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Lymphomas, Endocrine, Mesenchymal, and Other Rare Tumors of the Mediastinum Workup

  • Author: Mary C Mancini, MD, PhD, MMM; Chief Editor: John Geibel, MD, DSc, MSc, MA  more...
 
Updated: Nov 06, 2015
 

Laboratory Studies

See the list below:

  • Serum calcium, phosphorus, and PTH levels
    • Serum chemical findings diagnostic for primary hyperparathyroidism can be observed when parathyroid adenoma or carcinoma develops within ectopic parathyroid glands in the mediastinum. These findings include elevated serum calcium levels associated with a decrease of serum phosphorus. PTH levels are elevated.
    • In cases in which no pathology is found in the neck, extend the evaluation of the cause of primary hyperparathyroidism to the mediastinum.
  • Thyroid-stimulating hormone and thyroid function studies: Functioning thyroid adenomas can develop in ectopic mediastinal thyroid tissue and can cause thyroid stimulating hormone suppression and associated elevation of serum triiodothyronine levels.
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Imaging Studies

See the list below:

  • Chest radiography
    • Posteroanterior (PA) and lateral radiograph of the chest for an unrelated cause is the usual way in which an asymptomatic mediastinal mass is identified. Chest radiography is obviously the first study performed in an individual with symptoms referable to the thorax. See image below.
      Lymphomas, endocrine, mesenchymal, and other rare Lymphomas, endocrine, mesenchymal, and other rare tumors of the mediastinum. Posteroanterior chest radiograph of a 30-year-old man found to have Hodgkin disease of the mediastinum. Arrows indicate areas of prominent lymphadenopathy associated with his disease.
    • Lateral chest radiograph findings are very helpful in the determination of the involved compartment of the mediastinum. This information, combined with the age, sex, and associated clinical findings, aids the physician in the proper choice of subsequent diagnostic studies. See image below.
      Lymphomas, endocrine, mesenchymal, and other rare Lymphomas, endocrine, mesenchymal, and other rare tumors of the mediastinum. Lateral chest radiograph of a 30-year-old man found to have Hodgkin disease of the mediastinum (same patient as in previous image). Arrow indicates area of fullness in the anterior mediastinum, probably related to the presence of prominent lymphadenopathy.
  • CT scan of the chest and mediastinum
    • CT scan is a routine part of the diagnostic evaluation of mediastinal tumors, cysts, and other masses.
    • CT scan findings can greatly assist in determining the exact location of the mediastinal tumor and in determining its relationship to adjacent structures. They are useful also in differentiating those masses that originate in the mediastinum from those that encroach on the mediastinum from the lung or other structures.
    • While not infallible, the CT scan is very useful in helping differentiate tissue densities. This assists greatly in distinguishing cystic or vascular structures from those that are solid.
    • CT scan images can reveal evidence of local invasion of adjacent structures by a mass or the presence of intrathoracic metastases. In the past, CT scan was recommended in the evaluation of all paravertebral masses to help determine the presence of intraspinal extension or invasion. More recently, MRI has proven superior for this purpose.[20]
  • Magnetic resonance imaging
    • MRI is useful in both the initial diagnosis of a mediastinal mass and in follow-up evaluation after treatment. It provides superior vascular images and can help better delineate the relationship of an identified mediastinal mass to nearby intrathoracic vascular structures. MRI can help differentiate between a possible mediastinal mass and a vascular abnormality such as an aortic aneurysm.
    • MRI offers direct multiplanar imaging. It can be used when iodinated contrast is contraindicated. MRI provides increased detail in the subcarinal and aortopulmonary window areas and in the inferior aspects of the mediastinum at the level of the diaphragm.
    • MRI is superior to the CT scan images for the evaluation of masses located at the thoracic inlet or at the thoracoabdominal level. MRI is used increasingly for evaluation of residual or recurrent disease after treatment of lymphoma. Although histologic analysis of any residual mass after chemotherapy and radiotherapy remains the standard, MRI evaluation findings of questionable areas are found to correlate well with histologic findings in differentiating residual tumor from fibrosis.
  • Radionuclide scanning
    • Nuclear imaging can be used selectively in the workup of mediastinal masses when specific tumors are suggested. Gallium Ga 67 is used commonly in the evaluation of mediastinal lymphoma, both for initial evaluation and for posttherapy follow-up.
    • The iodine I 131 or iodine I 123 scans are very helpful in distinguishing thyroid tissue from other masses. They are often used in identifying an anterior mediastinal mass located at the level of the thoracic inlet as the substernal extension of a cervical thyroid goiter. A radioactive iodine scan also may help identify ectopic thyroid tissue within the mediastinum. These studies must be performed before any tests requiring the administration of iodinated contrast because this material may interfere with thyroid uptake and scanning.
    • Scanning with technetium Tc 99m sestamibi may be useful in the identification of mediastinal parathyroid tissue.
    • The octreotide scan, using indium In 111–labeled pentetreotide, is useful for localizing various neuroendocrine neoplasms, including carcinoid tumors, pheochromocytomas, and paragangliomas. It has also been used at some centers for the evaluation of certain lymphomas.[21]
  • Echocardiography and ultrasonography
    • Ultrasonographic methods have been used to help differentiate solid from cystic mediastinal masses and to assist in determining the connection between a mass and adjacent structures.
    • The findings from these studies are more useful in the evaluation of masses associated with the heart and in vascular abnormalities.
    • In general, given the accuracy and detail provided by CT scan images, MRI, and selected radionuclide scan findings, ultrasound techniques are generally not used as a primary tool in the evaluation of mediastinal tumors and cysts.[22, 23, 24]
  • Positron emission tomography
    • Positron emission tomography (PET) scan findings have been studied extensively for the evaluation of a number of neoplasms such as lung, colorectal, breast, lymphoma, and melanoma. It has become an extremely useful adjunct in the evaluation and staging of these pathologies.
    • This modality has now become the standard of care for staging these pathologies.[25, 26, 27, 28]
  • Arteriography
    • Conventional angiography findings have been used to differentiate mediastinal masses from vascular abnormalities and to exhibit the relationship between known masses and adjacent vascular structures. It is useful in determining the vascularity of the structure and in assessing the need for preoperative embolization to reduce the size of the tumor and make the intervention safer.
    • MRI and magnetic resonance angiography are useful adjuncts in these cases.
  • Video-assisted thoracoscopy
    • Video-assisted thoracoscopy (VATS) techniques have been used successfully for biopsy of various mediastinal masses and are used routinely for the sampling of perihilar lymph nodes.
    • VATS is one of the more commonly used methods for evaluation of mediastinal lymphoma.[29, 30, 31]
  • Sternotomy and thoracotomy
    • In spite of numerous minimally invasive options available for histologic diagnosis of mediastinal tumors and cysts, open surgical access is needed at times.
    • In some cases, standard sternotomy or thoracotomy may be the safest method available to obtain an adequate tissue diagnosis.
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Diagnostic Procedures

