathoracic goiters are asymptomatic, some may cause symptoms related to airway or esophageal compression. In 80 percent of cases, the goiter extends into the prevascular space, while posterior extension along the trachea occurs in 20 percent of cases. Typically, the intrathoracic mass is contiguous with the thyroid tissue in the neck; however, it may appear discontinuous (connected by a thin stalk to the main thyroid); rarely, it contains no connection to the thyroid.

Parathyroid adenomas

Parathyroid adenomas may be found in ectopic locations in the neck and mediastinum. When located in the mediastinum, 80 percent are found in the anterior compartment and are encapsulated, round, and small (<3cm). Patients typically have an elevated blood parathyroid hormone level that normalizes after resection of the adenoma.

Bronchogenic cyst

Bronchogenic cysts are foregut abnormalities that form during embryonic development. They are usually located adjacent to the trachea, bronchi, and the carina, although they are found in the lung parenchyma in approximately 15 percent of cases. Histologically, they are lined with ciliated, pseudostratified, columnar epithelium, and they frequently contain cartilage. Symptoms, which include cough, chest pain, and shortness of breath, occur in approximately 40 percent of patients. Bronchogenic cysts are more likely to produce symptoms in children than in adults, and they may be life-threatening in infants.

Esophageal Duplication Cyst

Representing approximately 5-10 percent of mediastinal cysts, esophageal duplication cysts are much less common than bronchogenic cysts. Esophageal duplication cysts are thought to develop during embryogenesis during vacuolization of the primitive solid. An aberrant vacuole that does not typically communicate with the new lumen may enlarge into an intramural or paraesophageal cyst.

Esophageal duplication cysts are often found in adults during evaluation for respiratory symptoms (cough, chest fullness, or discomfort) or upper GI complaints. Approximately 60 percent of these cysts occur in the distal esophagus, where swallowing difficulties are usually the presenting symptoms. Respiratory symptoms are more common in patients with proximal esophageal cysts (20% of cysts occur proximally) because of airway compression. Cyst rupture, infection, and hemorrhage have been reported. Malignant degeneration is rare.

Tracheal tumors

Tracheal tumors are an uncommon cause of a mediastinal mass, but most primary tracheal tumors in adults are malignant. The most common primary tumors of the trachea are squamous cell carcinomas S(SCC) and adenoid cystic carcinoma. Primary SCC may be exophytic, ulcerative, or longitudinally infiltrating. As it grows, a tracheal tumor may invade local structures. The most common sites of metastases are local lymph nodes. Adenoid cystic carcinoma is the second most common tracheal tumor. Although these tumors tend to grow into the mediastinum, they tend to displace adjacent structures before invading them.

Neurogenic tumors

The most common posterior mediastinal mass is the neurogenic tumor. These tumors arise from peripheral nerves (schwannoma, neurofibroma, malignant nerve sheath tumor), sympathetic ganglia (ganglioneuroma, ganglioneuroblastoma, and neuroblastoma), or (uncommonly) parasympathetic ganglia. Neuroblastomas are childhood tumors that are uncommon in adults.

The most common nerve sheath tumors are the schwannoma and neurofibroma. These slow-growing tumors, which can arise anywhere along the thoracic nerves, are usually found incidentally on chest x-ray. Neurofibromas are often associated with type I neurofibromatosis or multiple plexiform neurofibromas. Malignant tumors of nerve sheath origin are spindle cell in origin and are uncommon. They typically arise from a simple or plexiform neurofibroma or (rarely) from a pre-existing schwannoma.

Sympathetic ganglia tumors are rare tumors of nerve cell origin that range from being slow-growing to highly malignant. These tumors typically appear as well-circumscribed masses along the anterior spine in the region of the sympathetic ganglia. Ganglioneuromas are typically slow-growing, encapsulated tumors that are found incidentally. Symptoms may occur because of mass effect or from local extension into the spinal canal.

Beware: there are other diseases that can mimic mediastinal tumors.

The differential diagnosis of a mediastinal mass is dictated by the particular compartment that is involved. Tumors of the anterior mediastinum are thymoma, thymic carcinoma, lymphoma, thymolipoma, thymic cyst, thymic carcinoid tumor, germ cell tumor, thyroid (goiters), and parathyroid adenoma.

