Granulosa cell tumor

Granulosa cell tumor is a rare type of ovarian cancer that starts in the granulosa cells that surround eggs in the ovary. The cancer can spread to other parts of the body, which is why it's called a malignant tumor. However, most granulosa cell tumors are found before they spread outside the ovary, and many grow slowly.

Granulosa cell tumors can be serious and, in some cases, life-threatening. However, most granulosa cell tumors are found at an early stage, when outcomes are much better.

Granulosa cell tumors also can form in testicles, also called testes. This is extremely rare. When they form in the testes, granulosa cell tumors usually are not cancerous.

Granulosa cell tumors are a type of sex cord-stromal tumor. This means they start in ovary or testicle tissues that make hormones or that support the ovary or testicles.

There are two main types of granulosa cell tumor — adult-type and juvenile-type. The names do not reflect the age of the person with the tumor. Instead, the names describe how the tumor cells look under a microscope and how they behave.

• Adult-type granulosa cell tumor. This most common type makes up about 95% of granulosa cell tumors. It most often happens around or after menopause.
• Juvenile-type granulosa cell tumor. This much less common type most often happens in children, teenagers and young adults. But it also can happen in older adults.

Granulosa cell tumors are different from Sertoli-Leydig cell tumors. Both are sex cord-stromal tumors. Both can make hormones, including estrogen and androgens such as testosterone. But granulosa cell tumors more often make estrogen. Sertoli-Leydig cell tumors more often make androgens.

Granulosa cell tumor symptoms can be caused by the tumor itself. Symptoms also can be caused by hormones the tumor makes.

Granulosa cell tumor symptoms caused by the tumor itself may include:

• Pain in the belly.
• Swelling or a feeling of fullness in the belly.

Granulosa cell tumor symptoms caused by hormones made by the tumor may include:

• Breast tenderness.
• Changes in menstrual bleeding, such as missed periods, heavy periods or bleeding after menopause.
• Early puberty, such as breast growth or vaginal bleeding.
• Increased hair on the face or body, acne, or a deeper voice, though these symptoms are rare.

The exact cause of granulosa cell tumors is not known. A change in a gene called FOXL2 may play a role in many adult-type granulosa cell tumors. This gene change, also called a FOXL2 mutation, is found in the tumor cells. It seems to play an important part in how adult-type granulosa cell tumors grow. It is not an inherited gene change.

Juvenile-type granulosa cell tumors usually do not have the FOXL2 gene change. Juvenile-type granulosa cell tumors can have other gene changes. But no single inherited gene change is known to cause either type of granulosa cell tumor.

There are no definite risk factors for most granulosa cell tumors. Some research shows that adult-type granulosa cell tumors may be more common in people with a family history of breast or ovarian cancer.

Some juvenile-type granulosa cell tumors happen in children with Ollier disease and Maffucci syndrome.

However, more research is needed to understand these possible links.

Granulosa cell tumors can sometimes cause complications.

Possible complications from the granulosa cell tumor, itself, include:

• Fluid buildup in the belly. This is called ascites.
• Twisting of the ovary. This is called torsion.
• Bleeding inside the tumor.
• Bleeding inside the belly. The tumor can break open and cause bleeding in the belly.

Adult-type granulosa cell tumors can make extra estrogen. Possible complications from the extra estrogen made by granulosa cell tumors include:

• The lining of the uterus may grow too much. This is called endometrial hyperplasia, which can increase the risk of endometrial cancer.
• Cancer may form in the lining of the uterus. This is called endometrial cancer.

Granulosa cell tumors often are diagnosed when tests or surgery are done to look into symptoms caused by the tumor. Tests may include imaging, blood tests and examining tissue with a microscope.

Imaging tests

Imaging tests make pictures of the inside of the body. For granulosa cell tumor, imaging tests may include the following.

• Ultrasound is a common first imaging test for a possible tumor in the ovaries. An ultrasound can show how big the tumor is and whether it is solid, filled with fluid, or has some areas that are solid and some filled with fluid.
• CT and MRI also are sometimes done. These can give more information about a large tumor and may help look for signs that cancer has spread.

