Ovarian Dysgerminomas

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. Approximately 3-5% of ovarian GCTs are malignant. The most commonly occurring GCT is the dysgerminoma, which accounts for approximately 2% of all ovarian cancers.

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.

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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 germ cell tumor (GCT) formation. All dysgerminomas are considered malignant, but only one third of dysgerminomas behave aggressively. The exact etiology of dysgerminomas has not been determined, although recent molecular studies have implicated loss of function with potential tumor suppressor gene TRC8/RNF139 as a possible etiology.^[1]

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.

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Etiology

The exact etiology for this tumor type has not been elucidated.

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Epidemiology

Frequency

The US incidence of dysgerminomas has remained unchanged over the last 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

To date, no racial predilection exists for ovarian germ cell tumors (GCTs).

Sex

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.

Age

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 the mean age being 22 years.

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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:

• Stage Ia-Ic - 91%
• Stage III - 74%
• 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.^[2] 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 survived to 10 years and had received radiotherapy compared to 2% of those who had not received radiation treatment (P = .002).

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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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History

No specific symptoms are diagnostic of dysgerminoma tumors. Many of the presenting symptoms are universal for any adnexal/ovarian mass.

Most patients with dysgerminomas present with abdominal pain and a palpable abdominopelvic mass.

Frequently associated symptoms include the following:

• Pelvic fullness
• Pain
• Early satiety
• Urinary frequency
• Dysuria

Vague abdominal symptoms (eg, dyspepsia, digestive disturbances) are less common.

These tumors usually present as a unilateral mass and can occur during pregnancy.

These tumors can have rapid growth and predispose to rupture and torsion with associated acute change in symptoms in approximately 5-10% of patients.

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Physical Examination

The physical examination should be complete in order to look for signs of metastatic disease outside the abdominal cavity, including lymphadenopathy, pleural effusions, and other focal findings. Although not commonly seen with dysgerminomas, it may help in narrowing the differential.

A thorough abdominal and pelvic examination on a gynecology table with stirrups should include a careful rectovaginal examination because some enlarged adnexal masses can be detected from this approach. Moreover, it may identify patients with irregularities of the sidewall and cul-de-sac peritoneum.

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Laboratory Studies

Tests for pregnancy and sexually transmitted diseases

One should always initially obtain a pregnancy test. This test should be mandatory in any woman of reproductive age, even at the extremes of reproductive age, who presents with abdominopelvic symptoms.

Because dysgerminoma tumors affect women of a reproductive and sexually active age, cultures for gonorrhea and chlamydia and a wet mount are recommended at the time of speculum examination, especially if patients experience abdominopelvic pain and/or fevers. In this way, sexually transmissible diseases may be detected and treated before surgery.

Once a pelvic mass is detected, especially in younger female patients, the standard workup for suspected germ cell tumors (GCTs) requires lactate dehydrogenase (LDH), alpha-fetoprotein (AFP), and beta-human chorionic gonadotropin (beta-hCG) levels. If any levels are elevated, they may assist in diagnosis and/ or follow-up of women diagnosed with malignant ovarian GCTs.

Other laboratory studies

Dysgerminomas have most commonly been associated with elevations in LDH, although it is not elevated in all cases. Occasionally, dysgerminomas may become infiltrated with syncytiotrophoblastic giant cells, which produce beta-hCG. Elevations in AFP are even less common. However, preoperative evaluation of all of these markers is suggested in patients with suspected ovarian GCTs/dysgerminomas. Additionally, serum inhibin levels can be useful in this age group. Although inhibin B seems to be more sensitive and has a greater elevation in GCTs, inhibin A can also be elevated with inhibin B or, more rarely, without elevation of inhibin B, as sex cord stromal tumors are also in the differential for women in this age group who present with pelvic masses.

Therefore, useful tumor markers for the workup of dysgerminomas include the following:

• Beta-hCG
• AFP
• LDH
• Inhibin A and B
• Cancer antigen 125 (CA-125) - For epithelial tumors

Nuclear protein in the testis

A potentially useful test for ovarian germ cell tumors, including dysgerminomas, is immunoreactivity of nuclear protein in the testis (NUT).^[3] In situ and invasive germ elements of dysgerminoma associated with gonadoblastoma were positive for NUT in a study that evaluated NUT immunostaining in mature cystic teratomas and malignant ovarian germ cell tumors.^[3]

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Imaging Studies

Imaging should never replace a careful history and physical examination in evaluating a patient with an ovarian mass. The initial approach should be an attempt to determine the nature and extent of the mass.

