Grades, types and stages of lung neuroendocrine cancer

Lung neuroendocrine cancers start in the neuroendocrine cells of the lung.

Your healthcare team might call them lung neuroendocrine neoplasms, or lung NENs. This means the same thing as lung neuroendocrine cancer. There are 2 key groups of lung neuroendocrine cancer: 

• lung neuroendocrine tumours (NETs )
• lung neuroendocrine carcinomas (NECs )

There are also different sub-types of:

• lung NETs - these are typical carcinoid and atypical carcinoid
• lung NECs - these are small cell and large cell lung NEC

A specialist doctor (pathologist ) looks at the cancer cells under a microscope. This tells them:

• whether you have a NET or a NEC
• how fast or slow the cancer cells are growing - this is the grade

The tests and scans you have give information about the stage of your cancer. 

Grading and differentiation

The pathologist looks at a sample of neuroendocrine cancer cells under a microscope.

They look at:

• how abnormal the cancer cells look – doctors call this differentiation
• how quickly or slowly they are dividing and growing – this is grading

Differentiation

This refers to how different the neuroendocrine cancer cells look. This is in comparison to healthy neuroendocrine cells:

• Well differentiated cancers look abnormal. But they still have some similarities to normal neuroendocrine cells. 
• Poorly differentiated cancers look very abnormal. They are not like normal neuroendocrine cells at all.

Your doctor uses the differentiation to diagnose you with one of the following:

• a lung neuroendocrine tumour (lung NET) – these are well differentiated cancers
• a lung neuroendocrine carcinoma (lung NEC) – these are poorly differentiated cancers

Grading

This is about cell division and growth rate. To describe this, you might hear the terms mitotic rate or Ki67 score or percentage (%). The higher the mitotic rate or Ki67%, the faster the growth.

There are 3 grades of neuroendocrine tumours (NETs) – grade 1, 2 and 3:

• Grade 1 cancers grow slowly. They are low grade.
• Grade 2 grow at a moderate pace (between 1 and 3). They are intermediate grade.
• Grade 3 grow rapidly. They are high grade.

All neuroendocrine carcinomas (NECs) are grade 3.

Types of lung neuroendocrine cancers

Types of lung NET

Lung neuroendocrine tumours (NETs) include:

• typical carcinoid (TC)
• atypical carcinoid (AC)

Typical carcinoid (TC)

Typical carcinoids are grade 1 cancers.  They are slow growing and less likely to spread outside the lungs.

The cancer cells look very like normal cells. Doctors also call these well differentiated cancers.

Typical carcinoids are also called carcinoid tumours. Around 2 in every 100 lung cancers (around 2%) diagnosed in the UK every year are typical carcinoids.

Atypical carcinoid (AC)

Atypical carcinoids are grade 2 cancers. They behave somewhere between grade 1 and grade 3 cancers. They usually grow faster than typical carcinoids. And they are more likely to spread.

The cancer cells look more abnormal. Doctors also call these moderately differentiated cancers.

Atypical carcinoids are also called carcinoid tumours. Fewer than 1 in every 100 lung cancers (1%) diagnosed in the UK every year are atypical carcinoids.

Types of lung NEC

Lung neuroendocrine carcinomas (NECs) include:

• small cell neuroendocrine carcinoma
• large cell neuroendocrine carcinoma

Small cell lung cancer (SCLC)

Small cell lung cancers are grade 3 cancers. They tend to grow quickly and are more likely to spread.

The cancer cells look very abnormal. Doctors also call these cancers poorly differentiated cancers.

Around 15 out of every 100 lung cancers (around 15 %) diagnosed are this type. It is linked to smoking. SCLC tends to spread quickly early on.

Large cell neuroendocrine carcinoma (LCNEC)

Large cell neuroendocrine carcinomas are grade 3 cancers. They tend to grow quickly and are more likely to spread.

