Your pathology report for poorly differentiated neuroendocrine carcinoma of the colon and rectum

by Ipshita Kak MD FRCPC
July 19, 2025

Poorly differentiated neuroendocrine carcinoma (NEC) is a rare and aggressive type of cancer that starts in neuroendocrine cells found in the lining of the colon or rectum. Neuroendocrine cells help regulate various body functions by producing hormones in response to signals from the nervous system.

There are two main types of poorly differentiated neuroendocrine carcinoma: small cell and large cell. Both types are high-grade cancers, meaning they grow quickly and have a higher chance of spreading to other parts of the body. Poorly differentiated neuroendocrine carcinoma is different from well differentiated neuroendocrine tumour, which tends to grow more slowly and has a better overall prognosis.

Where in the body does it usually start?

Poorly differentiated neuroendocrine carcinoma can start anywhere in the colon or rectum. These tumors often look similar to other types of colorectal cancer when seen during colonoscopy or imaging studies.

What are the symptoms of poorly differentiated neuroendocrine carcinoma?

Many people with this type of cancer may not notice symptoms until the tumor has grown or spread. When symptoms are present, they may include:

  • Abdominal pain or cramping.

  • Changes in bowel habits (such as diarrhea or constipation).

  • Rectal bleeding or blood in the stool.

  • Weight loss.

  • Weakness or fatigue.

Because the symptoms can be similar to other conditions, tests such as colonoscopy and biopsy are needed to confirm the diagnosis.

How is this diagnosis made?

The diagnosis of poorly differentiated neuroendocrine carcinoma is made by examining a tissue sample from the tumor under the microscope. This sample is usually collected during a colonoscopy or surgery. A pathologist will look for cancer cells with specific features, such as large or small abnormal cells dividing rapidly. Special tests called immunohistochemistry may also be performed to help confirm the diagnosis and rule out other types of cancer.

What does poorly differentiated neuroendocrine carcinoma look like under the microscope?

Under the microscope, this tumor is made up of sheets or clusters of abnormal cells that may look very different from normal neuroendocrine cells. The cells often appear crowded and may show signs of rapid division, with many visible mitotic figures. There may be areas of dead tissue called necrosis. Based on the shape and size of the cancer cells, the tumor is classified as either small cell or large cell neuroendocrine carcinoma. Both types are considered aggressive and are treated in similar ways.

Immunohistochemistry

Immunohistochemistry is a type of laboratory test that uses antibodies to detect specific proteins in the tumor cells. In poorly differentiated neuroendocrine carcinoma, the tumor cells typically produce proteins such as synaptophysin, chromogranin A, and INSM1. These proteins help confirm that the cancer started from neuroendocrine cells. Other markers like CDX2 and TTF1 may be positive depending on the exact location and type of tumor.

Tumor grade

All poorly differentiated neuroendocrine carcinomas are considered high grade tumors. This means the cancer cells grow and divide quickly and are more likely to spread to other parts of the body. The tumor grade is usually determined by looking at how the cells appear under the microscope, how many cells are dividing, and the results of a test called the Ki-67 index. A high Ki-67 index supports the diagnosis of a high grade tumor.

What does invasion mean in a poorly differentiated neuroendocrine carcinoma?

Invasion refers to how deeply the tumour cells have grown into the wall of the colon or rectum. A poorly differentiated neuroendocrine carcinoma begins from special hormone-producing cells called neuroendocrine cells. These cells are normally found in small glands that sit on the inside surface of the colon and rectum, in a thin layer of tissue called the mucosa.

Beneath the mucosa are several other layers of tissue, including:

  • Submucosa – a layer of supportive tissue just under the mucosa.

  • Muscularis propria – a thick muscle layer that helps move stool through the colon.

  • Subserosal tissue – a thin layer of fat below the muscle.

  • Serosa – the outermost layer that covers the outside of the colon and rectum.

As the tumour grows, it can invade into these deeper layers. In more advanced cases, the tumour may grow all the way through the wall of the colon or rectum and spread directly into nearby organs or tissues.

The level of invasion refers to the deepest layer that the tumour has reached. This can only be determined by a pathologist who examines the tumour under a microscope after it is removed by surgery. This information is very important because tumours that invade deeper into the colon wall are more likely to spread to other parts of the body. The level of invasion is also used to determine the tumour stage, which helps guide treatment and predict the risk of recurrence.

What is perineural invasion?

