Lung neuroendocrine tumors (NETs) are uncommon cancers that begin in the specialized cells of the lung’s neuroendocrine system. These cells have traits of both nerve and hormone-producing endocrine cells, helping to regulate functions like airflow and blood flow. Unlike more common lung cancers, NETs arise from a different cell lineage, which influences the tumor’s behavior and treatment strategies. These growths represent a spectrum of diseases, ranging from slow-growing tumors to aggressive cancers.
Types of Lung Neuroendocrine Tumors
The classification of lung NETs is based on a microscopic evaluation of tumor cells. Pathologists examine the tumor’s growth pattern, the number of dividing cells (mitotic count), and the presence of tissue death (necrosis). This evaluation allows them to categorize the tumor into one of four main types on a spectrum from slow-growing to aggressive.
The slowest-growing type is the typical carcinoid (TC), a low-grade tumor whose cells resemble normal neuroendocrine cells and show few mitoses. Atypical carcinoid (AC) is an intermediate-grade tumor. Its cells show more mitotic activity and may have small areas of necrosis, giving them a higher potential to spread than typical carcinoids.
At the aggressive end of the spectrum are high-grade neuroendocrine carcinomas. Large cell neuroendocrine carcinoma (LCNEC) is characterized by large cells, a high mitotic rate, and widespread necrosis. The most aggressive form is small cell lung cancer (SCLC), a fast-growing cancer linked to smoking. SCLC cells divide rapidly and often spread early in the disease.
Common Symptoms and Syndromes
The signs of a lung NET depend on its location and whether it produces excess hormones. Many symptoms arise from the tumor’s physical presence within the airways. A persistent cough, wheezing, shortness of breath, or chest pain can occur if the tumor obstructs airflow. Coughing up blood (hemoptysis) may also be a sign, particularly with tumors in the central bronchial tubes.
Some lung NETs cause symptoms by releasing excess hormones like serotonin into the bloodstream. This leads to carcinoid syndrome, which is more common when the tumor has spread to the liver. The symptoms of carcinoid syndrome include sudden flushing of the skin, explosive diarrhea, and wheezing. Some individuals may also experience a rapid heartbeat or swelling in their feet and legs.
The Diagnostic Process
Diagnosing a lung NET combines imaging with tissue analysis. The process often begins with an imaging test, such as a chest X-ray or computed tomography (CT) scan, to reveal the location and size of a mass. These scans provide a detailed anatomical picture of the tumor.
A specialized Gallium-68 (Ga-68) DOTATATE PET/CT scan may be used for more specific information. This test uses a radioactive tracer that binds to somatostatin receptors on the surface of many NET cells. The scan can detect tumors throughout the body, helping determine if the cancer has spread and is highly sensitive for well-differentiated NETs.
A definitive diagnosis requires a biopsy for microscopic examination. A tissue sample is often collected during a bronchoscopy, where a thin tube is passed into the airways. A pathologist analyzes the tissue to confirm the tumor type and grade, which includes measuring the Ki-67 proliferation index to quantify cell division.
Treatment Approaches
Treatment for a lung NET is individualized based on the tumor’s type, stage, and hormonal activity. For localized typical and atypical carcinoids, surgery is the primary treatment and offers the best chance for a cure. The goal is to remove the entire tumor while preserving as much healthy lung tissue as possible.
For tumors producing excess hormones or to control the growth of advanced, low-grade NETs, doctors may prescribe Somatostatin Analogs (SSAs). These drugs mimic the natural hormone somatostatin to reduce hormone production and slow tumor growth. This approach manages symptoms like flushing and diarrhea while providing anti-tumor effects.
For aggressive or metastatic disease, other therapies are used. Peptide Receptor Radionuclide Therapy (PRRT) is a targeted treatment that delivers radiation directly to NETs with somatostatin receptors. Chemotherapy is reserved for high-grade tumors like LCNEC and SCLC, while radiation therapy may be used to target specific tumor sites.
Understanding Prognosis and Staging
A patient’s prognosis is influenced by the tumor’s type and its stage at diagnosis. Staging determines the extent of the cancer, meaning if it is confined to the lung or has spread to lymph nodes or distant organs. This is done using the TNM system, which assesses tumor size (T), lymph node involvement (N), and distant metastasis (M).
The tumor’s grade, which reflects how quickly its cells are dividing, is a primary driver of prognosis. Low-grade typical carcinoids removed at an early stage have a very favorable prognosis. In contrast, intermediate-grade atypical carcinoids are more likely to recur or spread, resulting in a more variable outlook.
High-grade cancers are more aggressive and tend to grow and spread quickly, often being diagnosed at an advanced stage. Because of this, their prognosis is less favorable than that of well-differentiated carcinoid tumors. The combination of tumor type and stage provides the most complete picture for predicting the disease’s course.