Mediastinal Pathology Compartmental Approach

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Mediastinal Pathology Compartmental Approach

  1. 1. Armed Forces Institute of Pathology Mediastinal Pathology: Compartmental Approach Teri J. Franks, MD Chairman Department of Pulmonary and Mediastinal Pathology
  2. 2. Faculty Disclosure Information At the time of the VTC, Teri J. Franks, MD had no significant financial interests or relationships to disclose. As a provider accredited by the Accreditation Council for Continuing Medical Education, the Department of Medical Education of The Armed Forces Institute of Pathology must insure balance, independence, objectivity and scientific rigor in all its individually sponsored or jointly sponsored educational activities. All faculty participating in a sponsored educational activity are expected to disclose to the activity audience any significant financial interest or other relationship (1) with the manufacturer(s) of any commercial product(s) and/or provider(s) of commercial services discussed in an educational presentation and (2) with any commercial supporters of the activity (significant financial interest or other relationship can include such things as grants or research support, employee, consultant, major stock holder, member of speakers bureau, etc.). The intent of this disclosure is not to prevent a speaker with a significant financial or other relationship from making a presentation, but rather to provide listeners with information on which they can make their own judgments. It remains for the audience to determine whether the speaker’s interests or relationships may influence the presentation with regard to exposition or conclusion.
  3. 3. Main Topics • Clinical features • Organization of lesions – Mediastinal anatomy – Compartment approach • Selected lesions – Thymoma and thymic carcinoma
  4. 4. Mediastinal Lesions Clinical features • Uncommon, 1% of all tumors • Infant to 83 years, mean 35.4 years • No gender bias • 60% benign, 40% malignant • 60% symptomatic – Chest pain, cough, dyspnea, dysphagia, superior vena cava syndrome • 97% can be detected on PA and lateral chest radiographs • Surgical resection – Low operative morbidity and mortality
  5. 5. Mediastinum Gross anatomy • Boundaries – Anterior: sternum – Posterior: vertebral column – Superior: thoracic inlet – Inferior: diaphragm – Lateral: parietal pleura
  6. 6. Mediastinum Compartments • Anterior • Middle • Posterior
  7. 7. Mediastinum Compartments • Anterior
  8. 8. Mediastinum Compartments • Anterior • Middle
  9. 9. Mediastinum Compartments • Anterior • Middle • Posterior
  10. 10. Mediastinum Distribution of lesions • Anterior 50% • Middle 25% • Posterior 25%
  11. 11. Mediastinum Contents • Anterior – Thymus – Lymph nodes – Heart and pericardium – Ascending aorta – Brachiocephalic vessels – Superior and inferior vena cava – Phrenic nerves – Fat – Ectopic tissue
  12. 12. Mediastinum Contents • Middle – Trachea – Mainstem bronchi – Esophagus – Lymph nodes – Descending aorta – Pulmonary arteries and veins – Azygos and hemiazygos veins – Thoracic duct – Vagus and phrenic nerves
  13. 13. Mediastinum Contents • Posterior – Sympathetic ganglia – Peripheral nerves – Paraganglia – Lymph nodes
  14. 14. Mediastinum Distribution of lesions (n=400) Anterior Middle Posterior Thymic lesions 30% 0% 0% Lymphomas 20% 21% 20% Germ cell tumors 18% 0% 0% Carcinoma 13% 7% 0% Cysts 7% 60% 34% Mesenchymal tumors 5% 9% 9% Endocrine tumors 5% 0% 2% Neurogenic tumors 0% 0% 53% Miscellaneous 2% 3% 2% Davis, Ann Thorac Surg, 1987
  15. 15. Mediastinum Lesions occurring in one compartment Anterior Middle Posterior Thymic lesions 30% 0% 0% Lymphomas 20% 21% 20% Germ cell tumors 18% 0% 0% Carcinoma 13% 7% 0% Cysts 7% 60% 34% Mesenchymal tumors 5% 9% 9% Endocrine tumors 5% 0% 2% Neurogenic tumors 0% 0% 53% Miscellaneous 2% 3% 2%
