Practice Essentials
The most common ovarian germ cell tumors are dysgerminomas, which typically affect young women. Although all dysgerminomas are considered malignant, only about one third are aggressive. These tumors usually respond well to therapy. [1]
Signs and symptoms
No specific symptoms are diagnostic of dysgerminomas. Most patients report abdominal pain and have a palpable abdominopelvic mass.
Other symptoms that are often associated with dysgerminomas include the following:
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Pelvic fullness
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Early satiety
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Urinary frequency
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Dysuria
A dysgerminoma typically presents as a unilateral mass and can grow rapidly.
Workup
Laboratory studies
The standard workup for suspected dysgerminomas includes the following tumor markers:
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Lactate dehydrogenase (LDH)
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Beta-human chorionic gonadotropin (beta-hCG)
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Alpha-fetoprotein (AFP)
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Inhibin A and B
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Cancer antigen 125 - For epithelial tumors
Dysgerminomas are most frequently associated with elevations in LDH, although levels are not raised in all cases. Other tumor markers are less commonly elevated.
A potentially useful test for ovarian germ cell tumors, including dysgerminomas, is immunoreactivity of nuclear protein in the testis (NUT). [2]
Imaging studies
Transvaginal ultrasound can be used as an initial study to determine whether a mass is ovarian and whether it has malignant features (eg, thickened septations, solid and cystic components). Pelvic MRI may be needed if a nonovarian origin for the mass is suspected. CT scanning of the chest, abdomen, and pelvis is often used to detect metastasis.
For patients with signs or symptoms of gastrointestinal or genitourinary obstruction, consider the following additional studies in the workup:
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Barium enema
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Upper gastrointestinal series
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Intravenous pyelography - No longer used if CT scanning is used
Procedures
The diagnosis of dysgerminomas requires either laparoscopy or laparotomy. The choice of surgical approach depends on clinical findings and imaging and laboratory results, as well as an index of suspicion for malignancy.
Treatment
Most ovarian dysgerminomas are stage I and thus can be treated by surgical resection alone, with a unilateral salpingo-oophorectomy and staging. Follow-up care with serial pelvic examinations and assessment of tumor markers (ie, beta-hCG, AFP, LDH) is required if resection is the only treatment.
Reserve adjuvant therapy for women with stage Ib-IV dysgerminomas. The standard of care for these patients is platinum-based chemotherapy, which is generally well tolerated.
Surgery
Women who wish to maintain fertility should undergo exploratory laparotomy, pelvic washings, unilateral salpingo-oophorectomy, ipsilateral pelvic and bilateral para-aortic lymphadenectomy, omentectomy, and peritoneal biopsies. Those who have completed childbearing should also undergo total abdominal hysterectomy and bilateral salpingo-oophorectomy.
If metastatic disease is identified at laparotomy, debulking should be undertaken with a goal of complete surgical cytoreduction. [3]
Chemotherapy
Patients with completely resected stage Ib and Ic tumors should receive 3 cycles of BEP (bleomycin, etoposide, platinum), and those with completely resected stage II-IV tumors should receive 4 cycles of BEP. Patients with bulky residual disease may require additional cycles.
The BEP protocol is generally preferred because of its high cure rates and favorable toxicity profile. [4]
Alternative chemotherapy regimens are as follows:
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Methotrexate, actinomycin D, and chlorambucil (MAC)
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Cisplatin, vincristine, and bleomycin (PVB)
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Vincristine, actinomycin D, and cyclophosphamide (VAC)
Background
The three major types of ovarian tumors are epithelial, sex cord, and germ cell. Epithelial cell tumors represent the majority of all ovarian neoplasms (82%). Conversely, germ cell tumors (GCTs) are rare, comprising approximately 20% of all ovarian tumors, both benign and malignant. About 3-5% of ovarian GCTs are malignant. The most commonly occurring GCT is the dysgerminoma, which accounts for approximately 2% of all ovarian cancers. [5]
Although rare, dysgerminomas are important irrespective of incidence because they most commonly affect women of reproductive age (ie, < 30 y). In fact, dysgerminomas make up two thirds of all malignant ovarian neoplasms in women younger than 20 years. Moreover, once diagnosed, dysgerminomas respond well to therapy, potentially sparing patients from infertility and early mortality.