Transvaginal ultrasound is a good preliminary imaging modality to determine if the mass is ovarian and, more importantly, if it has any malignant features (eg, thickened septations, solid and cystic components). Free abdominal fluid and bilateral masses heighten the suspicion of malignancy. Occasionally, pelvic MRI may be necessary to better assess anatomy if a nonovarian origin for the mass is suspected. CT scanning of the chest, abdomen, and pelvis are frequently used to evaluate for metastasis.

Occasionally, patients may present with signs or symptoms of gastrointestinal or genitourinary obstruction. In these cases, additional studies to consider in the workup include the following:

• Barium enema
• Upper gastrointestinal series
• Colonoscopy
• Intravenous pyelography (IVP) - No longer used if CT scanning is used

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Procedures

Diagnosis of malignant ovarian tumors must be made surgically through either laparoscopy or laparotomy. The appropriate surgical approach depends on findings from the clinical examination, imaging, and laboratory workup, as well as index of suspicion for a malignancy. Care should be taken not to rupture ovarian masses that are suggestive of malignancy. If laparoscopy is undertaken and cyst drainage or morcellation is to be performed, the mass should be placed into a laparoscopic bag to avoid tumor spillage or dissemination. Dysgerminomas, like all ovarian cancers, are staged surgically.

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Histologic Findings

Grossly, dysgerminomas have a solid texture, with a tan, fleshlike appearance. Microscopically, dysgerminoma cells are round and ovoid and contain an abundance of clear cytoplasm secondary to glycogen buildup. The nuclei are irregularly shaped and contain more than one prominent nucleolus. These cells tend to coalesce, forming cords and sheets that are identified easily through low-power magnification. Granulocytic and lymphocytic infiltration within the intervening fibrous stroma and granulomatous changes also can be observed. Interestingly, cystic teratomas occasionally have small nests of dysgerminomatous tissue and vice versa. Additional assays detecting transcription factors GATA-4, Ihh, and BMP-2 may also prove useful in differentiating between dysgerminoma and other germ cell tumors.

Note the image below.

View Image

Ovarian dysgerminomas. Microscopic image at 20 X.

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Staging

International Federation of Gynecology and Obstetrics (FIGO) staging 2014

Stage I (as follows) - Limited to ovaries:

• Ia - Limited to one ovary, capsule intact, negative washings, and no ovarian surface implants
• Ib - Limited to both ovaries, negative washings, and no ovarian surface implants
• Ic - Ascites with malignant cells on peritoneal washings or extension beyond the capsule in either Ia or Ib

  • Ic1- Surgical spill
  • Ic2- Capsule rupture before surgery or tumor on ovarian surface
  • Ic3- Malignant cells in the ascites or peritoneal washings

   

  

   

Stage II (as follows) - Pelvic extension:

• IIa - Involvement of uterus or fallopian tubes
• IIb - Extension to the bladder or rectum

Stage III (as follows) - Peritoneal implants outside of pelvis or positive lymph nodes:

• IIIa1 - Positive retroperitoneal lymph nodes

  • IIIa1(i) - Metastasis  ≤10 mm
  • IIIa1(ii) - Metastasis > 10 mm

   

  

   
• IIIa2- Microscopic seeding of abdominal surfaces, implants < 2 mm +/- positive retroperitoneal nodes
• IIIb - Abdominal peritoneal implants  < = 2 cm +/- positive retroperitoneal nodes - Includes extension to capsule of liver or spleen
• IIIc - Abdominal implants >2 cm +/- positive retroperitoneal nodes - Includes extension to capsule of liver or spleen

Stage IV (as follows) - Distant metastases:

• IVa- Pleural effusions - Must confirm with positive cytology to be deemed stage IV
• Hepatic and/or splenic parenchymal metastases and/or metastases outside of the peritoneal cavity (including positive inguinal or other extra-abdominal lymph nodes)
• See additional notes under Surgical Care.

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Medical Care

A preponderance (75-80%) of dysgerminomas present as stage I cancers and, therefore, can be treated by surgical resection alone with a unilateral salpingo-oophorectomy and staging. This is preferred when attempting to preserve fertility; however, diligent follow-up care, with serial pelvic examinations and tumor markers (ie, beta-human chorionic gonadotropin [beta-hCG], alpha-fetoprotein [AFP], lactate dehydrogenase [LDH]) is mandatory if resection is the only treatment modality.

