Endometrial Serous Carcinoma: Understanding Your Pathology Report

Section Editor: Kianoosh Keyhanian MD FRCPC
September 3, 2026

Endometrial serous carcinoma is an uncommon and fast-growing cancer that starts in the endometrium, the inner lining of the uterus. It is high-grade by definition, meaning it carries a higher risk of spreading beyond the uterus than most endometrial cancers.

It accounts for somewhere between 3 and 10 out of every 100 endometrial cancers, but for roughly 40 out of every 100 deaths from endometrial cancer. That gap between how often it occurs and how much harm it causes is the reason it is treated seriously even when it appears confined to the uterus.

This cancer also develops differently from the common type. Endometrioid carcinoma is driven by excess estrogen. Serous carcinoma typically arises in people with low estrogen levels, often in a thin atrophic endometrium after menopause, and it is sometimes found within an endometrial polyp.

What causes endometrial serous carcinoma?

The cause is not fully understood. Unlike endometrioid carcinoma, this cancer appears to be driven mainly by genetic changes within the cells of the lining rather than by hormones. Nearly all of these tumors carry a change in the TP53 gene, which normally helps control cell growth and repair damaged DNA.

Recognized risk factors include older age, a history of breast cancer or of tamoxifen use, and, in some cases, previous pelvic radiation therapy. Excess body weight raises the risk far less here than it does for endometrioid carcinoma. Some studies have found an association with BRCA gene changes in a minority of cases, though most people with this diagnosis do not have one.

What are the symptoms?

Abnormal vaginal bleeding — The most common symptom, particularly bleeding after menopause. Any bleeding after menopause should be assessed promptly.
Unusual vaginal discharge — May be watery or blood-tinged.
Pelvic discomfort, pressure, or pain — Less common than bleeding.

How is the diagnosis made?

The process usually begins with an endometrial biopsy, in which a small sample of the lining is removed and examined under the microscope by a pathologist.

Surgery follows, removing the uterus and usually the ovaries, fallopian tubes, and lymph nodes. Tissue from the omentum, the apron of fatty tissue hanging over the bowel, and samples from the lining of the abdomen are often taken as well.

That extra sampling is not routine caution. Serous carcinoma can spread beyond the uterus even when the tumor inside the uterus is small and has barely invaded the muscle wall. Looking beyond the uterus establishes the true extent of disease.

What does endometrial serous carcinoma look like under the microscope?

Endometrial serous carcinoma most often grows in papillary and glandular patterns, and some tumors also grow in solid sheets.

Papillary growth — The tumor forms finger-like projections.
Glandular growth — The tumor forms irregular gland-like spaces.
Marked nuclear abnormality — The nuclei are large, irregular, and dark-staining, and they vary considerably from cell to cell. This is one of the most characteristic features.
Frequent cell division — Dividing cells, called mitotic figures, are easy to find.
Necrosis — Areas of dead tumor tissue may be present.
Psammoma bodies — Small round calcium deposits are seen in some tumors.

What is serous endometrial intraepithelial carcinoma?

Your report may describe serous endometrial intraepithelial carcinoma, sometimes shortened to serous EIC. This means the cancer cells have replaced the surface lining of the endometrium without clearly growing into the tissue beneath.

The name sounds reassuring, and in most parts of the body, a cancer confined to a surface would be. Here it is not, and this is the exception worth understanding. Because the lining faces the open cavity of the uterus, these cells can shed from the surface, travel out through the fallopian tubes, and settle elsewhere in the abdomen. Serous EIC is therefore assessed and staged as though it may have already spread, and full surgical staging is performed even when no invasion is found.

Immunohistochemistry

Immunohistochemistry is a laboratory test that uses antibodies to detect specific proteins inside cells. It confirms the diagnosis and separates serous carcinoma from other uterine cancers.

p53. Almost always abnormal. The result is reported as either strong staining in nearly all tumor cells or complete absence of staining, and both patterns indicate an underlying TP53 mutation. This is the single most useful marker for this diagnosis.
p16. Usually positive throughout the tumor.
IMP3 and HMGA2. Often positive, and useful when the microscopic appearance is difficult to interpret.
Estrogen receptor and progesterone receptor. Variable, and often negative or only weakly positive. Strong staining for both would be more typical of a low-grade endometrioid carcinoma.

One pattern is worth knowing about. Loss of PTEN or ARID1A, changes in the CTNNB1 pathway, and loss of mismatch repair proteins are all uncommon in a true serous carcinoma. When one of these turns up, the pathologist reconsiders whether the tumor is a serous carcinoma at all, whether it has mixed features, or whether a different diagnosis fits better.

Grade

The FIGO grading system used for endometrioid carcinoma is based largely on how much of the tumor grows in solid sheets. Serous carcinoma is considered high grade by definition, so it is not assigned grades 1, 2, or 3.

For this tumor, the stage and the biomarker results carry the useful information rather than a grade.

Biomarkers

Biomarkers are tests performed on tumor tissue to understand how a cancer is likely to behave and which treatments may work.

