Endometrioid carcinoma - Uterus and endometrium -

This article will help you read and understand your pathology report for endometrioid carcinoma of the endometrium.

by Jason Wasserman, MD PhD FRCPC, updated June 5, 2020

Quick facts:
  • Endometrioid carcinoma is a type of cancer that starts in the endometrium, the tissue that lines the inside of the uterus.
  • Endometrioid carcinoma is the most common type of endometrial cancer among adult women.
  • Your pathology report for endometrioid carcinoma includes important information such as the tumour grade.
The anatomy of the uterus and endometrium

The uterus is a pear-shaped hollow organ found in the female pelvis between the rectum (the end of the large bowel) and the urinary bladder. The upper part of the uterus (fundus) is attached to the fallopian tubes while the lower part is connected to the vagina through the uterine cervix.

The walls of the uterus are made up of three layers:

  • Endometrium – The endometrium is the tissue on the inner surface of the uterus. The endometrium is made up of endometrial glands lined by one layer of cells that form a barrier called the epithelium. The epithelium is surrounded by supporting tissue called endometrial stroma.
  • Myometrium – The myometrium is the middle layer and is made up of smooth muscle which allows the uterus to change size and contract.
  • Perimetrium – The perimetrium is a thin layer of tissue that surrounds the outside of the uterus.

 

Gynecological tract

What is endometrioid carcinoma?

Endometrioid carcinoma is a type of cancer that develops from the glands within the endometrium. It is the most common type of endometrial cancer among adult women.

Endometrioid carcinoma is believed to develop from a pre-cancerous condition called atypical endometrial hyperplasia. The cells in atypical endometrial hyperplasia are not cancerous however they are abnormal and if left untreated have the potential to turn into a cancer such as endometrioid carcinoma.

Endometrioid carcinoma is usually diagnosed after a small sample of tissue is taken from the endometrium in a procedure called a biopsy or curettage. After the diagnosis, the tumour is removed in surgical procedure called a hysterectomy.​

Histologic grade (FIGO grade)

Pathologists use the word grade to describe how different the cancer cells in endometrioid carcinoma look compared the cells normally found in the endometrium.

Because the normal endometrial cells form glands, the grade of endometrioid carcinoma is based on the amount of cancer cells forming glands. Cancer cells that are not forming glands are described as showing a solid pattern of growth which means there is very little space between the cancer cells.

Pathologists divide the grade into three categories based on how the cancer cells look when examined under the microscope.

  • Grade 1 – Most of the tumour is forming glands. The tumour shows less than a 5% solid pattern of growth.
  • Grade 2 – Some of tumour is forming glands. The tumour shows a 6 to 50% solid pattern of growth.
  • Grade 3 – Very few glands are seen. The tumour shows more than 50% solid pattern of growth.

Grade 3 tumours are associated with worse prognosis compared to lower grade (1 or 2) tumours.

Myometrial invasion

The myometrium is a thick band of muscle just below the endometrium. The movement of cancer cells from the endometrium into the myometrium is called myometrial invasion.

The amount of myometrial invasion will be described in millimetres and as a percentage of the total myometrial thickness.

Myometrial invasion is usually only described in your report after the entire tumour has been removed.

Tumours with greater myometrial invasion are more likely to spread to other parts of the body. The amount of myometrial invasion is also used to determine the tumour stage (see Pathological stage below).

Cervical stromal involvement

The cervix is a structure at the very bottom of the uterus. The cervix connects directly with the endometrium. The wall of the cervix is made up of a type of tissue called stroma.

Endometrioid carcinoma may grow from the endometrium into the cervix. After the tumour is removed completely, your pathologist will carefully examine the tissue from the cervix to see if there are any cancer cells in the cervical stroma.

Finding cancer cells in the cervical stroma increases the tumour stage (see Pathologic stage below).

Other tissues or organs involved

Several other organs and tissues are directly attached or very close to the uterus including the ovaries, fallopian tubes, vagina, bladder, and rectum.

Cancer cells directly growing into any of these structures by endometrial carcinoma will increase the tumour stage (see Pathologic stage below) and is associated with poor prognosis.

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.

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 lungs.

Margins

A margin is the normal tissue that surrounds a tumour and is removed with the tumour at the time of surgery. The margins will only described in cases where the tumour extends into the cervical stroma or other tissues surrounding the uterus and after the entire tumour has been removed.

