Mediastinal tumor Zuzannawati, Erwin Arief * Sub-Section of Pulmonology, Department of Internal Medicine Universittas Medical Faculty of Hasanuddin INTRODUCTION
Mediastinal tumor is a tumor that is contained within the mediastinal cavity is located between the right and left lung. The mediastinum is an important part of the thorax. The mediastinum is the central area of the chest cavity between the pleural cavity located between pleuralis cavity and contains many vital organs and vital structures. [ 1 ] Important structures contained in it are the heart, arteries, veins, trachea, thymus gland, nerves, connective tissue, lymph nodes and ducts. Broadly speaking, the mediastinum is divided into 4 important parts of the superior mediastinum, the anterior, posterior and medial mediastinum. Important processes involving the mediastinum include emphysema, infection, bleeding, and many types of primary tumors and cysts. Mediastinal cavity is narrow and can not be expanded, the resolution of the tumor can press on nearby organs and can cause life-threatening severity. Most mediastinal tumors grow slowly so patients often come after a tumor is large enough, with complaints and symptoms due to tumor suppression surrounding organs. [ 2 , 3 ] Epidemiology Several reviews of the mediastinal mass shows the variation in incidence and clinical presentation depends on the age of the patient and the specific area of the mediastinum. In adult individuals, mediastinal tumors are the most common thymoma followed by neurogenic tumors, lymphomas, and germ cell tumors. [ 4 ] Based on a retrospective study from 1973 to 1995 in New Mexico, USA acquired 219 patients were identified malignant mediastinal tumors of 110,284 patients of primary malignant disease, dise ase, most types of lymphoma was 55%, 16% germ cells, thymoma 14%, 5% sarcoma, neurogenic 3% and 7% other types. [ 5 ] While the frequency of data mediastinal tumor in Indonesia, among others, obtained from SMF Thoracic Surgical Friendship Hospital, Jakarta. In the years 1970 - 1990 at the Friendship Hospital performed surgery on 137 cases. The study was conducted with a cross-sectional survey method through the perpetually retrospective medical record in the hospital over the next 5 years (January 2002-December 2006). Obtained a total of 184 cases with neoplastic group were recorded by examination of the PA during the years 2002-2006 as many as 164 cases. The number of samples collected through medical records of 98 people. Based on the obtained sex men numbered 69 (70.4%) and 29 women (29.6%). Respiratory symptoms in 87 mediastinal tumors with complaints of cough 68 (78.1%), shortness of breath 60 people (68.9%), chest pain, 39 (44.8%), wheezing sound 2 (2.3% ). 59 nonrespiratory symptoms with weight loss 45 (76.2%), fever 27 (45.7%), fatigue 16 (27.1%), other 37 (62.7%). 8 of 98 people came without complaint. Abnormalities associated ith suppression or tumor invasion into surrounding organs 2 (2.1%), superior vena cava syndrome, 25 (27.1%), pleural effusion 25 (27.1%) and myasthenia gravis 28 people (36 , 3%). Tumor diagnosis based PA; thymoma 37
(37.8%), germ cell tumors 10 (10.2%), teratom 20 people (20.4%), seminoma 4 (4.1%), nonseminoma 1 (1%), lymphoma 13 (13.3%), mediastinal malignancies other 10 (10.2%) and benign tumors of the mediastinum 3 (3.1%). Based on chest radiographs, 92 anterior mediastinal tumor, 4 medium, and 2 posterior. Data Hospital Dr. Soetomo describes the location of the tumor in the anterior mediastinum 67% of cases, 29% of the mediastinum medial and posterior mediastinum 25.5%. [ 4 , 6 ]
CLASSIFICATION
Mediastinum based on the division of anatomy divided into four: 1. Superior mediastinum, from the door on the chest cavity to the thoracic vertebrae and the bottom of the sternum: Struma, parathyroid adenoma and lymphoma 2. Anterior mediastinum, from the boundary line to the superior mediastinum diafargma in front of the heart: Struma, teratoma, thymoma, parathyroid adenoma, lymphoma, fibroma, hemangioma Limfangioma, and Morgagni Hernia 3. Posterior mediastinum, the superior mediastinum from the boundary line to the diaphragm in the back of the heart: neurogenic tumors, fibrosarcoma, lymphoma, aneurysm, kondroma, bochdalek hernia. 4. Mediastinum medial (middle), of the boundary line in the superior mediastinum to the diaphragm between the anterior and posterior mediastinum: bronchogenic cyst, lymphoma, pericardium cysts, aneurysms, and hernia. [ 2 ] The division of the mediastinum into the different cavities assist in diagnosis. This type of tumor in the mediastinum cavity can be either benign or malignant tumors with different management and prognosis, therefore diagnostic procedures play a pivotal role. Most cases come to the gravity or severity of cardiovascular breath, a condition that causes the diagnostic procedures had to be postponed for troubleshooting kegawatannya first. [ 2 , 4 ] Mediastinal tumor classification based on the organ / tissue origin of the tumor or histological type, as suggested by Rosenberg Table. 1 Classification of mediastinal tumor by histopathologic