Imaging can help show whether a tumor in an ovary may be cancer, but it cannot show whether it is a granulosa cell tumor.

Blood tests

Blood tests used to help diagnose granulosa cell tumor cannot tell your healthcare team whether you have cancer. But they can offer clues about your diagnosis. Blood tests may be used to:

• Look for tumor markers made by granulosa cell tumors. These include inhibin A, inhibin B and antimullerian hormone (AMH). High levels may help suggest a diagnosis of granulosa cell tumor.
• Check hormone levels. Tests can look for increased hormone levels, if symptoms suggest that the tumor is making extra hormones. This may include estrogen and, sometimes, testosterone.

Examining the cancer cells

Your healthcare team usually cannot be sure of a diagnosis until you have surgery to remove the tumor. Then a doctor called a pathologist looks at the tumor tissue under a microscope. How the tumor cells look help your care team know whether it is a granulosa cell tumor and if it is adult-type or juvenile-type.

Sometimes, different types of cancer can look similar. So other lab tests may be needed to help with the diagnosis. Tests for proteins or gene changes can help the pathologist tell what type of tumor you have. The FOXL2 gene change found in most adult-type granulosa cell tumors may suggest a granulosa cell tumor, for example.

Some people also may have a small amount of tissue taken from the lining of the uterus. This is called a biopsy. Your care team may do a uterine biopsy if you have vaginal bleeding changes or if imaging shows that the uterine lining is thickened. The tissue is checked for changes caused by extra estrogen, such as endometrial cancer, because this can affect your treatment plan.

Granulosa cell tumor treatment mainly includes:

• Surgery. This is the main treatment for all granulosa cell tumors.
• Chemotherapy. Chemotherapy may be used for granulosa cell tumors that are at a more advanced stage.

Surgery

Surgery is the main treatment for granulosa cell tumor and may be used to treat initial cancer and cancer that's come back, also called a recurrence. Surgery also helps the care team find out the cancer's stage. The type of surgery done depends on the cancer's stage. It also depends on whether you want to preserve fertility.

For an early-stage tumor limited to one ovary or fallopian tube, the surgeon may remove just that ovary and the nearby fallopian tube. This is called a salpingo-oophorectomy. The uterus and the other ovary are left in place. This means future pregnancy may be possible.

If preserving fertility is not a goal or if cancer has spread outside an ovary, the surgeon may remove the uterus and both ovaries and fallopian tubes.

Chemotherapy

Chemotherapy treats cancer with strong medicines. For granulosa cell tumor, chemotherapy may be used after surgery to treat:

• Cancer that has a higher risk of recurrence, including some stage 1C tumors. For stage 1C tumors, studies have not shown that chemotherapy clearly improves survival or delays the cancer's return. Because of this, your care team carefully considers details about your cancer and what you prefer before deciding whether to recommend chemotherapy for this stage.
• Cancer that's spread outside the ovary.
• Cancer that cannot be completely removed with surgery.
• A recurrence of cancer.

Chemotherapy may be given as a combination of medicines for granulosa cell tumors. One combination you may hear is called BEP. BEP stands for bleomycin, etoposide and cisplatin. But this is not the only chemotherapy option.

Chemotherapy can cause side effects such as nausea and vomiting. It also can affect the kidneys, nerves and lungs. Your care team checks for these side effects during treatment.

Radiation therapy

Radiation therapy treats cancer with powerful energy beams. It is rarely used for granulosa cell tumors. But radiation therapy may be used to ease symptoms. When it's used this way, it's called palliative care. It also is sometimes used to treat a cancer recurrence or for cancer that's spread to a small area.

Follow-up care and monitoring

Because granulosa cell tumors can recur, your care team may recommend follow-up care and monitoring after treatment. This may include:

• A physical exam 2 to 3 times a year.
• Blood tests to check for tumor markers such as inhibin or AMH 2 to 3 times a year.
• Imaging tests, but usually only if your tumor marker levels are high, you have symptoms or your care team sees signs of possible cancer during the exam.

After the care team diagnoses a granulosa cell tumor, the next step is to find the cancer's stage. The stage tells how far the granulosa cell tumor has spread. This helps the care team plan treatment. It also plays a role in prognosis, which means how likely it is the cancer can be treated or cured.

