Mediastinal tumors.pptxMMMMMMMMMMMMMMMMMMMMMMM

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1. Mediastinal tumors By- Mikias A. GSR Dr.sultan J. Consultant surgeon

2. outline Introduction Compartments of mediastinum Diagnostic approach Surgical consideration Common mediastinal tumors, SVC Syndrome Management References

3. Introduction The mediastinum is centrally located in the thoracic cavity. It extends from the thoracic inlet to the diaphragm and from the sternum to thoracic spine, and it is demarcated by the pleural cavities laterally. Generally, the mediastinum can be divided into four or three compartments , depending on whether the superior mediastinal compartment is considered as a separate anatomical entity . Clinically, the mediastinum is divided into anterior, middle, and posterior compartments Superiorly, there is free communication between the mediastinum and the neck, with fascial planes descending in continuity from the neck

4. Compartments most common type of anatomical subdivision is the four-compartment model, which was described in Gray’s anatomy.It divides the mediastinum into the superior, anterior, middle, and posterior compartments superior and the anterior mediastinum is separated by the anatomical line defined by the intersection of caudal margin of left innominate vein with the trachea. This boundary is linked with the definition of the paratracheal lymph nodes proposed by the International Association for the Study of Lung Cancer (IASLC) ,and JART shield classified the mediastinum into the anterior compartment, middle compartment (also referred to as the visceral compartment ), and bilateral paravertebral sulci .

5. The major lymphatic pathways of the mediastinum are divided into four categories: the anterior pathway , tracheobronchial pathway, thoracic duct, and pathway in paravertebral area Anterior pathway - the internal mammary chain, which is located along the bilateral internal thoracic arteries drains the upper anterior abdominal wall, anterior chest wall, anterior portion of the diaphragm, and medial portions of the breast.it also collect from left innominate vein,anterior to svc and ascending aorta The internal mammary chain is associated with metastasization from breast, lung, and esophageal cancers. Among these, breast cancer uses this route as the prominent lymphatic pathway .

6. tracheobronchial pathway originates from pulmonary hilum and ascends along with main bronchi and trachea. Finally , it merges with subclavian veins at venous angles in both sides. It communicates with the lymphatic vessels originating from the esophagus, forming a complicated lymphatic network . Since the left paratracheal channels are not as well developed as the right paratracheal ones, several sections of lymphatic vessels from the left side merge with the right paratracheal chain Thoracic duct it flows into the left subclavian vein at the left venous angle. It collects the lymphatics from esophagus and chest wall, and furthermore, it communicates with tracheobronchial pathway

7. paravertebral area has lymphatic flow which originates from the chest wall including intercostal spaces, parietal pleura, and vertebral column. The lymphatics in the paravertebral area communicate with the thoracic duct, and they finally merge in venous angles

8. Approach to mediastinal mass Most mediastinal masses are (>60 %) • Thymomas • Neurogenic tumors • Benign cysts • Lymphadenopathy In children most common mediastinal masses are (>80 %) Neurogenic tumors • Germ-cell tumors • Foregut duplication cysts In adults the most common mediastinal masses are Lymphomas • Lymphadenopathy • Thymomas • Thyroid masses

9. The approach to mediastinal masses is to 1. Localize the mass to the mediastinum 2. Localize the mass within the mediastinum 3. Characterize the mass on CT or MR The likelihood of malignancy is influenced by the tumor location, patient’s age, and the presence or absence of symptoms Primary mediastinal tumors represent a heterogenous group of neoplastic , congenital, and inflammatory conditions

10. Clinical presentation The most common symptoms at presentation are cough, chest pain, sensation of chest heaviness, and dyspnea . Compression or invasion of mediastinal structures by a mediastinal mass can lead to signs and symptoms of superior vena cava (SVC) syndrome, Horner syndrome, and vocal cord paralysis. Several mediastinal lesions contribute to paraneoplastic syndromes, such as myasthenia gravis, hypogammaglobulinemia or red cell aplasia with thymoma , recurrence fevers (B symptoms) with mediastinal lymphoma, and von Recklinghausen disease with neurofibromas .

