Understanding your pathology report

Well differentiated neuroendocrine tumour of the pancreas

This article will help you read and understand your pathology report for well differentiated neuroendocrine tumour of the pancreas.

by Stephanie Reid MD FRCPC, reviewed by our Patient Partners on August 26, 2020 

well differentiated neuroendocrine tumour pancreas

Quick facts:

  • Well differentiated neuroendocrine tumour (NET) is a type of pancreatic cancer.
  • People with the genetic syndrome multiple endocrine neoplasia type 1 (MEN1) are at higher risk for developing a pancreatic NET.
  • Up to half of all well differentiated NETs will produce hormones such as insulin, glucagon, or gastrin.

The function and anatomy of the pancreas

The pancreas is a long organ that sits in the abdomen just below the stomach. It plays an essential role in converting the food we eat into fuel for the body’s cells.  The pancreas has two main functions: an exocrine function that helps in digestion and an endocrine function that regulates blood sugar.

The exocrine part of the pancreas is made up of small structures called glands. These glands make different types of enzymes which help the body break down food. The glands send these enzymes into the small intestine through small channels called ducts.

The endocrine part of the pancreas is made up of small round structures called acini. The acini are made up of specialized neuroendocrine cells which are like nerve cells (neurons), but they also make hormones like cells of the endocrine system (endocrine cells). They receive messages (signals) from the nervous system and the blood and respond by making and releasing hormones. These hormones control many body functions including the way your body uses sugar.

Hormones made by the endocrine part of the pancreas include:

  • Insulin
  • Glucagon
  • Gastrin
  • Somatostatin
  • Vasoactive intestinal peptide

What is a well differentiated pancreatic neuroendocrine tumour?

A well differentiated neuroendocrine tumour is a type of pancreatic cancer which starts from the neuroendocrine cells in the endocrine (hormone producing) part of the pancreas.  These tumours are common in patients with the genetic syndrome multiple endocrine neoplasia type 1 (MEN1). However, most patients with these tumours do not have any known genetic syndrome.

How do pathologists make this diagnosis?

The diagnosis is usually made after a procedure that removes a small sample of tissue. This procedure may be called a fine needle aspiration (FNA) or a needle core biopsy. Some tumours are located in a part of the pancreas that cannot be reached by a biopsy needle. In this case the diagnosis may be made after a test called an Octreotide scan is performed.

After the diagnosis, surgery is usually performed to remove the entire tumour. There are two main types of surgeries for removing neuroendocrine tumours from the pancreas. The surgery which removes a tumour from the end of the pancreas is called a distal pancreatectomy. The surgery which removes the tumour along with part of the pancreas, small bowel, and stomach is called a Whipple procedure.

Hormones made by the tumour

As neuroendocrine tumours start from hormone producing endocrine cells, half of all pancreatic neuroendocrine tumours will continue to make hormones. Tumours that produce hormones are called functioning NETs and each is named for the type of hormone they make.

 

Type of tumour
Hormone produced
Insulinoma Insulin
Glucagonoma Glucagon
Gastrinoma Gastrin
Somatostatinoma Somatostatin
VIPoma Vasoactive intestinal peptide (VIP)
ACTH-secreting tumour Adrenocorticotropic hormone (ACTH)

 

Half of pancreatic neuroendocrine tumours do not produce hormones. These tumours are called non-functioning NETs. Because they do not produce any hormones or cause any significant symptoms, they can grow quite large before they are found.

Histologic grade

Grade is a word pathologists use to describe the difference between cancer cells and the normal, healthy cells they have replaced. For neuroendocrine tumours, the grade is determined by the number of tumour cells dividing to create new tumour cells. These dividing cells are called mitotic figures and the process is called mitosis. Some pathology reports will describe the number of mitotic figures in a defined area of tissue (for example 2 millimeter square).

Your pathologist may also perform a special test called immunohistochemistry to look for a marker called Ki-67. This marker identifies cells that are in the process of dividing. The percentage of Ki-67 positive cells is called the proliferative index or labeling index. If both mitotic figure count and Ki-67 labeling index are performed the one with the highest number is used to determine grade.

Mitotic count:

  1. Grade 1: < 2 mitoses/2mm2
  2. Grade 2: 2 to 20 mitoses/2mm2
  3. Grade 3: > 20 mitoses per 2mm2

Ki-67 labeling index:

  1. Grade 1: <3%
  2. Grade 2: 3% to 20%
  3. Grade 3: >20%

High grade (grade 3) tumour tend to grow more quickly and are more likely to spread to other parts of the body. The movement of tumour cells to another part of the body is called a metastasis.

Tumour size

This is the size of the tumour measured in centimetres. 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 in a biopsy report. The tumour size in neuroendocrine tumours is used to determine the tumour stage (see Pathologic Stage below).

Large tumours are more likely to grow beyond the pancreas and to spread to distant parts of the body such as the liver. The movement of tumour cells to another part of the body is called a metastasis.

How many tumours were found in the pancreas?

For most patients, only one tumour is found in the pancreas. However, patients with the genetic syndrome multiple endocrine neoplasia type 1 (MEN1) may have multiple tumours found throughout the pancreas. A single tumour is described as unifocal while multiple tumours are described as multifocal.

