Endometrial Serous Carcinoma: Understanding Your Pathology Report

by Jason Wasserman MD PhD FRCPC
March 4, 2026

---

Endometrial serous carcinoma is an aggressive type of cancer that starts in the endometrium, the inner lining of the uterus. It is considered a high-grade tumour, meaning it has a higher chance of spreading beyond the uterus compared to some other types of endometrial cancer.

Unlike endometrial endometrioid carcinoma, which is often linked to excess estrogen, endometrial serous carcinoma typically develops in people with low estrogen levels. It often arises in a background of thin or atrophic endometrium (the natural thinning of the uterine lining that occurs after menopause) and may be found in an endometrial polyp.

What are the symptoms of endometrial serous carcinoma?

The most common symptom is abnormal vaginal bleeding, especially bleeding after menopause. Some people also notice unusual vaginal discharge, which may be watery or blood-tinged. Other symptoms may include pelvic discomfort, pelvic pressure, or pain.

Because bleeding after menopause is not normal, it should always be evaluated.

What causes endometrial serous carcinoma?

The exact cause of endometrial serous carcinoma is not fully understood, but it is believed to be driven mainly by genetic changes in endometrial cells rather than hormonal factors. Unlike endometrial endometrioid carcinoma, serous carcinoma is typically not strongly linked to long-term exposure to estrogen.

Risk factors include older age, a history of breast cancer and/or tamoxifen use, and, in some cases, prior pelvic radiation therapy. The relative risk associated with obesity is lower than it is for endometrial endometrioid carcinoma. Some studies suggest a possible association with BRCA gene alterations in a subset of cases, although this is not present in most patients.

How is this diagnosis made?

The diagnosis of endometrial serous 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 often the ovaries, fallopian tubes, and lymph nodes. The removed tissue is carefully examined to determine tumor spread, depth of invasion, lymph node involvement, and other important features. This is especially important for serous carcinoma because this tumour can spread beyond the uterus even when the tumour in the uterus is small.

Microscopic features

Under the microscope, endometrial serous carcinoma most often shows papillary and/or glandular growth patterns. Papillary growth means the tumour forms finger-like projections, while glandular growth means the tumour forms irregular gland-like spaces. Some tumours also show solid growth, with tumour cells growing in sheets.

The tumour cells usually show marked nuclear pleomorphism. This means the nuclei (the parts of the cell that contain genetic material) are very large, irregular, and dark-staining. Mitotic figures (dividing cells) are often easy to see, reflecting a fast-growing tumour. Necrosis (tumour cell death) may also be present. Psammomatous calcifications (small, round calcium deposits) can be seen in some cases.

A related finding, serous endometrial intraepithelial carcinoma, may be present. This refers to malignant cells replacing the surface lining of the endometrium without clear invasion. Even without definite invasion, these cells can shed from the surface and spread to extrauterine sites, so this finding is treated as potentially metastatic.

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 serous carcinoma from other types of uterine cancer.

Endometrial serous carcinoma almost always shows abnormal (mutation-pattern) p53 immunoreactivity. p53 results are typically reported as either diffuse strong staining in most tumour cells or complete absence of staining in tumour cells, both of which support an underlying TP53 mutation. Serous carcinoma also typically shows diffuse p16 immunoreactivity.

Additional markers may be used in some cases. For example, IMP3 and HMGA2 are often diffusely positive in serous carcinoma, and these results can support the diagnosis when the microscopic features are difficult to interpret. In contrast to high-grade endometrial endometrioid carcinoma, loss of PTEN, ARID1A, β-catenin (CTNNB1 pathway), or mismatch repair proteins is uncommon in true serous carcinoma.

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

FIGO grade

The FIGO grade system used for endometrial endometrioid carcinoma is based largely on the amount of solid growth. Endometrial serous carcinoma is considered high grade by definition, so it is not typically assigned FIGO grades 1, 2, or 3.

For this tumour type, the most important prognostic and treatment information is usually the stage and the presence of specific high-risk features described elsewhere in the pathology report.

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).

In endometrial serous carcinoma, loss of mismatch repair proteins is uncommon. When loss of one or more mismatch repair proteins is present, it may suggest that the tumour is not a “pure” serous carcinoma, has mixed features, or should be considered a different tumour type. If loss of mismatch repair proteins is identified, it may also be relevant to immunotherapy and may prompt consideration of Lynch syndrome testing in the appropriate clinical setting.

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.

In endometrial serous carcinoma, ER and PR staining are variable, and many tumours are negative or only weakly positive. This pattern can help distinguish serous carcinoma from low-grade endometrial endometrioid carcinoma, which is often strongly ER- and PR-positive.

p53

p53 is a tumour suppressor protein that helps control cell growth and repair damaged DNA. In endometrial serous carcinoma, p53 is usually abnormal due to a TP53 mutation. This is typically reported as aberrant, mutant-type, or abnormal p53 expression.

Abnormal p53 expression is an important feature because it supports the diagnosis of serous carcinoma and is associated with more aggressive tumour behaviour.

HER2 (ERBB2)

HER2 is a protein that promotes cell growth. Some endometrial serous carcinomas produce too much HER2 due to amplification of the ERBB2 (HER2) gene.

HER2 is usually tested using immunohistochemistry, and results are commonly reported as 0, 1+, 2+, or 3+. A result of 3+ is considered positive. A result of 2+ is considered equivocal and may be followed by additional testing to confirm gene amplification.