A. thymoma Thymoma is a primary tumor in the anterior mediastinum are most commonly found. Men and women are equal number of events and most often at the age of 40 years. Thymoma is rare in children and adolescents. Thymoma is a tumor or a benign epithelial tumor with a low degree of malignancy and is found in the anterior mediastinum. Thymoma including slow-growing t ype of tumor. [ 5 , 7 ] Frequent local invasion into surrounding tissues but rarely metastasizes outside the thorax. Most are asymptomatic. If patients present with the common complaint was chest pain, coughing, tightness or other symptoms associated with invasion or tumor suppression to the surrounding tissue. One or more signs of the syndrome paratimik often found in patients with thymoma, such as myasthenia gravis, hipogamaglobulinemi and red blood cell aplasia. The incidence of approximately 30-50% Myastenia gravis in patients with thymoma. 25% of patients with thymoma with myasthenia myastenia are young women. Can be diagnosed with an increase in antibody titer antiacetylcholine receptor. 10% of patients with hipogammaglobulinemia tymoma, 5% of thymoma patients with red cell aplasia. [ 4-6 ]
Radiology picture of the thorax x-ray posteroanterior lobular mass appeared in the anterior-superior left parahillar opaque area. In the lateral position showed a mass in the anterior portion of the thoracic cavity and the retrosternal area that is not clean. On CT scan usually manifests as soft tissue in the anterior mediastinum, size can be of various kinds, with smooth and firm boundaries. [ 8 ] From the description of anatomic pathology is difficult to distinguish benign or malignant thymoma. Definition of malignant thymoma (invasive) if the tumor is microscopic (histopathological) and macroscopic invasive been outside the capsule or surrounding tissue. [ 9 ] Table 2. Classification of histological thymoma (7)
Table 3. Masaoka staging system based
Noninvasive thymoma is still limited to the thymus gland and has not spread to other organs. All tumor cells contained or encased by a capsule and microscopically invisible invasion of the capsule. If the tumor cell invasion has reached the capsule then categorized invasive thymoma (malignant thymoma). Data at the Friendship Hospital of 31 surgical cases in 1992 to 1999 cases of invasive categorized amounted 90.3% and only 9.7% of cases are diagnosed noninvasive or stage I. 2000-2001 data from 12 patients with thymoma were dissected no cases of noninvasive. [ 1 ] Data in Section of Thorax and Cardiovascular surgery in patients with thymoma Torino University operated from years 1958-1988 (30 years), 107 patients with 134 men and women aged between 16-76 years found 52 of 241 patients (21.6%) died. 7 postoperative, 5 people died with myastenia gravis. 11 people without myastenia gravis. 80% survive for 5 years, 75.6% over 10 years. Patients with stage I thymoma good prognosis, whereas in stage II, III and IVa poor prognosis. [ 10 ]
B. Germinal Cell Tumors Germ cell tumor composed of seminoma tumors, teratomas and nonseminoma. Germ cell tumors in the mediastinum are less common than thymoma, more frequently in males and young adults an average age of 27 years. Approximately 10-15% of cases of anterior mediastinal tumor. Most cases are a primary tumor in the testes so that when the diagnosis was mediastinal germ cell tumors, it must be ensured that the primary in the testis has been removed. Most locations in the anterior (superoanterior) mediastinum. Histologically the tumor in the mediastinum together with germ cell tumors in the testes and ovaries. Serologic evaluation of α-fetoprotein (AFP) and β-human chorionic gonadotropin (β-HCG) to help evaluate patient-psien suspected malignant germ cell tumors. [ 5 , 6 ] Teratomas are germ cell tumors are the most common followed by seminoma tumors can form cysts or solid or a mixture of both composed of germ cell layers, namely ectoderm. mesoderm or endoderm. Mature teratoma is the most common mediastinal germ cell tumors and are usually benign. The tumor is not as testicular teratoma metastatic potential and can be surgical resection. Therefore, the anatomical location and pascaoperaif intraoperative complications can affect morbidity due to intrathoracic structures usually involved. [ 11 ] Intrathoracic teratoma usually appears in the cavity is very rare in the mediastinum and lung. Most of these tumors are benign, although there are malignant. The tumor usually found in the mid-line of the body. Symptoms can appear in case of