  16. 16. Mediastinum Lesions occurring in two compartments Anterior Middle Posterior Thymic lesions 30% 0% 0% Lymphomas 20% 21% 20% Germ cell tumors 18% 0% 0% Carcinoma 13% 7% 0% Cysts 7% 60% 34% Mesenchymal tumors 5% 9% 9% Endocrine tumors 5% 0% 2% Neurogenic tumors 0% 0% 53% Miscellaneous 2% 3% 2%
  17. 17. Mediastinum Lesions common to all compartments Anterior Middle Posterior Thymic lesions 30% 0% 0% Lymphomas 20% 21% 20% Germ cell tumors 18% 0% 0% Carcinoma 13% 7% 0% Cysts 7% 60% 34% Mesenchymal tumors 5% 9% 9% Endocrine tumors 5% 0% 2% Neurogenic tumors 0% 0% 53% Miscellaneous 2% 3% 2%
  18. 18. Mediastinum Most common lesion in each compartment Anterior Middle Posterior Thymic lesions 30% 0% 0% Lymphomas 20% 21% 20% Germ cell tumors 18% 0% 0% Carcinoma 13% 7% 0% Cysts 7% 60% 34% Mesenchymal tumors 5% 9% 9% Endocrine tumors 5% 0% 2% Neurogenic tumors 0% 0% 53% Miscellaneous 2% 3% 2% Davis, Ann Thorac Surg, 1987
  19. 19. Mediastinum Lesions occurring in one compartment • Thymic lesions – Anterior • Germ cell tumors – Anterior • Neurogenic tumors – Posterior
  20. 20. Thymus • Thymic lesions dominant mediastinal pathology – 50% of mediastinal lesions occur in the anterior compartment – Major organ of the anterior mediastinum
  21. 21. Thymus Embryology • 6th week – Primordia arise from 3rd pharyngeal pouches
  22. 22. Thymus Embryology • 6th week – Primordia arise from 3rd pharyngeal pouches • 8th week – Primordia elongate – Fragment during migration • 14th week to 16th week – Cortex and medulla complete – Phenotypic characterization
  23. 23. Thymus Location • Anterior mediastinum – Base rests on pericardium and great vessels
  24. 24. Thymus Location • Anterior mediastinum – Base rests on pericardium and great vessels – Upper poles extend along trachea, attach to corresponding lobe of thyroid via thyrothymic ligament
  25. 25. Thymus Gross • X- or H-shaped • Fibrous capsule • Wide variation in weight – Mainly related to age – Affected by state of health – Average • 15 grams at birth • 30-40 grams at puberty • 10-15 grams at 60 years
  26. 26. Lobules
  27. 27. Starry sky
  28. 28. Corticomedullary junction
  29. 29. Cortex Medulla
  30. 30. Thymus Involution • Decrease in weight and size • Atrophy – Cortical lymphocytes – Epithelial elements
  31. 31. Thymus Involution • Decrease in weight and size • Atrophy – Cortical lymphocytes – Epithelial elements • Cystic Hassall corpuscles
  32. 32. Thymus Involution • Decrease in weight and size • Atrophy – Cortical lymphocytes – Epithelial elements • Cystic Hassall corpuscles • Increasing adipose tissue
  33. 33. Thymus Involution • Small lymphocytes • Islands of epithelial cells
  34. 34. Thymus Involution • Small lymphocytes • Islands of epithelial cells – Spindle-shaped – Rosettes – Solid nests – Elongated strands • Involution accelerated by – Stress – Radiotherapy – Chemotherapy
  35. 35. Tumors of the Thymus and Mediastinum WHO Classification • Epithelial tumors • Germ cell tumors • Lymphomas and hematopoietic neoplasms • Mesenchymal tumors • Rare tumors • Metastasis
  36. 36. Tumors of the Thymus and Mediastinum WHO Classification • Epithelial tumors – Thymoma – Thymic carcinoma • Germ cell tumors • Lymphomas and hematopoietic neoplasms • Mesenchymal tumors • Rare tumors • Metastasis
  37. 37. Thymoma and Thymic Carcinoma Clinical features • Uncommon – Incidence of 1-5/million population/year – Incidence has not changed significantly over past three decades • Wide age range, 7-89 years – Peak 55-65 years – Rare in children and adolescents • No gender bias • Increased incidence of second cancers – Irrespective of histologic type of thymic epithelial tumor • Autoimmune disease – MG: variable in thymoma (10-80%), rare in thymic carcinoma – Other: common in thymoma, rare in thymic carcinoma