Adjuvant therapy should be reserved for women with stage Ib-IV ovarian dysgerminomas. Platinum-based chemotherapy has become the standard of care for these patients and is generally well tolerated. Radiation therapy has also been administered to patients with stage I-III tumors, with excellent response rates overall. However, this has been mostly abandoned due to high success rates with platinum-based chemotherapy, as well as avoiding long-term complications from radiation, including sterility and early menopause.

Stage Ia dysgerminomas

Typically, the authors do not recommend any adjuvant chemotherapy for stage Ia dysgerminomas. Although 10-15% of stage Ia tumors may recur, essentially all of them are salvaged with 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. However, care should be taken to watch for pulmonary toxicity with bleomycin and the potential for secondary leukemias with high cumulative doses of etoposide; these precautions should be discussed with the patient.

Fertility after chemotherapy

In studies of young women who received platinum-based chemotherapy for ovarian germ cell tumors (GCTs), 62 (87%) of 71 resumed regular menstrual function and 24 of these women delivered 37 children after chemotherapy.^[4] In a study by Weinberg et al,^[5] 40 women with malignant ovarian GCTs were followed for reproductive outcomes. Twenty-two women underwent fertility-sparing surgery and 16 of these received chemotherapy. The majority of patients (14 of 16) received BEP. Follow-up was available for 14 of the 16 patients. All 14 returned to normal menstrual function. Eight of the 10 women who attempted pregnancy had 11 pregnancies with 14 live births.

Adjuvant chemotherapy regimens

The 4 regimens for chemotherapy are as follows: (1) BEP, which is the preferred regimen; (2) methotrexate, actinomycin D, and chlorambucil (MAC); (3) cisplatin, vincristine, and bleomycin (PVB); and (4) vincristine, actinomycin D, and cyclophosphamide (VAC). Although the efficacy has been analyzed for each protocol, the BEP protocol has been favored in recent years owing to high cure rates with a favorable toxicity profile.

Important to note is that the authors attempt to keep patients on schedule despite bone marrow toxicity that may develop. Given the high cure rates and relatively low rates of neutropenic fever, it is best to continue treatment as scheduled even if blood counts are lower than what is typically considered acceptable to begin a new cycle. Consideration for dose reduction and addition of growth factors should be made on a case-by-case basis and should be used after neutropenic fever.

BEP protocol (generally preferred)

The protocol is as follows^[6] :

• Bleomycin - Maximum 30 U IV per week for 9 weeks; dose at 20 U/m²
• Etoposide (ie, VP-16) - 100 mg/m² on days 1-5 q3wk for 3 courses; reduced 20% for granulocytic fever or previous radiotherapy
• Cisplatin - 20 mg/m² on days 1-5 q3wk for 3 courses

In 2004, the Gynecologic Oncology Group (GOG) published their experience using carboplatin and etoposide in ovarian dysgerminomas.^[7] They followed 39 eligible patients with completely resected stage Ib-III disease for a median follow-up of 7.8 years. There were no disease recurrences, although one patient had an intercurrent death from lung cancer. Although not considered the standard, this regimen may be considered in patients with preexisting renal or neurologic disease.

This regimen is carboplatin t 400 mg/m² on day 1 and etoposide at 120 mg/m² on days 1-3 q4wk for 3 cycles.

A study by Shah et al reported comparable survival outcomes between carboplatin and cisplatin in patients with advanced-stage dysgerminoma and may be considered as well.^[8]

Antiemetics

Antiemetics that may be used in chemotherapy are as follows:

• Chlorpromazine - 25-50 mg PO/IM/PR q4h
• Odansetron 4-8 mg IV/PO prior to chemotherapy
• Lorazepam 1-2 mg PO/IV q6h
• Dexamethasone 8 mg IV prior to cisplatin and 4 mg q4h for 2 doses

Radiation therapy

Primary therapy with radiation is reserved for patients who cannot tolerate chemotherapy or surgical resection.

Radiation is used to treat periaortic and pelvic lymph node metastases. Shielding the remaining ovary in an attempt to preserve fertility is not uncommon. Oophoropexy may be used to mechanically hold the remaining ovary away from the radiation field.

Radiation therapy may be used for any dysgerminomas staged Ib-III. The field of exposure extends from T11 to L5, with shielding of the contralateral ovary and the femur head.