The cancer cells look very abnormal. Doctors also call these cancers poorly differentiated cancers.

Around 3 out of every 100 lung cancers (3%) diagnosed in the UK every year are this type. They are linked to smoking.

Mixed cell carcinoma (MiNEN)

You can also get neuroendocrine cancer cells mixed in a tumour with a different type of cancer. Doctors call this MiNEN or mixed cell carcinoma.

Other terms you might hear

Primary and secondary cancer

A neuroendocrine cancer that starts in the lung is called a primary lung neuroendocrine cancer. A cancer that spreads to your lung from somewhere else in your body is a secondary lung cancer. Secondary cancers are also called metastases.

This is important. The primary cancer tells your doctor which type of treatment you need. The information on this page is about primary lung neuroendocrine cancers.

Functioning and non functioning neuroendocrine tumours (NETs)

Cancer can disrupt how much hormone the neuroendocrine cells make. It is much more common for NETs to produce abnormal levels of hormones than NECs.

Doctors sometimes group NETs depending on whether they make abnormal levels of hormones:

• Non functioning NETs make and release normal levels of hormones.
• Functioning NETs make and release abnormal levels of hormones. 

Most lung neuroendocrine cancers are non functioning.

Central and peripheral

You might hear or read these terms. They refer to the position of the cancer in your lung.

Central lung neuroendocrine cancers start in the bronchi. These are the large airways in the centre of your lungs.

Peripheral lung neuroendocrine cancers start in the smaller airways. These are on the edges of the lungs.

DIPNECH

DIPNECH stands for diffuse idiopathic pulmonary neuroendocrine cell hyperplasia. It’s a very rare condition where the neuroendocrine cells of the lung start to grow in an uncontrolled, rapid way. Doctors call this hyperplasia.

In some people these cells develop into a typical or atypical carcinoid. Some doctors call DIPNECH a pre cancer. The abnormal cells are all contained within the lining of the lung and have not spread.

Stages of lung neuroendocrine cancer

The stage of a lung neuroendocrine cancer tells you its size and whether it has spread. There are different ways to stage lung neuroendocrine cancer.

You have tests and scans to diagnose a lung neuroendocrine cancer. These give some information about the stage of the cancer. Sometimes it’s not possible to be certain about the stage until after surgery.

Knowing the stage can help your doctor decide which treatment you need.

Types of staging systems

There are different systems for staging cancer. Doctors use the number system or the TNM system to stage lung neuroendocrine cancers. They are the same staging systems as for other types of lung cancer.

There is also a simplified staging system for small cell lung cancer (SCLC).

TNM staging

The TNM staging system is the most common way to stage lung neuroendocrine cancers. TNM stands for tumour, node and metastasis:

• T describes the size of the tumour
• N describes whether there are cancer cells in the lymph nodes
• M describes whether the cancer has spread to a different part of the body

Number staging

Your doctor might tell you the number stage of your lung neuroendocrine cancer. Number staging systems use the TNM system to divide cancers into stages. Most types of cancer have 4 stages, numbered from 1 to 4.The groups depend on the size of the tumour and whether it has spread.

Stage 1 is the earliest stage. It means that the cancer is small and hasn’t spread to the lymph nodes or other parts of the body. Stage 4 is the most advanced stage.

Limited and extensive stage

Doctors often use a simple system to stage small cell lung cancer (SCLC). This describes your cancer as limited disease or extensive disease.

Limited disease is when the cancer is in a single area that can be treated with radiotherapy. Extensive disease means that the cancer has spread beyond a single area. Or there are cancer cells in the fluid around the lung (a malignant pleural effusion).

Treatment for lung neuroendocrine cancers

Treatment depends on what type of lung neuroendocrine cancer you have. Treatment also depends on:

• the stage of the lung neuroendocrine cancer

• where the cancer is

• your health and general fitness

• your choice - your doctor talks to you about how you feel about different treatments and side effects