Endometrial Endometrioid Carcinoma: Understanding Your Pathology Report

by Jason Wasserman MD PhD FRCPC
March 3, 2026

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Endometrial endometrioid carcinoma is a type of cancer that begins in the endometrium, the inner lining of the uterus. It is the most common type of endometrial cancer and most often affects women after menopause.

This type of cancer frequently develops from a precancerous condition called atypical endometrial hyperplasia, in which the endometrial cells show abnormal growth but have not yet spread into deeper tissues.

What are the symptoms of endometrial endometrioid carcinoma?

The most common symptom is abnormal uterine bleeding. This may include bleeding between periods or any bleeding after menopause. Other symptoms may include pelvic discomfort, unusual vaginal discharge, or pain during intercourse. Bleeding after menopause should always be evaluated.

What causes endometrial endometrioid carcinoma?

This cancer is strongly linked to long-term exposure to estrogen without progesterone. Obesity increases estrogen levels and is an important risk factor. Cancer is more common in postmenopausal women.

Other risk factors include polycystic ovary syndrome, diabetes, and inherited conditions such as Lynch syndrome.

How is this diagnosis made?

The diagnosis of endometrial endometrioid carcinoma usually begins with an endometrial biopsy, in which a small sample of tissue is removed from the lining of the uterus and examined under the microscope by a pathologist.

If cancer is identified, surgery is often performed to remove the uterus and sometimes the ovaries, fallopian tubes, and lymph nodes. The removed tissue is carefully examined to determine tumor grade, depth of invasion, lymph node spread, and other important features.

Microscopic features

Under the microscope, endometrial endometrioid carcinoma forms abnormal glands that resemble normal endometrial glands but are irregular in size and shape.

Some tumors show solid growth, with cells forming sheets rather than glands. The percentage of solid growth is used to determine the FIGO grade (see below).

Squamous differentiation is common. This means some areas of the tumor resemble squamous cells. This feature is frequently seen and does not automatically indicate a worse prognosis.

Immunohistochemistry

Immunohistochemistry is a laboratory test that uses antibodies to detect specific proteins inside tumor cells. These tests help confirm the diagnosis and distinguish endometrial endometrioid carcinoma from other types of uterine cancer.

In low-grade endometrial endometrioid carcinoma, tumor cells usually show strong, diffuse positivity for estrogen receptor (ER) and progesterone receptor (PR). “Diffuse” means most tumor cells stain positive. These tumors often show patchy p16 staining, meaning only some cells are positive.

This pattern is helpful because endocervical adenocarcinoma (a cancer that begins in the cervix) typically shows strong, diffuse p16 positivity and is usually negative for ER and PR if HPV-associated. HPV-independent cervical tumors are often negative for p16, ER, and PR. These differences help determine whether the tumor started in the uterus or the cervix.

In higher-grade tumors, additional markers may be used. Loss of staining for ARID1A, PTEN, or one of the mismatch repair (MMR) proteins supports a diagnosis of endometrial endometrioid carcinoma.

The protein p53 is also tested. Results are reported as either wild-type (normal pattern) or abnormal (mutant-type pattern). Abnormal p53 expression is more common in high-grade tumors and may indicate more aggressive behavior.

These immunohistochemical results are included in your pathology report because they help confirm the tumor type and may influence treatment decisions.

FIGO grade

The FIGO grade describes how abnormal the tumor cells look under the microscope and how much of the tumor forms solid sheets instead of glands. Grade helps estimate how aggressively the tumor is likely to behave.

Endometrial endometrioid carcinoma is divided into three grades based on the percentage of non-squamous solid growth:

• Grade 1: Less than 5% solid growth.

• Grade 2: 6% to 50% solid growth.

• Grade 3: More than 50% solid growth.

Grades 1 and 2 are considered low-grade and usually grow more slowly. Grade 3 tumors are considered high-grade and are more likely to spread or recur.

Your pathology report will include the FIGO grade because it plays an important role in determining treatment and prognosis.

Biomarkers

Biomarkers are tests performed on tumour tissue to understand better how a cancer behaves and which treatments may be most effective. These tests may include immunohistochemistry (to detect specific proteins in tumour cells) and molecular testing (to detect changes in DNA). Not all biomarkers are tested in every case.

Mismatch repair proteins (MMR)

Mismatch repair proteins help normal cells fix small mistakes that occur during DNA replication. The four most commonly tested proteins are MLH1, PMS2, MSH2, and MSH6, which work together in pairs.

Pathologists usually test MMR proteins using immunohistochemistry. Results are reported as either retained expression (normal) or loss of expression (abnormal).

Loss of one or more MMR proteins means the tumour is MMR-deficient. This is important because MMR-deficient tumours may respond well to immunotherapy. MMR testing is also used to identify patients who may have Lynch syndrome, a hereditary condition associated with an increased risk of several cancers, including endometrial cancer.

