What Are Granulosa Cell Tumors?
Granulosa cell tumors are tumors that develop from the granulosa cells (a somatic cell of the sex cord). It is a sex cord-stromal tumor (tumors derived from the ovary's stromal components that accounts for two to five percentage of all ovarian tumors. It occurs mainly in the ovaries, and it rarely develops in the testes. It mostly affects patients aging 50 to 55, but it may occur at any age. It is a malignant tumor that tends to recur; hence, regular follow-up is required after the treatment.
What Are the Types of Granulosa Cell Tumors?
Granulosa cell tumors are classified into two types based on the age of onset and histopathological findings. The two types include;
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Juvenile granulosa cell tumor.
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Adult granulosa cell tumor.
What Is a Juvenile Granulosa Cell Tumor?
Juvenile granulosa cell tumor is a rare malignant sex cord-stromal tumor that develops in the ovary. It is a subtype of granulosa cell tumor. It is less common than the adult granulosa cell tumor and accounts for five percent of all granulosa cell tumors. It differs from adult granulosa cell tumors in both ages of onset and histopathological features. It is usually found during the first three decades, and the mean age is 13 years. Juvenile granulosa cell tumor in premenarchal girls causes pseudo precocious puberty as a consequence of estrogen secretion by the tumor. It is an ovarian neoplasm, and it rarely affects testes in males.
What Causes Juvenile Granulosa Cell Tumors?
The exact cause of juvenile granulosa cell tumors is not known. But recent studies have found mutations in the AKT1 (a gene that encodes the alpha serine or threonine-protein kinase enzyme) gene associated with the pathogenesis of juvenile granulosa cell tumors.
What Are the Symptoms of Juvenile Granulosa Cell Tumors?
Juvenile granulosa cell tumors are clinically present as a solid, cystic, and unilateral mass confined to the ovary. The common presenting symptoms of juvenile granulosa cell tumor include;
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Abdominal swelling and pain.
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Pelvic pain.
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Precocious pseudopuberty.
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Irregular menstruation.
It may rarely lead to symptoms like hirsutism (a condition causing male pattern hair growth in females) and virilization (a condition in which females develop characteristics associated with male sex hormone) as a consequence of secondary steroid hormone (androgen) production by the tumor.
How Is Juvenile Granulosa Cell Tumor Diagnosed?
The diagnosis is usually made at the time of removal of the tumor. Precocious puberty in a prepubertal patient is a diagnostic feature in juvenile granulosa cell tumors. The doctor can suggest other diagnostic measures to have a more accurate diagnosis.
1) Blood Test:
Juvenile granulosa cell tumors cause estrogenic manifestations as a consequence of estrogen secretion by the tumor. Therefore, doctors may suggest a blood test to check for abnormal estrogen levels in the blood.
2) Tumor Marker Test:
Inhibin is a tumor marker secreted by the granulosa cells. High levels of inhibin are observed in juvenile granulosa cell tumors. Therefore, doctors may suggest a tumor marker test to check for high levels of inhibin in the blood.
3) Imaging Tests:
Imaging tests like CT (computed tomography) scan, ultrasound, and MRI (magnetic resonance imaging) help detect the tumor size and check for metastatic growth. MRI in juvenile granulosa cell tumors typically shows a large, unilateral, multicystic mass with a characteristic sponge-like appearance.
4) Histopathological Examination:
Histopathological examination of juvenile cell granulosa cell tumors gives a definitive diagnosis. In addition, it helps differentiate juvenile granulosa cell tumors from the adult variant. A small amount of tissue is removed from the tumor following laparotomy or ovarian cystectomy, and further, the removed tissue sample is sent for pathological examination.
How Does Juvenile Granulosa Cell Tumor Differ From Adult Granulosa Cell Tumor?
Juvenile granulosa cell tumors differ from the adult variant based on the age of onset and histopathological features.
1) Age of Onset:
Juvenile granulosa cell tumors typically occur in the first three decades, with a mean age of 13. In contrast, adult granulosa cell tumors are seen at 50 to 55 years of age.
2) Histopathological Features:
Juvenile granulosa cell histologically resembles focal hemorrhagic areas composed of polygonal cells clear to amphophilic (having affinity for both acid and base) cytoplasm. Call-Exner bodies (small fluid-filled spaces between granulosa cells) are rarely seen in juvenile granulosa cell tumors.
Adult granulosa cell tumors exhibit a scant cytoplasm with pale, oval-shaped nuclei. Unlike juvenile granulosa cell tumors, numerous Call-Exner bodies are seen in the adult variant.
How Is Juvenile Cell Granuloma Treated?
The treatment options for juvenile cell granulosa cell tumors depend on the stage of the disease. Most juvenile granulosa cell tumors are diagnosed early, and surgery is the best treatment for early-stage tumors. The most common surgical treatment option for juvenile granulosa cell tumors is unilateral salpingo-oophorectomy.
A) Unilateral Salpingo-oophorectomy:
In unilateral salpingo-oophorectomy, the ovary and the fallopian tube of the same side of the uterus are removed. It is usually done in premenarchal girls in whom preserving fertility is desired. It can be performed using several techniques by the surgeon, such as;
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Laparotomy - In laparotomy, the surgeon makes a vertical or horizontal incision on the lower abdomen and removes the tumor in the ovary.
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Laparoscopy - In laparoscopy, the surgeon makes small incisions on the abdomen through which a laparoscope (a fiber-optic instrument) is inserted. The laparoscope images the inside of the stomach and helps doctors surgically remove the tumor with the help of images. It is a minimally invasive surgery carried out under general anesthesia; therefore, the patient will not feel any pain.
If the tumor is diagnosed at an advanced stage, then multimodal treatment options may be required. Surgery followed by adjuvant chemotherapy is effective for the treatment of late-stage tumors. The chemotherapy drugs used in the advanced stage of juvenile granulosa cell tumor include:
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Paclitaxel is used either alone or in combination with platinum-based chemotherapy.
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Platinum-based chemotherapy combined with Doxorubicin and Cyclophosphamide.
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Combining chemotherapy with Bleomycin, Etoposide, and Cisplatin is an effective treatment option in juvenile granulosa cell tumor recurrence.
Conclusion:
If diagnosed at an early stage, a juvenile granulosa cell tumor shows a favorable prognosis. In advanced stages, using BEP (Bleomycin, Etoposide, and Cisplatin) chemotherapy will help treat the condition and improve the outcomes. However, since it is malignant and has the tendency to recur, a long-term follow-up for patients is required after the treatment.
