by Emily Goebel, MD FRCPC
April 16, 2026
Low-grade serous carcinoma of the ovary is a type of ovarian cancer that develops from cells similar to those lining the fallopian tube. It is called “low grade” because the tumor cells look less abnormal under the microscope and tend to grow more slowly than those seen in high-grade serous carcinoma.
Low-grade serous carcinoma accounts for about 5% of ovarian carcinomas and tends to affect people at a younger age than high-grade serous carcinoma, with a typical diagnosis in the early to mid-40s. Although it grows slowly, it often spreads widely within the abdomen before it is detected, and it responds differently to treatment than most other ovarian cancers.
This article will help you understand the findings in your pathology report — what each term means and why it matters for your care.
What are the symptoms?
Some patients have symptoms related to a pelvic mass, while others have no symptoms at the time of diagnosis. Symptoms may include abdominal swelling or bloating, pelvic pain or pressure, and a feeling of fullness. In some patients, fluid builds up in the abdomen — a condition called ascites — which can cause visible abdominal swelling and discomfort. Because this cancer grows slowly, it may be discovered incidentally during imaging or surgery performed for another reason, even when it has already spread.
What causes low-grade serous carcinoma of the ovary?
The exact cause is not fully understood. Low-grade serous carcinoma frequently arises from a precursor tumor called a serous borderline tumor — a tumor with abnormal cells but without the invasive growth that defines cancer. Over time, additional genetic changes allow these cells to become invasive.
Several genetic alterations are commonly found in low-grade serous carcinomas. Mutations in the KRAS, NRAS, and BRAF genes are particularly important: these genes act as switches in the MAPK signaling pathway, which regulates cell growth and division. When one of these genes is mutated, the pathway is stuck in the “on” position, and the cell grows continuously without the normal signals that would slow it down. These mutations are found in approximately 30–60% of low-grade serous carcinomas and are the basis for a specific targeted treatment approach in recurrent disease (discussed in the biomarker section below). Other alterations affecting genes involved in cell cycle regulation, such as the CDKN2A/2B locus, have also been reported.
Relationship to serous borderline tumors
Low-grade serous carcinoma is closely related to serous borderline tumors of the ovary. In many cases, the carcinoma develops from a pre-existing borderline tumor, and both may be present at the same time in the same specimen. When the pathologist examines the tissue under the microscope, areas of borderline tumor and invasive carcinoma may be found side by side, supporting the stepwise development of this cancer. This close relationship explains why low-grade serous carcinoma tends to develop more slowly and affect younger patients than high-grade serous carcinoma, which arises through an entirely different pathway.
How is the diagnosis made?
The diagnosis is usually made after a tissue sample is examined under the microscope by a pathologist. The sample is most often obtained by removing a mass in the ovary during surgery. A biopsy of an abdominal implant or pelvic mass may also provide the diagnosis in some cases. If surgery is performed, the pathologist examines all removed tissues — including the fallopian tubes, uterus, lymph nodes, omentum, and peritoneal samples — to determine how far the tumor has spread.
Under the microscope, low-grade serous carcinoma shows several characteristic growth patterns. The tumor may form small nests of cells, glands, papillae (finger-like projections), or micropapillae (tiny finger-like projections). The tumor cells show mild to moderate nuclear atypia — the nuclei are somewhat abnormal but not as strikingly irregular as in high-grade serous carcinoma, and they vary less than threefold in size. Mitotic figures (dividing cells) are uncommon. Small, round calcifications called psammoma bodies are frequently present. Necrosis (dead tissue) is uncommon. Areas of coexisting serous borderline tumor are often found in the same specimen.
To confirm the diagnosis and distinguish low-grade serous carcinoma from other ovarian cancer types, the pathologist uses immunohistochemistry (IHC). This technique uses antibodies to detect specific proteins in tumor cells. Low-grade serous carcinomas typically show strong staining for CK7, PAX8, WT1, and estrogen receptor (ER). The tumor usually shows a normal (wild-type) p53 staining pattern, which is one of the most important features distinguishing it from high-grade serous carcinoma, where abnormal p53 staining is almost universal. Staining for p16 is usually patchy rather than diffuse. These IHC findings help the pathologist confirm the diagnosis and rule out high-grade serous carcinoma or other tumor types that can look similar.
Once the cancer is confirmed, imaging — typically CT of the chest, abdomen, and pelvis — is performed to determine the full extent of disease and guide staging and treatment planning.