  38. 38. Thymoma and Thymic Carcinoma • Thymomas – Arise from thymic epithelial cells – Exhibit organotypic (thymus-like) architectural features • Lobular pattern, perivascular spaces, immature TdT/CD1a/CD99+ T-cells – No, mild, or moderate atypia of epithelial cells – CD5, CD70, CD117 negative epithelial cells – Not observed in organs other than thymus • Arise from heterotopic tissue in head, neck, mediastinum, pleura, lung – Absent/low to moderate biologic potential • Often curable by surgery • Variable invasion, metastases rare • Typically long survival due to indolent clinical course
  39. 39. • 33 year old male • Three month history – Cough – Intermittent chest pain
  40. 40. Thymoma Gross • Well-circumscribed, firm • Up to 34 cm • Fibrous capsule • Pink-tan lobulated cut surface
  41. 41. Thymoma Gross • Well-circumscribed, firm • Up to 34 cm • Fibrous capsule • Pink-tan lobulated cut surface • Cystic change common • Adherence to adjacent structures
  42. 42. Thymoma • Biphasic cell population
  43. 43. Thymoma • Biphasic cell population – Neoplastic epithelial cells • Keratin positive
  44. 44. Thymoma Histology • Biphasic cell population – Neoplastic epithelial cells • Keratin positive – Nonneoplastic lymphocytes • CD1a positive T-cells
  45. 45. Thymoma • Biphasic population • Organotypic features – Lobular pattern
  46. 46. Thymoma • Biphasic population • Organotypic features – Lobular pattern – Perivascular spaces
  47. 47. Thymoma • Biphasic population • Organotypic features – Lobular pattern – Perivascular spaces • Longitudinal spaces
  48. 48. Thymoma • Biphasic population • Organotypic features – Lobular pattern – Perivascular spaces • Longitudinal spaces • Hyalinized
  49. 49. Thymoma • Biphasic population • Organotypic features – Lobular pattern – Perivascular spaces – Immature T-cells • TdT+/CD1a+/CD99+
  50. 50. Thymoma and Thymic Carcinoma • Thymic carcinoma – Arise from thymic epithelial cells – No or abortive organotypic architectural features – Clear-cut cytologic atypia – Frequent CD5, CD70, CD117 expression in epithelial cells, ~ 60% – Resemble carcinomas in other organs – Malignant • Often unresectable • Almost always invasive, metastases frequent • Short survival due to progressive disease
  51. 51. • 56 year old male • Two month history – Chest pain – Cough
  52. 52. Thymic Carcinoma Gross • Firm, gritty, gray-white mass • Usually lacks well-defined capsule and fibrous bands
  53. 53. Thymic Carcinoma Gross • Firm, gritty, gray-white mass • Usually lacks well-defined capsule and fibrous bands • Foci of hemorrhage and necrosis
  54. 54. Thymic Carcinoma Histology • Loss of organotypic features • Cytologically malignant – High N:C ratio – Cellular pleomorphism – Nucleoli – Mitoses – Necrosis
  55. 55. B3 Ca
  56. 56. Thymoma and Thymic Carcinoma Classification Bernatz Suster & Moran WHO WHO 1961 1999 1999 2004 Spindle cell Well-diff thymoma Type A Type A - “ “ Type AB Type AB Lymphocyte rich “ “ Type B1 Type B1 Mixed “ “ Type B2 Type B2 Epithelial rich Atypical thymoma Type B3 Type B3 - Thymic carcinoma Type C Thymic carcinoma
  57. 57. Tumors of the Thymus and Mediastinum Epithelial tumors • Epithelial tumors – Thymoma • Type A (spindle cell; medullary) • Type AB (mixed) • Type B1 (lymphocyte-rich; lymphocytic; predominantly cortical; organoid • Type B2 (cortical) • Type B3 (epithelial; atypical; squamoid; well-differentiated thymic ca) • Rare thymomas – Micronodular thymoma with lymphoid stroma – Metaplastic – Microscopic – Sclerosing – Lipofibroadenoma