mechanical effects such as chest pain (52%), hemoptysis (42%), cough (39%), shortness of breath, or symptoms associated with recurrent pneumonitis. Other respiratory symptoms are trikoptisis (trichoptysis) (13%) are in the productive cough sputum containing hair or sebaceous gland secretions. This would occur if there is a relationship between the mass of the tracheobronchial tumors. Other symptoms of superior vena cava syndrome or lipoid pneumonia. Mediastinurn teratomas are usually discovered by accident in the photo the piston. [ 5 , 12 ] In radiology teratomas appear round and often lobulated and contain elements of soft tissue with fluid and fat, calcification seen in 20-43% of cases. Seminoma, histology obtained approximately 40% of germ cell tumors. Seminoma appears as a large mass is homogeneous whereas nonseminoma heterogeneous mass with irregular edge caused by the invasion of the surrounding tissue. To distinguish seminoma to nonseminoma used serum marker of beta-HCG and alpha-fetoprotein. Approximately 10% of patients with pure seminoma menglami increase in serum beta-HCG but there is no increase in serum alpha-fetoprotein. Although the pure seminoma beta-HCG concentrations are sometimes high but not high alphafetoprotein. While the concentrations of both markers nonseminoma was always high. The concentration of beta-HCG and alpha-fetoprotein more than 500 mg / mL is a definite diagnosis for nonseminoma. Radiological picture, looks like a large lobulated mass and homogeneous in the anterior mediastinum region. [ 5 , 6 ] Below can be seen histological classification of germ cell tumors Table 4. Classification of germ cell tumor histology
C. Neural Tumors Nerve tumors occur approximately 20% in adults and 35% in children. These tumors can grow on nerve cells disembarang places, more frequently in the posterior mediastinum. Most are asymptomatic. The tumor can be benign or malignant and are usually classified according to the network that formed it. Benign tumors are very rarely become malignant. Although it is said often in children but can also be found in adults. Topcu from Turkey analyzed 60 patients with tumors of nerves and get 13 people with babies and children age (<15 years), 47 adults (age> 15 years), more women (39) than men (21). Only 20% (12 of 60) are malignant. [ 4 ] Table 5. Histological classification of tumors of nerve Tumors derived from peripheral blood cells usually asymptomatic lesions with spherical morphology, treatment with excision. Meanwhile, a neuroblastoma tumor cell derived neural chest. Neuroblastoma is an aggressive tumor and metastasize quickly. This mass is not encapsulated and usually shows cystic degeneration, hemorrhage, and necrosis. Most often occur in children. Clinical manifestations of pain, neurological deficits, compressing the airway and ataxia. On CT scans, 80% appear to calcification. Treatment with resection when the tumor is still being limited, then resection enough, but if it has spread, it is necessary to chemotherapy and radiation. Table 6. Neuroblastoma Staging Stage Characteristics I Non-invasive, ipsilateral II Local invasion without extension. Ipsilateral lymph node involvement III Tumor spread and lymph node meewati midline bilaterally IV Metastasis IVs Stage I or II and metastasis to the liver, skin and bone marrow D. Lymphoma Lymphoma is the most common mass in the mediastinum around 50% among all mediastinal masses. Tumor is located in the medial area and usually manifests as a primary tumor. Hodgkin lymphoma is approximately 25-30% of cases of lymphoma. Lymphoma is composed of a diverse group of neoplasms originating from malignant proliferation of lymphocytes in the lymphoid system. Lymphoma can occur as a result of genetic mutation or a viral infection. Produce malignant transformation of cells with uncontrolled and excessive growth that accumulates in the lymph nodes so
as to form a mass. Lymphomas generally start in the lymph nodes and lymphoid tissue in the stomach and intestines. [ 6 ] Hodgkin lymphoma is a malignant lymphoma that occurs at a median age of 38 years. More common in whites than blacks. Characteristic is a progression from one group of lymph nodes to other places and the appearance of systemic symptoms, and the presence of Reed Sternbeg cell on histopathologic features. Patients with Hodgin's lymphoma, usually found in cervical lymphadenopathy or supraclavikular. 