Dysgerminoma

Dysgerminoma is the ovarian counterpart of testicular seminoma. It is the most common malignant germ cell tumour of the ovary, accounting for about 30 to 40 percent of malignant germ cell tumours and 1 to 3 percent of all ovarian cancers.

It is typically seen in adolescents and women under 30 (median age 22). It is bilateral in 10 to 20 percent, the highest of any germ cell tumour. About 70 to 75 percent are stage I at diagnosis.

Pure dysgerminoma is composed of large primitive germ cells with clear cytoplasm and vesicular nuclei. The cells are arranged in sheets separated by fibrous septa with lymphocytes. They are positive for OCT3/4, SALL4, CD117 (KIT), D2-40 and PLAP.

It is highly radio- and chemosensitive. 5-year survival is 95 to 100 percent in early disease and about 85 to 90 percent for advanced disease.

About 5 percent occur in dysgenetic gonads with a Y chromosome (Swyer syndrome 46,XY, androgen insensitivity, Turner mosaic 45,X/46,XY), where gonadoblastoma is a precursor. Karyotype is therefore mandatory.

• Rapidly growing abdominal or pelvic mass, abdominal pain or pressure, distension, and early satiety.
• Acute abdomen from torsion, rupture or haemorrhage.
• Primary amenorrhoea or delayed puberty in dysgenetic gonad cases.
• Menstrual irregularity, symptoms of pregnancy mimicry (rarely hCG-secreting).
• Fever, hypercalcaemia (paraneoplastic, rare), and ascites in advanced disease.
• Examination: a solid, lobulated, mobile adnexal mass (about 15 cm on average); signs of ascites, lymphadenopathy, and a bilateral mass.

• Ultrasound and MRI: solid, lobulated mass with fibrovascular septa that enhance intensely.
• CT chest, abdomen and pelvis for stage and nodal involvement. Retroperitoneal para aortic nodes are the main route of spread.
• Tumour markers: lactate dehydrogenase markedly raised (a useful marker of tumour burden). Alpha fetoprotein is normal in pure dysgerminoma; a raised AFP indicates a yolk sac component, i.e. mixed germ cell tumour. hCG is mildly raised in about 5 percent (from syncytiotrophoblast giant cells). CA-125 can be raised.
• Karyotype in all young patients, and especially in those with primary amenorrhoea or virilisation.
• Histological confirmation at surgery; intraoperative frozen section can guide fertility sparing surgery.
• Baseline pretreatment tests: full blood count, renal function, liver function, audiometry, lung function (before bleomycin) and fertility counselling.

• Surgery is the primary treatment.
• Young women wanting fertility: unilateral salpingo oophorectomy with full staging. This comprises peritoneal washings, omentectomy, peritoneal biopsies, and palpation or sampling of pelvic and para aortic nodes. Inspect and biopsy the contralateral ovary only if abnormal; routine wedge biopsy is not advised.
• Preserve the uterus and contralateral ovary even when there is advanced disease, as the tumour is chemosensitive.
• Women who have completed childbearing, or who have dysgenetic gonads (46,XY): hysterectomy and bilateral salpingo oophorectomy; prophylactic gonadectomy in Swyer syndrome.
• Stage IA pure dysgerminoma: surveillance only after surgery. Recurrence is about 15 to 25 percent, salvaged with chemotherapy with survival close to 100 percent.
• Follow up with examination, LDH, and imaging (CT or MRI) every 3 to 4 months for 2 years, then every 6 months to year 5.
• Stage IB or higher: adjuvant chemotherapy with BEP, three to four cycles every 21 days. Give bleomycin 30 units on days 1, 8 and 15 (or 15 units/m2), etoposide 100 mg/m2 intravenously on days 1 to 5, and cisplatin 20 mg/m2 on days 1 to 5.
• Carboplatin with etoposide is an alternative with less toxicity in stage I to II disease: carboplatin AUC 5 to 6 on day 1 and etoposide 120 mg/m2 on days 1 to 3, 3 cycles.
• Give granulocyte colony stimulating factor with severe neutropenia risk.
• Toxicity monitoring: cisplatin nephrotoxicity (hydration, magnesium and potassium supplementation), ototoxicity and neuropathy. Bleomycin pulmonary fibrosis (cumulative dose below 400 units, lung function tests, avoid high inspired oxygen concentrations during anaesthesia). Myelosuppression and infertility risk.
• Radiotherapy is effective but not preferred because it causes ovarian failure and infertility.
• Relapse: salvage chemotherapy with etoposide, ifosfamide and cisplatin (VIP) or paclitaxel, ifosfamide and cisplatin (TIP) for 4 cycles, or high dose chemotherapy with autologous stem cell support. Cure rates are 60 to 80 percent.
• Fertility: ovarian function and fertility are retained in 80 to 90 percent after fertility sparing surgery and chemotherapy. Pregnancy is deferred for 1 to 2 years after therapy. Ovarian function may be protected with a GnRH agonist or by oocyte cryopreservation before chemotherapy.
• Long term follow up: second malignancy, cardiovascular risk, and bone health; yearly clinical assessment, including renal and hearing tests.