HER2 is important because patients with recurrent or advanced-stage HER2-positive endometrial serous carcinoma may benefit from HER2-targeted therapy added to chemotherapy.

CTNNB1

CTNNB1 is a gene involved in cell signaling and growth. Mutations in CTNNB1 are common in low-grade endometrial endometrioid carcinoma but are uncommon in true endometrial serous carcinoma.

When a CTNNB1 mutation is identified in a tumour diagnosed as serous carcinoma, it may raise the possibility of mixed tumour features or an alternative diagnosis, depending on the microscopic findings and other biomarkers.

KRAS

KRAS is a gene involved in pathways that regulate cell growth. KRAS mutations are more often associated with endometrial endometrioid carcinoma than serous carcinoma, but they can be identified in a subset of serous carcinomas as part of broader molecular profiling.

When present, KRAS mutations are reported as mutated or wild-type (normal). These results are most relevant in advanced disease when molecular profiling is being used to explore treatment options.

PIK3CA

PIK3CA regulates cell growth and survival. Alterations in this gene are observed in endometrial serous carcinoma.

PIK3CA mutations are reported as mutated or wild-type (normal). In some cases, these results may be considered when evaluating targeted therapy options, particularly in advanced or recurrent disease.

POLE

POLE mutations occur in a small subset of endometrial cancers and are associated with an excellent prognosis. POLE mutations are uncommon in true serous carcinoma, but they can be seen in tumours with serous-like features.

If a POLE mutation is identified, it may influence how risk is assessed and how aggressively the tumour is treated.

PTEN

PTEN is a tumour suppressor gene that helps regulate cell growth. PTEN loss or mutation is very common in endometrial endometrioid carcinoma, but is uncommon in true endometrial serous carcinoma.

If PTEN loss is identified in a tumour with serous features, the pathologist may consider whether the tumour has mixed features or whether another tumour type is present.

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.

Most endometrial serous carcinomas fall into the p53-abnormal (copy-number high) molecular subtype. This group is associated with TP53 mutation, genomic instability, and more aggressive behaviour.

POLE-ultramutated tumours are uncommon in serous carcinoma but are associated with an excellent prognosis. Mismatch repair–deficient tumours are also uncommon in true serous carcinoma. The no specific molecular profile (NSMP) category is not typical for serous carcinoma.

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.

In endometrial serous carcinoma, myometrial invasion remains important for staging. Still, it is also important to know that serous carcinoma can spread beyond the uterus even when invasion is minimal or not identified.

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.

Invasion of surrounding organs or tissues

The uterus is closely connected to several other organs and tissues, such as the ovaries, fallopian tubes, vagina, bladder, and rectum. The term “adnexa” refers to the fallopian tubes, ovaries, and ligaments directly linked to the uterus.

As a tumour grows, it can spread into any of these organs or tissues. In such cases, some parts of these organs or tissues may have to be removed along with the uterus. A pathologist will thoroughly examine these organs or tissues for tumour cells, and the findings will be detailed in your pathology report.

In endometrial serous carcinoma, spread to peritoneal sites and the omentum is relatively common compared to endometrial endometrioid carcinoma. The presence of tumour cells in other organs or tissues raises the pathologic tumour stage and is linked with a poorer prognosis.

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.

Pathologists look for tumour cells inside these channels under the microscope. This finding does not mean the tumour has already spread, but it does increase the risk of spread. Because of this, lymphatic and vascular invasion is considered a high-risk feature and may lead your doctor to recommend additional treatment after surgery.

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 serous 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.

Lymph nodes

Lymph nodes are small, bean-shaped structures in the lymphatic system that help fight infection and remove waste from the body. Lymph nodes contain immune cells that filter lymph fluid as it travels through lymphatic vessels and help trap harmful substances such as bacteria or cancer cells.

In endometrial serous carcinoma, lymph nodes are carefully examined because this type of cancer has a higher risk of spreading beyond the uterus. During surgery, lymph nodes from the pelvis and sometimes the abdomen may be removed and sent to a pathologist. Each lymph node is examined under the microscope to look for metastatic cancer, meaning cancer cells that have spread from the uterus.

Examining lymph nodes is important for determining the stage of the cancer, guiding treatment decisions, and estimating prognosis. If cancer cells are found in the lymph nodes, your doctor may recommend additional treatment such as chemotherapy, radiation therapy, or targeted therapy.

Isolated tumour cells (ITCs)

Pathologists use the term “isolated tumour cells” to describe a group of tumour cells measuring 0.2 mm or less and found in a lymph node. If only isolated tumour cells are found in all the lymph nodes examined, the pathologic nodal stage is pN1mi.

Micrometastasis

Micrometastasis is a group of tumour cells measuring 0.2-2 mm found in a lymph node. If only micrometastases are found in all the lymph nodes examined, the pathologic nodal stage is pN1mi.

Macrometastasis

Macrometastasis is a group of tumour cells measuring more than 2 mm in a lymph node. Macrometastases are associated with a worse prognosis and often lead to recommendations for additional treatment.

Pathologic stage (pTNM)

The pathologic stage for endometrial serous carcinoma 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 serous carcinoma

Endometrial serous carcinoma 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 serous carcinoma

Based on examination of lymph nodes from the pelvis and abdomen, endometrial serous 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 stage?

• Was the tumour confined to the uterus or had it spread beyond the uterus?

• How deeply did the tumor invade the myometrium?

• Were lymph nodes involved?

• Was lymphatic and vascular invasion present?

• Was p53 abnormal, and was HER2 testing performed?

• Do my biomarker results affect treatment options?