SURGICAL TREATMENT IN THYMOMAS

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• SURGICAL TREATMENT IN THYMOMAS
• ANALYSIS OF 58 CASES
• Dr. Ertan AYDIN
• ATATÜRK CHEST DISEASES and CHEST SURGERY TRAINING
  and RESEARCH HOSPITAL

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• Thymomas are primary tumors of thymic epitheial
  cells
• The incidence of thymomas in the U.S is
  approximately 0.15 per 100.000 person-years
• Typically slow-growing tumors that spread by
  local extension
• The distinction between thymomas and thymic
  carcinomas is not as clear, because thymic
  carcinomas have malignant cytologic features,
  whereas thymomas are generally considered
  cytologically benign
• Engels EA et al.Malignant thymoma in the United
  States demographic patterns in incidence and
  associations with subsequent malignancies.Int J
  Cancer 2003105546-551
• Levine GD et al. Thymic hyperplasia and
  neoplasia a review of current concepts.Hum
  Pathol 19789495-515

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• Thymoma is the most common tumor of the anterior
  mediastinum.
• 95 of thymomas are located in the anterior
  mediastinum.
• They most commonly present in adults between
  40-60 ages and there is an equal distribution
  between genders for these tumors.

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SYMPTOM

• 30 of patients are asymptomatic
• 30 of them present with MG
• chest pain
• cough
• dyspnea
• hoarseness
• phrenic nerve paralysis
• pleural effusions
• weight loss
• superior vena cava (SVC) syndrome
• TNM stating system is not particularly useful for
  thymomas as most patients do not have nodal
  disease or metastases
• It generally exhibits a weak growth pattern but
  malignant because of potential for local
  invasion, pleural dissemination, and even
  systemic metastases

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• Extrathoracic metastases are very rare.
  Metastases are usually seen in the pleura,
  pericardium or diaphragm
• Thymomas have a tendency for late recurrence even
  after complete resection
• Myasthenia gravis is the most frequent autoimmune
  disease associated with thymoma. In reported
  series, 3065 of patients with thymoma have been
  diagnosed with myasthenia gravis.1015 of
  patients with myasthenia gravis have a thymoma
• Autoantibodies to neuromuscular antigens, the
  acetylcholine receptor and titin, astriated
  muscle antigen can be produced in patients with
  myasthenia gravis
• Other immune disorders can occur up to 28 of
  thymoma patients. Pure red cell aplasia, lupus
  erythematosus and hypogammaglobulinemia are the
  most common
• Gray GF, Gutowski WT3. Thymoma. A
  clinicopathologic study of 54 cases. Am J Surg
  Pathol 1979323549.
• Regnard JF, Magdeleinat P, Dromer C, et al.
  Prognostic factors and long-term results after
  thymoma resection a
• series of 307 patients. J Thorac Cardiovasc Surg
  199611237684.
• Ruf?ni E, Mancuso M, Oliaro A, et al.
  Recurrence of thymoma analysis of
  clinicopathologic features, treatment, and
  outcome. J Thorac Cardiovasc Surg 19971135563.
• Awad WI, Symmans PJ, Dussek JE. Recurrence of
  stage I thymoma 32 years after total excision.
  Ann Thorac Surg 19986621068.

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DIAGNOSIS

• The diagnosis of the thymoma is usually made with
  clinical findings and radiological examinations.
  Computed tomography (CT) mostly shows the
  presence of an anterior mediastinal tumor.
  Thymomas usually appear as well-defined round
  masses on CT scan
• Calci?cations may be seen in about 15 of the
  patients and a small percentage of them may be
  cystic.
• The tumor extension into the mediastinal fat and
  surrounding structures (vascular invasion,
  encasement and pleural dissemination ) may be
  suggested by CT. CT scan findings carries a
  false-positive rate of 20 and a false negative
  rate of 7 for these patients
• Souza CA, Muller NL. Imaging of the
  mediastinum. In Patterson GA, Cooper JD,
  Deslauriers J, Lerut AEM, Luketich JD, Rice TW,
  editors. Pearsons thoracic and oesophageal
  surgery. 3rd edition, Churchill Livingstone
  2008. p. 1477505
• Jung KJ, Lee KS, Han J, Kim J, Kim TS, Kim EA.
  Malignant thymic epithelial tumors. Am J
  Roentgenol 20011764339.
• LeBlanc J, Wood DE. Diagnosis of mediastinal
  tumors. In Wood DE, Thomas CR, editors.
  Mediastinal tumors update 1995, medical
  radiology. Diagnostic imaging and radiation
  oncology volume. Heidelberg,
• Germany Springer-Verlag 1995. p. 110.