The use of radiation in stage Ia cancers is considered precautionary. Most patients present with stage I disease and usually can be treated with simple resection (eg, unilateral salpingo-oophorectomy). Some authors have advocated radiation therapy for stage IA tumors larger than 10 cm. However, owing to the high sensitivity for radiation and platinum-based chemotherapy, the authors do not recommend treating stage Ia tumors with any adjuvant therapy.

De Palo,^[9] Freed, and Lawson developed the 3 major radiation therapy protocols. These protocols differ mainly in their treatment of the abdomen for node-positive disease and in prophylactic treatment of the mediastinum.

Transfer

The need for transfer to a tertiary facility is predominantly determined by the availability of specialists to assist with surgery if the index of suspicion for malignancy in women with a pelvic mass is high. Otherwise, transfer should be considered for complications of surgery or chemotherapy requiring more intensive treatment than what can be offered at smaller facilities.

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Surgical Care

Full surgical staging is recommended for ovarian germ cell tumors (GCTs) to identify women with greater than stage Ia disease. Pattern of spread for ovarian dysgerminomas often follows a lymphatic rather than peritoneal route, with up to 25% of patients having lymphatic involvement. Therefore, complete lymphadenectomy should be performed.

Fertility preservation

Since many women with ovarian dysgerminomas are be in their 20s and 30s, any woman who wishes to maintain fertility should undergo exploratory laparotomy, pelvic washings, unilateral salpingo-oophorectomy, ipsilateral pelvic and bilateral para-aortic lymphadenectomy, omentectomy, and peritoneal biopsies. It is not recommended to leave the ipsilateral tube, owing to the rich lymphovascular connection between the tube and the ovary.

It should be noted that contralateral positive pelvic nodes may be seen in 10-50% of women with positive pelvic lymph nodes at surgery for epithelial ovarian cancers. Although no data exist for dysgerminomas, bilateral pelvic lymphadenectomy should be performed if there is extraovarian pelvic involvement and should be considered in patients in whom disease appears to be confined to the ovary.

Additionally, note that the contralateral ovary may be involved in 5-10% of patients who appear to have stage Ia disease. Historically, a wedge biopsy of the contralateral ovary was recommended to rule out microscopic spread in the contralateral ovary. However, the authors of this article advocate leaving the opposite ovary undisturbed if it is of normal size and appearance. This is suggested for 2 reasons. First, dysgerminomas are highly responsive to both radiation and platinum-based chemotherapy, so adjuvant therapy for advanced-stage disease and treatment of recurrence are typically very successful. Second, performing a biopsy of a normal contralateral ovary may diminish fertility as a result of adhesion formation following the biopsy.

A study by Nasioudis et al reported that uterine preservation was not associated with decreased survival in women advanced stage ovarian germ cell tumors.^[10]

Women who have completed childbearing

These women should undergo exploratory laparotomy, pelvic washings, total abdominal hysterectomy, bilateral salpingo-oophorectomy, ipsilateral pelvic and bilateral para-aortic lymphadenectomy, omentectomy, and peritoneal biopsies.

Women with metastatic disease

Identification of disease extending beyond the ovary at laparotomy should lead to an attempt at complete surgical cytoreduction. Although no prospective data comparing outcomes of surgical debulking in advanced-stage ovarian GCTs are available, evidence suggests that women treated with chemotherapy after optimal surgical cytoreduction have a better prognosis than those with bulky residual or unresectable disease. However, one should bear in mind that these tumors do have an excellent response to platinum-based chemotherapy, so the risk-to-benefit ratio of radical surgical procedures should be considered in this context.

Incompletely staged patients with presumed stage Ia disease

National Comprehensive Cancer Network (NCCN) guidelines suggest checking tumor markers and CT scanning of the chest, abdomen, and pelvis. If results are normal, patients may be observed. If any abnormalities are noted on these tests, laparotomy and complete surgical staging should be performed.

An Italian study of 26 women with ovarian dysgerminomas showed only 19.2% had complete surgical staging. Three of these women (11.5%) suffered recurrence, with 2 having lymph nodes as part of their recurrent disease.^[11] All of them were salvaged with chemotherapy with or without surgery. The overall recurrence risk in unstaged women was 20% in this study, which may help in counseling women in this situation.

Laparoscopy

Case reports describe laparoscopic management and staging of ovarian GCTs. However, data on outcome are lacking and should still be considered investigational, as the standard is still laparotomy.

Surgical preparation

Traditionally, patients undergoing surgery for ovarian cancer often undergo a mechanical and/or antibiotic bowel preparation before surgery. This was once felt to be critical in the case of unsuspected gastrointestinal spread requiring bowel resection. However, current data in the colorectal literature suggests that bowel preparation can be safely abandoned.