See the list below:

  • Transthoracic needle biopsy
    • In the past, percutaneous biopsy methods were considered too dangerous to be used in the evaluation of mediastinal masses, and open surgical biopsy was the diagnostic procedure of choice. Although still controversial, increased success using CT-guided fine-needle aspiration (FNA) and core needle biopsy techniques is reported at several centers.
    • Differentiation between thymomas, lymphomas, and germ cell tumors can be made in a number of cases when tissue obtained from a core needle biopsy is subjected to special histologic staining methods, including immunohistochemical techniques. In some cases, lymphoma subtypes can also be identified. Note that expert clinical judgment is necessary in selecting appropriate cases for this diagnostic method. In addition, considerable expertise in tissue processing and analysis is necessary for diagnostic accuracy.
    • FNA has been used occasionally to aid in the diagnosis of primary bronchogenic cysts. However, most authorities do not recommend aspiration of a cyst because a sample of the cyst wall, required for diagnosis, is not obtained by this method. Also, most cysts recur after simple aspiration. This technique is not recommended for esophageal cysts. FNA has been described for neurogenic tumors, although because surgical resection is the treatment for these lesions after adequate workup, needle biopsy may be deemed an unnecessary step.[32, 33]
  • Cervical mediastinoscopy and substernal extended mediastinoscopy
    • Cervical mediastinoscopy is a commonly used surgical diagnostic procedure in the evaluation of the retrovascular pretracheal area of the mediastinum. It is used most commonly for staging of bronchogenic carcinoma and for evaluation of hilar and paratracheal lymphadenopathy.
    • It can be modified into what has been termed a substernal extended mediastinoscopy to evaluate the prevascular area of the mediastinum. The thymus and any tumors or cysts found in this area and in lymph nodes of the aortopulmonary window are accessible for biopsy using this approach.
  • Anterior mediastinotomy
    • This parasternal approach to the mediastinum is used most commonly in situations in which standard cervical mediastinoscopy is considered, or has been found to be, inadequate.
    • The classic approach is to perform it in the upper left parasternal area in order to gain access to the aortopulmonary window and areas of the anterior mediastinum inferior to the aortic arch.
    • Anterior mediastinotomy is being replaced in many centers, either by extended cervical mediastinoscopy or by VATS techniques.[34]
  • Posterior mediastinotomy
    • This is a rarely used procedure for biopsy of some of the posteriorly situated lymph nodes or a mass in the paravertebral sulcus. Posterior mediastinotomy is performed most commonly on the right side in a paravertebral location immediately lateral to the paravertebral muscles.
    • As with the anterior mediastinotomy, small segments of several ribs in the area may be excised for extrapleural access to the ipsilateral paravertebral sulcus. The mediastinoscope may also be used for lymph node biopsy with this approach.
    • It is rarely used for mediastinal tumors and cysts because these are more appropriately managed by either standard thoracotomy or VATS techniques.
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Histologic Findings

