Neuroendocrine Tumor of the Lung: Stages and Grades

Approved by the Cancer.Net Editorial Board, 02/2023

ON THIS PAGE: You will learn about how doctors describe a tumor’s growth or spread. This is called the stage. In addition, you can read about how doctors compare cancer cells to healthy cells, called grading. Use the menu to see other pages.


What is tumor staging?

Staging is a way of describing where the tumor is located, if or where it has spread, and whether it is affecting other parts of the body.

Doctors use diagnostic tests to find out the tumor’s stage, so staging may not be complete until all of the tests are finished. Knowing the stage helps the doctor recommend the best kind of treatment, and it can help inform a patient’s prognosis, which is the chance of recurrence or survival. There are different stage descriptions for different types of neuroendocrine tumors (NETs).

The staging of a lung NET is the same as the staging of non-small cell lung cancer (NSCLC).

In general, a lower number stage is linked with a better outcome. However, no doctor can predict how long a patient will live with a lung NET based only on the stage of disease.

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Stage groups for a lung NET

The stage of lung NET is based on a combination of several factors, including:

  • The size and location of the tumor

  • Whether it has spread to the lymph nodes and/or other parts of the body.

There are 5 stages for lung NETs: stage 0 (zero) and stages I through IV (1 through 4). An important treatment assessment is to find out whether the tumor can be completely removed by a surgeon. If it is possible, the surgeon must remove the tumor, along with the surrounding, healthy lung tissue. In general, the lymph nodes should also be tested or removed in a systematic fashion.

Stage 0

This is called in situ disease, meaning the tumor is “in place” and has not grown into nearby tissues and spread outside the lung. This tumor is not invasive.

Stage I

A stage I lung NET is a small tumor that has not spread to any lymph nodes. Stage I is divided into 2 substages based on the size of the tumor:

  • Stage IA tumors are 3 centimeters (cm) or less in size. Stage IA tumors may be further divided into IA1, IA2, or IA3, based on the size of the tumor.

  • Stage IB tumors are more than 3 cm but 4 cm or less in size.

Stage II

A stage II lung NET is divided into 2 substages:

  • Stage IIA describes a tumor larger than 4 cm but 5 cm or less in size that has not spread to the nearby lymph nodes.

  • Stage IIB describes a tumor that is 5 cm or less in size that has spread to the lymph nodes. Or, stage IIB can describe a tumor more than 5 cm wide but less than 7 cm in size or a tumor with more nodules in the same lobe that has not spread to the lymph nodes.

Stage III

Stage III lung NETs are classified as either stage IIIA, IIIB, or IIIC. The stage is based on the location and size of the tumor and which lymph nodes the cancer has spread to. Stage III cancers have not spread to other distant parts of the body.

For many stage III cancers, the tumor is difficult, and sometimes impossible, to remove with surgery. For example, the lung NET may have spread to the lymph nodes located in the center of the chest on the opposite side of the tumor. Or, the tumor may have grown into nearby structures in the lung. In either situation, it is less likely that the surgeon can completely remove the cancer. Sometimes it is not possible to remove a lung NET if it has spread to the lymph nodes above the collarbone or if it has grown into vital structures within the chest. These vital structures include the heart, large blood vessels, or the main breathing tubes leading to the lungs.

Stage IV

Stage IV means the lung NET has spread to more than 1 area in the opposite lung, the fluid surrounding the lung or the heart, or distant parts of the body through the bloodstream. Once cancer cells get into the blood, the cancer can spread anywhere in the body. A lung NET is more likely to spread to the bones, liver, adrenal glands, and less commonly, the brain. Stage IV is divided into 2 substages:

  • Stage IVA cancer has spread within the chest, such as the opposite lung or the lining of the heart or lung, and/or has spread to only 1 area outside of the chest.

  • Stage IVB has spread outside of the chest, with more than 1 metastases outside the lung, in 1 or more organs.

In general, surgery is not successful for most stage IV lung NETs. In these situations, the doctor will recommend other treatment options.

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Grade (G) and differentiation

Doctors also describe a lung NET by its grade (G) and degree of differentiation, both features that are determined when the tumor cells are viewed under the microscope. Based on the grade, a lung NET may be called a "typical carcinoid" or an "atypical carcinoid." Typical and atypical carcinoids can grow slowly for years without being found. Although these types of lung NETs are cancerous, they are often described as "cancer in slow motion."

For lung NETs, the grade describes how fast the tumor cells are growing and dividing, measured by mitosis. To measure mitosis, the doctor counts the number of dividing cells seen in a square 2 millimeters in size under a microscope. This is called the mitotic index. A low value means that the cells are slowly dividing and indicates that the NET is less aggressive. A higher value means that the cells are rapidly dividing and the NET is more aggressive. Necrosis, or cell death, is also an important pathology feature used to determine grade. The tumor may outgrow its blood supply in the area, which leads to dying cells (necrosis). This grading system is developed by the World Health Organization (WHO).

The tumor’s grade may help the doctor predict how quickly the cancer will grow and spread. In general, the lower the tumor’s grade, the better the prognosis.

Degree of differentiation is also determined by looking at cells under a microscope. Differentiation refers to how much a tumor cell looks like a healthy cell. Well-differentiated tumors look more like healthy cells and grow more slowly. Poorly differentiated cells look less like healthy cells and grow more quickly. Poorly differentiated tumors are usually referred to as neuroendocrine carcinomas (NECs) and are divided into large-cell and small-cell types.

GX: The tumor grade cannot be identified.

Low grade, typical carcinoid: A limited number of cells are dividing, when measured by mitotic index. The mitotic index is less than 2, and there is no necrosis. These are also well-differentiated.

Intermediate grade, atypical carcinoid: The mitotic index is 2 to 10, meaning an intermediate number of cells is dividing. The tumor may outgrow its blood supply in the area, which leads to necrosis. These are also well-differentiated.

High grade, large cell and small cell neuroendocrine carcinoma: The mitotic index is more than 10, meaning that a large number of cells are dividing, and generally the tumor has outgrown its blood supply in many areas, which leads to necrosis. These are poorly differentiated.

The classification system for NETs can be confusing for both doctors and patients and is different for lung NETs compared to NETs of the pancreas and small intestine. A group of pathologists has proposed a common classification framework for NETs, which would help reduce this confusion (Rindi G, Klimstra DS, Abedi-Ardekani B, et al.: A common classification framework for neuroendocrine neoplasms: an International Agency for Research on Cancer (IARC) and World Health Organization (WHO) expert consensus proposal. Mod Pathol 31, 1770–1786 (2018).

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Recurrent NETs

Recurrent cancer is cancer that has come back after treatment. If the NET does return, there will be another round of tests to learn about the extent of the recurrence. These tests and scans are often similar to those done at the time of the original diagnosis.

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Used with permission of the American College of Surgeons, Chicago, Illinois. The original and primary source for this information is the AJCC Cancer Staging Manual, Eighth Edition (2017), published by Springer International Publishing.

Information about the tumor’s stage and grade will help the doctor recommend a specific treatment plan. The next section in this guide is Types of Treatment. Use the menu to choose a different section to read in this guide.