Tumors of the middle mediastinum are bronchogenic cyst, esophageal duplication cyst, tracheal tumor, and lymphoma.

Tumors of the posterior mediastinum are schwannoma, neurofibroma, malignant nerve sheath tumor, ganglioneuroma, ganglioneuroblastoma, and neuroblastoma.

How and/or why did the patient develop a mediastinal tumor?

Not applicable

Which individuals are at greatest risk for developing a mediastinal tumor?

Thymoma

With an incidence of 0.15 cases per 100,000, thymoma is the most common tumor of the anterior mediastinum. The median age at time of diagnosis is approximately fifty-four years, although a broad range of ages (eight months to ninety-four years) has been reported. The incidence in men and women is equal.

Thymic Carcinoma

These cancers typically occur in middle-aged men (mean age of forty-six years).

Hodgkins Lymphoma

There is a bimodal distribution of Hodkgins lymphoma, with a peak seen in young adults and in patients over age fifty.

Non-Hodgkins Lymphoma

The overall incidence of non-Hodgkins Lymphoma is greatest in men over age fifty-five.

Thymic neuroendocrine tumors

Thymic neuroendoicrine tumors usually occur during the fourth or fifth decade of life.

Germ cell tumors

Mature teratomas usually occur in children and young adults, and males and females are affected equally.

Primary mediastinal seminomas usually occur in men 20-40 years of age. Mediastinal seminomas can occur, though rarely, in women with histologically normal ovaries. Non-seminomatous germ cell tumors are six times more common in males than in females. NSGCTs are seen most often in patients with Klinefelter's syndrome.

What laboratory studies should you order to help make the diagnosis, and how should you interpret the results?

Serum beta HCG and alpha fetoprotein may be useful when germ cell tumors are in the differential diagnosis. Elevated beta-hCG is observed in 60 percent of patients with nonseminomatous germ cell tumors, and AFP is elevated in 70 percent. Approximately 10 percent of patients may have normal serum markers, and an NSGCT is diagnosed histologically following resection. By contrast, patients with pure seminomas usually have normal alpha fetoprotein, while 10 percent have an elevated beta-HCG.

Anti-acetylcholine receptor antibodies (myasthenia gravis), a complete blood count (pure red cell aplasia associated with thymoma), serum calcium level, and PTH level (parathyroid adenoma) may be helpful, depending upon the appearance of the mass on imaging studies and the index of the clinician's suspicion.

What imaging studies will be helpful in making or excluding the diagnosis of a mediastinal tumor?

Imaging studies should include a posteroanterior and a lateral chest x-ray. Loss of the normal mediastinal contour is frequently present, and displacement of adjacent structures like the trachea may be apparent. CT scan of the chest is highly useful in characterizing the mass and determining whether there is associated lymhadenopathy, pleural or pericardial effusions, or evidence of associated pulmonary or pleural nodules. CT may also suggest invasion of the mass by loss of normal tissue planes. Although not routinely ordered, MRI may be a helpful study in further characterizing the mass as cystic or solid and in assessing vascular and spinal involvement. MRI is also the appropriate study with which to ascertain invasion of the diaphragm.

Thymoma

Chest X-ray, which is frequently the first study performed, often shows widening of the mediastinum on postero-anterior views with loss of the normal mediastinal contour. Lateral films may demonstrate an opacity in the space anterior to the heart, behind the posterior table of the sternum.

CT scan, the next most often recommended imaging study, typically shows an encapsulated, lobulated, or round-appearing mass that often extends into one side of the mediastinum. The mass usually appears homogeneous, but it may contain focal areas of calcification and/or cyst formation. CT is also helpful in finding adenopathy outside of the anterior mediastinum that may suggest lymphoma. Invasion of adjacent structures may be evident from loss of normal tissue planes between the mass and surrounding structures.

The role of PET scan is yet to be defined, but it may be helpful in further characterizing pleural nodules seen on CT scan. MRI, which is usually reserved for assessing vascular invasion, may further characterize the mass.

Thymic carcinoma

A CT scan typically demonstrates a heterogeneous, large, and infiltrative mass. Cystic changes may be present within the tumor. Metastases are common in the pleura and pericardium, and unlike thymomas, pleural and pericardial effusions occur.

