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.