Bronchial NETs

Introduction of bronchial NETs (bronchial carcinoids)
Bronchial NETs (carcinoids) are potentially malignant. Many patients are asymptomatic. The main treatment is surgery. Chemotherapy or 177Lu may be used against metastatic disease. Most patients have an excelllent prognosis.

Epidemiology of bronchial NETs
Bronchial carcinoids are rare tumors. Women are affected slightly more often than men. The disease may occur in all ages, even in children, but is most common in middle ages. The etiology is not known, except that patients with the MEN1 syndrome have an increased risk.

Histopathology of bronchial NETs
Bronchial carcinoids are subdivided into typical, containing <2 mitoses/2 mm2 (10 HPF), and atypical containing 2–10 mitoses/2 mm2. Atypical carcinoids have a more malignant behaviour than typical ones. Metastases, developing in 5–20% of patients with typical carcinoids and in up to 70% of patients with atypical carcinoids, most frequently occur to regional lymph nodes, but also distantly to the liver, bones, brain, subcutis and mammary glands. Metastases may occur late, up to 30 years after diagnosis.

Symptoms of bronchial NETs
Up to 50% of patients with bronchial carcinoids are asymptomatic, and the diagnosis is made on routine chest X-ray. Common symptoms are cough, hemoptysis, recurrent pneumonias, persisting lung infiltrate on chest X-ray, dyspnea, wheezing and chest pain. Endocrine symptoms, which are uncommon, include the classical carcinoid syndrome with elevated urinary 5’HIAA, an atypical carcinoid syndrome because of histamine secretion and ectopic Cushing’s syndrome.

Diagnosis of brochial NETs
Chest x-ray can detect the tumor in more than 60% of the patients. CT scan or MRI should always be performed to detect satellite lesions and enlarged lymph nodes. Octreoscan, which visualizes the tumor in about two thirds of the patients, is recommended preoperatively to clarify if this method may be used for follow-up. PET with 5-HTP may be of value to localize small tumors. Central tumors can be seen and biopsied by bronchoscopy. Plasma chromogranin A should be analyzed preoperatively, but is usually normal unless the tumor has metastasized.

Treatment of bronchial NETs
The only curative treatment for patients with bronchial carcinoids is surgery, which should include removal of the primary tumor and a thorough lymph node dissection aided by frozen sections, sparing as much normal lung parenchyma as possible. External radiotherapy is mainly used against bone or brain metastases, but may also be administered against inoperable primary tumors. Patients with distant metastases may be treated with various chemotherapy regimens such as temozolomide as monotherapy or combined with capecitabine and/or bevazicumab (Avastin), cisplatin or carboplatin + etoposide or streptozotocin + 5-fluorouracil. 177Lutetium-octreotate is promising in patients with metastatic lung carcinoids showing high uptake on octreoscan. Biotherapy with alpha-interferon and somatostatin analogs may be tried in patients with low proliferative tumors. The choice of treatment is influenced by the proliferative rate (Ki-67 index).

Prognosis of bronchial NETs
The prognosis is usually excellent; most patients with bronchial carcinoids are cured by surgery. Prognostically unfavourable conditions are lymph node metastases at surgery, high proliferative rate (Ki-67 index) and atypical carcinoid. Long-term follow-up, at least 10 years, is important.