Second-look surgery

According to current American College of Obstetricians and Gynecologists (ACOG) recommendations, second-look laparotomies are not considered the standard of care for dysgerminomas.^[12] . However, second-look surgery should be considered for patients with persistent elevation in tumor markers, especially if associated with abnormal findings on posttreatment imaging.

Management in pregnancy

Most adnexal masses found in pregnancy resolve spontaneously within the first trimester. Two percent of all adnexal masses persisting during pregnancy are malignant (dysgerminomas included). For this reason, a more cautious observational approach is advocated up to 16 weeks' gestation. Moreover, the risk of aborting a viable fetus with surgery in the first trimester approaches 30%.

If surgery is indicated, the ideal intervention time is 16-18 weeks' gestation. General anesthesia should be used. Placement of a higher-than-usual vertical incision is necessary because the ovary becomes an abdominal structure after 16 weeks' gestation.

Frozen sections should be taken at the time of surgery. If the pathology is hyperreactio luteinalis or luteoma, no intervention is indicated and the abdomen should be closed. Since the majority (90%) of dysgerminomas found in pregnancy are unilateral, one should avoid biopsy of the contralateral ovary if this ovary appears normal. Lymphadenectomy may also be limited if the uterus is obstructive to the pelvic sidewalls or paraaortic regions.

Benign or low-grade tumors generally require unilateral salpingo-oophorectomy, whereas bilateral involvement of malignant or widely metastatic tumors requires bilateral salpingo-oophorectomy with or without total abdominal hysterectomy. If patients are at or near term, delivery of the fetus is performed and hysterectomy may be performed.

Postoperative progesterone and uterotonic agents (eg, nifedipine, magnesium sulfate, terbutaline) have unproven efficacy postoperatively for the prevention of preterm labor, so treatment should be individualized and plans made in conjunction with consultation from obstetrical or maternal-fetal medicine specialists.

The 5-year patient survival rate for dysgerminoma in pregnancy is 90%. The fetal mortality rate approaches 25%, especially if surgery is performed in the first trimester.

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Consultations

Consultation with a gynecologic oncologist is recommended when suspicion for an ovarian malignancy is high, especially if resection requires surgery beyond the straightforward unilateral or bilateral salpingo-oophorectomy and hysterectomy.

Further follow-up with a medical oncologist and/or radiation oncologist is dictated by the stage and extent of disease.

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Diet

No specific dietary restrictions are mandated during therapy for dysgerminoma.

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Activity

During the immediate postoperative recovery period, heavy lifting and vigorous activity should be discouraged to prevent strain on the abdominal wound.

Sexual activity should be limited during the postoperative period if hysterectomy was performed. However, sexual activity can resume postoperatively for other patients as long as there is no discomfort. There are no limitations for sexual activity during chemotherapy, although patients may experience vaginal dryness during chemotherapy if menstrual function is reduced.

Attempts to become pregnant should be postponed until completion of postoperative convalescence and/or chemotherapy.

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Complications

Standard surgical complications (eg, bleeding, infection, bowel or bladder injury) and anesthetic complications apply.

Adhesion formation following surgery or radiation therapy can lead to bowel obstruction and/or decreased fertility.

Medical complications from chemotherapy are common. The most common medical complications from chemotherapy for dysgerminomas are bone marrow abnormalities and renal toxicity. Care should be taken to monitor for signs of pulmonary toxicity in patients receiving bleomycin-containing regimens. Secondary malignancies are rare, but leukemias may occur in patients receiving etoposide, especially if doses exceed 2000 mg/m² (ie, >4 cycles of standard BEP [bleomycin, etoposide, platinum] regimen).

Observe pregnant patients with presumed dysgerminoma until 16 weeks' gestation before performing surgery.

Dysgerminomas in patients with karyotypic abnormalities

Remove all gonads in patients with concomitant karyotypic abnormalities, owing to the risk of gonadoblastoma formation.

Five percent of all dysgerminomas are associated with genetic disorders of the ovaries (ie, karyotypic abnormalities [46,XY testicular feminization], gonadal dysgenesis, 45,X/46,XY mixed gonadal dysgenesis). Typically, these individuals have streak gonads. Under these unusual circumstances, the surgeon must remove both the dysgerminoma and the contralateral streak gonad to prevent gonadoblastoma formation. Because these individuals already are sterile, fertility preservation is not an issue.

