Introduction:
Ovarian cancer is a leading cause of death in women, more than any other type of cancer. It is estimated that one in every 108 women may die from ovarian cancer. Cancer can originate from various ovary cells, including epithelial (cells that line the surface of organs), germ cell, sex cord-stromal, and borderline (abnormal) cells. Amongst them, epithelial ovarian cancer is the most common type. Sex cord-stromal cancers arise from the cell of the tissues that support the ovaries. These can be benign (non-cancerous) or malignant (cancerous). Granulosa cell tumor is a type of cancer originating from the sex cord-stromal cells.
What Is an Adult Granulosa Cell Tumor?
Adult granulosa cell tumor (AGCT) is a rare ovarian cancer representing two to five percent of all ovarian malignancies. This cancer usually occurs in post-menopausal women around the age of 50 to 55 years. Adult granulosa cell tumors also secrete female hormones (functioning tumors) and cause alterations in the uterus lining. Usually, these tumors are low-grade and are caught during the initial stages. Granulosa cell tumors originate from sex cord-stromal cells (cells that support the ovaries). Pure sex cord-stromal tumors are of adult (95 percent) and juvenile types (five percent). Adult granulosa cell tumors develop in middle-aged females, whereas the juvenile form occurs in females before reaching puberty.
What Are the Signs and Symptoms of an Adult Granulosa Cell Tumor?
Adult granulosa cell tumors can develop in one or both ovaries. As these tumors are functional and secrete active hormones, symptoms are expected during the initial stages. Symptoms are primarily due to excess estradiol (estrogen steroid hormone) production. They are as follows:
2. Abdominal pain.
3. Post-menopausal vaginal bleeding.
4. Bloating in the abdomen.
5. Irregular bowel movements (constipation) and frequent urination.
6. Breast tenderness and changes.
7. Ovarian torsion (twisting of ovaries) or rupture occurs in ten percent of affected females.
8. Endometrial (lining of the uterus) overgrowth or the development of endometrial cancer has been reported.
9. Excess hormones may cause hyperandrogenism presenting with virilization (development of male characteristics) or hirsutism (excessive and unwanted hair growth).
How Does an Adult Granulosa Cell Tumor Occur?
The exact reason for the development of this cancer is unknown. Although the tumor originates from ovarian cells, a mutation in the protein FOXL2 plays a role. The mutant gene causes an adverse effect and regulates tumor development.
How Are Adult Granulosa Cell Tumors Diagnosed?
Various diagnostic tools are available to confirm the presence of the tumor. These include:
1. USG (Ultrasonography) - It is a non-invasive scanning modality without using radiation. Ultrasonography is a safe diagnostic method for tumor detection. This technique uses sound waves to create images of the organs.
2. Blood Tests - Most granulosa cell tumors produce chemicals or hormones that can be used as tumor markers. These markers include inhibin, CA125, and the anti-mullerian hormone. They can be measured in blood.
3. CT (Computed Tomography) Scan - A CT scan produces images in sections by utilizing radiation. These scans can detect the exact location of the tumor. However, there is a risk of getting exposed to ionizing radiation.
4. PET (Positron Emission Tomography) Scan - This scan is used to detect metabolic or biochemical changes in the body. A radioactive chemical is used to show metabolic activity. PET scans can detect the disease even before appearing on other scans such as CT or MRI (magnetic resonance imaging).
What Is the Treatment for Adult Granulosa Cell Tumors?
A. Surgical Excision of the Tumor: Surgery comprises the removal of the affected ovary (unilateral oophorectomy). It is the primary treatment of choice for tumors that are detected in the early stages as they are confined. If the cancer is in the end stage, adjuvant chemotherapy is given after the surgery. If patients have endometrial overgrowth, a hysterectomy is preferred. For recurrent cases, surgery along with chemotherapy is performed. Radiologic surveillance is performed periodically to monitor the recurrence.
B. Chemotherapy: Combination chemotherapy regimens have been used for decades. Chemotherapy is preferred when the tumor is in an advanced stage and poses high-risk features. Some tumor cells that remain even after complete resection of the tumor are eliminated by chemotherapy. The chemotherapeutic drugs consist of Cisplatin, Bleomycin, Paclitaxel, etc. However, many reports have shown no significant improvement with chemotherapy in advanced tumors.
C. Hormonal Therapy: Hormonal therapy was introduced to interrupt hormone signaling to initiate the antitumor effect. This was similar to the treatment used for breast cancer. Initially, the hormonal agents included Tamoxifen and Progestins to regulate estrogen function. Endocrine or hormonal therapies are preferred if the initial chemotherapies fail. They have no beneficial role after the surgery.
What Is the Prognosis After Treating an Adult Granulosa Cell Tumor?
The adult granulosa cell tumor, although malignant, has a good prognosis. However, several factors affect the outcome of the treatment. These include:
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Stage of the tumor and extent of tumor development in the ovaries.
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Large tumors of more than 15 cm have a poor prognosis.
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If the tumor is associated with FLOX2 gene mutation, recurrence is possible.
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Higher FLOX2 gene mutations have poor outcomes after the treatment.
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Granulosa cell tumors detected and treated in stage I have a good prognosis with a five-year survival rate of 90 to 100 percent and a ten-year survival rate of 84 to 95 percent.
Conclusion:
Adult granulosa cell tumors are low-grade malignant tumors occurring in post-menopausal women. It is a rare ovarian cancer representing two to five percent of all ovarian malignancies. These tumors are functional and produce hormones that cause uterine changes. The exact etiology of its occurrence is unknown, but an association with the mutation in the FOXL2 gene is seen. Symptoms of this cancer include abnormal uterine bleeding, abdominal pain, post-menopausal vaginal bleeding, bloating in the abdomen, ovarian torsion (twisting of ovaries), etc. The tumor has a good prognosis if detected early. Surgery is the first line of treatment, followed by chemotherapy and hormonal therapy. The five-year survival rate of 90 to 100 percent and a ten-year survival rate of 84 to 95 percent if treated early.
