GENERAL THORACIC SURGERY CHAPTER 167 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.