Poorly differentiated neuroendocrine carcinoma of the colon and rectum

by Ipshita Kak MD FRCPC
May 9, 2022

What is poorly differentiated neuroendocrine carcinoma?

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

How do pathologists make the diagnosis of poorly differentiated neuroendocrine carcinoma?

The diagnosis of poorly differentiated neuroendocrine carcinoma is usually made after a small sample of the tumour is removed in a procedure called a biopsy. The diagnosis can also be made after the entire tumour is removed in a procedure called a resection.

What is the difference between small cell and large cell neuroendocrine carcinoma?

Pathologists divide poorly differentiated neuroendocrine carcinoma into two types – small cell and large cell – based on the size and shape of the tumour cells. As the names suggest, small cell neuroendocrine carcinoma is made up of small tumour cells with very little cytoplasm. Large cell neuroendocrine carcinoma is made up of much larger tumour cells with more cytoplasm and round pieces of genetic material called nucleoli. 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.

What other tests may be performed to confirm the diagnosis?

A test called immunohistochemistry may be performed to confirm the diagnosis. This test 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 poorly differentiated 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%.

What does invasion mean?

Pathologists use the word invasion to describe the spread of tumour cells from the inside of the colon into the surrounding tissues. Poorly differentiated neuroendocrine carcinoma starts from cells normally found within the glands on the inside surface of the colon. The glands are part of a thin layer of tissue called the mucosa. The layers of tissue below the mucosa include the submucosa, muscularis propria, subserosal adipose tissue, and serosa. As the tumour grows the cells can spread into these layers. Eventually, the tumour cells can break through the outside surface of the colon and spread directly into nearby organs and tissues.

The level of invasion is the deepest point of invasion and it can only be measured after the tumour is examined under the microscope by a pathologist. The level of invasion is important because tumours that invade deeper into the wall of the colon are more likely to spread to other parts of the body. The level of invasion is also used to determine the pathologic tumour stage (pT).

What is perineural invasion?

Nerves are like long wires made up of groups of cells called neurons. Nerves are found all over the body and they are responsible for sending information (such as temperature, pressure, and pain) between your body and your brain. Perineural invasion is a term pathologists use to describe tumour cells attached to a nerve. Perineural invasion is important because tumour cells that have become attached to a nerve can grow along the nerve and into surrounding tissues. This increases the risk that the tumour will re-grow after treatment.

What is lymphovascular invasion?​

Blood moves around the body through long thin tubes called blood vessels. Another type of fluid called lymph which contains waste and immune cells moves around the body through lymphatic channels. The term lymphovascular invasion is used to describe tumour cells that are found inside a blood vessel or lymphatic channel. Lymphovascular invasion is important because once the tumour cells are inside a blood vessel or lymphatic channel they are able to metastasize (spread) to other parts of the body such as lymph nodes or the lungs.

​What is a margin?

A margin is any tissue that was cut by the surgeon in order to remove the tumour from your body. The types of margins described in your report will depend on the organ involved and the type of surgery performed. Margins will only be described in your report after the entire tumour has been removed.

A negative margin means that no tumour cells were seen at any of the cut edges of tissue. A margin is called positive when there are tumour cells at the very edge of the cut tissue. A positive margin is associated with a higher risk that the tumour will recur in the same site after treatment.

What are tumour deposits?

A tumour deposit is a group of tumour 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 tumour cells will spread to a distant body site such as the liver. The spread of cancer cells to another part of the body is called metastasis.

What are lymph nodes?

Lymph nodes are small immune organs located throughout the body. Cancer cells can travel from the tumour to a lymph node through lymphatic channels located in and around the tumour (see Lymphovascular invasion above). The movement of cancer cells from the tumour to a lymph node is called metastasis.

Most reports include the total number of lymph nodes examined and the number, if any, that contain cancer cells. Your pathologist will carefully examine all lymph nodes for cancer cells. Lymph nodes that contain cancer cells are often called positive while those that do not contain any cancer cells are called negative.

Finding cancer cells in a lymph node is important because it 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. The examination of lymph nodes is also used to determine the nodal stage (see Pathologic stage below).

How do pathologists determine the pathologic stage (pTNM) for poorly differentiated neuroendocrine carcinoma?

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 a more advanced disease.

The 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 spread 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

Poorly differentiated neuroendocrine carcinoma is given a nodal stage between 0 and 2 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 a metastatic stage of 0 or 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.