Granulosa cell tumor stages range from 1 to 4. A lower stage means the cancer is more limited. A higher stage means the cancer has spread beyond the ovary.

Staging tests

To find the stage, your care team uses the results of tests and procedures, including:

• Imaging tests. Tests such as CT and MRI may show if cancer has spread outside the ovary. This information helps decide the stage.
• Surgery and tissue testing. Granulosa cell tumors usually are staged during surgery to remove the tumor. The care team looks for signs that cancer has spread beyond the ovary. The team may collect samples of tissue or fluid from the belly. Later, a pathologist looks at the samples under a microscope to check for cancer cells.

Stage 1

Stage 1 granulosa cell tumor has not spread beyond one or both ovaries or fallopian tubes. Stage 1 is divided into several groups.

• Stage 1A. This means the cancer is in one ovary or fallopian tube only and the tumor has not broken open. It also means there's no cancer on the outside surface of the ovary or fallopian tube. And no cancer cells were found in the fluid sample taken from the belly during surgery.
• Stage 1B. This means the cancer is in both ovaries or fallopian tubes. The rest is the same as stage 1A.
• Stage 1C. This means the cancer is still located only in one or both ovaries or fallopian tubes. But the tumor has broken open before or during surgery. Or cancer is found on the outside surface of an ovary or fallopian tube. Or there were cancer cells in the fluid sample taken from the belly during surgery.

Stage 2

Stage 2 granulosa cell tumor has spread beyond the ovaries or fallopian tubes. Stage 2 is split into two groups.

• Stage 2A. This means the cancer has spread to the uterus, fallopian tubes or both.
• Stage 2B. This means the cancer has spread to other tissues in the pelvis.

Stage 3

Stage 3 granulosa cell tumor has spread outside the pelvis. Stage 3 is split into several groups.

• Stage 3A1. This means the cancer has spread to lymph nodes in the lining of the back of the belly. Lymph nodes are part of a network of vessels and nodes that help drain fluid and fight infection.
• Stage 3A2. This means cancer cells are found on the lining of the back of the belly, but the cancer is still too small to be seen without a microscope. Lymph nodes in the belly also may be affected.
• Stage 3B. This means cancer has spread to the lining of the back of the belly and is big enough to be seen without a microscope but is about 1 inch (2 centimeters) or smaller. Lymph nodes in the belly also may be affected.
• Stage 3C. This means cancer has spread to the lining of the back of the belly and is larger than about 1 inch (2 centimeters). Lymph nodes in the belly also may be affected. Cancer may be on the outer surface of the liver or spleen, too, but not inside these organs.

Stage 4

Stage 4 granulosa cell tumor has spread farther in the body. Stage 4 is split into two groups.

• Stage 4A. This means cancer cells are found in fluid around the lungs.
• Stage 4B. This means cancer has spread to organs farther away, such as inside the liver, spleen, lungs, bones or lymph nodes in areas outside the belly.

How stage affects granulosa cell tumor treatment and prognosis

Stage is an important part of granulosa cell tumor treatment planning. It also affects prognosis for granulosa cell tumor. Stage 1 tumors may be treated with surgery alone. Higher stage tumors, and sometimes stage 1C granulosa cell tumors, may be treated with chemotherapy too.

Stage 1 cancer that is limited to the ovary has a better prognosis than higher stage cancer that's spread past the ovary. Most granulosa cell tumors are found at an early stage.

Survival rates estimate how many people with a cancer are alive a certain number of years after diagnosis. Because survival rates are based on groups of people, they cannot predict how long any one person will live. For rare cancers such as granulosa cell tumor, less information is available to estimate survival than for more common cancers. But survival rates may help give you a general idea of what to expect.

Remission and relapse rates

Granulosa cell tumors can return, sometimes years after treatment. You may hear this called a relapse or recurrence. The recurrence rate for granulosa cell tumor depends on the stage of the cancer. In one study of stage 1 tumors, cancer returned in roughly 1 of every 4 stage 1A tumors and roughly 2 in 5 of stage 1C tumors.