11. Diagnosis History and Physical Findings Compartment Location of Mass Lymphoma Night sweats, weight loss, fatigue, extrathoracic adenopathy, elevated erythrocyte sedimentation rate or C-reactive protein level, leukocytosis Any compartment Thymoma with myasthenia gravis Fluctuating weakness, early fatigue, ptosis, diplopia Anterior Mediastinal granuloma Dyspnea, wheezing, hemoptysis Visceral (middle) Germ cell tumor Male gender, young age, testicular mass, elevated levels of human chorionic gonadotropin and/or alpha-fetoprotein Anterior

12. Diagnostic evaluation Imaging CXR The initial workup of a mediastinal mass Detect asymptomatic mediastinal masses CT- spiral,angiography The most common imaging modality Contrast-enhanced CT scans Clear delineation of anatomy MRI - invasion of vascular structure - spinal involvement - follow up

13. fluorine-18-fluorodeoxyglucose positron emission tomography (FDG-PET) allows the identification of intratumoral increased metabolic activity by measuring FDG Single-photon emission computed tomography (SPECT) technology has been used to assess the malignant nature of primary lesions and identify residual or recurrence tumors. Octreotide or m - iodobenzylguanidine (MIBG) scans are helpful in the diagnosis and localization of pheochromocytomas and neuroblastomas

14. Tumor Compartement CT finding Thymic hyperplasia Anterior TRUE THYMIC HYPERPLASIA Enlargement of the thymus which remains organized LYPHOID HYPERPLASIA Normal,enlarged or as focal thymic mass Thymoma Anterior Soft tissue attenuation Mild to moderate contrast enhancement Occasional focal hemmorhage , necrosis,cyst or calcification Thymic carcinoma Anterior Pleural nodules Ill defined ST mass Necrotic or cystic component

15. Tumor Compartement CT finding Teratoma Anterior Well defined unilocular or multilocular mass containing fluid ,ST and fat attenuation Calcification (15%) NSGCTs Anterior Hetrogenous ill circumscribed large mass Pleural/pericardial mass Invvt of great vessels Distant mets Cysts Middle Well defined homogenous fluid attenuation (10-20 HU) Lymphoma All Homogenous soft tissue mass Mild to moderate contrast enhancement Absence of vascular invvt Schwannoma Posterior Markedly convex mass “ dumbshell ” or “hourglass” configuration Cyst change,hemorrhage and areas of calcification

16. Cysts Middle Well defined homogenous fluid attenuation (10-20 HU) Lymphoma All Homogenous soft tissue mass Mild to moderate contrast enhancement Absence of vascular invvt Schwannoma Posterior Markedly convex mass “ dumbshell ” or “hourglass” configuration Cyst change,hemorrhage and areas of calcification

17. Cytopathologic diagnosis is often required to confirm a presumed diagnosis EUS-FNA/EUS-TBNA/Core biopsy Selection depends on: Expected diagnosis Planned treatment Age Expected risk of malignancy Risk of complication Availablity

18. Can be invasive or non invasive . Non invasive Endoscopic or percutaneous radiologically guided FNA or CNB. Invasive ( surgical) anterior mediastnotomy sternotomy Videomediastenoscopy VATS Open procedures

19. Surgical aspects median sternotomy is the optimal approach to remove anterior mediastinal tumors. Even in the presence of pulmonary involvement, upper lobe lobectomy and main pulmonary artery resection can be done using this approach . axillary anterolateral thoracotomy , lateral thoracotomy with sternal extension ( hemiclamshell ), and clamshell thoracotomy can also be used. posterolateral thoracotomy is usually used for posterior mediastinal tumor resection

20. Thymic tumors Lesions of the thymus account for approximately 50% of anterior mediastinal masses. Includes Thymic hyperplasia Thymoma Thymic carcinoma Thymic neuroendocrine tumors Carcinoid Small-cell carcinoma Thymic cysts Thymolipoma Metastases to the thymus

21. Thymic hyperplasia separated into two categories based on gross and histologic criteria. lymphoid or follicular hyperplasia , characterized by the presence of lymphoid follicles with activated germinal centers true hyperplasia, characterized by an increase in the size and weight of the thymus gland, which retains a normal or nearly normal morphology for the patient’s age (a) idiopathic or true hyperplasia with marked to massive enlargement of the gland of no apparent cause and (b) rebound thymic hyperplasia in children after treatment of various tumors

22. Thymoma most common type of neoplasm in the mediastinum and they account for 45% of anterior mediastinal tumors. equal frequency in men and women, and are often detected during the fourth to seventh decade of life A third present with cough , dyspnea and chest pain 60% of thymomas are associated with various systemic or paraneoplastic disorders, such as myasthenia gravis, hypogammaglobulinemia , and red cell aplasia . Myasthenia gravis exhibits in 30% to 60% of patients with thymomas , whereas only 5% to 15% of patients with myasthenia gravis have thymomas .