HER2

HER2 is a protein on the surface of cells that drives growth. About 25 to 35 out of every 100 endometrial serous carcinomas produce too much of it, usually because the gene has been copied too many times.

Testing is done by immunohistochemistry, with results reported as 0, 1+, 2+, or 3+. A result of 3+ is positive. A result of 2+ is equivocal and is usually followed by a test that directly counts gene copies.

This matters because HER2-targeted treatment can be added to chemotherapy for advanced or recurrent HER2-positive disease, and a randomized trial found that doing so improved outcomes. Newer HER2-directed drugs have also shown activity in this setting. One practical difference from breast cancer is that HER2 is often unevenly distributed across a uterine serous carcinoma, so more than one area may need to be tested.

p53

p53 is the protein made by the TP53 gene. In serous carcinoma, it is abnormal in nearly every case and is reported as aberrant, mutant-type, or abnormal expression.

This result supports the diagnosis, and it places the tumor in the least favorable molecular group. For tumors confined to the uterus, it also raises the stage under the current staging system.

Mismatch repair proteins

Mismatch repair proteins fix small errors that occur during DNA replication. The four tested are MLH1, PMS2, MSH2, and MSH6. Results are reported as retained or lost.

Loss is uncommon in a true serous carcinoma. When it does occur, it prompts the pathologist to reconsider the diagnosis. It is also clinically useful because a mismatch repair-deficient tumor may respond to immunotherapy, and the finding may prompt testing for Lynch syndrome.

POLE

POLE is a gene involved in copying DNA accurately. Tumors with a POLE mutation behave far better than their appearance suggests.

POLE mutations are uncommon in true serous carcinoma but do occur in tumors with serous-like features. When one is found, it changes the risk assessment considerably and lowers the stage under the current staging system.

Other genetic changes

Broader molecular profiling may identify changes in PIK3CA, KRAS, CTNNB1, PTEN, and other genes. As noted above, changes in CTNNB1 and PTEN are unusual here and raise a question about the diagnosis rather than guiding treatment.

PIK3CA changes are relevant in one specific way: they have been linked to resistance to HER2-targeted treatment in this tumor type. Otherwise, these results matter mainly in advanced disease, where they may open up a clinical trial.

Molecular subtypes

Large genomic studies group endometrial cancers into four molecular subtypes. Serous carcinoma sits almost entirely in one of them.

p53 abnormal — Where nearly all serous carcinomas fall. This group carries widespread genetic instability and the least favorable outlook.
POLE ultramutated — Uncommon here, and the most favorable group when present.
Mismatch repair deficient — Uncommon, and raises a question about the diagnosis.
No specific molecular profile — Not typical of serous carcinoma.

What other findings will be described in the report?

Myometrial invasion

The myometrium is the thick muscular wall of the uterus. Myometrial invasion means the tumor has grown from the lining into that wall. The pathologist measures the depth and usually reports it as a percentage of the full thickness.

For staging, what matters is whether the tumor invades the muscle at all, since any invasion places this tumor at stage IIC under the current system. Even so, a small or absent measurement is not on its own reassuring here, because serous carcinoma can spread beyond the uterus with minimal invasion.

Cervical stromal invasion

Cervical stromal invasion means the tumor has grown from the body of the uterus into the cervix’s supporting tissue. Involvement of only the surface lining of the cervix does not count. This finding may influence whether radiation therapy is recommended.

Involvement of other organs and tissues

The uterus sits against the ovaries, fallopian tubes, vagina, bladder, and rectum. The fallopian tubes, ovaries, and attached ligaments are together called the adnexa.

Spread to the lining of the abdomen and to the omentum is considerably more common in serous carcinoma than in endometrioid carcinoma. This is why surgeons sample those tissues during surgery. Involvement of any of these sites raises the stage.

Lymphovascular invasion

Lymphovascular invasion means tumor cells have been seen inside small lymphatic channels or blood vessels. These pathways allow cells to reach lymph nodes or distant organs.

Your report will describe it as absent, focal, or substantial. It is common in this tumor type and frequently leads to a recommendation for additional treatment.

Margins

A margin is the edge of the tissue removed during surgery. The pathologist examines the margins for tumor cells. Depending on the operation, these may include the cervical margin, the vaginal cuff margin, the tissue on either side of the uterus, and the peritoneal surface.

A positive margin means tumor cells reach the cut edge and some cancer may remain. A negative margin means no tumor cells were found at the edges.

Lymph nodes

Lymph nodes are small immune organs that filter fluid draining from tissues. Cancer cells can travel to them and form a metastasis.

Nodes from the pelvis, and often from higher in the abdomen, are removed for this diagnosis and examined individually. The risk of nodal spread is higher than for most endometrial cancers. Your report will state how many were examined and how many contained cancer. When cancer is found, the size of the largest deposit determines the nodal stage.

Isolated tumor cells — A group measuring 0.2 mm or less. These are recorded as N0(i+) and are not counted as node-positive disease.
Micrometastasis — A deposit measuring more than 0.2 mm and up to 2 mm. This gives a nodal stage of N1mi or N2mi, depending on which nodes are involved.
Macrometastasis — A deposit measuring more than 2 mm. This gives a nodal stage of N1a or N2a and is associated with a less favorable outlook.