30% is accompanied by fever, night sweats, or weight loss. Most mediastinal lymphoma are asymptomatic and found incidentally on chest radiographs. It can also be the symptom of chest pain, coughing, and wheezing sound or dysphagia due to the mass invasion of mediastinal structures. Superior vena cava syndrome (SVCS) and the invasion of the chest wall is rare. [ 6 , 12 ] Non-Hodgkin lympoma including β-cell neoplasms. The median age of patients between 55-68 years older. Lymphadenopathy can occur locall y and general. Superior vena cava syndrome is common in these cases. The symptoms most frequently found in the superior vena cava syndrome, coughing, hoarseness, tightness, and chest pain. Biopsy is the primary diagnostic tool. [ 12 ] Radiologically the photo posteroanterior chest x-ray showed mediastinal widening medially and superiorly, the lateral thorax can be seen retrosternal space. [ 8 ] DIAGNOSIS To perform diagnostic procedures mediastinal tumor to be seen if the patient comes to the gravity. Most mediastinal tumor with no symptoms and is found during chest X-ray done for a variety of reasons. Patients who come to the gravity of breath often require emergency action. Patient complaints are usually related to the size and invasion or compression of surrounding organs, such as severe shortness of breath, superior vena cava syndrome (SVKS) and swallowing disorders. Not infrequently the patient comes to the gravity of breath, cardiovascular or gastrointestinal tract. When patients present with life-threatening severity, the diagnostic procedures may be delayed. Meanwhile, therapy and measures to overcome gravity, when it allows diagnostic procedure was performed. [ 4 , 12 ] In general, the diagnosis of mediastinal tumor is established as follows: 1. Clinical Overview • Anamnesis Mediastinal tumors often do not give symptoms and detected on chest Xray done. For benign tumors, complaints usually starts when there is an increase in the size of the tumor that causes suppression of mediastinal structures, whereas malignant tumors can cause symptoms due to compression or invasion of mediastinal structures. Symptoms and signs that may arise depending on the organ involved : 1. Cough, shortness or stridor arise when compressing or invasion of the trachea and / or main bronchi, 2. Dysphagia caused by an emphasis or invasion of the esophagus 3. Superior vena cava syndrome (SVKS) are more common in mediastinal tumors were malignant compared with benign tumors, 4. Hoarseness and dry cough appears when laringel involved nerve, paralysis of the diaphragm phrenic nerve arises when emphasis 5. Chest wall pain or neurogenic tumors arise in the nervous system suppression.
• Physical examination The physical examination will provide information in accordance with the location, size and limitations of other organs, such as has occurred emphasis to surrounding organs. The possibility of mediastinal tumors can be thought of or associated with some clinical circumstances, for example : 1. myasthenia gravis may indicate thymoma 2. lymphadenopathy may indicate lymphoma • Laboratory studies (3, 4) 1. The results of routine laboratory tests often do not provide information relating to the tumor. LED sometimes increases in lymphoma and tuberculosis. 2. Examination of the levels of T3 and T4 is required for thyroid tumors. 3. Examination of α-fetoprotein and β-HCG performed for mediastinal tumors including germ cell tumor group, that is, if there is any doubt between seminoma or nonseminoma. Levels of α -fetoprotein and β-HCG nonseminoma higher in group [ 4 , 13 ] • Radiology Procedures (3) 1. CXR Of CXR PA / lateral tumor location can be determined, the anterior, medial or posterior, but in cases with large tumor size is difficult to determine the exact location. 2. Thoracic CT scan with contrast Besides being able to decrypt the location of the tumor can also decrypt disorder better and with the possibility to determine the expected types of tumors, such as teratoma and thymoma. CT scan can also determine the stage in the case of thymoma by finding whether there has been an invasion or not. The development of this tool facilitates the retrieval of materials for cytology. To determine the extent of radiation several types of tumors of the mediastinum should be performed a CT scan of thoracic and abdominal CTScan. [ , , 8 9 11 , 14 ] 3. Flouroskopi This procedure is done to see the possibility of aortic aneurysm. 4. Esofagografi This examination is recommended if there is suspicion of invasion or emphasis to the esophagus. 5. Ultrasound, MRI and Nuclear Medicine Although rare, sometimes the tests should be done for some cases of mediastinal tumor. • Endoscopic procedures [ 4 , 13 , 15 ] 1. Bronchoscopy should be performed when indicated operation. Action bronchoscopy can provide information about the encouragement or suppression of tumors to respiratory and location. In addition, via bronchoscopy can also be seen whether there was tumor invasion into the airway. Bronchoscopy is often unable to distinguish mediastinal tumors from primary lung cancer. 2. Mediastinokopi. This action is preferred for tumors located in the anterior mediastinum. 3. Esofagoskopi