Histologic grade
Low-grade serous carcinoma is not assigned a histologic grade in the traditional sense because its low grade defines it. It is a specific diagnosis that by definition refers to a carcinoma with low-grade nuclear features — mild to moderate nuclear atypia, infrequent mitotic figures, and a relatively uniform cell population. A separate and distinct tumor type, high-grade serous carcinoma, exists as a completely different diagnosis arising through a different molecular pathway, not as a “higher grade” of the same tumor. If your pathology report says “low-grade serous carcinoma,” the grade is already captured in the name.
Tumor spread
The pathologist examines all tissue samples to determine whether the tumor has spread beyond the ovary. Low-grade serous carcinoma has a strong tendency to spread to the peritoneum — the thin lining of the abdominal cavity — and to deposit on the surfaces of abdominal organs, including the omentum, bowel surfaces, and diaphragm. Although this cancer grows slowly, the majority of patients are diagnosed at an advanced stage (stage III or IV) because the tumor can spread widely within the abdomen before causing noticeable symptoms. Unlike most other cancer types, the slow growth rate of low-grade serous carcinoma means that patients can live for many years even with peritoneal spread.
Ovarian capsule status
The outer covering of the ovary is called the capsule. The pathologist will note whether the capsule is intact or ruptured and whether a tumor is present on the outer surface. These findings affect the stage:
- Intact capsule, no surface tumor — Suggests the cancer is still contained within the ovary, associated with an earlier stage.
- Ruptured capsule or tumor on the surface — Even if no other spread is identified, capsule rupture or surface involvement increases the stage.
- Intraoperative rupture — If the capsule ruptures during surgery rather than before, this is noted separately and also affects staging.
Lymphovascular invasion
Lymphovascular invasion means that tumor cells have been found inside small blood vessels or lymphatic channels within the tissue. This finding indicates that tumor cells may have had an opportunity to travel to lymph nodes or distant sites, and it can influence staging and treatment planning.
Lymph nodes
Lymph nodes are small, bean-shaped structures that help filter the body’s lymphatic fluid and support the immune system. In ovarian cancer surgery, lymph nodes from the pelvis and along the major abdominal blood vessels (para-aortic nodes) may be removed and examined. If tumor cells are found in the lymph nodes, the cancer is considered to have spread beyond the ovary, and the stage increases.
The pathology report will describe:
- The total number of lymph nodes examined.
- The number of lymph nodes containing tumor cells.
- The size of the largest tumor deposit.
- The location of any involved nodes (pelvic vs. para-aortic).
Lymph node deposits are classified by size. Isolated tumor cells (measuring 0.2 mm or less) are recorded as pN0(i+) and are not counted as definitive metastases in all staging systems. Deposits between 0.2 mm and 10 mm are classified as pN1a (small metastases), and deposits larger than 10 mm are classified as pN1b (large metastases). These size distinctions affect the N stage.
Biomarker and molecular testing
Biomarker testing in low-grade serous carcinoma examines specific proteins and genetic changes in tumor cells that help guide treatment decisions. The biomarker landscape for this tumor type is distinct from high-grade serous carcinoma: BRCA mutations and HRD are uncommon, and PARP inhibitors are not a standard treatment. Instead, the most clinically important biomarkers involve the MAPK signaling pathway and hormone receptor expression.
KRAS, NRAS, and BRAF (MAPK pathway mutations)
KRAS, NRAS, and BRAF are three genes that work together in a signaling chain called the MAPK pathway. Think of this pathway as a relay race: a growth signal is passed from one protein to the next, ending with an instruction for the cell to divide. KRAS and NRAS are near the start of the relay; BRAF is in the middle. When any of these genes carries a mutation, the relay signal gets stuck in the “on” position — the cell keeps receiving the instruction to divide even when no growth signal was sent. KRAS mutations are the most common, found in approximately 25–35% of low-grade serous carcinomas. BRAF mutations are found in approximately 5–10%, and NRAS mutations in a smaller proportion.
These mutations are clinically important because drugs called MEK inhibitors — which block a step in the MAPK pathway — can interrupt this runaway signaling. Trametinib (Mekinist) is a MEK inhibitor that has been shown in a randomized clinical trial (the GOG-0281/LOGS trial) to significantly improve progression-free survival compared to standard physician’s choice chemotherapy in patients with recurrent or persistent low-grade serous carcinoma. Binimetinib is another MEK inhibitor recommended for use in the recurrent setting. Clinical trial data suggest that patients whose tumors harbor a KRAS, BRAF, or NRAS mutation may have improved response rates to MEK inhibitor therapy compared with those without these mutations. However, patients with wild-type tumors can also respond.
