Neuroendocrine tumours of the lung are a rare group of cancers that develop in specialised cells within the respiratory system, accounting for approximately 20% of all lung cancers diagnosed each year.
Understanding Neuroendocrine Tumours of the Lung
Neuroendocrine tumours of the lung, commonly referred to as lung NETs, are unusual types of cancer that originate from neuroendocrine cells, which are specialised cells found throughout the body, including the lungs. These cells perform important roles in the body by producing hormones and helping to regulate various functions such as breathing patterns and blood flow within the respiratory system.[1]
While lung cancer is often associated with more common types such as adenocarcinoma or squamous cell carcinoma, lung NETs represent a distinct category with their own unique characteristics. These tumours behave differently from other lung cancers and require specialised approaches to diagnosis and treatment. Each patient’s experience with lung NETs is unique, shaped by factors including the tumour type, location, and how the disease affects their body.[1]
Lung NETs are classified into several subtypes, each with different growth patterns and treatment needs. The main types include typical carcinoid, which are slow-growing tumours accounting for the majority of lung NET cases; atypical carcinoid, which are also slow-growing but somewhat more aggressive; and small cell carcinoma, the most aggressive type that tends to grow rapidly. There is also a rare and aggressive variant called large cell neuroendocrine carcinoma (LCNEC), which shares features with both small cell lung cancer and non-small cell lung cancer.[1][12]
Epidemiology
Neuroendocrine tumours of the lung are relatively uncommon compared to other types of lung cancer. Around 20 out of every 100 lung cancers diagnosed each year are lung neuroendocrine cancers. Breaking this down further, approximately 15 out of 100 lung cancers are small cell neuroendocrine carcinomas, around 3 out of 100 are large cell neuroendocrine carcinomas, and about 2 out of 100 are lung neuroendocrine tumours, which doctors also call lung carcinoids.[3]
Although most neuroendocrine cancers begin in the digestive system, the lungs are the second most common location for these tumours to develop. Roughly 20 out of every 100 neuroendocrine cancers diagnosed in the United Kingdom start in the lungs. This pattern reflects the widespread distribution of neuroendocrine cells throughout the body.[3]
Globally, approximately 35 in every 100,000 people are living with neuroendocrine tumours of various types, with lung NETs accounting for 27% of all NET cases. This makes lung NETs more prevalent than many people realise, despite being considered rare within the broader landscape of cancer diagnoses.[21]
Regarding age and gender patterns, lung NETs often affect people in their 40s and 50s. While specific gender distribution varies by subtype, these tumours can occur in both men and women across different age groups.[1][12]
Causes
The exact cause of lung neuroendocrine tumours remains unclear, despite ongoing research into these rare cancers. Unlike some other types of lung cancer, the development of lung NETs cannot be traced to a single definitive cause. Scientists continue to investigate why certain individuals develop these tumours while others do not.[1][12]
What is known is that lung NETs develop when neuroendocrine cells in the lung begin to grow abnormally and multiply uncontrollably. These cells, which normally help regulate breathing and blood flow in the lungs through hormone production, undergo changes that transform them into tumour cells. The process that triggers this transformation is not fully understood.[1]
Lung neuroendocrine tumours are not infectious diseases and cannot be transmitted from one person to another. They develop within an individual’s own cells as a result of changes that occur over time. Understanding that these tumours arise from the body’s own cells, rather than from external pathogens, is important for patients and families navigating this diagnosis.[3]
Risk Factors
While the root causes of lung NETs remain uncertain, research has identified several factors that may increase a person’s likelihood of developing these tumours. Having one or more risk factors does not mean someone will definitely develop a lung NET, but awareness of these factors can be helpful for both patients and healthcare providers.[3]
Genetic factors play a role in some cases of lung NETs. A family history of lung neuroendocrine tumours may elevate risk, suggesting that inherited genetic factors could contribute to tumour development. Additionally, certain genetic syndromes, particularly multiple endocrine neoplasia type 1 (MEN1), have been associated with an increased risk of developing neuroendocrine tumours, including those in the lung. People with MEN1 have inherited changes in a specific gene that makes them more susceptible to developing various types of endocrine tumours.[1][12]
Having a previous history of cancer is another factor that may increase risk. This could be related to genetic predisposition, environmental exposures, or other factors that made someone vulnerable to developing cancer in the first place. However, this does not mean that all cancer survivors will develop lung NETs.[3]