Hodgkins Lymphoma

An abnormal CXR is seen in 76 percent of patients with Hodgkins disease. Asymmetric mediastinal nodal disease may be apparent on plain films because of paratracheal and prevascualr nodal enlargement. CT scan may demonstrate a mediastinal mass with adjacent adenopathy or a cluster of enlarged mediastinal nodes. The mass, which may appear homogeneous or heterogeneous on CT scan, is often infiltrative, with loss of tissue planes between mediastinal structures.

MRI typically demonstrates a homogeneous mass with low signal intensity on T1 weighted images. A high signal intensity may be seen on T2 weighted images, signifying tumor inflammation or fibrosis.

Thymolipoma

Imaging (CT and MR) of a thymolipoma demonstrates a fat density mass in anterior mediastinum.

Germ cell tumors

Radiologically mature teratomas appear as multilocular cystic tumors that typically extend off to one side of the midline. Calcifications are present in 25 percent of tumors. The presence of fluid, calcium, soft tissue and/or fat in an anterior mediastinal mass on CT is highly suggestive of a mature teratoma.

Seminomas appear as bulky, homogeneous anterior mediastinal masses, and calcification is rare.

Substernal goiter

CT scan typically confirms the association of the mass with the thyroid gland. Long-standing goiters may have calcium deposits within the tissue. Radionucleotide imaging of the thyroid typically shows some functioning thyroid tissue in the intrathoracic goiter.

Parathyoid adenoma

Sestamibi scans are usually helpful in identifying the location of mediastinal parathyroid adenomas. MRI and CT have also been used if sestamibi is inconclusive.

Bronchogenic cyst

CT scan show a well-defined mass with homogeneous density similar to that of water. Viscous fluid within the cyst may give the appearance of the mass's being solid, and MRI may be helpful in further characterizing the mass when necessary. Bronchogenic cysts typically show an MRI signal intensity higher than that of muscle on T1 weighted images because of the high protein content in the cyst fluid. The signal intensity on the T2-weighted images is typically is high, suggesting a cystic lesion. Bronchogenic cysts typically remain stable in size except when complicated by hemorrhage or infection.

Esophageal Duplication Cyst

Plain films often demonstrate a well-circumscribed central opacity that usually protrudes into the lower right chest. CT scan usually shows them as well-demarcated, spherical lesions with variable enhancement. MRI may demonstrate variable signal intensity on T1 weighted images and high intensity on T2 weighted images.

Neurogenic tumors

Radiologically, nerve sheath tumors appear well-circumscribed and round or lobulated with homogeneous tissue density and attenuation density that is often lower than muscle because of areas of low cellularity. MRI may be helpful in characterizing neurogenic tumors. Schwannomas have a signal intensity similar to or higher than that of muscle with T1 weighted imaging and significantly higher than that of muscle on T2 imaging. Neurofibromas have characteristic high peripheral signal intensity and lower central signal intensity on T2 weighted images. MRI is essential when assessing intraspinal involvement prior to surgical resection.

What non-invasive pulmonary diagnostic studies will be helpful in making or excluding the diagnosis of a mediastinal tumor?

Not applicable

What diagnostic procedures will be helpful in making or excluding the diagnosis of a mediastinal tumor?

Diagnosis of most mediastinal masses is made at the time the tumor is excised. Invasive procedures, including fine-needle aspiration, core-needle biopsy, and cervical or anterior mediastinoscopy, may be required in a mass that appears invasive on imaging. A biopsy should also be performed during diagnosis of tumor that might not be treated surgically, such as lymphoma or a germ cell tumor.

Thymoma

Beyond the potential for possible tumor spillage or needle-track seeding, it is generally not helpful or necessary to obtain a preoperative biopsy in a suitable operative candidate unless serious consideration is being given to a diagnosis other than thymoma. Biopsies for a suspected thymoma should be done if nonoperative or neoadjuvant treatment is indicated because of dissemination of the disease, unresectability, or the patient's physical condition.

