Mediastinum

-“Malignant germ cell tumors of the mediastinum are uncommon, representing only 3 to 10% of tumors originating in the mediastinum. They are much less common than germinal tumors arising in the testes, and account for only 1 to 5% of all germ cell neoplasms. Others hypothesize a widespread distribution of germ cells to multiple sites during normal embryogenesis, with these cells conveying genetic information or providing regulatory functions at somatic sites." 7 || - “The great majority of mediastinal malignant germ cell tumors occur in patients between 20 and 35 years of age. For unknown reasons, most are found in males. In the rare occurrences reported in females, mediastinal malignant germ cell tumors have appeared histologically and biologically identical to those occurring in males. 7 ” Pure Seminomas occur most commonly in the third decade of life, the fourth and lastly the second decades. Nonseminomatous germ cell tumors (pure or mixed histology) occur in young adults ( 15 to 35 years). " 2 || - Symptoms may include chest pain, dyspnea, hoarseness, and superior vena cava syndrome. - Dysphagia, fever, weight loss, and anorexia may also be present. - Approximetely 33% to 50% of thymomas are associated with myasthenia gravis, 5% with red cell aplasia, and 5 % with hypogammaglobulinemia. 4 || - CT is well suited for staging of many of these tumors and is helpful for monitoring response to irradiation or chemotherapy. - Because most mediastinal tumors are surgically removed, tissue diagnosis is most often done at thoractomy. - Bronchoscopy, mediastinoscopy, or anterior mediastinotomy may yield the diagnosis, especially if enlarged lymph nodes are present.
 * Epidemiology: ||  -Thymomas are the most common tumors of the anterior mediastinum. They account for approximately 20% of all mediastinal tumor in adults. 2  “The incidence of thymoma in the United States is estimated to be 0.13 to 0.15 per 100,000 people." 3
 * Etiology: || -“The median age of patients with thymoma is older than 50 years and thymomas are diagnosed equally in men and women. Thymomic lesions also occurs in the elderly, but with a male predominance .” Thymomas are less common in children. There is some reported association between the Epstein bar virus and thymoma tumor development, more frequently seen in far eastern countries ." 3
 * Signs & Symptoms: || - Approximately 30% to 40% of thymomas are asymptomatic; the tumor is usually an incidental finding on chest x-rays.
 * Diagnostic Procedures: || - Computed tomography (CT) is the most valuable radiologic technique. It defines size, contour, tissue density, homogeneity of the lesion, and the lesion's relationship to other structures, and is imperative for planning radiation portals.

TABLE 31-2 Diagnostic Workup for Mediastinal Tumors 4

History Physical examination - For male patients with mediastinal germ cell tumors, this should include a thorough examination of the testes
 * GENERAL**

Chest x-ray CT scan MRI Barium swallow Fluoroscopy Arteriography Iridium 131 scan Gallium scan Ultrasonography of testes (in mediastinal germ cell tumors) Lymphangiogram (in mediastinal germ cell tumors) Complete blood cell count, blood chemistries, urinalysis Germ cell tumors: alpha-fetoprotein, human chorionic gonadotropin, carcinoembryonic antigen Thymoma: radioimmunoassay for acetylcholine receptors Mediastinoscopy Anterior mediastinotomy with biopsy Bronchoscopy Esophagoscopy Biopsy of palpable supraclavicular lymph nodes 4 || inferior medastiunum and are then separated number and location.
 * RADIOGRAPHIC STUDIES**
 * Standard**
 * Complementary**
 * Laboratory Studies**
 * Special tests/procedures**
 * Histology: || Mediastinal germ cell tumors are divided into germinomas (seminomas), adult (mature) teratomas, embryonal carcinomas, teratocarcinomas, choriocarcinomas, yolk sac tumors (endodermal sinus tumors), and mixed tumors. A simpler system of classification divides tumors into pure seminomas or nonseminomatous carcinomas. 4 ||
 * Lymph Node Drainage: || The mediastinum is rich in lymphatics. They are subdivided into those in the superior mediastinum and those in the