Estrogen receptor (ER) and progesterone receptor (PR)

ER and PR are proteins that allow tumour cells to respond to the hormones estrogen and progesterone. These markers are tested by immunohistochemistry and reported as positive or negative, sometimes with a percentage indicating how many tumour cells express the receptor.

Endometrial endometrioid carcinomas are often ER- and PR-positive, especially in low-grade tumours. Tumours that express these receptors generally have a better prognosis and may respond to hormone-based therapies in certain clinical settings.

p53

p53 is a tumour suppressor protein that helps control cell growth and repair damaged DNA. In most low-grade endometrial endometrioid carcinomas, p53 exhibits a wild-type pattern, meaning the protein behaves normally. This is reported as p53 wild type and is associated with more typical, less aggressive tumour behaviour.

An abnormal p53 result indicates that the TP53 gene is altered. This is usually reported as aberrant, mutant-type, or abnormal p53 expression. Tumours with abnormal p53 tend to behave more aggressively and may be treated similarly to serous carcinoma, even if they appear endometrioid under the microscope.

CTNNB1

CTNNB1 is a gene involved in cell signaling and growth. Mutations in CTNNB1 are commonly found in low-grade endometrial endometrioid carcinoma of the endometrium.

When present, CTNNB1 mutations may be associated with a higher risk of recurrence, even in early-stage disease. Results are usually reported as mutated or wild-type (normal).

KRAS

KRAS is a gene involved in pathways that regulate cell growth. Mutations in KRAS are found in a subset of endometrial endometrioid carcinomas.

These mutations may be associated with more aggressive tumour behaviour and may influence how the tumour responds to certain targeted treatments.

PIK3CA

PIK3CA regulates cell growth and survival. Mutations in this gene are common in endometrial endometrioid carcinoma.

PIK3CA mutations may influence tumour growth and, in some cases, help guide decisions about targeted therapies, particularly in advanced or recurrent disease.

POLE

POLE mutations occur in a small subset of endometrial endometrioid carcinomas. These tumours typically have many DNA mutations but are less aggressive.

Tumours with POLE mutations are associated with an excellent prognosis and a very low risk of recurrence, even when other high-risk features are present.

PTEN

PTEN is a tumour suppressor gene that helps regulate cell growth. Loss or mutation of PTEN is very common in endometrial endometrioid carcinoma and is often an early event in tumour development.

Although PTEN mutations are frequent, they are not usually used alone to predict prognosis or guide treatment decisions.

TCGA molecular subtypes

Many endometrial cancers can be grouped into four molecular subtypes, based on large genomic studies such as those from The Cancer Genome Atlas (TCGA). The biomarkers described above help place a tumour into one of these categories, which can provide important prognostic information.

• POLE-ultramutated tumours: These tumours have POLE mutations and are associated with an excellent prognosis, even when other features appear high risk.
• Mismatch repair–deficient (MMR-D): These tumours show loss of one or more MMR proteins. These tumours often have an intermediate prognosis and may respond well to immunotherapy.
• p53-abnormal (copy-number high): These tumours show abnormal p53 expression. These tumours tend to behave more aggressively and are often managed similarly to serous carcinoma.
• No specific molecular profile (NSMP): These tumours lack POLE mutations, retain MMR proteins, and show wild-type p53 expression. Many tumours in this group are ER- and PR-positive and have a more typical endometrioid behaviour, although other features (such as CTNNB1 mutations) can influence risk.

Understanding which molecular subtype a tumour belongs to helps doctors better estimate prognosis and choose the most appropriate treatment.

Other features to look for in your pathology report

Myometrial invasion

Myometrial invasion describes how deeply the tumor has grown into the muscle wall of the uterus.

The uterus is made up of an inner lining (the endometrium) and a thick outer muscle layer called the myometrium. When the tumor spreads from the lining into this muscle, it is called myometrial invasion.

Pathologists measure the depth of invasion in millimetres and often report it as a percentage of the total thickness of the myometrium. Invasion of less than 50% of the myometrial thickness is associated with a lower risk. Invasion of 50% or more is associated with a higher risk of spread to lymph nodes.

This measurement is critical because it directly affects the tumor stage.

Cervical stromal invasion

Cervical stromal invasion means the tumor has grown from the body of the uterus into the supportive tissue of the cervix.

The cervix is the lower part of the uterus that connects to the vagina. If the tumor involves only the surface lining of the cervix, this does not change the stage. However, if it invades the deeper cervical stroma, the stage increases.

This finding may influence the need for additional treatment such as radiation therapy.

Spread to the surrounding organs

In more advanced cases, the tumor may spread beyond the uterus to nearby structures such as the ovaries, fallopian tubes, vagina, bladder, bowel, or peritoneum (the lining of the abdominal cavity).

If tumor cells are identified in these structures, the pathologic stage increases. Spread beyond the uterus is associated with a higher risk of recurrence and often requires more intensive treatment.

Lymphatic and vascular invasion

Lymphatic and vascular invasion means tumor cells are seen inside small lymphatic channels or blood vessels.