Smoking has been identified as a risk factor for lung neuroendocrine cancers. While the relationship between smoking and lung NETs may differ from that seen with more common lung cancers, tobacco use does appear to play a role in increasing risk for some types of lung neuroendocrine tumours, particularly the more aggressive forms.[3]
Symptoms
The symptoms of lung neuroendocrine tumours can vary considerably depending on the type, location, and size of the tumour. Some people with lung NETs experience no symptoms at all, particularly in the early stages. In these cases, the tumour may be discovered incidentally when doctors perform imaging tests for unrelated medical concerns. This situation highlights the importance of routine medical check-ups and appropriate diagnostic imaging.[3]
When symptoms do occur, they typically result from the physical presence of the tumour in the lung or airway, from the tumour spreading to other parts of the body, or occasionally from hormones produced by the tumour. The most common symptoms are related to the respiratory system and how the tumour affects breathing.[3]
A persistent cough that does not go away is one of the most frequent symptoms reported by people with lung NETs. This cough may be different from a typical cough associated with a cold or respiratory infection because it continues for weeks or months without improvement. Some patients also experience wheezing, which is a whistling sound when breathing that occurs when airways are narrowed or obstructed.[3]
Coughing up blood, medically termed haemoptysis, can occur when a tumour grows in or near the airways and causes bleeding. While this symptom can be alarming, the amount of blood can range from small streaks in mucus to larger amounts. Any instance of coughing up blood warrants immediate medical attention, as it can indicate various serious conditions.[3]
Shortness of breath, or feeling unable to take a full breath, may develop as the tumour grows and interferes with normal lung function. This sensation can occur during physical activity or even at rest, depending on the size and location of the tumour. Aching or pain in the chest is another symptom that some patients experience, which may be constant or intermittent.[3]
Recurring chest infections can be a sign of lung NETs, as tumours in the airways may prevent proper drainage of mucus and create conditions where infections can develop more easily. If someone finds themselves experiencing repeated respiratory infections despite treatment, further investigation may be needed.[3]
Systemic symptoms, meaning those that affect the whole body rather than just the lungs, can also occur. Feeling very tired, or fatigue, is common among people with lung NETs and can significantly impact daily activities. This fatigue is often more profound than normal tiredness and does not improve with rest. Unexplained weight loss, meaning losing weight without trying to do so through diet or exercise changes, is another symptom that may indicate the presence of a tumour.[3]
Some lung neuroendocrine tumours, particularly certain types of carcinoids, can produce and release excess hormones into the bloodstream. When this happens, patients may experience a collection of symptoms known as carcinoid syndrome. This is less common in lung NETs compared to neuroendocrine tumours that start in the digestive system, but it can occur, especially if the tumour has spread to other parts of the body, particularly the liver.[3]
Symptoms of carcinoid syndrome include skin flushing, which appears as sudden redness and warmth of the face and upper body; diarrhoea that can be frequent and disruptive; wheezing or difficulty breathing; and a fast heart rate. These symptoms occur because the hormones produced by the tumour affect blood vessels, intestinal function, and other body systems. Carcinoid syndrome typically develops when hormone-producing tumours have spread to the liver, which is unable to filter out the excess hormones before they enter the general circulation.[3]
Prevention
Because the exact causes of lung neuroendocrine tumours are not fully understood, specific prevention strategies remain unclear. However, understanding risk factors and taking steps to maintain overall health can be beneficial.[1]
Since smoking has been identified as a risk factor for lung neuroendocrine cancers, avoiding tobacco use or quitting smoking if you currently smoke is a prudent step. Smoking cessation has numerous health benefits beyond potentially reducing cancer risk, including improved cardiovascular health and respiratory function. Support for quitting smoking is available through healthcare providers, quitlines, and various cessation programs.[3]
For individuals with a family history of neuroendocrine tumours or genetic syndromes such as multiple endocrine neoplasia type 1 (MEN1), discussing screening options with healthcare providers may be appropriate. While routine screening for lung NETs in the general population is not currently recommended, people with specific genetic risk factors might benefit from closer monitoring or genetic counselling services.[1]
