THYMIC TUMORS
GENERAL THORACIC SURGERY CHAPTER 167
Thymic tumor
• Almost in the anterior mediastinum. • Secondary to neurogenic tumor in mediastinal tumor. • Rare in children younger than 16 y/o.
Thymic tumor
• Separated into three histologic categories— Thymoma. Thymic carcinoma. Neuroendocrine tumor.
THYMOMA
Location
• • • • • 95% in anterior mediastinum. Neck. Left hilar region. Within lung parenchynma. Anterior cardiophrenic angle.
Pathology
• All thymoma derive from thymic epithelial cell. • Predominantly lymphocytic thymoma （more than 66% lymphocyte）. • Predominantly epithelial thymoma （more than 66% epithelial cell）. • Mixed lymphoepithelial thymoma. • Spindle cell tumor.
Pathology
• Most important gross feature — The presence or absence of encapsulation of tumor and the gross invasion into adjacent structure. • The invasion present — The thymoma must be considered malignant lesion regardless the microscopic appearance. • Extensive spread. • Incidence of distal metastasis is 3%. • Stage.
Another class
• • • • Cortical. Medullary. Mixed thymoma. Immunohistochemistry.
Clinical presentation
• 50-60 y/o. • Sex distribution — Equal. • s/s — chest pain, SOB, cough, SVC syndrome, paralysis of hemidiaphragm, hoarseness, weight loss, fatigue, fever, night sweats.
Parathymic syndrome
• • • • • 40% with parathymic syndrome. Myasthenia gravis. Pure red cell aplasia. Immunoglobulin deficiency. Systemic lupus erythematosus—infrequently, 2.5%, poor prognosis. • Nonthymic cancer—17-21%. • Inappropriate antidiuretic hormone secretion （SIADH）-- rarely, malignant thymoma and spindle cell thymoma.
Myasthenia gravis
• • • • Most commonly associated disease. 30% of patient with thymoma associate with MG. Only 5-15% patient with MG have thymoma. 10-15 older than patient with MG without tumor, younger than patient with thymoma without MG. • Any type of thymoma except spindle type, marked associated squamous elements in thymus. • Little affect on local presention, clinical behavior, prognosis. • Better prognosis than patient with thymoma without MG.
Pure red cell aplasia
• Anemia. • Suppression erythrogenesis in bone marrow. • Mechanism--Not clear, IgG antibodies inhibit erythropoietin or hemoglobin synthesis, cytotoxic to erythroblast, decrease B cell. • 50 % patients with red cell aplasia have thymoma, 5% thymoma with red cell aplasia. • Most （70%）are non-invasive spindle cell. • 25-33% patient with red cell aplasia benefit from excision of the thymoma.
Immunoglobulin deficiency
• Spindle cell type. • Acquired hypogammaglobulinemia. • Suppressor T-cell inhibiting immunoglobulin synthesis.
Diagnostic studies
• Standard posteroanterior and lateral chest radiographies. • CXR—Smooth or lobulated mas, right side the silhouette sign present, left side the sign abscent. • Calcification — 10%. • CT—Delineate the extent of mass, cannot not differentiating benign and malignant, assessing intrathoracic spread of an invasive thymoma.
Surgical biopsy
• Unnecessary for a suspected locally symptomatic thymoma, because the capsule of tumor may be violated by invasive procedure. • Only distinguish the tumor from the other malignant tumor, or locally symptomatic, clearly nonresectable, biopsy is to establish the diagnosis before making decision of therapy. • Fine needle biopsy by CT or sono-guide. • Extend substernal mediastinoscopy. • Anterior mediastinotomy. • Lateral thoracotomy. • VATS.
Treatment
• Depend on clinical presentation. • Surgical resection — thymoma is encapsulated and free from adjacent structure. • Radiation — in atage II, III. • chemotherapy — in locally nonresectable, presence distal metastasis, neoadjuvant therapy for initially advanced local diasease or in locally recurrent disease.
