Neuroendocrine tumors (NETs) of the lung account for approximately 25% of lung cancers and are classified as either typical carcinoid (TC), atypical carcinoid (AC), large cell neuroendocrine carcinoma or small cell lung cancer. The lower grade carcinoid tumors only make up about 2% of all lung cancer but represent about 30% of all NETS. The incidence of pulmonary carcinoids (PC) is increasing and most likely multifactorial based on better awareness and improved imaging modalities. Diagnosis can still be challenging as symptoms can be nonspecific and mimic those of COPD or asthma. Some symptoms can mimic those of non-small cell lung cancer including cough, weight loss, hemoptysis, dyspnea and chest pain. Uncommonly, pulmonary carcinoid tumors can be functional and secrete hormones resulting in flushing, diarrhea and wheezing. Even more rare acromegaly and Cushing’s syndrome can occur.
The diagnosis is most commonly based on tissue sampling either by needle biopsy or surgical resection. Pulmonary carcinoids are defined by size > 0.5cm and delineated into TC (mitotic index <2 data-preserve-html-node="true"/10 HPF without necrosis) and AC (mitotic index 2-10/10 HPF or presence of necrosis). The role of Ki-67 in PCs is evolving but sometimes obtained with the pathological evaluation. The staging for PCs follow that of the American Joint Committee on Cancer 8th edition for Lung Cancer.
The primary treatment for PCs is surgical resection. The principles of surgery follow those followed for resection for non-small cell lung cancer, however, parenchymal sparing approaches are sometimes used in TCs. Lymph node examination is considered the standard of care. There is no prospective data showing that adjuvant treatment for PCs produces a survival benefit. Patients are generally followed with physical exams and chest CTs post operatively and can recur many years later.
The only FDA approved treatment for advanced disease is the mTOR inhibitor everolimus. This approval is based off the RADIANT 4 trial which demonstrated an improvement in progression free survival in PCs versus placebo from 3.6 months to 9.2 months. Other options for therapy include somatostatin analogs (octreotide LAR and lanreotide), albeit prospective data is lacking. Pulmonary carcinoids were not included in the NETTER-1 trial which examined the peptide receptor radionuclide therapy, Lutetium Lu-177 dotatate; however, there are several retrospective series that show benefit and prospective trials are needed. Other options for advanced disease may also follow that of gastroenteropancreatic NETs including liver directed therapy and cytoreductive surgery.
By Dr. Robert Ramirez, FACP, of Ochsner Medical Center