The success rate of fine-needle aspiration in making the diagnosis of a thymoma is approximately 60 percent. These tumors are typically located in a place favorable to percutaneous-needle biopsy, which may be performed using CT or ultrasound guidance. Therefore, when a mass appears resectable and is thought most likely to be a thymoma in a healthy patient, many thoracic surgeons favor proceeding to surgery without a needle biopsy.

Thymic carcinoma

Needle biopsy of the mass is usually diagnostic.

Hodgkins lymphoma

Ultrasound or CT-guided biopsy may be attempted to obtain tissue with which to diagnose Hodgkins lymphoma. The identification of Reed-Sternberg cells is pathonomonic of Hodgkins disease. Reed-Sternberg cells are characterized by bi-lobed eosinophilic nuclei, and immunohistochemistry demonstrates CD15 and CD30 positive cells. However, Reed-Sternberg cells may be difficult to identify on the small samples provided by needle aspiration, particularly with the nodular sclerosing variant of Hodgkins. A core-needle or surgical biopsy may be required if FNA is not feasible or if it is non-diagnostic.

Non-Hodgkins Lymphoma

The diagnosis of non-Hodgkins lymphoma requires adequate tissue, and subclassification of lymphoma depends in part upon architectural pattern and immunophentyping. Therefore, fine-needle aspiration is less useful for the initial diagnosis of lymphoma, but it may be helpful in the setting of a relapse. Core-needle biopsy has been reported to be successful in diagnosing lymphoma in 70 percent of cases. Open surgical biopsy using mediastinoscopy, mediastinomy, or video-assisted thoracoscopic surgery (VATS) provides a large amount of tissue and remains the definitive means for diagnosing mediastinal lymphoma.

Germ cell tumors

Definitive diagnosis of teratomas requires surgical excision of the tumor. Subtotal resection for symptom relief, followed by adjuvant chemotherapy, may also be beneficial.

Fine-needle aspiration typically confirms the diagnosis of medistinal seminomas.

What pathology/cytology/genetic studies will be helpful in making or excluding the diagnosis of a mediastinal tumor?

None

If you decide the patient has a mediastinal tumor, how should the patient be managed?

Thymoma

Surgical resection of the thymoma with complete thymectomy is the initial treatment of choice when there are no metastases or evidence of invasion. The most common surgical approach is via a median sternotomy. After opening the sternum, the thymus is dissected from the pericardium and inominate vein. The lateral extent of the dissection involves removing all thymic tissue from the left to the right phrenic nerves. Superiorly, the left and right cornu of the thymus are dissected into the neck and resected with the specimen. The thymus and thymoma are removed en block.

Less invasive methods include transcervical thymectomy, video-assisted thoracoscopic (VATS), thymectomy, and robotic thymectomy. Although cervical thymectomy is an accepted--perhaps optimal--approach for thymectomy to treat myasthenia, it remains controversial for resection of thymic tumors. Robotic and VATS thymectomy, which allow more visualization, angles of attack, and preservation of oncologic principles compared to cervical thymectomy, are gaining acceptance.

Patients with thymomas and concurrent myasthenia gravis may require medical treatment and should be referred to a neurologist for an evaluation and recommendations for treatment prior to surgery. Surgeons must work in concert with neurologists for symptomatic patients, as surgery can precipitate a potentially fatal episode of myasthenic crisis.

Neoadjuvant chemotherapy, with or without radiation, may be used in patients with advanced thymomas prior to resection when CT scan demonstrates loss of tissue planes or evidence of local tumor invasion. Complete resection (negative surgical margins) is associated with significantly improved survival, so en bloc resection of invaded structures is warranted when feasible. Evidence of invasion of surrounding structures, either intraoperatively or on the pathology report, should point to the need for a radiation oncology consultation.

Thymic carcinoma

Complete surgical resection, the treatment of choice when it is feasible, can be curative. Induction therapy (chemotherapy and radiation or chemotherapy alone), followed by resection and postoperative radiation (if not given pre-operatively) in patients with no evidence of metastatic disease, has had some success. A variable response has been observed with chemotherapy in patients with unresectable disease, and studies are underway to determine the best regimen.

Hodgkins lymphoma

Treatment of Hodgkins lymphoma depends upon the disease stage and whether the disease is bulky. Favorable stage I or stage II disease is typically treated with combined involved-field radiation and chemotherapy. Stage I or stage II bulky disease can be treated using chemotherapy, followed by radiation, while stage III or stage IV Hodgkins lymphoma is best treated using chemotherapy alone.