Pathophysiology
Typically, germ cells are encapsulated at birth within the primordial follicle. If they somehow escape encapsulation, cell death usually occurs. If the germ cells survive, rapid growth ensues, owing to the lack of normal contact inhibition: hence the formation of a germ cell tumor (GCT). All dysgerminomas are considered malignant, but only one third of dysgerminomas behave aggressively. The exact etiology of dysgerminomas has not been determined, although molecular studies have implicated loss of function with potential tumor suppressor gene TRC8/RNF139 as a possible cause. [6]
Additionally, 5% of all dysgerminomas occur in dysgenetic gonads and may be associated with gonadoblastomas. Genetic disorders of the ovary are associated with karyotypic abnormalities and are discussed in Dysgerminomas in patients with karyotypic abnormalities in Complications.
Epidemiology
United States data
The US incidence of dysgerminomas has remained unchanged over the past 30 years. The frequencies of the most common malignant ovarian neoplasms in women of reproductive age are as follows: epithelial tumors (42%); dysgerminoma and other germ cell tumors (GCTs) (30%); metastatic Krukenberg tumors (14%); and sex cord stromal tumors (ie, Sertoli-Leydig cell tumors) (13%).
Race-, sex-, and age-related demographics
To date, no racial predilection exists for ovarian GCTs.
These tumors mostly occur in women, although the disease also occurs in pseudohermaphrodites and patients with gonadal dysgenesis (see Complications). Testicular seminomas are the male histologic counterparts to dysgerminomas.
Although most ovarian cancers occur during the menopausal and perimenopausal years (ie, 50-59 y), dysgerminomas tend to occur frequently in the pediatric population. Dysgerminomas are most commonly observed in younger women. Seventy-five percent of dysgerminomas occur in patients in the third and fourth decades of life, with a mean age of 22 years.
Prognosis
The 5-year survival rate is 96% if the tumor is confined to the ovary and 63% if extension occurs beyond the ovaries. Pregnancy does not alter the prognosis of most ovarian malignancies, but complications such as torsion and rupture may increase the incidence of spontaneous abortion or preterm delivery.
Prognosis depends on the staging of the tumors.
Five-year survival rates are as follows:
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Stage Ia-Ic - 91%
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Stage III - 74%
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Stage III with retroperitoneal disease - 24%
Ten-year survival rates, comparing conservative surgery alone versus surgery plus radiation, are 92% and 85%, respectively.
As a rule, any peritoneal involvement carries a poor prognosis. No correlation exists between tumor size and prognosis.
In a 2014 retrospective review (1978-2010) of data from the Surveillance, Epidemiology and End Results program that evaluated cause-specific survival (CSS) in patients with malignant ovarian germ cell tumors, investigators found a 97% 5-year CSS in those with ovarian dysgerminoma compared with a 92% 5-year CSS for those with non-dysgerminoma. [7] Significant prognostic factors for cause-specific mortality in ovarian dysgerminoma included age older than 40 years at diagnosis and metastatic disease. In addition, a second cancer occurred in 10% of all patients who had survived 10 years and had received radiotherapy compared with 2% of those who had not received radiation treatment (P=.002).
Patient Education
Educate patients about the importance of follow-up care during the first 2 years after initial therapy because 90% of recurrences manifest during this time.
Prior to and following chemotherapy, discuss with patients the potential for lung toxicity with bleomycin and the rare occurrence of secondary leukemias.
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Ovarian dysgerminomas. Microscopic image at 20 X.