Pathologic stage

The pathologic stage uses the TNM system from the American Joint Committee on Cancer, which describes the tumor (T), the lymph nodes (N), and distant spread (M).

Tumor stage (pT):

T1 — The tumor involves only the body of the uterus.
T2 — The tumor has grown into the supporting tissue of the cervix.
T3 — The tumor has reached the outer surface of the uterus, or has spread to the fallopian tubes, ovaries, or vagina.
T4 — The tumor has grown into the lining of the bladder or the bowel.

Nodal stage (pN): N0 means no tumor cells in the nodes examined. N0(i+) means only isolated tumor cells. N1mi and N1a describe involvement of pelvic nodes. N2mi and N2a describe involvement of nodes higher in the abdomen. The “mi” categories are used for deposits of 2 mm or less. NX means no nodes were examined.

Metastatic stage (pM): M1 means the cancer has spread to a distant site. This can only be assigned when tissue from that site has been examined, so most reports list it as MX and use imaging instead.

FIGO stage

The International Federation of Gynecology and Obstetrics substantially revised the staging system in 2023, and the change matters for this diagnosis.

The current system divides endometrial cancers into two groups according to how they tend to behave. Serous carcinoma sits in the higher-risk group, alongside clear cell carcinoma, carcinosarcoma, undifferentiated carcinoma, and high-grade endometrioid carcinoma. Tumors in that group are staged differently from the rest.

Stage IC — The tumor is confined to the lining, with no growth into the muscular wall.
Stage IIC — The tumor has grown into the muscular wall to any depth. Under the previous system, this would have been stage IA or IB depending on the depth. Many patients are therefore assigned a higher stage now than they would have been before 2023.
Stage IIIA — The tumor involves the outer surface of the uterus, or the ovaries or fallopian tubes.
Stage IIIB — The tumor involves the vagina or the tissue on either side of the uterus.
Stage IIIC — The tumor has spread to lymph nodes. IIIC1 is pelvic nodes,s and IIIC2 is nodes higher in the abdomen.
Stage IVA — The tumor has grown into the lining of the bladder or bowel.
Stage IVB — The tumor has spread within the abdomen beyond the pelvis.
Stage IVC — The tumor has spread to distant organs such as the lungs or liver.

Molecular results can change the stage for tumors confined to the uterus. An abnormal p53 result raises it to IICmp53abn, which applies to nearly all serous carcinomas. A POLE mutation lowers it to IAmPOLEmut, though this is uncommon here. Molecular results do not change stage III or stage IV disease.

Your report or your oncologist may use a stage that does not match what you have read elsewhere. The difference between the 2009 and 2023 systems is a likely explanation, and it is worth asking which one was used.

What is the prognosis?

Stage is the strongest factor, and this cancer is more often advanced when found than the common type. Reported five-year survival across all stages is under %00. For disease confined to the uterus, the figure is around 70 out of 100, which is better but still lower than for a stage I endometrioid carcinoma.

Recurrence tends to appear outside the pelvis, in the abdomen or at distant sites, rather than locally. That pattern shapes treatment, since chemotherapy addresses distant risk while radiation addresses local risk.

Published figures come from groups of patients and cannot tell you what will happen in your case. They do not account for your stage, your surgery, your biomarker results, or your treatment. Your own team is far better placed to discuss what the outlook means for you.

How is endometrial serous carcinoma treated?

Surgery — Removal of the uterus, cervix, fallopian tubes, and ovaries, with lymph node assessment and sampling of the omentum and the lining of the abdomen. Complete surgical staging is standard.
Chemotherapy — Recommended for most people, including many whose tumor appeared confined to the uterus. Carboplatin and paclitaxel are the usual regimen.
HER2-targeted treatment — Added to chemotherapy for advanced or recurrent disease when the tumor is HER2 positive.
Radiation therapy — Used in some situations, including vaginal brachytherapy to reduce the risk of the cancer returning at the top of the vagina.
Immunotherapy — An option for the small number of tumors that are mismatch repair deficient, when disease is advanced or has returned.

Hormone-blocking treatment is generally not useful here, because these tumors are usually negative or only weakly positive for hormone receptors. Because this diagnosis is uncommon and treatment involves several modalities, care at a center experienced with gynecologic cancers is generally recommended.

Questions to ask your doctor

What stage is my cancer, and was the 2023 FIGO system used?
Was HER2 testing performed, and what was the result?
If HER2 was equivocal, will further testing be done?
Was p53 abnormal?
Did my report mention serous endometrial intraepithelial carcinoma, and what does that mean for me?
Were the omentum and the lining of the abdomen sampled?
Did the tumor grow into the muscle wall of the uterus?
Was lymphovascular invasion present, and was it focal or substantial?
Were lymph nodes examined, and did any contain cancer?
Do you recommend chemotherapy, and would radiation add anything?
Was mismatch repair testing done, and should I be tested for Lynch syndrome?
Should I be referred to a gynecologic oncology center?
What will follow-up involve, and how often?