The superior mediastinal nodes include:  The inferior mediastinal nodes include:  At the bifurcation of the trachea, the lymph channels have access to the circulatory system as the lymph flow enters the thoracic duct and aorta. <span style="color: #008000; font-family: 'Comic Sans MS',cursive; vertical-align: super;"> <span style="color: #298000; font-family: 'Times New Roman',Times,serif; font-size: 110%;">Figure 1. Diagram of mediastinal lymph nodes. <span style="color: #298000; font-family: 'Times New Roman',Times,serif; font-size: 90%; vertical-align: super;">5 || <span style="color: #008000; font-family: 'Comic Sans MS',cursive; font-size: 110%;">"Types A and AB are considered to be non-cancerous (benign). Types B1 to B3 are classed as low-grade (slow-growing); on the borderline between being benign or malignant. Type C is definitely cancer." <span style="color: #298000; font-family: 'Comic Sans MS',cursive; font-size: 99%; vertical-align: super;">6 ||
 * <span style="color: #008000; font-family: 'Comic Sans MS',cursive; font-size: 110%;">Highest mediastinal
 * <span style="color: #008000; font-family: 'Comic Sans MS',cursive; font-size: 110%;">Upper paratracheal
 * <span style="color: #008000; font-family: 'Comic Sans MS',cursive; font-size: 110%;">Pretracheal and retrotracheal
 * <span style="color: #008000; font-family: 'Comic Sans MS',cursive; font-size: 110%;">Lower paratracheal (including azygos)
 * <span style="color: #008000; font-family: 'Comic Sans MS',cursive; font-size: 110%;">Subcarinal
 * <span style="color: #008000; font-family: 'Comic Sans MS',cursive; font-size: 110%;">paraesophageal
 * <span style="color: #008000; font-family: 'Comic Sans MS',cursive; font-size: 110%;">pulmonary ligament
 * Metastatic Spread: || <span style="color: #008000; font-family: 'Comic Sans MS',cursive; font-size: 110%;">Metastatic spread is uncommon but distant metastasis has been reported in the liver, lung, and bone. Advanced disease can have direct spread into the SVC, brachialcephalic vein, lung, and pericardium. <span style="color: #298000; font-family: 'Comic Sans MS',cursive; font-size: 99%; vertical-align: super;">2 ||
 * Grading: || <span style="color: #008000; font-family: 'Comic Sans MS',cursive; font-size: 110%;">Thymus tumors have been classified according to grade and type by the World Health Organization (WHO):
 * <span style="color: #008000; font-family: 'Comic Sans MS',cursive; font-size: 110%;">**A** Medullary thymoma
 * <span style="color: #008000; font-family: 'Comic Sans MS',cursive; font-size: 110%;">**AB** Mixed thymoma
 * <span style="color: #008000; font-family: 'Comic Sans MS',cursive; font-size: 110%;">**B1** Mainly cortical thymoma
 * <span style="color: #008000; font-family: 'Comic Sans MS',cursive; font-size: 110%;">**B2** Cortical thymoma
 * <span style="color: #008000; font-family: 'Comic Sans MS',cursive; font-size: 110%;">**B3** Thymic carcinoma
 * <span style="color: #008000; font-family: 'Comic Sans MS',cursive; font-size: 110%;">**C** Thymic carcinoma – high grade (malignant)
 * Staging: || <span style="color: #0000ff; font-family: Georgia,serif;">The staging of thyomas are classified as invasive and noninvasive. The Masaoka pathologic staging system is the most widely used. See table below. <span style="color: #0000ff; font-family: 'Times New Roman',Times,serif; font-size: 90%; vertical-align: super;">2 <span style="color: #0000ff; font-family: Georgia,serif;"> There is not a universal staging system used for mediastinal germ cell tumors.


 * Thymoma staging system

Stage I -** Macroscopically completely encapsulated and no microscopic capsular invasion

2. Microscopic invasion in capsule
 * Stage II -** 1. Macroscopic invasion into surrounding fatty tissue or mediastinal pleura or


 * Stage III -** Invasive growth into neighboring intrathoracic organs


 * Stage IVA -** Pleural or pericardial implants


 * Stage IVB -** Lymphogenous or hematogenous metastases ||
 * Radiation Side Effects: || <span style="color: #0000ff; font-family: Georgia,serif;">Thymoma patients treated with radiation have reported pneumonitis, pericarditis ,and, rarely, myelopathy. <span style="color: #0000ff; font-family: 'Times New Roman',Times,serif; font-size: 90%; vertical-align: super;">2 <span style="color: #0000ff; font-family: Georgia,serif;"> Acute symptoms of thoracic irradiation include fatigue, dysphagia, cough, and mild skin reactions. ||
 * Prognosis: || Thymoma- invasiveness of the tumor is the most important prognostic factor. <span style="color: #ff00ff; font-family: 'Times New Roman',Times,serif; font-size: 90%; vertical-align: super;">2 " Patients with complete or radical excision have significantly better survival than those with subtotal resection or biopsy only ." <span style="color: #ff00ff; font-family: 'Times New Roman',Times,serif; font-size: 90%; vertical-align: super;">3 ||
 * Treatments: || <span style="color: #008080; font-family: 'Times New Roman',Times,serif; font-size: 110%;">**__Thymoma: General Management__**
 * <span style="color: #008080; font-family: 'Times New Roman',Times,serif; font-size: 110%;">The treatment of choice for all thymomas is complete surgical resection, regardless of invasiveness, except in rare cases with extrathoracic or extensive intrathoracic metastasis.
 * <span style="color: #008080; font-family: 'Times New Roman',Times,serif; font-size: 110%;">Survival with encapsulated, noninvasive thymomas are excellent and post-op radiation in not recommended for these cases.
 * <span style="color: #008080; font-family: 'Times New Roman',Times,serif; font-size: 110%;">Radiation therapy is excellent adjuvant therapy for invasive thymomas, which are generally radioresposive.
 * <span style="color: #008080; font-family: 'Times New Roman',Times,serif; font-size: 110%;">Pre-op radiation therapy is recommended for large, invasive thymomas thought to be marginally resectable. However, with the high response rate with chemotherapy, pre-op radiation is not often used.
 * <span style="color: #008080; font-family: 'Times New Roman',Times,serif; font-size: 110%;">Post-op radiation therapy is neccessary for invasive thymomas regardless of completeness of surgery.
 * <span style="color: #008080; font-family: 'Times New Roman',Times,serif; font-size: 110%;">Chemotherapy's role as an adjuvant treatment after resection has not been established, but it has been used in combination with irradiation in unresectable surgical cases.

