High Grade Serous Carcinoma of the Ovary: Understanding Your Pathology Report

by Jason Wasserman MD PhD FRCPC
March 5, 2026

---

High-grade serous carcinoma of the ovary is the most common type of ovarian cancer. It develops from epithelial cells that resemble the cells lining the fallopian tube.

This tumour accounts for about 70% of ovarian carcinomas. Many cases are diagnosed after the cancer has already spread within the abdomen. For this reason, high-grade serous carcinoma is considered an aggressive tumour.

Even though this tumour is aggressive, it often responds well to chemotherapy, especially at the start of treatment. Treatment decisions and prognosis depend largely on the stage of the tumour, how much tumour can be removed at surgery, and specific biomarker results found in the tumour cells.

What are the symptoms of high-grade serous carcinoma of the ovary?

The symptoms of high-grade serous carcinoma are often nonspecific and may develop gradually over time.

Common symptoms include abdominal swelling or bloating, pelvic or abdominal pain, a feeling of fullness after eating small amounts of food, changes in bowel habits, and urinary frequency or urgency. Some patients also experience fatigue or unexplained weight loss.

A blood test called CA125 is elevated in most patients with this cancer. However, CA125 is not specific for ovarian cancer and can be elevated in other conditions. For this reason, CA125 is most useful for monitoring disease over time rather than for making the diagnosis on its own.

What causes high-grade serous carcinoma of the ovary?

The exact cause is not fully understood. Most high-grade serous carcinomas are believed to begin in the fimbria of the fallopian tube, which is the part of the tube closest to the ovary. Tumour cells can then spread to the ovary and to surfaces inside the abdomen.

Risk factors include increasing age and a family history of ovarian or breast cancer. Some cases occur in people with inherited mutations in genes involved in DNA repair, most importantly BRCA1 or BRCA2.

Protective factors include pregnancy, breastfeeding, and use of oral contraceptives.

How is this diagnosis made?

The diagnosis of high-grade serous carcinoma usually begins when a pelvic mass or abdominal abnormality is detected by imaging or during surgery.

The tumour is removed and examined under the microscope by a pathologist. The pathologist evaluates the appearance of the tumour cells and their growth pattern to determine the type of ovarian cancer.

If surgery is performed, the pathologist also examines other tissues removed during the operation, including the fallopian tubes, uterus, lymph nodes, omentum, and other abdominal tissues. This examination helps determine how far the tumour has spread and is essential for staging.

Microscopic features

Under the microscope, high-grade serous carcinoma can show several growth patterns, including papillary (finger-like projections), solid sheets of cells, glands, cribriform growth, or slit-like spaces.

The tumour cells show marked nuclear atypia, with nuclei that vary greatly in size and shape and appear very abnormal. Mitotic figures, which represent dividing cells, are numerous. Areas of tumour necrosis are common, and multinucleated tumour cells may be present.

Some tumours show “SET” patterns (solid, endometrioid-like, and transitional-like patterns). Tumours with these patterns are sometimes associated with defects in DNA repair.

Immunohistochemistry

Immunohistochemistry is a laboratory test that uses antibodies to detect specific proteins inside tumour cells. These tests help confirm the diagnosis and distinguish high-grade serous carcinoma from other types of ovarian cancer.

Most high-grade serous carcinomas show diffuse nuclear staining for WT1 and PAX8, supporting Müllerian origin.

Most tumours show abnormal p53 staining, reflecting TP53 gene mutation. Abnormal p53 staining may appear as strong staining in most tumour cells or a complete absence of staining.

Many tumours also show strong p16 staining and often express CK7, CA125, and the estrogen receptor (ER).

Biomarkers

Biomarker testing looks for specific proteins or DNA changes in tumour cells. These results help doctors estimate prognosis and choose the most effective treatments. In high-grade serous carcinoma, the most important biomarkers relate to the tumour’s ability to repair DNA damage.

BRCA1 and BRCA2

BRCA1 and BRCA2 are genes involved in repairing damaged DNA. Some people are born with a mutation in one of these genes (called a germline mutation). Tumours can also acquire BRCA mutations later in life (called a somatic mutation).

BRCA testing may be performed on blood or saliva (to look for inherited mutations) and/or on tumour tissue (to look for acquired tumour mutations). Results are usually reported as a pathogenic mutation detected or no mutation detected, and the report may specify whether the mutation is germline or somatic.

These results matter because tumours with BRCA mutations often respond very well to platinum-based chemotherapy and may be eligible for PARP inhibitor therapy, which targets tumours with DNA repair defects.

Homologous recombination deficiency (HRD)

Homologous recombination is one of the main ways cells repair serious DNA damage. A tumour is described as homologous recombination–deficient (HRD-positive) when it cannot repair this type of damage properly.