Individuals with a Y chromosome require a delayed gonadectomy after puberty because secondary sexual characteristics should be allowed to develop before removal.

Medical abnormalities associated with each respective genetic disease also must be addressed.

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Prevention

No methods of deterrence or prevention for this disease are known.

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Long-Term Monitoring

No precise recommendations are known based on any randomized controlled trials. However, follow-up should maximize the ability to identify recurrences while minimizing risks (ie, from repetitive imaging). Follow-up care depends on the stage of disease, which is typically predictive of recurrence risk. Ovarian dysgerminomas tend to recur most often in the first 2-3 years after treatment. Therefore, most authors suggest follow-up observation and a physical examination every 3-4 months for the first 3 years, every 6 months during the fourth and fifth year, and annual surveillance thereafter.

CT imaging should be considered during months 6 and 12, especially if tumor markers were negative at the time of diagnosis. However, the risks of repetitive imaging in women with no symptoms and a normal examination should be considered in this young population of women.

Tumor markers should be drawn (see Lab Studies), especially if known to be elevated preoperatively. The authors recommend following lactate dehydrogenase, but if marker status is unknown, they add serum alpha-fetoprotein (AFP) and beta-human chorionic gonadotropin (beta-hCG). An increasing trend in tumor markers warrants repeat body imaging and possible surgical exploration. Tumor marker levels may begin to rise several months before a clinical recurrence can be identified. Moreover, pregnancy should be ruled out in patients who underwent fertility-sparing surgery and have elevations in AFP and beta-hCG.

Given the potential for late recurrences, patients should be observed for up to 10 years, although they are rare.

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Medication Summary

The goal of pharmacotherapy in most women is remission. During chemotherapy, supportive medications are used to reduce morbidity and prevent the complications of chemotherapy.

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Bleomycin (Blenoxane)

• Dosing, Interactions, etc.

Clinical Context:  Bleomycin is a copper-chelating glycoprotein capable of inducing DNA strand scission breaks via oxidative processes. This drug is eliminated by the kidneys.

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Carboplatin (Paraplatin)

• Dosing, Interactions, etc.

Clinical Context:  Carboplatin is an analog of cisplatin. This is a heavy metal coordination complex that exerts its cytotoxic effect by plastination of DNA, a mechanism analogous to alkylation, leading to interstrand and intrastrand DNA cross-links and inhibition of DNA replication. Carboplatin binds to protein and other compounds containing the SH group. Cytotoxicity can occur at any stage of the cell cycle, but the cell is most vulnerable to action of these drugs in G1 and S phase.

Carboplatin has the same efficacy as cisplatin but with a better toxicity profile. Its main advantages over cisplatin include less nephrotoxicity and ototoxicity not requiring extensive prehydration and less likelihood of inducing nausea and vomiting, but it is more likely to induce myelotoxicity.

The dose is based on the following formula: total dose (mg) = (target AUC) x (GFR+25), where AUC (area under plasma concentration-time curve) is expressed in mg/mL/min and GFR (glomerular filtration rate) is expressed in mL/min.

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Etoposide (Toposar)

• Dosing, Interactions, etc.

Clinical Context:  Etoposide inhibits topoisomerase II and causes DNA strand breakage, causing cell proliferation to arrest in the late S or early G2 portion of the cell cycle.

Therapy should be withheld or suspended if platelet counts are less than 50,000 or absolute neutrophil counts are less than 500/µL.

Reduce the dose by 20% for granulocytic fever or previous radiotherapy.

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Cisplatin (Platinol)

• Dosing, Interactions, etc.

Clinical Context:  Cisplatin inhibits DNA synthesis and, thus, cell proliferation, by causing DNA cross-links and denaturation of the double helix.

In general, the drug should not be administered if the leukocyte count is less than 4000/µL and platelet count is less than 100,000/µL. Cisplatin is renally excreted; those with impaired renal function should postpone therapy. Do not administer to patients with serum creatinine greater than 1.5 mg/dL and BUN greater than 25 mg/dL.

It is administered intravenously in saline solution.

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Class Summary

Treatment entails chemotherapy and radiation therapy. Lesions staged higher than stage Ia require a combination of BEP (bleomycin, etoposide, platinum). Alternate combinations are VAC (vincristine, actinomycin D, cyclophosphamide) or PVB (cisplatin, vincristine, bleomycin), but these combinations have higher toxicity and/or lower response rates. Etoposide and carboplatin should be considered if the patient has significant renal, pulmonary, or neurologic impairment.

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