<span style="color: #008080; font-family: 'Times New Roman',Times,serif; font-size: 110%;">**__Thymoma: Radiation Therapy Techniques__**
 * <span style="color: #008080; font-family: 'Times New Roman',Times,serif; font-size: 110%;">Volume treated should include the entire mediastinum and part of the involved adjacent lung if there is any parenchymal involvement, or as delineated by CTscan or surgical clips, with an additional 1.5 cm margin.
 * <span style="color: #008080; font-family: 'Times New Roman',Times,serif; font-size: 110%;">Treatment set-ups usually include AP and PA fields with various combinations of photon beams and anterior wedged oblique fields.
 * <span style="color: #008080; font-family: 'Times New Roman',Times,serif; font-size: 110%;">Recommended dosage for malignant thymomas after resection is 45-50 Gy in 23-25 fractions; doses up to 56 Gy have been used, with excellent tumor control with all doses over 40 Gy.
 * <span style="color: #008080; font-family: 'Times New Roman',Times,serif; font-size: 110%;">Local recurrence has been reported with doses less than 40 Gy.
 * <span style="color: #008080; font-family: 'Times New Roman',Times,serif; font-size: 110%;">In cases that surgery is limited or not possible, an addition 5 Gy boost through reduced fields is warranted.

<span style="color: #008080; font-family: 'Times New Roman',Times,serif; font-size: 110%;">**__Malignant Mediastinal Germ Cell Tumors: General Management__**


 * Seminomas**
 * <span style="color: #008080; font-family: 'Times New Roman',Times,serif; font-size: 110%;">Thoracotomy with radical intent has been performed in approximately 50% of patients who had surgery. Complete tumor removal was possible in only 40-50% of the patients undergoing radical surgery.
 * <span style="color: #008080; font-family: 'Times New Roman',Times,serif; font-size: 110%;">If radical resection is not performed, excellent results still may be obtained with radical post-op radiation, or even radiation after biospy alone.
 * <span style="color: #008080; font-family: 'Times New Roman',Times,serif; font-size: 110%;">Chemotherapy usually is reserved for locally extensive tumors, failures of surgery or radiation, or metastatic disease.


 * <span style="color: #008080; font-family: 'Times New Roman',Times,serif; font-size: 110%;">Nonseminomas Germ Cell Neoplasms **
 * <span style="color: #008080; font-family: 'Times New Roman',Times,serif; font-size: 110%;">Because of their propensity for distant metastasis, primary treatment for nonseminomatous malignant tumors is chemotherapy and radical resection, if possible.
 * <span style="color: #008080; font-family: 'Times New Roman',Times,serif; font-size: 110%;">Mediastinal NSGCT does not respond as well to chemotherapy as other extragonadal or testicular presentations. Relapses are more frequent, and survival is worse.
 * <span style="color: #008080; font-family: 'Times New Roman',Times,serif; font-size: 110%;">For better local tumor control, resection of postchemotherapy residual disease may be necessary.
 * <span style="color: #008080; font-family: 'Times New Roman',Times,serif; font-size: 110%;">The role of radiation has not yet been highly debated. Because of a poor resectionability rate and frequent residual masses after chemotherapy, radiation therapy mainly has been used to increase local tumor control.
 * <span style="color: #008080; font-family: 'Times New Roman',Times,serif; font-size: 110%;">Irradiation given before chemotherapy adversely affects the patient's ability to tolerate full cytotoxic doses.