  58. 58. Tumors of the Thymus and Mediastinum Epithelial tumors • Epithelial tumors – Thymic carcinoma • Squamous cell carcinoma • Basaloid carcinoma • Mucoepidermoid carcinoma • Lymphoepithelial-like carcinoma • Sarcomatoid carcinoma (carcinosarcoma) • Clear cell carcinoma • Adenocarcinoma • Papillary adenocarcinoma • Carcinoma with t(15;19) translocation • Neuroendocrine carcinoma – Typical and atypical carcinoid – Large cell neuroendocrine and small cell carcinoma • Undifferentiated carcinoma • Combined thymic epithelial tumors
  59. 59. Thymoma and Thymic Carcinoma Terms • Encapsulated – Completely surrounded by a fibrous capsule • Minimally or microscopically invasive – Invasive through the capsule to involve pericapsular tissue • Usually identified only after microscopic examination • Generally appears encapsulated to surgeon • Widely invasive – Spread by direct extension into adjacent structures • Implants – Nodules separate from main mass on pericardium or pleura • Lymph node metastases – Nodes separate from main mass, excludes direct extension into node • With distant metastases – Most commonly to lung, liver, skeletal system
  60. 60. Capsular Invasion • Evaluation of capsule is essential – Ink margins • Adherence to adjacent structures – Common – Doesn’t always indicate true invasion
  61. 61. Tumor 400x Involution
  62. 62. Thymoma and Thymic Carcinoma Principles of classification • Thymoma – Two major types • Uniformly bland spindle or oval epithelial cells – Type A • Predominantly round or polygonal epithelial cells – Type B – Type B subdivided by extent of lymphoid infiltrates and cellular atypia • B1 – lymphocyte rich • B2 and B3 – epithelial cell rich – Type A plus B1-like, and rarely B2-like, are designated AB • Thymic carcinoma – Thymic carcinomas are termed according to differentiation – Combined thymomas are termed by WHO histology and % – “Malignant thymoma” is discouraged
  63. 63. Thymoma Type A • Lymphocyte poor • Solid sheets – No pattern
  64. 64. Thymoma Type A • Lymphocyte poor • Solid sheets – No pattern or storiform
  65. 65. Thymoma Type A • Lymphocyte poor • Solid sheets – No pattern or storiform – Cysts – Lobules and bands less conspicuous than other types
  66. 66. Thymoma Type A • Lymphocyte poor • Solid sheets – No pattern or storiform – Cysts – Lobules and bands less conspicuous than other types • Spindle or oval epithelial cells – Reticulin fibers surround cells
  67. 67. Thymoma Type A • Lymphocyte poor • Solid sheets – No pattern or storiform – Cysts – Lobules and bands less conspicuous than other types • Spindle or oval epithelial cells – Reticulin fibers surround cells • Bland nuclei – Dispersed chromatin – Inconspicuous nucleoli
  68. 68. Thymoma Type AB • Mixture of Type A and Type B – Discrete separate nodules or
  69. 69. Thymoma Type AB • Mixture of Type A and Type B – Discrete separate nodules or – Intermixed A and B
  70. 70. Thymoma Type AB • Mixture of Type A and Type B – Discrete separate nodules or – Intermixed A and B • Type B epithelial cells – Small polygonal – Dispersed chromatin – Inconspicuous nucleoli
  71. 71. Thymoma Type AB • Mixture of Type A and Type B – Discrete separate nodules or – Intermixed A and B • Type B epithelial cells – Small polygonal – Dispersed chromatin – Inconspicuous nucleoli • B areas – Medullary differentiation rare – Hassall corpuscles absent – Reticulin around B nodules • Not around individual cells
  72. 72. Thymoma Type B1 • Resembles cortex
  73. 73. Thymoma Type B1 • Resembles cortex • Scant small epithelial cells – Pale nuclei – Small nucleoli
  74. 74. Thymoma Type B1 • Resembles cortex • Scant small epithelial cells – Pale nuclei – Small nucleoli • Dispersed epithelial cells – Do not from groupings
  75. 75. Thymoma Type B1 • Resembles cortex • Scant small epithelial cells – Pale nuclei – Small nucleoli • Dispersed epithelial cells – Do not from groupings • Medullary differentiation always present