Maintaining overall health through regular exercise, a balanced diet, and routine medical check-ups supports the body’s natural defences and helps ensure that any health concerns are identified promptly. While these measures cannot guarantee prevention of lung NETs, they contribute to better health outcomes in general.[1]
Being aware of symptoms and seeking medical attention promptly when concerning signs appear is also important. While this is not prevention in the traditional sense, early detection often leads to better treatment outcomes. If you experience persistent respiratory symptoms such as a cough that won’t resolve, coughing up blood, or unexplained weight loss, consulting with a healthcare provider is essential.[3]
Pathophysiology
Understanding the pathophysiology of lung neuroendocrine tumours means exploring how these cancers alter normal body functions at the cellular and tissue level. The changes that occur involve mechanical, physical, and biochemical processes that distinguish healthy lung tissue from tumour tissue.[1]
Neuroendocrine cells in the lungs are normally scattered throughout the airways and play important regulatory roles. They produce hormones that help control airflow and blood flow in the respiratory system. These cells have characteristics of both nerve cells, which send and receive signals, and endocrine cells, which secrete hormones. In healthy lungs, neuroendocrine cells function in a controlled manner to maintain respiratory homeostasis.[1][7]
When lung NETs develop, the neuroendocrine cells begin to divide and grow in an uncontrolled fashion. This abnormal growth creates a mass of tumour tissue that can interfere with normal lung structure and function. The rate at which these cells grow varies significantly depending on the type of tumour. Typical carcinoid tumours grow slowly, sometimes taking years to become clinically apparent. Atypical carcinoids grow somewhat faster and are more likely to spread. Small cell carcinomas and large cell neuroendocrine carcinomas are aggressive tumours that grow rapidly and tend to spread early in the disease course.[1][12]
The physical presence of the tumour in the lung can cause mechanical obstruction of airways. When a tumour grows in or near a bronchus (one of the major airways), it can partially or completely block the passage of air. This obstruction leads to symptoms such as coughing, wheezing, and shortness of breath. The blocked airway may also prevent proper drainage of mucus, creating an environment conducive to repeated infections in the affected part of the lung.[3]
Some lung neuroendocrine tumours retain the hormone-producing capability of normal neuroendocrine cells, but in a dysregulated manner. These functional tumours produce and release excess amounts of hormones into the bloodstream. The hormones can include serotonin, histamine, and various peptides. When produced in large quantities, these substances cause widespread effects throughout the body, leading to carcinoid syndrome symptoms such as flushing, diarrhoea, and heart problems.[3][7]
However, not all lung NETs are functional. Non-functional tumours either do not produce hormones or produce them in amounts too small to cause noticeable symptoms. The distinction between functional and non-functional tumours is important because it affects how the disease manifests and how it is monitored during treatment.[7]
As lung NETs grow, they can invade surrounding tissues and structures. More aggressive types of lung NETs have a greater tendency to spread, or metastasise, to other parts of the body. Common sites of metastasis include lymph nodes near the lungs, the liver, bones, and other organs. When tumours spread to the liver, this is particularly significant for functional tumours because the liver normally metabolises hormones before they circulate throughout the body. When liver metastases are present, this filtering function is compromised, allowing higher levels of hormones to reach the systemic circulation and often triggering or worsening carcinoid syndrome.[3]
The biochemical changes in lung NET cells involve alterations in cellular processes that control growth, division, and death. Normal cells have checkpoints that prevent uncontrolled growth and trigger programmed cell death when appropriate. In NET cells, these regulatory mechanisms are disrupted, allowing cells to continue dividing when they should not and to avoid the natural death process that eliminates damaged or unnecessary cells.[1]
Different types of lung NETs show varying degrees of cellular differentiation. Well-differentiated tumours, such as typical carcinoids, contain cells that still resemble normal neuroendocrine cells in appearance and retain some of their normal functions. Poorly differentiated tumours, such as small cell carcinomas, have cells that look very abnormal under the microscope and have lost most characteristics of normal neuroendocrine cells. The degree of differentiation correlates with how aggressive the tumour behaves, with poorly differentiated tumours generally growing faster and being more likely to spread.[9]