• Procedures Pathology [ 4 , 16 ] 1. Cytology Diagnostic procedures to obtain material for cytology examination are: biopsy, fine needle (fine needle aspiration BJH or biopsy / FNAB), performed when enlarged superficial lymph node or tumor. a. pleural puncture if there is pleural effusion b. washings or bronchial brushings during bronchoscopy c. needle aspiration biopsy, which is taking a material with a needle that is done when the future looks intrabronkial during bronchoscopy procedures are very easy to bleed, so the biopsy is very dangerous transthoracal transthoracic biopsy or biopsy (TTB) is done when the mass can be achieved with a needle that is inserted in the chest wall and not near the location of the tumor blood vessel aneurysm or no suspicion. For small tumors (<3cm>, have many blood vessels and nearby organs at risk can be done with the guidance flouroskopi TTB or guiding ultrasound or CT scan. This method provides a high diagnostic yield and are not influenced by the size and location of the tumor. [ 4 , 13 , 16 ] 2. Histologic examination [ 4 , 16 , 17 ] When BJH not been able to establish histologic type, needs to be carried out the following procedure: a. biopsy of palpable lymph nodes in the neck or supraclavicular. If there is no palpable lymph nodes, network nodes can be done lifting that might be there. This procedure is called a biopsy Daniels. b. mediastinal biopsy, performed when the above actions have not obtained results. Tao tahin FW et al in 2007 reported that the anterior mediastinal tumor area for diagnostic histology can be done is to do a mini mediastinotomi making a small incision of approximately 3 cm area parasternalis line intercostal spaces 2 or 3. Mini mediastinotomi This is a method that is safe, minimally invasive, reasonably priced and give satisfactory results. c. excisional biopsy of the tumor mass is large d. diagnostic thoracoscopic e. Video-assisted thoracic surgery (VATS), performed for tumors in all locations, especially in the posterior part of the tumor. 3. Measures Surgery Exploratory thoracotomy for diagnostic if all diagnostic efforts 4. Inspection Other EMG is the investigation of mediastinal tumor or tumor type thymoma tumorvlainnya. The usefulness of this examination is exploring the possibility of miestenia gravis or myesthenic reaction. MANAGEMENT The management of mediastinal tumors depend on the nature of the tumor, benign or malignant. Actions for mediastinal tumors that are benign are surgical, while malignant tumors by type. Malignant mediastinal tumor types most commonly found are thymoma, lymphoma, germ cell tumor and nerve. In general, therapy for malignant tumors of the mediastinum is multimodaliti ie surgery, chemotherapy and radiation. Some types of tumors are resistant to radiation and / or chemotherapy to surgery becomes the treatment of choice, but many other types should get multimodaliti action. Chemoradiotherapy
may be given before surgery (neoadjuvant) or after surgery (adjuvant). Therapeutic options for thymoma is determined by staging the disease at diagnosis. For germ cell tumors depend on tumor subtypes whereas nerve tumors based on tumor tissue dominant. [ 4 ] 1997 data from the Department of Radiology University of Pittsburgh: neurogenic tumors, thymoma, and approximately 60% of benign cysts can be resected compared limphoma, teratoma and granulomatous about 30% that can be resected. Approximately 2/3 of all mediastinal tumors are benign tumors. More than 75% of patients had no complaints is a benign tumor lesion, while almost two thirds of patients with symptoms of a malignant mediastinal mass lesions. [ 4 ] Management of mediastinal tumor
Flow management nonseminoma germ cell tumors
Management of germ cell tumors
CONCLUSION • Mediastinal tumor is a tumor that is contained within the mediastinal cavity is located between the right and left lung • Mediastinal cavity is narrow and can not be expanded, enlarged tumors can press on nearby organs and can cause life-threatening severity • Mediastinal tumors are asymptomatic and discovered a lot at the time of chest Xray for a variety of reasons. • Complaints in patients with mediastinal tumors are usually associated with the size and the compression of the surrounding organs such as severe shortness of breath, superior vena cava syndrome and swallowing disorders • Differences in lung tumors and mediastinal tumors: a mass in the mediastinum will not have water bronchogram, lung mass was forming a sharp angle mediastinal mass forms an obtuse angle. • The management of mediastinal tumors are very dependent on the tumor is benign or ferociously. Benign tumors surgical intervention, whereas for malignant tumors depending on the species, but in general is multimodaliti therapy is surgery, chemotherapy and radiation
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