Lymphatic vessels are part of the immune system and allow fluid to drain from tissues. Blood vessels carry blood throughout the body. When tumor cells enter these channels, they have a pathway to spread to lymph nodes or distant organs.

This finding does not mean the tumor has already spread, but it does increase the risk. Because of this, lymphatic and vascular invasion are considered high-risk features and may influence decisions about additional therapy.

Lymph nodes

Lymph nodes are small immune organs located in the pelvis and abdomen. They filter lymph fluid and are a common first site of spread for endometrial cancer.

During surgery, lymph nodes may be removed and examined under the microscope.

If no tumor cells are found, the nodes are described as negative (pN0).

If tumor cells are present, the nodes are described as positive, and the size of the tumor deposit is recorded:

• Isolated tumor cells measure 0.2 mm or less

• Micrometastases measure between 0.2 mm and 2 mm

• Macrometastases measure more than 2 mm

The number and location of positive lymph nodes determine the nodal stage (N stage). Lymph node involvement increases the overall stage and may lead to recommendations for chemotherapy or radiation therapy.

Margins

A margin refers to the edge of the tissue removed during surgery, such as a hysterectomy. After the surgery, pathologists examine the tissue margins under a microscope to check for any remaining cancer cells. In the case of endometrial endometrioid carcinoma, several specific margins are carefully evaluated:

1. Cervical margin: This is the edge where the uterus meets the cervix. Pathologists examine this margin to see if the cancer has spread into or beyond the cervix.
2. Vaginal cuff margin: If the top portion of the vagina is removed along with the uterus, the pathologist will check the vaginal cuff margin to ensure no cancer cells are present at the surgical edge.
3. Parametrial margin: This margin includes the tissue around the uterus, including ligaments and connective tissue. It is examined to see if cancer has spread into these areas.
4. Peritoneal margin: If the peritoneum (the lining of the abdominal cavity) is removed, it will be examined to check for cancer cells in this area.

If any of these margins contain cancer cells, it is referred to as a positive margin, which may mean that some tumour cells were left behind after surgery. A negative margin means no cancer cells were found at the edges, suggesting that the tumour was completely removed. Clear margins are important for reducing the risk of the cancer returning, and positive margins may lead to recommendations for additional treatments, such as radiation therapy.

Pathologic stage (pTNM)

​The pathologic stage for endometrial endometrioid adenocarcinoma is based on the TNM staging system, an internationally recognized system 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 submitted tissue and assign each part a number. In general, a higher number means a more advanced disease and a worse prognosis.

Tumour stage (pT) for endometrial endometrioid adenocarcinoma

Endometrial endometrioid adenocarcinoma is given a tumour stage between T1 and T4 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) for endometrial endometrioid adenocarcinoma

Based on examination of lymph nodes from the pelvis and abdomen, endometrial endometrioid carcinoma is staged from N0 to N2.

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

FIGO stage

The FIGO staging system, developed by the International Federation of Gynecology and Obstetrics, is a standardized method for classifying endometrial cancers based on their extent of spread. This system is important because it helps doctors determine the extent of the cancer, plan appropriate treatment, and estimate the prognosis (the likely disease outcome).

• Stage I: The cancer is confined to the uterus.
  • IA: The cancer is limited to the endometrium or has invaded less than halfway into the myometrium.
    Prognosis: Cancers in Stage IA have an excellent prognosis, with a high likelihood of being successfully treated through surgery alone.
  • IB: The cancer has invaded more than halfway into the myometrium.
    Prognosis: Although Stage IB is more advanced than Stage IA, it generally has a good prognosis, especially if treated promptly.
• Stage II: The cancer has spread from the uterus to the cervix but has not gone beyond the uterus.
  Prognosis: Stage II cancers are more likely to require additional treatments, such as radiation or chemotherapy, but many patients still have a favourable outcome with appropriate treatment.
• Stage III: The cancer has spread beyond the uterus but is still within the pelvis.
  • IIIA: The cancer has spread to the outer surface of the uterus or to nearby tissues.
  • IIIB: The cancer has spread to the vagina or the pelvic wall.
  • IIIC: The cancer has spread to the lymph nodes.
    Prognosis: Stage III cancers are more advanced and often require a combination of surgery, radiation, and chemotherapy. The prognosis is more guarded, but treatment can still be effective in many cases.
• Stage IV: The cancer has spread to distant organs, such as the bladder, bowel, or lungs.
  • IVA: The cancer has spread to nearby organs such as the bladder or rectum.
  • IVB: The cancer has spread to distant organs, such as the lungs or liver.
    Prognosis: Stage IV cancers are the most advanced and carry a more serious prognosis. Treatment at this stage is usually focused on managing symptoms and slowing disease progression.

Questions to ask your doctor

• What is my FIGO grade and stage?

• How deeply did the tumor invade the myometrium?

• Were lymph nodes involved?

• Was lymphovascular invasion present?

• What molecular subtype does my tumor belong to?

• Do my biomarker results affect treatment options?