Colon -

Poorly differentiated neuroendocrine carcinoma

This article was last reviewed and updated on July 22, 2018
by Ipshita Kak MD FRCPC

Quick facts:

  • Poorly differentiated neuroendocrine carcinoma is a type of cancer that develops from neuroendocrine cells.

  • Neuroendocrine cells are normally found in the tissue that lines the inside of the colon.

  • This tumour can start anywhere in the colon.

  • Neuroendocrine carcinoma is divided into two groups called small cell and large cell carcinoma.

The normal colon

The colon is part of a system called the gastrointestinal tract. It has six sections: cecum, ascending colon, transverse colon, descending colon, sigmoid colon, and rectum.

The inner surface of the colon is lined by epithelial cells that form structures called glands. Within the glands and hidden in between the epithelial cells, there is a small population of specialized cells, called neuroendocrine cells. These cells can receive signals from the nervous system and in turn release substances called proteins. There are many kinds of proteins and each has a specific function.
 

What is poorly differentiated neuroendocrine carcinoma?

Poorly differentiated neuroendocrine carcinoma is a type of cancer. It starts from the neuroendocrine cells normally found in the colon. Neuroendocrine carcinoma can develop anywhere along the length of the colon (from the cecum to the rectum). These are aggressive cancers that often present at a late stage (the tumour is often large, or the cancer cells have already traveled to a distant body site).

The diagnosis of poorly differentiated neuroendocrine carcinoma is can be made after a biopsy has been performed and sent to a pathologist for examination. The entire tumour may then be removed, or you may receive treatment with chemotherapy or radiation therapy.

Tumour type - Small cell and large cell carcinoma

Neuroendocrine carcinoma is divided into two groups depending on how the cells look under the microscope.  These two groups are called small cell carcinoma and large cell carcinoma.

 

Some tumours have features of both small cell and large cell carcinoma. In this situation your pathologist may simply call the tumour a poorly differentiated neuroendocrine carcinoma.

Tumour size

This is the size of the tumour measured in centimeters. Your report may only describe the greatest dimension. For example, if the tumour measures 5.0 cm by 3.2 cm by 1.1 cm, the report may describe the tumour size as 5.0 cm in greatest dimension.

 

The tumour size is only described after the entire tumour has been removed. Tumour size is not reported after a biopsy.

Tumour extension

All neuroendocrine carcinomas start in glands found on the inner surface of the colon. Tumour extension describes how far the cancer cells have traveled from the glands into the wall of the colon or the surrounding tissues.

 

The colon is made up of five layers of tissue:

 

  1. Mucosa - The mucosa is the tissue that lines the inside surface of the colon. The mucosa is made up of glands. The glands are surrounded and supported by a tissue called lamina propria. Neuroendocrine cells are normally found at the bottom of the glands in the mucosa.

  2. Submucosa - The submucosa sits directly below the mucosa. It contains many thick blood vessels and lymphatic channels.

  3. Muscularis propria - The muscularis propria is a thick bundle of muscle. The muscles in the muscularis propria help move digested food and waste along the colon.

  4. Subserosal adipose tissue - This is a layer of fat that sits directly below the muscularis propria. The subserosal adipose tissue is near the outside surface of the colon.

  5. Serosa - The serosa is a thin layer of tissue that covers the subserosal adipose tissue and the outside of the colon. 

The movement of cancer cells from the glands into the tissue below is called invasion. Once the cancer cells cross the serosa, they are on the outer surface of the colon and may invade nearby organs and tissues such as the bladder or abdominal wall.

 

Why is this important? Cancer cells that travel deeper in the wall are more likely to come back (recur) in the area of the original tumour or to travel (metastasize) to a distant site such as the liver.

Perineural invasion

​Cancer cells wrapped around a nerve is called perineural invasion. Cancer cells that become attached to a nerve can use the nerve to travel away from the tumour.

 

Why is this important? Perineural invasion is associated with a higher risk that the tumour will come back either at the same site or travel (metastasize) to a distant site such as the liver after treatment.