<span style="color: #008080; font-family: 'Times New Roman',Times,serif; font-size: 110%;">**__Malignant Mediastinal Germ Cell Tumors: Radiation Therapy Techniques__**
 * <span style="color: #008080; font-family: 'Times New Roman',Times,serif; font-size: 110%;">The volume treated should include the entire mediastinum and part of the involved adjacent lung if there is parenchymal involvement, or as delineated by CTscan or surgical clips, with an additional 1.5 cm margin.
 * <span style="color: #008080; font-family: 'Times New Roman',Times,serif; font-size: 110%;">Treatment set-ups usually include AP and PA fields with various combinations of photon beams and anterior wedged oblique fields.
 * <span style="color: #008080; font-family: 'Times New Roman',Times,serif; font-size: 110%;">Recommended dosage for malignant thymomas after resection is 45-50 Gy in 23-25 fractions; doses up to 56 Gy have been used, with excellent tumor control with all doses over 40 Gy.
 * <span style="color: #008080; font-family: 'Times New Roman',Times,serif; font-size: 110%;">Local recurrance has been reported with doses less than 40 Gy.
 * <span style="color: #008080; font-family: 'Times New Roman',Times,serif; font-size: 110%;">In cases that surgery is limited or not possible, an addition 5 Gy boost through reduced fields is warrented. <span style="color: #008080; font-family: 'Times New Roman',Times,serif; font-size: 80%; vertical-align: super;">2

<span style="color: #008000; font-family: 'Times New Roman',Times,serif; font-size: 110%;"> Figure 2. Isodose curves of treatment used in mediastinal tumors. A) Three wedge port arrangment. B) Two anterior wedge ports. <span style="color: #298000; font-family: 'Times New Roman',Times,serif; font-size: 99%; vertical-align: super;">2 <span style="color: #008000; font-family: 'Comic Sans MS',cursive; font-size: 110%;"> Figure 3. Treatment portal used to irradiate a malignant thymoma. <span style="color: #298000; font-family: 'Times New Roman',Times,serif; font-size: 99%; vertical-align: super;">2 <span style="color: #008080; font-family: 'Times New Roman',Times,serif; font-size: 80%; vertical-align: super;"> || <span style="color: #008080; font-family: 'Times New Roman',Times,serif; font-size: 110%;">Tolerance dose chart provided by Wikibooks. <span style="color: #008080; font-family: 'Times New Roman',Times,serif; font-size: 88%; vertical-align: super;">1 || References: <span style="color: #008080; font-family: 'Times New Roman',Times,serif; font-size: 110%;">1. Radiation Oncology/Toxicity/Emami. Wikibooks. Available at: []. <span style="color: #008080; font-family: 'Times New Roman',Times,serif; font-size: 110%;">Accessed: January 5, 2010. <span style="color: #0000ff; font-family: Georgia,serif;">2. Chao CK, Perez CA, Brady LW. //Radiation Oncology Management decisions//. Philadelphia, PA: Lippincott Williams & Wilkins. 1999; 322-328. 3. <span style="color: #ff00ff; font-family: 'Arial','sans-serif'; font-size: 10.8pt; line-height: 200%;"> Gunderson, LL & Tepper, JE. (Eds.) //<span style="font-family: 'Arial','sans-serif';">Clinical Radiation Oncology //. 2nd edition. Philadelphia, PA: Elsevier, Churchill & Livingstone. 2007: 974-985. <span style="color: #ff0000; font-family: Georgia,serif;">4. Chao KS, Perez CA, Brady LW. Radiation Oncology Management Decisions. 2nd edition. Philadelphia, PA: Lippincott Williams & Wilkins. 1999,2002.Pg. 322-323,327. <span style="color: #008000; font-family: 'Comic Sans MS',cursive; font-size: 110%;">5. Washington CM, Leaver D. //Principles and Practice of Radiation Therapy.// 2nd edition. St. Louis, MO: Mosby, Inc. 2004: 395, 654. 6. Macmillan Cancer Support. //Thymoma and Thymic Cancer.// Available at: http://www.macmillan.org.uk/Cancerinformation/Cancertypes/Thymus/Thymomathymiccarcinoma.aspx#DynamicJumpMenuManager_6_Anchor_6. Access January 23, 2010. <span style="color: #ff00ff; font-family: 'Comic Sans MS',cursive; font-size: 110%;">7. <span style="color: #ff00ff; font-family: 'Arial','sans-serif'; font-size: 110%;">Hainsworth, JD & Greco, FA. (n.d.) //Malignant Mediastinal Germ Cell Tumors//. Retrieved January 20, 2010, from American Medical Network’s website: http://www.health.am/cr/malignant-germ-cell-tumors/ <span style="color: #ff00ff; font-family: 'Comic Sans MS',cursive; font-size: 12pt;">
 * TD5/5: || [[image:TD_5.5_Mediastinumnew.jpg width="307" height="223"]]

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