23. MG The most common parathymic syndromes which occurs in approximately 45% of cases. Conversely, 10% to 15% of patients with MG are found to have a thymoma . MG is widely recognized to be an autoimmune disease. Thymectomy leads to improvement or resolution of symptoms of myasthenia gravis in only about 25% of patients with thymomas . In contrast, in patients with myasthenia gravis and no thymoma , thymectomy results are superior: up to 50% of patients have a complete remission and 90% improve.

24. At presentation approximately : 40% of thymomas are stage I, 25% each are stage II or stage III, 10% are stage Iva and, 1% to 2% are stage IVb .

25. Treatment Surgery after preoperative optimization Resectablity Surgeons preference and experience- safe and complete thymectomy Stage Resectability rates are uniformly high in patients with stage I thymomas and high in most reports in patients with stage II thymomas as well. Approximately half of patients with stage III and only about a fourth of patients with stage IV tumors can be completely resected on average . Neoadjuvant chemotherapy followed by complete surgical resection is for extensive stage III and selected cases of stage IVA disease. All patients with thymoma except those with grossly nonresectable disease or with spread beyond the thorax should undergo a complete resection of their disease . Mortality 0-5%,myasthenic crisis

26. debulking surgery can protect the adjacent organs from irradiation toxicity by reducing the adjuvant radiotherapy field. The presence of an intrapulmonary metastasis should not negate this approach, but the pulmonary lesion should be excised at the same time Phrenic nerve involvement – unilateral, excision is recommended, but patient should be carefully evaluated for MG. Bilateral involvement- debulking with chemoradiotherapy . SVC involvement- excision and reconstruction is recommended Adjuvant radiotherapy is indicated for patients with macroscopic capsular invasion, WHO type B thymomas , and tumor adherent to the pericardium

27. Survival After Surgical Resection. The 5 -year survival rates are : for stage I and II , 89% to 100%, 59% to 75% for stage III and Iva 34% to 71%, and 0 % to 53% Recurrence Masaoka stage: I tumors -3% II and III tumors-16% and 26% resp. IV tumors shows wide variability. The mean time to recurrence was 10 years in patients with a stage I thymoma , compared with 3 years in patients with a stage II-IV thymoma . The recurrence of thymoma does not necessarily imply a poor prognosis and an aggressive approach is justified . definitive chemoradiation for patients with systemic and distant metastatic recurrence

28. The median improvement rates were total remission 25 %, asymptomatic with medication 39%, and clinically improved 70%. The benefits of thymectomy are often delayed with 25% achieving remission in the first year, 40% by the end of the second year, and 55% in the third year Octreotide , which is an octapeptide SST analog with a high affinity for SST receptors, demonstrated an overall response rate of 32% when combined with prednisone in 38 stage III and IV thymic tumors EGFR is overexpressed in 71% of thymomas , epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors,especially in stage III and IV tumors

29. Prognosis The Masaoka stage completeness of resection In stage III thymomas , involvement of great vessels and the WHO classification (type A vs . B2 or B3)

30. Thymic carcinoma Thymic carcinomas account for almost 15% of thymic epithelial tumors, mean age of 50 years. Most are either squamous cell carcinomas or are lymphoepithelioma -like carcinomas . two-thirds of thymic carcinomas are high grade, and one-third are low grade. The low-grade thymic carcinomas are usually well localized, whereas the high-grade types are usually found to have extensive spread, at presentation Unlike thymomas , most thymic carcinomas are locally invasive and frequently metastasize to regional lymph nodes and distant sites at initial diagnosis. The typical radiological appearance of a thymic carcinoma is a bulky, poorly defined, and heterogeneous mass that is associated with pleural and pericardial effusion. tri- modality approach that includes induction therapy, surgery, and adjuvant therapy. Worse than the prognosis of thymomas .

