One of the rarest forms of ovarian cancer and is classified as a sex cord stromal tumor.
Most common in post-menstrual women,
Has the ability to be present in both male and female children as well as in men of any age.
If discovered in stage I, survival is extremely likely.
Appears as a solid, smooth-surfaced, and cystic lesion with blood-filled cysts.
Granulosa cell tumors can reoccur up to two decades later.
Sometimes it is associated with endometrial hyperplasia, due to excessive amounts of estrogen produced by the tumor.
Production of hormones can contribute to an increase in hair growth, a deepening of the voice, balding, excessive muscle mass, and enlargement of the clitoris.
Manifest at the peak age of 50-55.
Multiparity reduces likelihood.
Associated with high fat dietary intake.
Associated with ovarian cancer in family.
Associated with infertility drug use.
Accounts for 25,000 new cases of ovarian cancer in the U.S. annually, and generally, 2% of all ovarian tumors.
70% of cases are hormonally active.
90-95% survival rate for stage I tumors.
20-25% survival rate for advance staged tumors.
10% of GCTs occur in pregnant women.
95% occur in adults and 5% occur in children.
The measurement of serum inhibin levels is useful in the diagnosis of granulosa cell tumours in postmenopausal women.
Serum inhibin levels can monitor the disease following oophorectomy.
Surgery is the primary treatment.
Hormonal therapy for patients with advanced stages or recurrent disease has resulted in varying outcomes.
GCT can occur in men, and is the least common sex cord stromal tumor found in the testes.
It account for 27% of non- germ cell gonadal tumors.
Associated with defects of the Y chromosome, and appear as cystic, painless testicular masses.
Juvenile tumors do not produce estrogen.
Presentation includes: nausea, vomiting, dizziness, post menopausal- abnormal vaginal bleeding, abdominal/pelvic pain, bloating, frequent urination, fatigue, backaches, fatigue, enlarged breasts, and dyspareunia.
Approximately 10% of tumors occur during pregnancy.
Many women are treated with a total abdominal hysterectomy and bilateral salping-oophorectomy and omentectomy, but chemotherapy is also an option.
Primary treatment is surgical.
Chemotherapy and/or radiotherapy are reserved for patients with advanced disease by surgical staging, and for patients with recurrent tumor.
Surveillance for patients postoperatively consists of frequent pelvic examinations, and assessment of tumor markers, and abdominopelvic CT scan or other diagnostic imaging modalities to diagnose recurrence as soon as possible.
Radiotherapy appears to have limited efficacy is considered an option for advanced-stage patients and, in patients with pelvic recurrence.
Adjuvant therapy for GCTs utilizes chemotherapy.
Hormonal manipulation of these tumors using GnRH analogues and aromatase inhibitors.
Preoperative imaging and laboratory studies are helpful for measuring the extent of disease.
Appropriate staging with removal of the tumor and optimal cytoreduction are the main goals of surgical therapy.
FIGO stage is the most prognostic factor for granulosa cell tumors.
There is a survival benefit for patients with lower-stage tumors.
In patients who had no residual disease at surgery, there is a mean overall survival 108 mo versus those with residual disease at the end of surgery with mean 42 mo survival.
Complete surgical staging consists of an examination of the pelvic and intra-abdominal structures, and if disease is identified outside the ovary, optimal debulking should be performed so that all remaining tumor nodules are smaller than 1 cm.
The goal of surgery is complete resection of all visible tumor.
Optimal tumor debulking improves overall survival and decreases recurrences.
In younger patients who desire future fertility, a unilateral salpingo-oophorectomy provides sufficient treatment because most of these tumors are stage I.
Staging consists of pelvic washings, selective ipsilateral pelvic and bilateral periaortic lymph node sampling, peritoneal biopsies, partial omentectomy, and biopsy of the contralateral ovary if it appears abnormal.
Biopsy of the contralateral ovary is not routine part of the staging procedure because only 2% of tumors are bilateral.
The need for lymphadenectomy is questionable due to the low risk of lymph node metastasis, even in cases of advanced stage disease in GCT.
Surgical treatment of recurrent GCTs utilizes debulking if the tumor appears to be localized on imaging studies.
Chemotherapy, radiotherapy, and hormonal treatments have been used with variable success for recurrence disease.
Mean survival after a recurrence has been diagnosed is approximately 5 years for adult GCTs.
The rarity of this tumor has precluded randomized clinical trials.
The optimal chemotherapy regimen has not been hard identified.
Current chemotherapy regimens usually consist of multidrug regimens, usually containing a platinum based agent, with the most frequent combination therapy being the bleomycin, etoposide, and cisplatin (BEP) regimen.
BEP in patients with residual disease and undergoing a second-look surgery, 37% of patients have had a complete response, with an additionally, 40% of having an objective response to this regimen.
The cisplatin (Platinol), vinblastine, and bleomycin (PVB) regimen shows moderately high response rates of complete and partial response rates of 28% and 24%, respectively, with 25.4-month median survival in patients who had not received prior chemotherapy or radiation.
Older useful multidrug regimens include: cyclophosphamide, doxorubicin (Adriamycin), and cisplatin regimen, which includes cyclophosphamide at 500 mg/m2 IV, Adriamycin at 40-50 mg/m2 IV, and cisplatin at 40-50 mg/m2 IV all given q4wk for 4-6 courses;
Cisplatin and doxorubicin; and cyclophosphamide, actinomycin, and 5-fluorouracil.
Response to taxanes with or without platinum may be similar to that of the BEP regimen with less toxicity.
Use of antiangiogenic therapy in GCTs with bevacizumab revealed promising results, and responses to medroxyprogesterone acetate, GnRH agonists, and megestrol have been reported.
The use of the aromatase inhibitors, which inhibit the conversion of androstenedione to estrone, in the management of patients who previously received surgery and chemotherapy have been reportedly been effective.
At least 50% of recurrences are found more than 5 years after initial treatment.
Prognosis generally is very favorable, as tumors are of low malignant potential.
Approximately 90% of GCTs are at stage I at the time of diagnosis, with a 10-year survival rate in adults of 90-96%.
GCTs of more advanced stages are associated with 5- and 10-year survival rates of 33-44%.
A recurrence rate of 43% has been observed in stage I-III GCT over 10 years.
Average recurrence is approximately 5 years after treatment, with more than half of these occurring more than 5 years after primary treatment.
Recurrent tumors tend to follow an indolent course, with a mean survival of 5 years after the recurrence is diagnosed.
The 10-year overall survival after an AGCT recurrence is in the 50-60% range.
Juvenile GCTs recur much sooner, with more than 90% of recurrences occurring in the first 2 years., and rapidly fatal.
Tumor stage at the time of initial surgery is the most important prognostic factor.
Early stage disease and age younger than 50 years to be statistically significant factors in predicting survival.
Poor prognosis associated with high mitotic rates, higher grade, preoperative rupture of the capsule, and tumors larger than 15 cm.
Higher grade histology and intraoperative tumor rupture does not affect prognosis.