HRD testing is usually performed on tumour tissue. Depending on the laboratory, results may be reported as HRD-positive or HRD-negative, or as a numerical HRD score with a threshold used to classify the tumour. Some reports also describe the underlying cause, such as a BRCA mutation, BRCA1 promoter methylation, or other alterations in DNA repair genes.

HRD results are important because HRD-positive tumours are often more sensitive to platinum chemotherapy and are more likely to benefit from PARP inhibitor maintenance therapy after chemotherapy. HRD-negative tumours may still be treated with PARP inhibitors in some settings, but the expected benefit is usually smaller.

p53

p53 is a protein that helps control cell growth and repair DNA damage. In high-grade serous carcinoma, the TP53 gene is altered in almost all tumours.

p53 is usually assessed by immunohistochemistry as either wild-type (normal pattern) or mutant-type (abnormal pattern). Abnormal patterns include strong diffuse staining, complete absence of staining with an internal control present, or, less commonly, cytoplasmic staining.

In high-grade serous carcinoma, abnormal p53 staining supports the diagnosis and reflects the tumour’s underlying biology.

Mismatch repair proteins (MMR)

Mismatch repair proteins help fix small errors that occur during DNA replication. The four most commonly tested proteins are MLH1, PMS2, MSH2, and MSH6.

Results are reported as retained (normal) expression or loss (abnormal) expression, sometimes with additional detail such as subclonal loss.

Mismatch repair deficiency is uncommon in high-grade serous carcinoma, but when present, it may suggest a different tumour type or mixed features. If mismatch repair deficiency is identified, immunotherapy may be considered in advanced disease.

PD-L1

PD-L1 is a protein that can help tumour cells avoid detection by the immune system.

PD-L1 is tested using immunohistochemistry and is often reported as a Combined Positive Score (CPS). A CPS of 1 or higher is considered positive in many reporting systems.

In ovarian cancer, PD-L1 results may be used along with other clinical factors when considering immunotherapy, particularly in advanced or recurrent disease.

Folate receptor alpha (FOLR1)

Folate receptor alpha is a protein that helps transport folate into cells. Some ovarian cancers produce high levels of this protein.

Testing is performed using immunohistochemistry. Results are commonly reported as positive or negative based on the percentage of tumour cells with membrane staining and the strength of staining. A commonly used definition of positivity is at least 75% of viable tumour cells exhibiting moderate-to-strong membrane staining.

FOLR1 is important because patients with FOLR1-positive ovarian cancer may be eligible for targeted therapy with mirvetuximab soravtansine.

Other features to look for in your pathology report

Tumor spread

High-grade serous carcinoma commonly spreads within the abdomen. Tumour cells may involve the peritoneum (the lining of the abdomen), omentum, bowel surfaces, diaphragm, and other organs.

Because spread beyond the ovary is common at diagnosis, the pathology report often includes information from multiple sites to determine the stage.

Intact versus ruptured ovary

Whether the ovarian capsule is intact or ruptured is important for staging.

If the tumour is confined to the ovary and the capsule is intact with no tumour on the surface, the cancer may be at an early stage. If the capsule is ruptured, tumour is present on the surface, or tumour cells are found outside the ovary, the stage may be higher.

Lymphatic and vascular invasion

Lymphatic and vascular invasion means tumour cells are seen inside small lymphatic channels or blood vessels. This finding increases the risk that tumour cells may spread to lymph nodes or distant organs.

Lymph nodes

Lymph nodes are small, bean-shaped structures in the lymphatic system. They help filter harmful substances from the body and play an important role in the immune system.

In ovarian cancer surgery, lymph nodes from the pelvis and abdomen may be removed and examined under the microscope. These are called regional lymph nodes. They include pelvic lymph nodes (such as obturator, internal iliac, external iliac, common iliac, and sacral nodes) and para-aortic lymph nodes.

If tumour cells are found in these lymph nodes, the cancer is considered to have spread beyond the ovary, and the tumour stage increases. Lymph node involvement may also influence treatment decisions, such as the use of chemotherapy or other systemic therapies.

When tumour cells are found in lymph nodes, the pathology report often describes the size of the tumour deposits. The size helps doctors determine the extent of lymph node involvement.

Isolated tumour cells (ITCs)

These are very small clusters of tumour cells measuring 0.2 mm or less. When only isolated tumour cells are present, the lymph nodes are often reported as N0(i+), meaning that only very small deposits of tumour cells were found.

Small lymph node metastases

These tumour deposits measure more than 0.2 mm but 10 mm or less. These are considered true lymph node metastases, indicating that the cancer has spread to the lymph nodes.

Large lymph node metastases

These tumour deposits measure more than 10 mm. Larger tumour deposits generally indicate greater tumour involvement of the lymph node.