Perineural invasion means that tumour cells are seen growing around or along a nerve. Nerves are found throughout the body, including in the colon and rectum, and they help carry signals such as pain or muscle movement. When tumour cells grow around a nerve, they may use it as a pathway to move into nearby tissues. Perineural invasion is an important feature because it may be associated with a higher risk of the tumour coming back after treatment. Not all neuroendocrine carcinomas show perineural invasion, and your pathology report will say whether this feature was seen.

What is lymphovascular invasion?

Lymphovascular invasion means that tumour cells have entered small blood vessels or lymphatic channels in the tissue around the tumour. These vessels are important because they can serve as pathways for tumour cells to travel to other parts of the body, including nearby lymph nodes or more distant organs. When lymphovascular invasion is seen, it may increase the risk of tumour spread. If your tumour shows lymphovascular invasion, your doctor may consider additional testing or closer follow-up to look for signs of spread.

What is a margin and why is it important?

A margin is the edge of the tissue that was removed during surgery. If the tumour is completely removed and there are no tumour cells at the margin, it is called a negative margin. This means that the tumour was likely removed entirely. If tumour cells are found at the margin, it is called a positive margin, and it may mean that some tumour was left behind. This information helps doctors decide whether additional treatment or monitoring is needed.

What does it mean if tumour cells are found in lymph nodes?

Lymph nodes are small, bean-shaped structures that help filter harmful substances and are part of the body’s immune system. They are often the first place tumour cells go when they begin to spread. During surgery, your doctor may remove one or more nearby lymph nodes to see if tumour cells have spread. These nodes are carefully examined under the microscope by a pathologist.

If no tumour cells are found, the lymph nodes are considered negative. If tumour cells are found, they are considered positive, which means the tumour has started to spread beyond its original location. The number of lymph nodes involved helps determine the stage of the disease and can guide decisions about treatment and follow-up.

How do pathologists determine the stage of a poorly differentiated neuroendocrine carcinoma?

The stage of a poorly differentiated neuroendocrine carcinoma in the colon or rectum describes how far the tumour has grown and whether it has spread to other parts of the body. The stage is important because it helps doctors understand how advanced the tumour is and guides decisions about treatment and follow-up care.

Pathologists use a system called the TNM staging system, which was developed by the American Joint Committee on Cancer. TNM stands for:

  • T (Tumour) – how large the tumour is and how far it has grown into the wall of the colon or rectum or nearby tissues.

  • N (Nodes) – whether the tumour has spread to nearby lymph nodes.

  • M (Metastasis) – whether the tumour has spread to distant parts of the body such as the liver or lungs.

After examining the tumour and any lymph nodes removed during surgery, the pathologist assigns a number to each part. In general, a higher number means the tumour is more advanced.

Tumour stage (T)

The tumour stage is based on the size of the tumour and how deeply it has grown into the layers of the colon or rectum:

  • T1 – The tumour is 2 centimetres or smaller and is located entirely within the innermost layer of the colon or rectum (the mucosa).

  • T2 – The tumour is larger than 2 centimetres or has grown into the thick muscle layer of the wall (called the muscularis propria).

  • T3 – The tumour has grown through the entire muscular wall and into the soft tissue just under the outer surface of the colon or rectum.

  • T4 – The tumour has reached the outer surface of the colon or rectum or has grown into nearby organs such as the bladder or small intestine.

Lymph node stage (N)

The lymph node stage describes whether tumour cells have spread to nearby lymph nodes:

  • N0 – No tumour cells were found in any of the lymph nodes examined.

  • N1 – Tumour cells were found in at least one lymph node.

  • NX – No lymph nodes were available for the pathologist to examine.

What is the prognosis for a person with poorly differentiated neuroendocrine carcinoma?

Poorly differentiated neuroendocrine carcinoma is an aggressive cancer that grows quickly and often spreads to other parts of the body. The prognosis depends on several factors, including the size and location of the tumor, how deeply it has invaded, whether lymph nodes are involved, and whether the cancer has spread to distant organs. In general, these tumors have a poorer prognosis compared to well differentiated neuroendocrine tumors or typical colorectal adenocarcinoma.

However, treatment is available and may include surgery, chemotherapy, radiation, or a combination of these. Your doctor will review your individual case and recommend the best treatment plan based on the pathologic findings and overall stage of the disease.

Questions to ask your doctor

  • Has the tumour spread to lymph nodes or other organs?

  • What is the cancer stage?

  • What treatment options are available for my diagnosis?

  • Will I need additional tests or follow-up care?

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