31. Mediastinal parathyroids The superior parathyroid glands arise from the fourth pharyngeal pouch. When a superior gland is ectopic, it is typically associated with the esophagus, airway, thyroid gland, carotid sheath, or great vessels . The inferior parathyroid glands arise from the third pharyngeal pouch,twice as likely to be ectopic,located within or around the thymus . Supernumerary glands appear to have a predilection for the mediastinum as 60% are located in the mediastinum (typically in the thymus) 85% of primary hyperparathyroidism is the result of a solitary parathyroid adenoma, hyperfunctional parathyroid gland in the mediastinum secondary hyperparathyroidism, the vast majority of patients will have hyperplasia ,from mediastinal /neck-patient to be informed

32. Thymomas have been identified in patients with primary hyperparathyroidism . The thymoma may mimic ectopic parathyroid gland, positive by parathyroid localization studies( Tc-99m sestamibi scan) Thymic carcinoids in MEN-1,thymus itself PTHism Localization is important Magnetic resonance imaging (MRI) performs well in patients with persistent hyperparathyroidism after treatment of cervical disease, with a sensitivity of 88% and an accuracy of 84 %, but does not perform as well for hyperplasia 11Cmethionine PET/CT in negative 99mTc-sestamibi SPECT imaging

33. Management Preoperative planning Denovo mediastinal exploration Surgical approaches - transcervical thymectomy - sternotomy - thoracotomy - VATS serial PTH measurements can be used intraoperatively to assess whether or not the source of hyperparathyroidism has been eliminated. A reduction in PTH 50% in 15 minutes corresponds to high surgical success rates, however, the value will often fall more dramatically (80% in 10 minutes) Perioperative calcium supplement –hungry bone syndrome

34. lymphomas Common malignancy of the mediastinum ,specially in children Hodgkin lymphoma(75%), primary mediastinal B-cell lymphoma, and lymphoblastic lymphoma In approximately 50% the mediastinum is the primary site. The anterior compartment is most commonly involved

35. Diagnosis Clinical presentation Fatigue, diffuse pruritus , weight loss, fevers, and/or night sweats. Nontender cervical or supraclavicular lymphadenopathy Workup CT scan - large anterior heterogeneous mass involving the thymus and the neck lymph nodes. Non-Hodgkin lymphomas are more commonly detected in younger children and frequently involve the subcarinal , posterior mediastinal , and intra-abdominal lymph nodes Biopsy with adequate tissue sample

36. Treatment Early stage- chemoradiation Combinatio chemotherapy with radiation on involved field in Advanced stage High dose chemotherapy,transplant NHL(PMBL) can present with SVC Syndrome Treatment with xdrug chemotherapy ?radiation LL subtype of NHL,most common childhood mediastinal lymphoma Treatment –high dose intensive xdrug chemotherapy ?radiation

37. GCT About 5% to 10% of all germ cell tumors arise within the anterior mediastinum . Primary mediastinal GCTs have a peak age of incidence between 20 and 35 years and they are categorized into three cell types : Although mature teratomas occur with equal frequency between men and women, malignant GCTs are much more common in men (>90 %). Includes Mature teratoma seminomatous germ cell tumors and nonseminomatous germ cell tumors .

38. Mature teratomas mature or benign teratomas are the most common germ cell tumor arising in the mediastinum . They represent 60% to 70% of all mediastinal germ cell tumors, but they constitute 5% to 10% of all mediastinal tumors. Mature teratomas are usually characterized by the presence of mature tissues derived from all three germinal layers.