  76. 76. Thymoma Type B1 • Resembles cortex • Dispersed epithelial cells – Do not from groupings • Scant small epithelial cells – Pale nuclei – Small nucleoli • Medullary differentiation always present • Hassall corpuscles may be present
  77. 77. Thymoma Type B2 • Large course lobules – Separated by delicate septa
  78. 78. Thymoma Type B2 • Large course lobules – Separated by delicate septa • Large polygonal epithelial cells – Open chromatin – Prominent nucleoli
  79. 79. Thymoma Type B2 • Large course lobules – Separated by delicate septa • Large polygonal epithelial cells – Open chromatin – Prominent nucleoli • Medullary differentiation absent or inconspicuous • Abortive Hassall in 25% – Typical Hassall rare • B3 occurs in B2 – 17-29% of cases – Designate B2/B3
  80. 80. Thymoma Type B3 • Lobules with thick septa
  81. 81. Thymoma Type B3 • Lobules with thick septa • Paucity of lymphoctyes – Results in sheet-like growth
  82. 82. Thymoma Type B3 • Lobules with thick septa • Paucity of lymphoctyes – Results in sheet-like growth – Solid or epidermoid pattern • No intercellular bridges
  83. 83. Thymoma Type B3 • Lobules with thick septa • Paucity of lymphoctyes – Results in sheet-like growth – Solid or epidermoid pattern • No intercellular bridges • Medium-size epithelial cells – Small nucleoli – Often grooved nuclei
  84. 84. Thymoma Type B3 • Lobules with thick septa • Paucity of lymphoctyes – Results in sheet-like growth – Solid or epidermoid pattern • No intercellular bridges • Medium-size epithelial cells – Small nucleoli – Often grooved nuclei • Perivascular palisading
  85. 85. Thymoma Type B3 • Lobules with thick septa • Paucity of lymphoctyes – Results in sheet-like growth – Solid or epidermoid pattern • No intercellular bridges • Medium-size epithelial cells – Small nucleoli – Often grooved nuclei • Perivascular palisading • Foci of keratinization – Mimicking Hassall corpuscles • Medullary differentiation usually absent
  86. 86. A B3
  87. 87. B1 B2 B3 Ca
  88. 88. B1 B2
  89. 89. Thymoma and Thymic Carcinoma Prevalence of subtypes • AB – 20-35% • B2 – 20-35% • A – 5-10% • B1 – 5-10% • Thymic carcinoma 10-25%
  90. 90. Thymoma and Thymic Carcinoma Spectrum of Malignancy • Thymoma – Type A – Type AB – Type B1 – Type B2 – Type B3 • Thymic carcinoids • Thymic carcinoma – Squamous cell, basaloid, mucoepidermoid – Other subtypes • Small cell and large cell neuroendocrine
  91. 91. Thymoma and Thymic Carcinoma Prognosis • Most important prognostic factors – Tumor stage • Masaoka stage is the most important and statistically most significant independent prognostic indicator of survival in most studies – WHO histologic type – Completeness of resection
  92. 92. Thymoma and Thymic Carcinoma Prognosis Histology Stage Biologic Potential A, AB, B1 l and ll None/very low lll Low B2, B3 l Low ll and lll Moderate Squam, basaloid, l and ll Moderate mucoep, carcinoid lll High Other histology Any High
  93. 93. Staging TNM • T1 – tumor completely encapsulated • T2 – tumor invades pericapsular connective tissue • T3 – tumor invades into neighboring structures, such as pericardium, mediastinal pleura, thoracic wall, great vessels and lung • T4 – tumor with pleural or pericardial dissemination • Currently no authorized TNM system for thymic epithelial or neuroendocrine tumors
  94. 94. Staging Modified Masaoka • Stage 1: intact capsule or growth within capsule • Stage 2a: microscopic invasion through capsule 2b: gross and microscopic invasion • Stage 3: invasion into surrounding structures • Stage 4a: pleural or pericardial dissemination 4b: lymphatic or hematogenous metastases
  95. 95. Thymoma and Thymic Carcinoma Diagnosis • Thymoma – Encapsulated – Invasive (term malignant thymoma is discourage) • Surgical pathology report – Correct diagnosis • Up to 20% in some studies incorrectly diagnosed – Assessment of surgical margins • Requires inking – Determination of invasiveness • Multiple sections through capsule