Lymphoma

Hodgkin disease and non-Hodgkin lymphoma are the 2 main subclassifications of this large area.

  • Hodgkin disease
    • According to the Rye classification, Hodgkin lymphoma is divided into the histopathologic types of (1) nodular sclerosing, (2) lymphocyte predominant, (3) mixed cellularity, and (4) lymphocyte depleted.[35]
    • A characteristic feature of all forms of Hodgkin lymphoma is the presence of Reed-Sternberg cells. These are large cells with acidophilic cytoplasm that usually have binucleated or have bilobed nuclei with large, prominent, deeply eosinophilic nucleoli.
    • The nodular sclerosing variety is generally composed of broad bands of collagenous material, which appear to subdivide the tumor into nodular components. Cellular components include Reed-Sternberg cells, lymphocytes, neutrophils, plasma cells, eosinophils, and histiocytes. Some variants of the nodular sclerosing type have been described.
    • Lymphocyte-predominant Hodgkin disease displays L and H cells, which are lymphocytic and histiocytic cells that possess lobulated nuclei and pale cytoplasm. These are found within a predominant framework of small lymphocytes. Epithelioid histiocytes are very evident, while Reed-Sternberg cells are present but infrequent.
    • The mixed cellularity type of Hodgkin disease has a diffusely cellular appearance composed of plasma cells, histiocytes, eosinophils, and lymphocytes. Reed-Sternberg cells are common, and fibrosis in this form is minimal. The lymphocyte-depleted form of Hodgkin disease is very similar in appearance to large cell non-Hodgkin disease. Immunophenotyping is a necessary addition to histopathologic analysis for proper classification of Hodgkin disease.
  • Non-Hodgkin lymphoma
    • While many types of non-Hodgkin lymphoma have been described, those types particular to the mediastinum are (1) large cell lymphoma, (2) anaplastic large cell lymphoma, (3) mucosa-associated lymphoid tissue lymphoma, (4) lymphoblastic lymphoma, and (5) other lymphomas.
    • The mediastinal form of large cell lymphoma has some features that appear to distinguish it from large cell lymphomas at other locations. Intermediate- to large-sized lymphoid cells are found in the presence of significant sclerosis. Bands of sclerosis may be seen surrounding groups of the tumor cells. The nuclei of tumor cells are commonly multilobulated, and cytoplasm can be acidophilic or clear. While the lymphoid cells are large in this tumor, they are actually smaller than those of large cell lymphomas in other areas. Some authors have termed this tumor B-cell lymphoma.
    • Anaplastic large cell lymphomas are generally found in a cutaneous or systemic form, but primary mediastinal involvement has been described. The tumors have highly atypical lymphoid cells with evenly dispersed chromatin, large nucleoli, and significant amounts of mitotic figures. Cells have distinct borders, and nuclei are often pleomorphic and multilobated, simulating Reed-Sternberg cells.
    • Mucosa-associated lymphoid tissue lymphoma (ie, MALToma) tumors are rare in the mediastinum and are often associated with autoimmune vascular disease. They are composed of monotonous sheets of small lymphoid cells.
    • Lymphoblastic lymphoma is closely associated with acute lymphoblastic leukemia. Lymphoblastic lymphoma is characterized by a diffuse infiltrate of immature lymphoid cells, having nuclei with evenly dispersed chromatin and indistinct nucleoli. Fibrosis is sparse and necrosis is common in these tumors. Numerous mitotic figures are present.
    • Other lymphomas include mantle cell lymphoma, which is otherwise known as lymphocytic lymphoma of intermediate differentiation. Mediastinal lymphadenopathy due to this form has been identified. These tumors are composed of small- to intermediate-sized lymphoid cells with somewhat irregular nuclei. Their architecture is not distinct, but it is somewhat nodular in appearance. The tumor cells have commonly been noted to occupy the border zone surrounding the reactive germinal centers of lymph nodes. Differentiating these tumors from lymphoblastic lymphoma may be challenging in some cases. Immunohistologic studies are usually needed.