Non-Hodgkins Lymphoma

Treatment of non-Hodgkins lymphoma depends upon tumor stage, grade, type of lymphoma, and clinical factors.

Thymolipoma

The recommended treatment for thymolipomas is surgical excision.

Thymic cyst

Histologically, thymic cysts appear identical to cystic thymic neoplasms, so complete resection is usually recommended

Thymic neuroendocrine tumors

When surgical resection is feasible, it is the treatment of choice for thymic neuroendocrine tumors. The use of chemotherapy and/or radiation has been reported with limited benefit.

Germ cell tumors

When a mediastinal germ cell tumor is suspected, imaging, including a CXR and a CT scan of the chest, abdomen, and pelvis, are warranted. A testicular exam and scrotal ultrasound is recommended when a mediastinal mass is found in a male patient.

Definitive treatment of teratomas involves surgical excision of the tumor. Sub-total resection for symptom relief, followed by adjuvant chemotherapy. may also be beneficial.

Patients with localized and relatively small mediastinal seminomas are usually treated with radiation. Bulky tumors or non-localized tumors are treated with systemic chemotherapy, including etoposide or cisplatinum-based regimens. The treatment of a residual mass depends upon size: tumors smaller than 3cm may be followed, while those larger than 3cm are typically resected.

Substernal goiter

Substernal goiters are typically approached through a neck incision, with delivery of the substernal portion through this incision. Rarely, a partial or complete sternotomy is required to help remove the intrathoracic portion of the gland.

Bronchogenic cyst

Resection of bronchogenic cysts can be performed thoracoscopically or via a thoracotomy, depending upon the skill of the operator and the character of the cyst. Complete cyst excision prevents recurrence, while incomplete resection may result in infection, a chronic draining sinus, or (rarely) a fistula to the esophagus or the bronchus. The usual recommendation for bronchogenic cysts is to remove them to prevent complications and to avoid the very rare occurrence of malignant transformation.

Esophageal Duplication Cyst

Treatment of esophageal duplication cysts involves cyst resection; preoperative biopsy is not recommended. The procedure usually involves an operative approach through the right chest since most of the intrathoracic esophagus is accessible via this approach. The traditional thoracotomy approach is rapidly being replaced by less invasive methods, including video-assisted thoracoscopy and robotic resection.

Tracheal tumors

Treatment of primary tracheal neoplasms involves resection of the portion of trachea involved, followed by reconstruction of the remaining trachea. Tracheal tumors are often not amenable to resection because of the extent of tumor and are best treated with local therapies: laser ablation, stenting, or external beam radiation for palliation.

Neurogenic tumors

The majority of neurogenic tumors are treated by surgical resection. Biopsy is not usually necessary prior to resection because of the common location and radioagraphic appearance of these tumors. MRI is required prior to resection to assess intra-spinal involvement in paravertebral tumors.

What is the prognosis for patients managed in the recommended ways?

Thymoma

Features associated with a poor prognosis include large size (>10cm), age less than thirty years, epithelial or mixed cytology, and the presence of a hematologic paraneoplastic syndrome. The ten-year survival rates after surgical resection depend primarily upon the tumor stage. The best survival is seen in stage I (90% ten-year survival), while stage IVa patients have the worst prognosis (35% ten-year survival).

Thymic carcinoma

Prognosis is determined largely by morphologic features present within the tumor. Poor prognostic indicators include the presence of high-grade atypia and necrosis, greater than 10 mitoses/high powered field, absence of lobular growth, and infiltration of the tumor margins. Overall, five-year survival rates of 33 percent have been reported; survival correlates with histologic grade.

What other considerations exist for patients with mediastinal tumors?

None

What’s the evidence?

Quint, LE. "Imaging of anterior mediastinal masses". Cancer Imaging. vol. 7. 2007. pp. S56-S62.

Carter, C, Bibro, MC, Touloukian, RJ. "Benign clinical behavior of immature mediastinal teratoma in infancy and childhood". Cancer. vol. 49. 1982. pp. 398-402.

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