39. Presentation chest pain is the most common symptom, followed by dyspnea and cough. cystic component can become infected –systemic manifestation. cyst contents may rupture- expectoration of hair or sebum . Diagnosis MRI Typical CT multilocular but well-circumscribed cystic anterior mediastinal mass containing fluid and fat density half of these tumors radiographically demonstrate calcification

40. Treatment Surgery to prevent malignant somatic transformation of teratomatous elements or the complications of compressive conditions or chronic fistula forma tion with infection Surgical Resection Removal of the inner lining of the cyst, and injection of tetracycline into the mass to prevent the reaccumulation of fluid that had caused symptoms for the patient Surgical approach Median sternotomy Posterior lateral thoracotomy VATS Pathologic analysis mature teratoma Excellent long-term prognosis is anticipated, and no specific long-term follow-up is necessary

41. Malignant teratoma found only in the postpubescent population and represent teratomas that have undergone malignant transformation or have another associated GCT malignancy contained within . these teratomas are found to have a germinal layer that has transformed into frank malignancy , such as sarcoma, adenocarcinoma , or squamous cell carcinoma Preoperatively, if serum tumor markers (AFP and betaHCG ) are elevated, presence of NSGCT should undergo surgical resection after an induction course of intensive chemotherapy targeted against the nonseminomatous elements. Conversely, if tumor marker serology and preoperative biopsy is negative for GCT involvement, surgery should be undertaken as first-line therapy .

42. Adjuvant treatment should be considered after resection in cases of malignant sarcomatous transformation to help prevent recurrence . When teratoma recurrences and metastases are identified , they should be treated aggressively with surgery, provided all sites of disease can be reasonably resected pediatric population these tumors behave in a benign fashion ; however, they can be very aggressive in adults

43. NSGCT Nonseminomatous germ cell cancers comprise slightly more than one half of the malignant germ cell tumors arising in the mediastinum . PMGCTs originating in the mediastinum are rare . PMNSGCTs occur almost exclusively in young adult males who are 20 to 40 years of age. PMNSGCTs have a distinctly worse prognosis with a similar treatment approach with their testicular counterparts.

44. Diagnosis CT For diagnosis Demonstrate a large heterogeneous mass, with occasional evidence of necrosis and hemorrhage. For staging Local invasion CT of the abdomen and pelvis Serum markers CT guided biopsy

45. Chemotherapy PMNSGCTs are usually large and infiltrative neoplasms . Appropriate therapy begins with four cycles of cisplatin -based chemotherapy Regimens BEP regimen VIP regimen

46. Surgery Surgery is planned after adequate functional and hematologic recovery, which usually occurs from 4 to 6 weeks after completion of chemotherapy. any residual Mediastinal mass after chemotherapy needs to be surgically removed. Reconstructions Metatestectomy If CT imaging does identify a residual abnormality, or if surveillance imaging identifies relapse, then surgery should be considered when complete resection is possible . In this setting, elevated tumor markers (AFP and beta-HCG) are not a contraindication for resection, since further chemotherapy has proven to be ineffective. persistently elevated tumor markers postchemotherapy , persistent unresectable disease postchemotherapy , and presence of viable tumor after resection signals worse prognosis

47. SGCTs Constitute slightly less than half of all malignant PMGCTs. PMSGCTs occur almost exclusively in young adult males who are 20 to 40 years of age Seminomas are typically slow growing and become quite large before the symptoms such as chest pain, dyspnea , and cough develop. Sixty to 70 percent of patients will have metastatic disease at the time of diagnosis Surgery is NOT the management ,unless persistent ,viable tumor

48. Treatment Chemotherapy Cisplatin based The role of surgery in patients with pure PMSGCT is usually negligible Local growth of a residual mass-second-line cisplatin -based chemotherapy is usually offered with surgery and/or radiation therapy considered.

49. Mediastinal goiter Usually extension of thyroid masses True ectopic thyroid mass is rare The most common presentation is obstructive symptoms Exertional dyspnea in 30-60% of patients Can be detected incidentally on chest radiographs Usually accessible for percutaneous FNAC

50. Surgical approaches Standard cervical approach with or without partial or complete sternotomy 95% completely resected through a cervical approach Thoracotomy may be required in very large goiters or invasive cancers .

