B24. Gonadal ovarian tumors

Ovarian germ cell tumours

Ovarian germ cell tumours are those ovarian tumour which originate from primordial germ cells in the ovary. These can develop into foetus-like structures, placenta-like structures, extraembryonal structures, or grow completely undifferentially. It’s a heterogenous group of tumours with many different types with different characteristics.

Germ cell tumours account for < 3% of ovarian cancers. They mostly affect younger women, rarely affecting those over 30. They’re most commonly benign. Most are diagnosed at an early stage and are highly curable (5-year survival > 95%).

Classification

• Teratoma
  • Dermoid cyst (mature teratoma)
  • Immature teratoma
  • Struma ovarii
• Dysgerminoma
• Yolk sac tumour
• Embryonal carcinoma

A teratoma is a germ cell tumour which grows into somatic structures originating from ectoderm, endoderm, and mesoderm. They may contain structures like hair and teeth. The benign mature teratoma (dermoid cyst) is more common than the malignant immature teratoma. Struma ovarii is a rare type of teratomy which consists of thyroid tissue and produces thyroid hormones. Anti-NMDA receptor encephalitis is associated with teratomas.

A dysgerminoma is a germ cell tumour which has grown into an undifferentiated structure. It’s more frequent in those with streak gonads (see topic B5). It’s the most common malignant ovarian germ cell tumour.

A yolk sac tumour is a germ cell tumour which has grown into a yolk sac-like structure. They characteristically produce AFP.

Embryonal carcinoma of the ovary is one of the most aggressive ovarian tumours. It’s very rare.

Many germ cell tumours can be bilateral, especially dysgerminoma.

Clinical features

Germ cell tumours grow quickly and therefore often cause pelvic pain or symptoms of bladder or bowel compression. They may also cause abdominal distension (like other ovarian tumours).

Diagnosis and evaluation

It’s important to distinguish germ cell tumours from other ovarian tumours during the diagnostic evaluation, as the treatment is different.

The basic evaluation is the same as for other suspected ovarian tumours (physical examination, ultrasonography, imaging to look for spread). Germ cell tumours are more often solid on ultrasound than epithelial tumours. Because germ cell tumours frequently are bilateral, both sides must be examined (bilateral examination is performed routinely in all cases anyway).

If germ cell tumour is suspected in a young girl, we may perform karyotyping (as the probability of intersex disorder is high).

Ovarian germ cell tumours often produce tumour markers, especially hCG, AFP, and lactate dehydrogenase (LDH).

The diagnosis is highly suggested preoperatively when an adnexal mass has been diagnosed on imaging and the level of tumour markers is elevated. Like for other ovarian tumours, the histological diagnosis is made at the time of surgical excision.

Treatment

These tumours often occur in fertile women, and as such special measures should be taken to preserve fertility if possible, if the patient wants to. If a germ cell tumour is highly suspected, bilateral oophoerctomy may not be required, and we may opt for fertility-sparing surgery instead (unilateral salpingo-oophorectomy with preservation of the uterus).

If the contralateral ovary appears to also be affected by the tumour at the time of surgery, we may resect this tumour affection while preserving the rest of the contralateral ovary to preserve fertility. Even if the whole tumour can’t be removed during surgery, cure is likely with adjuvant chemotherapy.

Adjuvant chemotherapy cures most patients with germ cell tumours as they’re highly chemosensitive. The standard chemotherapy regimen consists of bleomycin, etoposide, and carboplatin/cisplatin (BEP).

Ovarian sex cord-stromal tumours

In an earlier version of this topic, I’d mistakenly believed that the topic name referred to ovarian sex cord-stromal tumours. Now, I’m sure that it actually refers to ovarian germ cell tumours (as the topics are identical for German and Hungarian program and the German and Hungarian names for this topic is literally “germ cell tumours”). Not sure how I made that mistake. I’ll leave the sex cord-stromal tumour topic below, but it shouldn’t be necessary to know.

Ovarian sex cord-stromal tumours (SCSTs) are a group of ovarian tumours. Some of them are benign, some of them are malignant. These tumours arise from sex cord cells, like Sertoli or granulosa cells, or from stromal cells, like fibroblasts and gonadal stroma.

In contrast to epithelial ovarian cancers, malignant SCSTs are often diagnosed at an early stage, and so the prognosis is good. SCSTs account for < 5% of all ovarian tumours.

Classification

WHO classifies SCSTs as the following:

• Pure stromal tumours
  • Fibroma
  • Thecoma
  • Fibrosarcoma
  • Leydig cell tumour
• Pure sex cord tumours
  • Granulosa cell tumour
  • Sertoli cell tumour
• Mixed sex cord-stromal tumours
  • Sertoli-Leydig cell tumour

We can also classify them according to their dignity:

• Benign tumours
  • Fibroma
  • Thecoma
• Malignant tumours
  • Fibrosarcoma
  • Granulosa cell tumour
• May be benign or malignant
  • Sertoli-Leydig cell tumour (adrenoblastoma)
  • Sertoli cell tumour

Most types are most prevalent in postmenopausal women. The only exception is Sertoli-Leydig cell tumour, which primarily affects 30 – 40 year old women.

Fibroma is the most common benign SCST, while granulosa cell tumour is the most common malignant SCST.

Clinical features

Fibromas may present as Meigs syndrome, which is the presence of ascites and/or hydrothorax simultaneously as a fibroma.

Granuloma cell tumour produce oestrogens. Thecomas are often mixed with granulosa cells and can therefore also be oestrogen-secreting. The symptoms of this depends on the age of the patient:

• Before puberty – causes precocious puberty
• Reproductive age – causes bleeding disorder (metrorrhagia, hypermenorrhoea)
• After menopause – causes postmenopausal bleeding

Sertoli-Leydig cell tumours produce androgens, which may cause virilisation, hirsutism, acne, etc.

SCSTs present similarly as epithelial or germ cell ovarian tumours, with some exceptions.

General symptoms of ovarian cancer include (from topic A11):

• Asymptomatic
• Abdominal enlargement
  • Sometimes due to ascites
• Symptoms of pressure on surrounding organs
  • Dysuria
  • Constipation
  • UTI
• Symptoms relating to complications of the tumour (usually acute)
  • Torsion – acute pain and vomiting
  • Rupture – generalised abdominal pain
  • Haemorrhage – abdominal pain and haemorrhagic shock

Diagnosis and evaluation

Diagnosis and evaluation are the same as for other ovarian cancers, except that hormones should be measured depending on the symptoms of the patient.

From topic A11:

Physical examination should be performed for an adnexal mass as well as inguinal and cervical lymphadenopathy. Ultrasound of the adnexal mass can reveal a solid mass, ascites. Chest, abdominal, and pelvic CT or MRi are used to look for ascites and diseases spread.

There are some tumour markers which may be elevated in ovarian cancer. These are mainly used for follow-up rather than for diagnosis:

• CA-125
• HE4
• β-hCG
• AFP

The diagnosis of ovarian cancer is histological and is generally made based on the excised tumour after exploratory laparotomy. Biopsy causes tumour seeding and is not performed, so histology can only be performed after surgical excision.

Treatment

The treatment of malignant SCSTs is generally the same as for other ovarian cancers and includes bilateral salpingo-oophorectomy (adnexectomy) and total hysterectomy.

Adjuvant chemotherapy may be used in some cases.

Surgical removal of the tumour generally causes resolution of the tumours effects. In patients with Meigs syndrome, surgical removal of the fibroma leads to complete resolution of the symptoms. In patient with hormonal changes, these changes are reversed after surgery.