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WHO PATHOLOGIC CLASSIFICATION (1999)

• Type Histologic description
  Incidence ()
• A Medullary thymoma 9
  
• AB Mixed thymoma 24
• B1 Predominantly cortical thymoma 13
• B2 Cortical thymoma 24
• B3 Well-differantiated thymic
• carcinoma 15
• C Thymic carcinoma 15

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MASAOKA CLINICAL STAGING (1981)

• Stage Diagnostic Criteria
• I Macro- and microscopically completely
  encapsulated
• (tumor invading into but not through the
  capsule is included)
• II A. Microscopic transcapsuler invasion
• B. Macroscopic invasion into surrounding
  fatty tissue or grossly adherent to but not
  through mediastinal pleura or pericardium
• III Macroscopic invasion into neighboring
  organs
• ( i.e.,pericardium, great vessels, or lung)
• A. Without invasion of great vessels
• B. With invasion of great vessels
• IV A.Pleural or pericardial dissemination
• B. Lymphogenous or hematogenous metastases

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• The most effective treatment modality for thymoma
  is surgical resection.
• The principles of successfull surgery include
  careful exploration of the whole mediastinum, en
  bloc thymectomy with removal of all the
  surrounding mediastinal fat, protection the
  phrenic nerve from injury and avoidence of
  intrapleural spread
• The operative mortality is lower than 2 in most
  of the recent series
• Port JL, Ginsberg RJ Surgery for thymoma.
  Chest Surg Clinics of NA. 11421-437, 2001
• Rea F, Marulli G, Girardi R, Bortolotti L,
  Favaretto A, Galligioni A, Sartori F. Long term
  survival and prognostic factors in thymic
  epithelial tumors. Eur J Cardiothorac Surg
  2004264128.
• Crucitti F, Doglietto GB, Bellantone R, Perri
  V, Tommasini O, Tonali P. Effects of surgical
  treatment in thymoma with myasthenia gravis our
  experience with 103 patients. J Surg Oncol
  199250436.
• Wilkins EJ, Grillo HC, Scannell JG, Moncure AC,
  Mathisen DJ. Role of staging in prognosis and
  management of thymoma. Ann Thorac Surg
  19915188892.

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5 year survival

• Stage I 89-100
• Stage II 71-97
• Stage III 68-89
• Stage IV 47-69
• Despite reduced survival in advanced disease,
  maximal debulking surgery seems benefical,
  facilitating RT and thereby improving survival
• Falkson C.B et al. The management of thymoma A
  systematic review and practice guideline.J Thorac
  Oncol 20094911-919
• Liu H.c et al.Debulking surgery for advanced
  thymoma. Eur J Surg Oncol 2006321000-1005

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• Chemotherapy as a single treatment modality
• Overall response 32-56
• Complete response 0-38
• Overall 2-year survival 30-79
• Progression-free survival 13-56
• Radiotherapy as a single treatment modality
• Overall 5-year survival 72
• Progression-free survival 81
• Recurrence at 5 years 15
• Neoadjuvant Chemoradiotherapy
• Complete response 6-22
• 5-year survival 31-95
• Progression-free survival 31-77
• Falkson C.B et al. The management of thymoma A
  systematic review and practice guideline.J Thorac
  Oncol 20094911-919

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TREATMENT

• Stage I Complete resection of the entire thymus
  without neoadjuvant or adjuvant therapy
• Stage II Complete resection of the entire thymus
  with consideration of adjuvant radiation for
  high-risk tumors
• Stage IIIASurgery either initially or after
  neoadjuvant therapy,or surgery followed by
  adjuvant therapy
• Stage IIIBTreatment may include a combination of
  chemotherapy, radiation,and/or surgery, or if
  technically possible,surgery in combination with
  chemoradiotherapy ( cisplatin based).For bulky
  tumors, consideration should be given to
  sequential chemotherapy followed by radiation
• Stage IVA as per stage III,with surgery only if
  metastases can be resected
• Stage IVB Treatment based on individual case

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58 cases ( 1999-2009)

• Male 35 (60 ),female 23 (40 )
• Age 22 74 (median50,92)
• Tumor size 1.5-12 cm (med6,9)
• Asymptomatic11 (20 )
• Chest pain 21 (36)
• Dyspnea 14 (24 )
• Weakness 6 (10 )
• Cough3 (5 )
• Pitosis 3 (5 ).

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• Postoperative complications occurred in eight
  patients (13,7)
• - Pleural effusion
• Atelectasis
• Prolonged air leak
• Arrhythmia

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SURGERY

• Three of the cases could not be resected totally(
  5) 55 cases were resected completely (95)
• Median sternotomy 40 (69)
• Right thoracotomy 11 (19)
• Left thoracotomy 7 (12)

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HISTOPATHOLOGIC CLASSIFICATION NUMBER OF PATIENTS RATIO ()
A 4 7
AB 21 36
B1 6 10
B2 16 28,5
B3 6 10
C 5 8,5
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STAGE PATIENT 5 -YEAR SURVIVAL
I 26 (44) 93
II 13 (22) 88
III 11 (19) 79
IV 8 (15) 58

• Overall 5 year survival 87

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62y, MaleType B2 Thymoma
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27y,MaleTYpe B1 Thymoma
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42y, FemaleType B3 Thymoma
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PROGNOSTIC FACTORS

• Stage is the most important prognostic factor
• Others
• Tumor size
• Completeness of resection
• Histologic subtype

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CONCLUSION

• Surgery is the best treatment choice
• Chemoradiation should be considered in all
  medically inoperable and technically inoperable
  patients
• Recurrent disease- consider surgery,radiation,and/
  or chemoradiation