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. A negative margin means that no tumour cells were seen at any of the cut edges of tissue.

Margin

Tumour size

This is the size of the tumour measured in millimeters. The tumour size is only measured after the entire tumour has been removed. Tumour size is not used to determine the tumour stage (see Pathologic stage below) as it has not been shown to be associated with prognosis.

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.

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

Lymph nodes on the same side as the tumour are called ipsilateral while those on the opposite side of the tumour are called contralateral.

Lymph nodes examined are usually divided into those found in the pelvis and those found around a large blood vessel in the abdomen called the aorta. The lymph nodes found around the aorta are called para-aortic.

If cancer cells are found in a lymph node, the size of the area involved by cancer will be measured and described in your report.

  • Isolated tumour cells – The area inside the lymph node with with cancer cells is less than 0.2 millimeters in size.
  • Micrometastases – The area inside the lymph node with with cancer cells is more than 0.2 millimeters but less than 2 millimeters in size.
  • Macrometastases – The area inside the lymph node with with cancer cells is more than 2 millimeters in size.

Cancer cells found in a lymph node are 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 number of lymph nodes with cancer cells is also used to determine the nodal stage (see Pathologic stage below).

Pathologic stage​

​The pathologic stage for endometrioid carcinoma 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 the 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 part a number. In general, a higher number means more advanced disease and worse prognosis.

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)

Endometrioid carcinoma is given a tumour stage between 1 and 4 based on the depth of myometrial invasion and growth of the tumour outside of the uterus.

  • T1 – The tumour only involves the uterus.
  • T2 – The tumour has grown to involve the cervical stroma.
  • T3 – The tumour has grown through the wall of the uterus and is now on the outer surface of the uterus OR it has grown to involve the fallopian tubes or ovaries.
  • T4 – The tumour has grown directly into the bladder or the colon.

Nodal stage (pN)

Endometrioid carcinoma is given an nodal stage from 0 to 2 based on the examination of lymph nodes from the pelvis and abdomen.

  • N0 – No cancer cells were found in any of the lymph nodes examined.
  • N1mi – Cancer cells were found in at least one lymph node from the pelvis but the area with cancer cells was not larger than 2 millimeters (only isolated cancer cells or micrometastasis).
  • N1a – Cancer cells were found in at least one lymph node from the pelvis and the area with cancer cells was greater than 2 millimeters (macrometastasis).
  • N2mi – Cancer cells were found in at least one lymph node outside the pelvis but the area with cancer cells was not larger than 2 millimeters (only isolated cancer cells or micrometastasis).
  • N2a – Cancer cells were found in at least one lymph node outside the pelvis and the area with cancer cells was greater than 2 millimeters (macrometastasis).
  • NX – No lymph nodes were sent for examination.

Metastatic stage (pM)

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

Mismatch repair testing

​Each cell in your body contains a set of instructions that tell the cell how to behave. These instructions are written in a language called DNA and the instructions are stored on 46 chromosomes in each cell. Because the instructions are very long, they are broken up into sections called genes and each gene tells the cell how to produce piece of the machine called a protein.

If the DNA becomes damaged or if it cannot be read accurately, the cell will be unable to produce the proteins it requires to function normally. An area of damaged DNA is called a mutation and mutations are one of the most common causes of cancer in humans.

For most patients, endometrioid carcinoma arises as a result of both environmental factors and genetic factors. These tumours are said to be ‘sporadic’ because they cannot be totally predicted.

Lynch syndrome

Some patients, however, inherit particular genes that put them at a much higher risk for developing endometrioid carcinoma. These people are said to have a syndrome and the most common syndrome associated with endometrial carcinoma is called Lynch.

Lynch syndrome is caused by the loss of one of 4 special proteins (MSH2, MSH6, MLH1, and PMS2) that normally function to remove errors from the genetic material (DNA) in your cells. When one of these proteins is lost, mutations start to accumulate and the normal cell can eventually turn into cancer.

As a precaution, pathologists test all endometrial carcinomas for Lynch syndrome using a test called ‘mismatch repair’. This test looks at the activity of MSH2, MSH6, MLH1, and PMS2 and if one or more of them is lost, additional testing may be performed to assess your risk for Lynch syndrome.

The diagnosis of Lynch syndrome is important not only for the patient but also for the patient’s family who may also be at risk of cancer as a result of the syndrome.

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