Thymic NETs

Introduction of thymic NETs
Thymic carcinoids may occur sporadically or in patients with MEN1. The tumor is often locally aggressive and/or metastatic. An ectopic Cushing’s syndrome is common. Treatment include surgery and chemotherapy.

Epidemiology of thymic NETs
Thymic carcinoids are rare tumors. Men are affected three times more often than women. The disease is most common in middle ages but may occur in all ages, even in children. About 20% of patients with thymic carcinoids have the MEN1 syndrome. The disease seems to be correlated with cigarette smoking.

Histopathology of thymic NETs
The tumor is usually located in the anterior mediastinum. The average size is 5–6 cm, but may be up to 25 cm. Grade 1 thymic carcinoids (previously called typical carcinoids) have <1 mitosis/10 high power fields, no necroses and minimal pleomorphism. Grade 2 thymic carcinoids (previously called atypical carcinoids) have >1 mitosis/10 high power fields and also necroses and moderate pleomorphism. Grade 3 thymic carcinoids (previously large-cell neuroendocrine carcinoma and small-cell carcinoma) have more mitoses and also necroses and pleomorphism.

Symptoms of thymic NETs
Many patients with thymic carcinoids are asymptomatic and diagnosed on routine chest X-ray or CT scan. About one third of the patients with sporadic thymic carcinoids present with the Cushing’s syndrome. Other symptoms include chest pain, cough, dyspnea, and the superior vena cava syndrome. Mediastinal lymph node metastases are frequently seen at presentation. Distant metastases, to the lungs, bones, liver and brain, are observed in approximately 20% of the patients.

Diagnosis of thymic NETs
Chest x-ray can frequently detect the tumor. CT scan should always be performed. MRI is sometimes recommended for detection of small tumors or pericardial or large vessel involvement, thereby assessing the indication for surgical treatment. Octreoscan is important for staging of the disease. The role of PET (with FDG or 5-HTP) in the diagnosis of thymic carcinoids remains to be established.

Treatment of thymic NETs
The only curative treatment is surgery, which should include complete excision of the primary tumor and lymph nodes. In patients with the MEN1 syndrome prophylactic thymectomy should be performed in association with parathyroidectomy. Postoperative thoracic radiotherapy is often recommended to prevent local recurrence of invasive tumors, but has not yielded any survival benefit. There is no standard chemotherapy for patients with distant metastases. Possible regimens are temozolomide as monotherapy or combined with capecitabine and/or bevazicumab (Avastin), cisplatin + etoposide or streptozotocin + 5-fluorouracil. 177Lutetium-octreotate is an alternative in patients with metastatic thymic carcinoids showing high uptake on octreoscan. Symptomatic treatment of an ectopic Cushing’s syndrome include ketoconazole, metyrapone, octreotide and lanreotide.

Prognosis of thymic NETs
Thymic carcinoids are aggressive tumors. Five year survival rate is 60–100% for localized disease, 40% for regional and only 29% for patients with distant metastases.