MAPK pathway mutation testing is performed by molecular sequencing — either a targeted panel or next-generation sequencing (NGS) — on tumor tissue. Results are reported as mutated or wild-type (normal) for each gene, with the specific mutation identified if present. This testing is most relevant when recurrent or persistent disease is being considered for systemic therapy.
Estrogen receptor (ER)
Most low-grade serous carcinomas are strongly positive for the estrogen receptor (ER) — a protein that allows tumor cells to respond to the hormone estrogen. ER is tested by immunohistochemistry, and results are typically reported as positive or negative, often with a percentage indicating the proportion of tumor cells that stain positive and a score reflecting staining intensity.
ER positivity is important because it means the tumor may be sensitive to hormone-blocking therapies, which are commonly used in both the maintenance and recurrent settings for low-grade serous carcinoma. Aromatase inhibitors (such as letrozole or anastrozole), which reduce estrogen production, and tamoxifen, which blocks estrogen receptors, are both used in clinical practice. These treatments are generally better tolerated than chemotherapy and can provide prolonged disease control in patients with recurrent or persistent low-grade serous carcinoma. Some guidelines recommend hormonal maintenance therapy after first-line treatment in patients with advanced disease.
Mismatch repair proteins (MMR)
Mismatch repair (MMR) proteins — MLH1, PMS2, MSH2, and MSH6 — work together to fix small copying errors that arise when cells divide. When one or more of these proteins is absent, the tumor is described as mismatch repair–deficient (dMMR) or microsatellite instability–high (MSI-H). MMR deficiency is uncommon in low-grade serous carcinoma. When present, it has two main implications: first, the potential for immunotherapy with pembrolizumab (Keytruda), which is approved for a wide range of tumors with dMMR/MSI-H, and second, the possibility of Lynch syndrome — a hereditary condition that increases the risk for several types of cancer, such as ovarian, uterine, and colorectal cancers. If MMR deficiency is identified, consulting a genetic counselor is a helpful next step.
Testing is performed by immunohistochemistry on tumor tissue, with results reported as retained or lost expression for each of the four proteins.
For more information about biomarker testing in ovarian cancer, see the Biomarkers and Molecular Testing section.
Pathologic stage (pTNM)
Staging describes how far the cancer has spread. For ovarian cancer, the pathologic stage is based on the AJCC TNM system, which closely corresponds to the FIGO staging system used by gynecologic oncologists. The stage is made up of three components: T (how far the tumor has grown locally), N (whether it has spread to lymph nodes), and M (whether it has spread to distant organs). M stage is determined by imaging and is not typically assigned in the pathology report unless distant spread was sampled at surgery.
Tumor stage (pT)
- pT1 (FIGO Stage I) — Tumor is limited to one or both ovaries or fallopian tubes.
- pT1a — Tumor in one ovary or fallopian tube only; capsule intact; no tumor cells in abdominal fluid.
- pT1b — Tumor involves both ovaries or fallopian tubes; capsules intact; no tumor cells in abdominal fluid.
- pT1c — Tumor limited to the ovary/fallopian tube but with capsule rupture, tumor on the outer surface, or cancer cells in abdominal fluid or washings.
- pT2 (FIGO Stage II) — Tumor has spread beyond the ovaries or fallopian tubes into the pelvis.
- pT2a — Spread to the uterus, the other fallopian tube, or the other ovary.
- pT2b — Spread to other pelvic tissues such as the bladder or rectum.
- pT3 (FIGO Stage III) — Tumor has spread beyond the pelvis to the peritoneum or regional lymph nodes.
- pT3a — Microscopic spread to the peritoneum outside the pelvis, with or without regional lymph node involvement.
- pT3b — Visible tumor deposits up to 2 cm on the peritoneum outside the pelvis, with or without lymph node involvement.
- pT3c — Visible tumor deposits larger than 2 cm outside the pelvis, or spread to the outer surface (capsule) of the liver or spleen, with or without lymph node involvement.
Note: Spread inside the substance of the liver or spleen (rather than only on their surface) is classified as M1 (Stage IVB).
Nodal stage (pN)
- pN0 — No cancer cells found in regional lymph nodes.
- pN0(i+) — Only isolated tumor cells (0.2 mm or less) found in lymph nodes; not counted as definitive metastases in all staging systems.
- pN1 — Cancer cells present in regional lymph nodes.
- pN1a — Tumor deposits up to 10 mm.
- pN1b — Tumor deposits larger than 10 mm.
What is the prognosis?