Perineural invasion

Nerves are located throughout all parts of your body. When cancer cells come in contact with nerves and wrap around them it is called perineural invasion. When cancer cells invade nerves, they can then travel along the nerve to areas far from the original location of the tumour.

perineural invasion

When perineural invasion is seen, there is a higher risk that the tumour will re-grow at the same site or spread (metastasize) to a distant site away from the pancreas.

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.

lymphovascular invasion

Cancer cells can use blood vessels and lymphatics to travel away from the tumour to other parts of the body. The movement of cancer cells from the tumour to another part of the body is called metastasis.

Before cancer cells can metastasize, they need to enter a blood vessel or lymphatic. This is called lymphovascular invasion. Lymphovascular invasion increases the risk that cancer cells will be found in a lymph node or a distant part of the body such as the liver. 

Tumour necrosis

Tumour necrosis occurs when cells in the tumour die. In well differentiated neuroendocrine tumours of the pancreas, reporting tumour necrosis is not required. However, when reported, it is often noted as being present or not identified.

Tumour necrosis is important because it is considered a sign that the tumour may re-grow after treatment or that the tumour cells may spread to another part of the body such as the liver.

Margins

A margin is any tissue that was cut by a surgeon in order to remove a tumour from the body. The number of margins described in your report will depend on the type of surgery that was performed and how many cuts were made through tissues or organs to remove the tumour. Most reports will describe margins in the pancreas and in any surrounding organs that were removed at the same time as the tumour.

Margin

Margins are only described in your report after the entire tumour has been removed. Margins are not described after a biopsy.

Commonly described margins in pancreatic resection specimens include:

  • Pancreatic margin – This is the part of the pancreas that was cut in order to remove the tumour. The amount of pancreas removed depends on the location of the tumour within the pancreas.
  • Common bile duct. The common bile duct is a channel that connects the liver to the pancreas and transports bile. Sometimes tumours within the pancreas can grow through the outside of the pancreas and involve the nearby common bile duct.
  • Uncinate process – This is a part of the pancreas that rests against the back of the abdomen. The tissue at the end of the uncinate process needs to be cut in order for the surgeon to remove the tumour.
  • Gastric (stomach) margin – In certain types of pancreas surgeries, a part of the stomach is removed at the same time as the tumour in the pancreas. The gastric margin is the place where a surgeon cuts the stomach to remove the tumour.
  • Small bowel or duodenal margin – In the same surgery involving removal of portion of stomach (Whipple procedure), a segment of small bowel, called the duodenum, will have to be removed as well. The small bowel margin is the place where the surgeon cuts across the small bowel to remove the tumour.

All of the margins are examined under a microscope by your pathologist to determine the margin status. A margin is considered positive when there are tumour cells within 1 millimeter of the edge of the cut tissue. A margin is negative when cancer cells are more than 1 mm from the cut tissue edge. A positive margin is associated with a higher risk of the tumour re-growing in the same site after surgery or treatment.

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 a metastasis.

Lymph node

Your pathologist will carefully examine each lymph node 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. Most reports include the total number of lymph nodes examined and the number, if any, that contain cancer cells. 

Pathologic Stage (pTNM)

The pathologic stage for well differentiated neuroendocrine tumours of the pancreas is based on the TNM staging system, an internationally recognized system originally created by the American Joint Committee on Cancer.

This system uses information about primary tumour (T), lymph nodes (N) and distant metastatic disease (M) to determine the complete pathologic stage (pTNM). Your pathologist will examine the tissue submitted and give each of the three parts a number. In general, a higher number means more advanced disease and a worse prognosis.

Tumour stage (pT) for well differentiated neuroendocrine tumour

Well differentiated neuroendocrine tumours are given a tumour stage of either 1, 2, 3, or 4. The tumour stage is based on the size of the tumour, and which organs or tissues it involves.

  • T1 – Tumour limited to the pancreas and is less than 2 cm.
  • T2 – Tumour limited to the pancreas and is 2 – 4 cm.
  • T3 – Tumour limited to the pancreas and is greater than 4 cm OR tumour invades the   duodenum or common bile duct.
  • T4 – Tumour invading adjacent organs (stomach, spleen, colon, adrenal gland) or the wall of large vessels.
Nodal stage (pN) for well differentiated neuroendocrine tumour

Well differentiated neuroendocrine tumour is given a nodal stage of 0 or 1. If no cancer cells are seen in any of the lymph nodes examined, the stage is pN0. If cancer cells are found in any lymph nodes, the stage is pN1. If no lymph nodes are sent for pathologic examination, the nodal stage cannot be determined and is listed as pNX.

Metastatic stage (pM) for well differentiated neuroendocrine tumour

Well differentiated neuroendocrine tumour is given a metastatic stage of 1 if there are cancer cells at a distant site in the body. The metastatic stage can only be determined if tissue from a distant site is submitted for pathological examination. If no tissue from a distant site has been sent for pathologic examination, the metastatic stage cannot be determined and is listed as pMX.

The metastatic stage can be further classified as follows:

  • M1a –  Metastasis is confined to liver.
  • M1b –  Metastatic in at least one extrahepatic site (an area of the body outside of the liver).
  • M1c – Both hepatic (liver) and extrahepatic metastases.
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