Low Grade Serous Ovarian Cancer

Low-grade serous ovarian cancer is the 4th most common ovarian cancer (there are over 30 types). It accounts for 2-6% of diagnoses. It is completely different to the more common high-grade serous ovarian cancer. Low-grade serous is challenging to treat and disproportionately affects younger women.

What is low grade serous ovarian cancer?

Low grade serous cancer is a type of carcinoma (epithelial cell cancer). It is usually hormone receptor positive (estrogen +/- progesterone). Epithelial ovarian cancer is the most common type of ovarian cancer. Approximately 10% of epithelial serous ovarian cancers are low-grade.

The ovaries are a pair of female reproductive organs located on either side of the uterus (womb). Epithelial cells line the surface of the ovary. Each ovary is about the size and shape of an almond. They connect to the uterus via a long thin tube called the Fallopian tube. The ovary produces eggs which travel through the Fallopian tube to the uterus. They also produce oestrogen and progesterone hormones.

How does low-grade serous ovarian cancer start?

Researchers don’t know for sure.

One hypothesis is that it develops in a stepwise progression.

1. Fallopian epithelial cells ->
2. Inclusion cyst on ovary ->
3. Ovarian Serous cystadenoma ->
4. Borderline tumour ->
5. Low-grade serous ovarian cancer

But in all likelihood this is one of many ways the cancer can develop.

What is low-grade serous peritoneal cancer?

Low-grade serous peritoneal cancer is considered a variant of low-grade serous ovarian cancer. The peritoneum is the internal layer of the abdomen. In some women low-grade serous cancer starts in the peritoneum instead of the ovary. The medical treatment for both conditions is the same.

What is the difference between low-grade and high-grade serous ovarian cancer (HGSOC)?

Grade

Since 2004, serous ovarian cancer has been divided into low-grade and high-grade. Traditionally ovarian cancer was described as grade 1,2 or 3. The grade of cancer describes how much the cancer cells look like normal cells. Low-grade cells grow slower than high-grade cells.

Pathologists decide whether a cancer is low or high-grade by looking at nuclear atypia, and mitotic count. Nuclear atypia refers to the appearance of the cell nuclei. Low-grade cells have mostly uniform round or oval nuclei with evenly distributed chromatin. High-grade cells have variable nuclear size and shape with irregular chromatin. A secondary consideration is mitotic count. The cut off is 13 mitotic figures/10 High Power Fields although 2-3 is more common for low-grade.

Mutations

Unlike high-grade serous ovarian cancer BRCA (found in ~20% of HGSOC) and TP53 (~95% of HGSOC)  mutations are rare. In contrast, KRAS/NRAS/BRAF mutations are more common. But approximately 40% of low-grade serous ovarian cancer tumours have no identifiable mutation.

Development

Scientists think some low and high-grade serous carcinoma originate in the fallopian tube. Conversion of low-grade serous cancer to high-grade is rare.

Treatment

Compared to high-grade, low-grade serous ovarian cancer is relatively resistant to chemotherapy.

What is the difference between borderline ovarian tumours and low-grade serous ovarian cancer?

Borderline ovarian tumours are also called low malignant potential tumours. They are a pre-cursor to low-grade serous ovarian cancer. 60% of low-grade cancers have co-existent borderline tumours. 10% of women with advanced borderline tumours will develop low-grade in their lifetime.

Stage

Low-grade serous ovarian cancer are typically diagnosed once the cancer has spread. The majority of borderline tumours are diagnosed at stage 1 (when it is contained in the ovary).

Invasion

Low-grade serous carcinoma is invasive. It grows destructively into cellular layers. Borderline is non invasive. This means it grows on the surface instead of invading deeper layers. The World Health Organisation classifies serous borderline tumour with coexisting invasive peritoneal implants as low-grade serous ovarian carcinoma.

Treatment

Serous borderline tumours are treated with surgery alone. Low-grade serous ovarian cancer is usually treated more aggressively because it has a worse prognosis.

What are the symptoms of low-grade serous ovarian cancer?

The symptoms are the same as other ovarian cancers .

They may include:
Bloating
Eating less and feeling fuller
Abdominal/back/pelvic pain
Needing to urinate urgently
Bowel motion changes

Learn more about ovarian cancer symptoms.

Because the symptoms are often gradual, and women tend to be younger – it is often misdiagnosed. Most women will be diagnosed at stage 2-4 when the cancer has spread beyond the ovaries.

How is low-grade serous ovarian cancer diagnosed?

There is no screening test for ovarian cancer. Ovarian cancer can be detected with a transvaginal (internal) ultrasound and Ca-125 blood test. A CT scan or MRI may sometimes be used. Read more about these tests in the National Comprehensive Cancer Network (NCCN) Ovarian Cancer Patient Guidelines 2017.

How is low-grade treated?

Initial treatment consists of surgery to remove all visible signs of the cancer. Usually the reproductive organs will be removed at the same time. However, fertility-sparing surgery may be possible in selected patients. If the cancer is contained in the ovary (stage 1) this may be the only treatment. For stage 2-4 chemotherapy, bevacizumab (Avastin) and hormone inhibitors are options.

Over 70% of people with low-grade serous carcinoma will have their cancer return. Potential treatments for recurrence include chemotherapy; bevacizumab; hormone, MEK and BRAF inhibitors.

Listen to Dr Gershenson, a world expert from the University of Texas MD Anderson Cancer Center, discuss the latest treatment options

If you would like to know more about low-grade serous carcinoma published research, interviews with researchers, and other topics visit our international low-grade serous cancer portal.

Research

Rare cancers like low-grade serous carcinoma currently receive disproportionately little of ovarian cancer research funding internationally. Cure Our Ovarian Cancer works with the low-grade serous cancer community and researchers globally to empower people to fund research to improve survival.

While treatment is not curative for many people currently – the hope is that with low-grade serous carcinoma’s longer average survival there will be time to find better treatments in women’s lifetimes if we act now.

To date we have funded three low-grade serous cancer research grants in NZ and helped raise hundreds of thousands overseas to support progress in this research area.

This information has been reviewed by a gynaecological oncologist specialising in low-grade.
Updated 17 August 2019.