Two competing realities shape the prognosis for low-grade serous carcinoma: it grows more slowly than high-grade serous carcinoma. Still, the majority of patients are diagnosed at an advanced stage, and they respond less well to standard platinum-based chemotherapy. As a result, patients often live for many years with this disease — sometimes more than a decade — but the cancer is difficult to cure once it has spread beyond the ovary.
Approximate five-year survival rates are:
- Stage I — 85–95%. Very few patients are diagnosed at this stage.
- Stage II — 70–80%.
- Stage III — 50–70%. The majority of patients with low-grade serous carcinoma are diagnosed at this stage. Five-year survival is meaningfully better than for stage III high-grade serous carcinoma, reflecting the more indolent behavior of this tumor.
- Stage IV — 30–45%.
Beyond the stage, the following features influence prognosis:
- Residual disease after surgery — Achieving no visible tumor after cytoreductive surgery (complete cytoreduction) is strongly associated with better outcomes, as in all ovarian cancers.
- MAPK pathway mutation status — Tumors with KRAS, BRAF, or NRAS mutations may have a better response rate to MEK inhibitor therapy in the recurrent setting.
- ER positivity — ER-positive tumors are candidates for hormonal maintenance therapy, which can provide prolonged disease control.
- Recurrence pattern — Low-grade serous carcinoma frequently recurs but tends to do so slowly, and patients often go through multiple lines of treatment over many years. Unlike platinum-resistant high-grade serous carcinoma, recurrent low-grade serous carcinoma is not primarily treated with platinum rechallenge.
- Capsule status — Capsule rupture before or during surgery increases the stage and is associated with a higher risk of abdominal recurrence.
What happens after the diagnosis?
Treatment is planned by a multidisciplinary team that typically includes a gynecologic oncologist, medical oncologist, pathologist, and radiologist. The approach for low-grade serous carcinoma differs in important ways from that used for high-grade serous carcinoma, reflecting its distinct biology.
Surgery is the cornerstone of treatment and aims to remove as much tumor as possible from the abdomen and pelvis (cytoreductive surgery). For most patients, this includes removal of the ovaries, fallopian tubes, uterus, and omentum, along with resection of any visible peritoneal deposits. Achieving no residual disease is the goal. In some younger patients with early-stage disease who wish to preserve fertility, conservative surgery affecting only the involved ovary may be discussed with the gynecologic oncologist.
After surgery, first-line chemotherapy with carboplatin and paclitaxel is typically given, though low-grade serous carcinoma responds less well to platinum-based chemotherapy than high-grade serous carcinoma. For this reason, hormonal maintenance therapy — most often an aromatase inhibitor such as letrozole — is frequently recommended after completion of chemotherapy in patients with advanced disease, to reduce the risk of recurrence. The evidence base for hormonal maintenance continues to grow.
For patients with recurrent or persistent low-grade serous carcinoma, MEK inhibitor therapy has become an important option. Trametinib (Mekinist) is approved for recurrent low-grade serous carcinoma and has been shown to delay progression significantly compared to standard chemotherapy. Patients with KRAS, BRAF, or NRAS mutations in their tumors may have an enhanced response. Hormonal therapies — including aromatase inhibitors, tamoxifen, and leuprolide — are also used in the recurrent setting and can provide durable disease control.
All patients should be assessed for Lynch syndrome risk if MMR deficiency is identified in the tumor. Referral to a genetic counselor is recommended in that setting.
Follow-up after treatment typically involves regular clinical assessments, CA-125 monitoring, and imaging when there are signs of recurrence. Because low-grade serous carcinoma can follow an indolent course over many years, long-term surveillance and ongoing treatment planning are an important part of care.
Questions to ask your doctor
- What stage is my ovarian cancer, and what does that mean for my treatment and long-term outlook?
- Has the tumor spread beyond the ovary to the peritoneum, lymph nodes, or other sites?
- Was the ovarian capsule intact, or did it rupture before or during surgery?
- How much tumor remained after surgery, and was complete cytoreduction achieved?
- Was molecular testing performed for KRAS, BRAF, and NRAS mutations, and what were the results?
- Does my tumor have a MAPK pathway mutation that would make me a good candidate for MEK inhibitor therapy, such as trametinib?
- Is my tumor ER-positive, and would hormonal therapy — such as an aromatase inhibitor — be recommended as maintenance treatment?
- Was mismatch repair testing performed, and were any MMR proteins lost?
- Given that low-grade serous carcinoma responds less well to platinum chemotherapy than other ovarian cancers, what treatment approach do you recommend?
- What follow-up schedule do you recommend, and what signs of recurrence should I watch for?
- Is there a clinical trial that might be appropriate for my situation?
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