51. SVC Syndrome 35% of SVCO patients will be asymptomatic or have only mild symptoms of head and neck edema and cyanosis. Moderate-to-severe symptoms will be seen in 60% of patients manifested by increasing degrees of cerebral edema resulting in visual disturbances, headache, laryngeal edema,and diminished cardiac reserve. Patients will present with lifethreatening symptoms 5% of the time Surgery is usually considered for NSCLC, thymoma , thymic carcinoma, or a residual germ cell mass . Chemoradiotherapy is the mainstay of treatment for patients with small-cell lung cancer, lymphoma, or germ cell tumor . Supportive care only may be indicated for patients with treatment refractory tumors or poor performance status

52. Neurogenic tumors Neurogenic tumors represent approximately 15% of all adult and 35% of all pediatric mediastinal neoplasms . Ninety percent of neurogenic tumors occur in the posterior mediastinum and they more commonly affect adolescents and children. In adults, approximately 90% of neurogenic tumors are benign.Conversely , half of these lesions are malignant in children symptoms of spinal cord compression, cough, dyspnea , chest wall pain, and hoarseness. Horner’s syndrome, due to involvement of the superior cervical ganglion of the sympathetic chain, is an unusual presentation

53. Neurogenic tumors originate in the peripheral nerve sheath, sympathetic ganglia, or parasympathetic ganglia. The differential diagnosis for neurogenic tumors arising from the intercostal nerves includes neurofibromas , neurilemomas , and neurogenic sarcomas. Sympathetic ganglia tumors include ganglioneuromas , ganglioneuroblastomas , and neuroblastomas . Pheochromocytomas can occur from paraganglia cells.

54. Nerve sheath tumors Benign intercostal nerve sheath tumors are typically schwannomas ( neurilemomas )-75% or neurofibromas . Patients with von Recklinghausen’s neurofi bromatosis are the lone identified population at risk for benign and malignant neurogenic tumors. Schwannomas usually appear as well-encapsulated , firm, gray-tan masses neurofibromas usually appear as homogenous, well-margined, but nonencapsulated , tumors . On CT imaging, schwannomas are frequently heterogeneous-high attenuation with Antoni type A tissue, whereas low attenuation Antoni type B tissue (which represents degenerated Antoni type A tissue ). Histologically , neurofibromas contain all the cellular elements of a peripheral nerve, such as Schwann cells , fibroblast, perineurial cells, and axons . Both schwannomas and neurofibromas can grow through the adjacent intervertebral foramen and extend into the spinal canal with a “dumbbell” configuration

55. Treatment Surgical resection ( thoracotomy /VATS) Risk of malignant transformation MRI in dumbbell tumors to evaluate spinal extension

56. Malignant NSTs sporadically or arise from a malignant transformation of schwannomas and neurofibroma (malignant schwannomas or neurofibrosarcomas ) 50% in neurofibromatosis patients more radical resection,often including a chest wall resection, is the better treatment option for malignant nerve sheath tumors. Adjuvant chemotherapy and radiotherapy may also be of value in cases where a patient underwent an incomplete resection or was ineligible for surgery.

57. Ganglion tumors in the sympathetic ganglia . most sympathetic ganglion tumors present malignant behavior and are regarded as pediatric tumors . Histologically divided into benign ganglioneuromas , the intermediate malignant potential ganglioneuroblastomas , and, the most malignant , neuroblastomas . Grossly , they are typically elongated in shape, well-circumscribed, and large masses along the paraspinal area . On CT scan, 20% to 80% of these tumors have punctuated calcification. These tumors should be resected whenever feasible. In patients with unresectable tumors, adjuvant chemotherapy and radiation are options for tumor control.

58. Paragangliomas rare neuroendocrine tumors of chromaffin cell (neural crest-derived cell) origin and are usually located at the sympathetic chain in the posterior mediastinum or aortopulmonary area. Paragangliomas secrete catecholamines that may cause signs and symptoms identical to those in patients with hyperfunctioning adrenal pheochromocytomas . The treatment of choice for paragangliomas is complete resection. combined α- and β-adrenergic blockades preoperatively to control blood pressure Postoperatively annual monitoring of 24-hour urinary homovanillic acid and vanillylmandelic acid (catecholamine metabolites) or plasma metanephrines were useful to identify the residual tumor, secondary primary lesion, or metastasis . all first-degree relatives of patient with paragangliomas should receive biochemical testing ,because 50 % of the paraganglioma cases are hereditary

59. Mediastinal cysts 25% of mediastinal masses Most common in middle compartment Pericardial cyst Bronchogenic cyst Enteric cyst Thymic cyst

60. References