Ectopic endocrine tissue

Thyroid and parathyroid tissue found in the mediastinum is histologically identical to that found in the neck. This is true for both benign and malignant lesions.

Mesenchymal tumors

The many mesenchymal tumors that can occur in the mediastinum are rare and are histologically identical to their counterparts occurring in other areas of the body.

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Staging

See the list below:

  • Well-established staging systems exist for several tumors that occur within the mediastinum. Most noted are those for thymoma, lymphoma, and neuroblastoma.
  • No specific staging systems are described for the many other types of tumors that occur, most likely because of their rarity.
  • Lymphomas found in the mediastinum are staged according to the Ann Arbor staging system.
    • Stage I - Involvement of 1 lymph node region on either side of the diaphragm
    • Stage II - Involvement of 2 or more lymph node regions on the same side of the diaphragm
    • Stage III - Involvement of 2 or more lymph node regions on both sides of the diaphragm
    • Stage IV - Disseminated organ involvement
  • Once the diagnosis of mediastinal lymphoma is made, additional studies are performed to determine the extent of disease present, ie, to stage the patient. The staging workup at present generally consists of CT scan with contrast, radionuclide studies, and lymphangiographic studies. Bilateral bone marrow biopsies are also recommended. Because incorrect staging can occur when imaging studies are the only study performed, many authorities still recommend the addition of staging laparotomy.
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Contributor Information and Disclosures
Author

Mary C Mancini, MD, PhD, MMM Professor and Chief of Cardiothoracic Surgery, Department of Surgery, Louisiana State University School of Medicine in Shreveport

Mary C Mancini, MD, PhD, MMM is a member of the following medical societies: American Association for Thoracic Surgery, American College of Surgeons, American Surgical Association, Society of Thoracic Surgeons, Phi Beta Kappa

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Daniel S Schwartz, MD, FACS Medical Director of Thoracic Oncology, St Catherine of Siena Medical Center, Catholic Health Services

Daniel S Schwartz, MD, FACS is a member of the following medical societies: Society of Thoracic Surgeons, Western Thoracic Surgical Association, American College of Chest Physicians, American College of Surgeons

Disclosure: Nothing to disclose.

Chief Editor

John Geibel, MD, DSc, MSc, MA Vice Chair and Professor, Department of Surgery, Section of Gastrointestinal Medicine, and Department of Cellular and Molecular Physiology, Yale University School of Medicine; Director, Surgical Research, Department of Surgery, Yale-New Haven Hospital; American Gastroenterological Association Fellow

John Geibel, MD, DSc, MSc, MA is a member of the following medical societies: American Gastroenterological Association, American Physiological Society, American Society of Nephrology, Association for Academic Surgery, International Society of Nephrology, New York Academy of Sciences, Society for Surgery of the Alimentary Tract

Disclosure: Received royalty from AMGEN for consulting; Received ownership interest from Ardelyx for consulting.

Additional Contributors

Richard Thurer, MD B and Donald Carlin Professor of Thoracic Surgical Oncology, University of Miami, Leonard M Miller School of Medicine

Richard Thurer, MD is a member of the following medical societies: American Association for Thoracic Surgery, American College of Chest Physicians, American College of Surgeons, American Medical Association, American Thoracic Society, Florida Medical Association, Society of Surgical Oncology, Society of Thoracic Surgeons

Disclosure: Nothing to disclose.

Acknowledgements

The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous author Jane M Eggerstedt, MD, to the development and writing of this article.

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Lymphomas, endocrine, mesenchymal, and other rare tumors of the mediastinum. Posteroanterior chest radiograph of a 30-year-old man found to have Hodgkin disease of the mediastinum. Arrows indicate areas of prominent lymphadenopathy associated with his disease.
Lymphomas, endocrine, mesenchymal, and other rare tumors of the mediastinum. Lateral chest radiograph of a 30-year-old man found to have Hodgkin disease of the mediastinum (same patient as in previous image). Arrow indicates area of fullness in the anterior mediastinum, probably related to the presence of prominent lymphadenopathy.
 
 
 
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