  96. 96. Thymoma and Thymic Carcinoma Diagnosis • Thymic carcinoma – Separation from metastatic carcinoma may be difficult • Lung, thyroid, breast, prostate are most common – May only be able to suggest or favor diagnosis • Clinical history and radiologic studies are essential
  97. 97. Thymoma and Thymic Carcinoma Diagnosis Tumor Thymic primary Lung or head/neck Squamous, basaloid, Lobular growth 70% Lobular growth rare lympho-epi ca Perivascular spaces 50% Perivascular spaces rare CD5 50% CD5 not expressed CD70 50% CD70 not expressed CD117 40-100% CD117 not expressed NE carcinoma TTF-1 absent TTF-1 frequent (lung)
  98. 98. Tumors of the Thymus and Mediastinum WHO Classification • Epithelial tumors • Germ cell tumors – 2003 WHO Classification of Germ Cell Tumors • Teratoma • Seminoma • Lymphomas and hematopoietic neoplasms • Mesenchymal tumors • Rare tumors • Metastasis
  99. 99. Tumors of the Thymus and Mediastinum WHO Classification • Epithelial tumors • Germ cell tumors • Lymphomas and hematopoietic neoplasms – 2001 WHO Classification of Hematopoietic and Lymphoid Tumors • NS Classical HL • PMLB-CL • T-lymphoblastic leukemia/lymphoma • MALT lymphoma • Mesenchymal tumors • Rare tumors • Metastasis
  100. 100. Tumors of the Thymus and Mediastinum WHO Classification • Epithelial tumors • Germ cell tumors • Lymphomas and hematopoietic neoplasms • Mesenchymal tumors – 2000 WHO Classification of Nervous System • Schwannoma – 2002 WHO Classification of Soft Tissue and Bone • Thymolipoma • Rare tumors • Metastasis
  101. 101. Tumors of the Thymus and Mediastinum WHO Classification • Epithelial tumors • Germ cell tumors • Lymphomas and hematopoietic neoplasms • Mesenchymal tumors • Rare tumors – Ectopic tumors of the thymus • Ectopic thyroid tumors • Ectopic parathyroid tumors • Metastasis
  102. 102. Rare Tumors Ectopic tumors • Uncommon, benign or malignant • Anterior or posterior compartment • Thyroid – Extension from neck or ectopic tissue • Parathyroid – Found adjacent to or within thymus
  103. 103. Tumors of the Thymus and Mediastinum WHO Classification • Epithelial tumors • Germ cell tumors • Lymphomas and hematopoietic neoplasms • Mesenchymal tumors • Rare tumors • Metastasis – Thymus and anterior (middle) mediastinum • Lung, thyroid, breast, prostate are most common
  104. 104. Mediastinal Pathology Summary • Three compartments • Mediastinal lesions – 50% of lesions • Anterior compartment – Thymic lesions dominate – Organization by compartment
  105. 105. Mediastinum Lesions occurring in one compartment Anterior Middle Posterior Thymic lesions 30% 0% 0% Lymphomas 20% 21% 10% Germ cell tumors 18% 0% 0% Carcinoma 13% 7% 0% Cysts 7% 60% 24% Mesenchymal tumors 5% 9% 9% Endocrine tumors 5% 0% 2% Neurogenic tumors 0% 0% 53% Miscellaneous 2% 3% 2%
  106. 106. Mediastinum Lesions occurring in two compartments Anterior Middle Posterior Thymic lesions 30% 0% 0% Lymphomas 20% 21% 10% Germ cell tumors 18% 0% 0% Carcinoma 13% 7% 0% Cysts 7% 60% 24% Mesenchymal tumors 5% 9% 9% Endocrine tumors 5% 0% 2% Neurogenic tumors 0% 0% 53% Miscellaneous 2% 3% 2%
  107. 107. Mediastinum Lesions occurring in all compartments Anterior Middle Posterior Thymic lesions 30% 0% 0% Lymphomas 20% 21% 10% Germ cell tumors 18% 0% 0% Carcinoma 13% 7% 0% Cysts 7% 60% 24% Mesenchymal tumors 5% 9% 9% Endocrine tumors 5% 0% 2% Neurogenic tumors 0% 0% 53% Miscellaneous 2% 3% 2%
  108. 108. Mediastinum Most common lesion Anterior Middle Posterior Thymic lesions 30% 0% 0% Lymphomas 20% 21% 10% Germ cell tumors 18% 0% 0% Carcinoma 13% 7% 0% Cysts 7% 60% 24% Mesenchymal tumors 5% 9% 9% Endocrine tumors 5% 0% 2% Neurogenic tumors 0% 0% 53% Miscellaneous 2% 3% 2%

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