Bronchial Carcinoid Tumor

Bronchial carcinoid is a well-differentiated pulmonary neuroendocrine tumor from Kulchitsky cells. It makes up 1 to 2% of lung cancers and is the commonest lung tumor in children. The mean age is about 50 years, with a slight female predominance, and smoking is not a clear risk factor (except for atypical tumors). About 5% occur in multiple endocrine neoplasia type 1.

Types

• Typical carcinoid: under 2 mitoses in 2 mm2 and no necrosis, about 80 to 90% of cases, with 5-year survival of 90 to 95% and nodal metastasis in about 10 to 15%
• Atypical carcinoid: 2 to 10 mitoses in 2 mm2 or punctate necrosis, with 5-year survival of 60 to 70% and nodal metastasis in 40 to 50%

Central tumors lie in the main, lobar or segmental bronchi and cause obstruction. Peripheral tumors are asymptomatic nodules. Carcinoid syndrome occurs in under 5% (usually with liver metastases), and ectopic ACTH-driven Cushing syndrome in 1 to 2%. Complications: recurrent pneumonia, bronchiectasis, hemoptysis, lobar collapse, carcinoid crisis and metastases (liver, bone).

• Cough, wheeze (often misdiagnosed as asthma), hemoptysis, recurrent pneumonia in the same lobe, dyspnea
• Asymptomatic in about a quarter, found as a nodule on imaging
• Cushing syndrome: weight gain, hypertension, proximal weakness, hypokalemia
• Flushing, diarrhea and wheeze in carcinoid syndrome
• Red flags: massive hemoptysis, a rapidly growing tumor, features of hormone excess and liver metastases

1. CT chest with contrast: a well-defined, avidly enhancing endobronchial or perihilar nodule, with calcification in about 30%, post-obstructive atelectasis or consolidation.
2. Bronchoscopy: a smooth, red-pink, vascular endobronchial mass. Biopsy is generally safe despite vascularity, with epinephrine 1:10,000 available.
3. Histology and Ki-67: nests and trabeculae of uniform cells, chromogranin, synaptophysin and CD56 positive, with Ki-67 under 5% in typical and 5 to 20% in atypical tumors. The mitotic count and necrosis define type.
4. Gallium-68 DOTATATE PET-CT (somatostatin receptor imaging) for staging, especially atypical tumors. Fluorodeoxyglucose PET is less sensitive in typical tumors.
5. Biochemistry when indicated: 24-hour urinary 5-hydroxyindoleacetic acid for carcinoid syndrome, 24-hour urinary free cortisol or late-night salivary cortisol and ACTH for Cushing syndrome, and calcium, parathyroid hormone, prolactin and pituitary tests for multiple endocrine neoplasia type 1.
6. Mediastinal node sampling (endobronchial ultrasound) for atypical tumors or enlarged nodes.

Differentials: small cell carcinoma, large cell neuroendocrine carcinoma, non-small cell carcinoma, hamartoma, mucoepidermoid carcinoma, adenoid cystic carcinoma, foreign body.

1. Surgical resection is the treatment of choice: anatomic, parenchyma-sparing resection (sleeve lobectomy, bronchoplasty, segmentectomy or lobectomy) with systematic mediastinal lymph node dissection. Pneumonectomy only when unavoidable. Cefazolin 2 g IV before incision (3 g if over 120 kg), enoxaparin 40 mg SC daily for 7 days.
2. Endoscopic resection (laser, electrocautery, cryotherapy, argon plasma coagulation) for small intraluminal typical carcinoids in patients unfit for surgery, or as a bridge to relieve obstruction.
3. Adjuvant therapy is not routine. For node-positive atypical carcinoid, consider carboplatin AUC 5 on day 1 with etoposide 100 mg/m2 on days 1 to 3, every 21 days for 4 cycles, though the benefit is uncertain.
4. Advanced or unresectable disease:
   • Lanreotide 120 mg deep SC every 28 days or octreotide long-acting 30 mg IM every 28 days for hormone symptoms and tumor control.
   • Everolimus 10 mg orally once daily (monitor mouth ulcers, pneumonitis, hyperglycemia and lipids).
   • Lutetium-177 dotatate 7.4 GBq IV every 8 weeks for 4 cycles with an amino acid infusion (lysine and arginine 25 g each in 1 L over 4 hours) for somatostatin receptor-positive tumors.
   • Temozolomide 150 to 200 mg/m2 orally on days 1 to 5 of each 28-day cycle, with capecitabine 750 mg/m2 orally twice daily on days 1 to 14, for progressive disease. Give ondansetron 8 mg before each dose.
   • Surgery or ablation of limited liver metastases.
5. Ectopic ACTH: resect the tumor, and control cortisol before surgery with metyrapone 250 mg orally twice daily, increasing to 6 g daily, or ketoconazole 200 mg orally twice daily, increasing to 400 mg three times daily (monitor liver tests every 2 weeks). Replace glucocorticoid after resection (hydrocortisone 15 to 25 mg daily).
6. Carcinoid crisis prevention for patients with syndrome: octreotide 100 to 500 micrograms IV bolus before induction and 50 to 100 micrograms/h infusion during surgery. Avoid catecholamines and histamine-releasing drugs.
7. Diarrhea: loperamide 4 mg orally then 2 mg after each loose stool (maximum 16 mg daily).

Follow-up: typical carcinoid with CT chest at 6 months, then yearly for at least 10 years. Atypical carcinoid with CT every 6 months for 2 years, then yearly for life. Counsel on genetic testing when multiple endocrine neoplasia type 1 is suspected.