Surgical excision
• All patient with thymoma should undergo as complete resection as possible. • Pulmonary lesion should be excised at the same time. • Tumor encapsulated — total thymectomy. • Simple enucleation is avoid except the unusual condition（excision through lateral thoracotomy with unknown preoperative diagnosis）.
Surgical excision
• Preferred median sternotomy. • Posterolateral thoracotomy — for large tumor in hemithorax or tumor from anterior cardiophrenic angle. • Bilateral anterior fourth intercostals incisionwith transverse section of sternum （clamshell） — for large midline tumors. • The use of video-assisted thoracoscopic removal of thymoma is unacceptable even for stage I tumor.
Surgical excision
• Extend procedure the entire thymus and adjacent fat should be removed if possible. • Tumor fixation to nonvital adjacent structure should be resect（pleura, lung, pericardium, ）.
Surgical excision
• One phrenic nerve involve could be resected if patient could tolerate loss of hemidiaphragm function. • If both phrenic are involved, only debulking is performed.
Surgical excision
• The wall of SVC involve — if no SVC syndrome, lateral wall resection of SVC and replace graft. • When the aorta, major pulmonary vessels, recurrent nerve trachea, are involve, only debulking. • Operative mortality 3.1%-7.7%.
Radiation therapy
• For invasive thymoma. • In stage I is uncertain. • For resected stage II or completely or incompletely resected stage III disease. • 4500-5000 cGy for suspected microscopic residual disease. • 6000 cGy for known residual disease. • Brachytherapy with I-125 seed placed in gross residual disease at time of operation.
Chemotherapy
• For stage III and IV. • Cisplatin, doxorubucin, vincristine, cyclophosphamide, neoadjuvant.
Treatment of recurrent local disease or distant metastases
• Recurrent I — 0-5%, II — 10%, III — 30%, IVa — 33%. • Second resection if possible. • 5-year survival is 65%. • For stage III recurrent — irradiation or chemotherapy.
Survival
• Depend on — stage, tumor size, histology, extent of resection. • Better in patient with thymoma associated with MG. • Poor in patient with red cell aplasia, hypogammaglobulinemia, SLE.
Thymic carcinoma
• Low and high grade. • Malignant cytologic and architectural feature. • Staging not standardized.
Squamous cell carcinoma
• • • • • • Most common. Men predominant. 60 y/o. Partially encapsulated. s/s — weight loss, chest pain, cough, hemoptysis. Treatment—Surgical resection, sensitive to radiation, combination chemotherapy. • Prognosis excellent in well-differentiated squamous cell carcnoma.
Lymphoepitheliomalike carcinoma
• Epstein-Barr virus. • Treatment—irradiation therapy, chemotherapy.
Tumor of neuroendocrine cell origin
• Thymic carcinoid tumor. • Small cell carcinoma.
Thymic carcinoid tumor
• • • • • • Large. One-half lesion infiltrative into adjacent structures. Associated Cushing’s syndrome. 3/4 are men. Mean age 42 y/o. s/s — asymptomatic, chest pain, cough dyspnea, SVC syndrome, fatigue fever, night sweat.
Thymic carcinoid tumor
• 1/3 have feature of Cushing sundrome — ectopic ACTH production. • 15-18% with multiple endocrine neoplasia（MEN） syndrome. • Most MEN I. • Few MEN II. • Thymic carcinoid associated with MEN syndrome is more malignant in behavior. • 1/3 with bone metastases.
Multiple endocrine neoplasia （MEN）
• MEN I（Werner syndrome)– Single or multiple parathyroid adenoma, islet cell tumor of pancrease, adrenal neoplasm, thyroid adenoma, multiple lipoma. • MEN II（Sipple syndrome)—Thyroid medullary carcinoma, pheochronocytoma, parathyroid neoplasia.
Thymic carcinoid tumor
• Treatment—complete surgical resction or debulking tumor, radiation therapy. • 73% local recurrence or metastases. • Overall cure rate is low — 13%. • Mean survival of metastases disease is 3 years.
Small （Oat）cell carcinoma
• Aggressive and metastases extensively, • Associated with MEN I. • Treatment—radiation therapy and chemotherapy.