Your pathology report may also describe:

• The number of lymph nodes examined.

• The number of lymph nodes containing tumour cells.

• The location of the involved lymph nodes.

• The size of the largest tumour deposit.

These findings are important because they help determine the pathologic stage of the tumour, which guides treatment decisions and helps estimate prognosis.

How do doctors stage ovarian cancer?

Staging describes how far a cancer has spread in the body. For ovarian cancer, two main systems are used: the TNM and FIGO systems. Both are internationally accepted and provide important information about prognosis (the expected outcome) and treatment planning.

The TNM system

The TNM system was developed by the American Joint Committee on Cancer (AJCC). It looks at three main factors:

• T (tumour): Describes the size of the tumour and how far it has spread in or around the ovary or fallopian tube.

• N (lymph nodes): Describes whether cancer cells have spread to nearby lymph nodes.

• M (metastasis): Describes whether cancer has spread to distant parts of the body.

Breakdown of the T stage:

• T1: The tumour is limited to one or both ovaries or fallopian tubes.

  • T1a: Tumour is inside one ovary or fallopian tube, with the outer surface intact and no cancer cells in fluid taken from the abdomen.

  • T1b: Tumour is inside both ovaries or fallopian tubes, but the outer surfaces are intact, and no cancer cells are found in the fluid.

  • T1c: The tumour is limited to one or both ovaries or tubes, but there has been a rupture, tumour on the outer surface, or cancer cells found in abdominal fluid.

• T2: The tumour has grown into tissues in the pelvis, such as the uterus or bladder.

  • T2a: Spread to the uterus or other fallopian tube or ovary.

  • T2b: Spread to other pelvic tissues.

• T3: The tumour has spread beyond the pelvis into the abdomen or to regional lymph nodes.

  • T3a: Cancer cells are found microscopically outside the pelvis or in nearby lymph nodes.

  • T3b: Visible tumour deposits up to 2 cm outside the pelvis or in nearby lymph nodes.

  • T3c: Visible tumour deposits larger than 2 cm outside the pelvis or involving the capsule of the liver or spleen (without entering the organ itself).

Breakdown of the N stage:

• N0: No cancer cells are seen in regional lymph nodes.

• N0(i+): Only isolated tumour cells smaller than 0.2 mm are seen in the lymph nodes.

• N1: Cancer cells are found in regional lymph nodes.

  • N1a: Deposits up to 10 mm.

  • N1b: Deposits larger than 10 mm.

The FIGO system

The FIGO (International Federation of Gynecology and Obstetrics) system is specifically designed for gynecologic cancers like ovarian cancer. It uses similar criteria to the TNM system but is grouped into broader stages that are easier to interpret clinically.

Breakdown of FIGO stages:

• Stage I: Cancer is limited to the ovaries or fallopian tubes.

  • IA: In one ovary or fallopian tube only.

  • IB: In both ovaries or fallopian tubes.

  • IC: Cancer is still limited to the ovaries or tubes, but there has been a rupture, tumour on the surface, or cancer cells found in fluid.

• Stage II: Cancer involves one or both ovaries or tubes with spread to pelvic organs such as the uterus, bladder, or rectum.

  • IIA: Spread to the uterus or other ovary/tube.

  • IIB: Spread to other pelvic tissues.

• Stage III: Cancer has spread outside the pelvis into the abdominal cavity or to regional lymph nodes.

  • IIIA1: Cancer in lymph nodes only.

  • IIIA2: Microscopic spread outside the pelvis.

  • IIIB: Visible spread outside the pelvis up to 2 cm.

  • IIIC: Visible spread larger than 2 cm or spread to the capsule of the liver or spleen.

• Stage IV: Cancer has spread to distant organs outside the abdomen.

  • IVA: Cancer cells are found in the fluid around the lungs.

  • IVB: Cancer has spread to organs such as the liver, spleen, or lymph nodes outside the abdomen.

Why staging is important

Both TNM and FIGO staging systems provide doctors with essential information about how far the cancer has spread. This helps guide treatment decisions, such as whether surgery alone is sufficient or whether chemotherapy or other treatments are needed.

Staging also helps predict prognosis. Early-stage disease (stage I) has a much better survival rate compared to advanced-stage disease (stage III or IV). By using staging information, doctors can personalize care and discuss treatment options and expectations with patients.

Questions to ask your doctor

• What stage is my ovarian cancer?

• Has the tumour spread beyond the ovary?

• Were lymph nodes involved?

• Was BRCA testing performed, and were the results germline or somatic?

• Was HRD testing performed, and what were the results?

• Do my biomarker results affect treatment options such as PARP inhibitors, immunotherapy, or targeted therapy?