Lymphovascular invasion

Lymphatics and blood vessels are channels that normal cells use to travel around the body. The presence of cancer cells within a lymphatic or blood vessel is called lymphovascular invasion and is associated with a higher risk that the tumour will travel (metastasize) to either a lymph node or a distant site such as the lungs.

Margins

In the colon, a margin is any tissue that was cut by the surgeon to remove the tumour from your body. In the colon, a margin is considered ‘positive’ when there are cancer cells at the very edge of the cut tissue.

 

Why is this important? A positive margin is associated with a higher risk that the tumour will recur in the same site after treatment.

Tumour deposits

A tumour deposit is a group of cancer cells that are separate from the main tumour but not in a lymph node. The presence of tumour deposits is associated with a higher risk that cancer cells will travel (metastasize) to a distant body site such as the liver.

Lymph nodes

Metastatic disease describes the process where cancer cells escape the main tumour and travel to another part of the body. Lymph nodes are small immune organs located throughout the body. They are a common target for metastatic disease.

Most reports include the total number of lymph nodes examined and the number that contain cancer cells.

 

Why is this important? The presence of cancer cells in a lymph node (also called lymph node metastases) is associated with a higher risk that the cancer cells will be found in other lymph nodes or in a distant organ such as the lungs.

Pathologic stage (pTNM)

The pathologic stage for poorly differentiated neuroendocrine carcinoma is based on the TNM staging system, an internationally recognized system originally created by the American Joint Committee on Cancer (AJCC).

 

The AJCC system incorporates information about the primary tumour (T), lymph nodes (N), and distant metastatic disease (M) with each variable being given a number (usually from 1 to 4). As a general rule, a higher stage number indicates more advanced disease.

 

Pathologic stage is not reported on a biopsy specimen. It is only reported when the entire tumour has been removed in an excision or resection specimen.

Tumour stage (pT) for poorly differentiated neuroendocrine carcinoma

This cancer is given a tumour stage between 1 and 4 based on how far the cancer cells have traveled into the wall of the colon or surrounding tissues.

  • T1 - The cancer cells have entered the submucosa.

  • T2 - The cancer cells have entered the muscularis propria of the colon.

  • T3 - The cancer cells have gone through the entire muscular wall and are near serosa on the outer surface of the colon.

  • T4 - The cancer cells have passed the serosa and are on the outer surface of the colon or they have gone into surrounding organs such as the bladder or abdominal wall.

 

Nodal stage (pN) for poorly differentiated neuroendocrine carcinoma

This cancer is given nodal stage between 0 and 2 is based on the presence or absence of cancer cells in a lymph node, the number of lymph nodes that contain cancer cells, or the presence of tumour deposits.

If no lymph nodes are involved the nodal stage is N0. If no lymph nodes are submitted for pathological examination, the nodal stage cannot be determined and the nodal stage is listed as NX.

 

Metastatic stage (pM) for poorly differentiated neuroendocrine carcinoma

Poorly differentiated neuroendocrine carcinoma is given metastatic stage between 0 and 1 based on the presence of cancer cells at a distant site in the body (for example the liver). The metastatic stage can only be given if tissue from a distant site is sent for pathological examination. Because this tissue is rarely present, the metastatic stage cannot be determined and is listed as MX.

Immunohistochemistry

Immunohistochemistry (IHC) is a commonly used test that allows pathologists to better understand cells based on the specific proteins they produce. This test allows pathologists to better understand both the function and origin of the cell.

The cells in a neuroendocrine carcinoma commonly express three proteins: CD56, synaptophysin and chromogranin. By performing immunohistochemistry, your pathologist can ‘see’ these proteins inside the cell. Most cancers produce all three proteins, but some may produce two or even just one of the three. Cells that produce a protein will be called 'positive' or 'reactive'. Those that do not produce the protein are called 'negative' or 'non-reactive'.

Your pathologist may also perform immunohistochemistry to look for a protein called Ki-67. This protein is produced by cells that can divide and create new cancer cells. The percentage of cancer cells that produce Ki-67 is called the ‘proliferative index’ and this number may be included in your report. The normal proliferative index for poorly differentiated neuroendocrine carcinoma is usually between 20% and 90%.

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