Malignant tumours of the ovary: د.نادية مضر الحلي
Most ovarian tumours are of epithelial origin. These are rare before the age of 35 years. The incidence increases with age to peak in the 50-70 years old age group.
Aetiology:
• Incessant ovulation theory: epithelial tumours are most frequently associated with nulliparity, an early menarche, a late age at menopause & a high estimated number of years of ovulation. Oral contraceptive use reduces the risk fourfold.
• Subfertility treatment: there might be a link between ovarian cancer & prolonged attempts at induction of ovulation.
• Genetic factors:
Familial ovarian cancer: There is a positive family history in 5-10 % of women with epithelial ovarian cancer. A woman with one effected close relative has a lifetime risk twice that in the general population. A particular feature of familial cancers is the relatively early age at which they occur. Most of these families also have cases of breast or colorectal cancer in the family. The defective gene is most commonly the tumour-suppressor gene BRCA1 (80% of cases), BRCA2 (14% of cases).
Management of women with a family history of ovarian cancer:
Once identified, women with a high risk of ovarian & breast cancer are difficult to advise. Annual ovarian ultrasonography with a color-flow Doppler studies & serum CA 125 estimation every 6-12 months are recommended, but it is uncertain how much protection this offers. Prophylactic bilateral oophorectomy, combined with hysterectomy is recommended for clearly defined high-risk women after completion of their family after 45 years of age.
Classification of malignant ovarian tumours:
1. Epithelial tumours:
• Serous cystadenocarcinoma
• Mucinous cystadenocarcinoma
• Endometrioid cystadenocarcinoma
• Clear cell (mesonephroid ) tumour
• Brenner tumour
• Undifferentiated carcinoma
2. sex cord tumours
• Granulosa cell tumour
• Androblastoma ( Sertoli-Leydig cell tumour)
• Gynandroblastoma
3. Germ cell tumour
• Dysgerminoma
• Endodermal sinus tumour (yolk sac tumour)
• Embryonal cell tumour
• Choriocarcinoma
• Teratoma
• Mixed tumours
4. Metastatic tumours
Serous cystadenocarcinoma: have both solid & cystic components, affect both ovaries. Well differentiated tumours have papillary pattern & stromal invasion with psammoma bodies inside. At the other end of the spectrum anaplastic tumour composed of sheets of undifferentiated neoplastic cells.
Mucinous cystadenocarcinoma: usually multilocular, thin-walled cysts with smooth external surface containing mucinous fluid. They are amongst the largest tumours of the ovary.
Endometrioid cystadenocarcinoma: resemble endometrial carcinoma. Most are cystic, unilocular & contain turbid brown fluid. 15% of cases are associated with endometrial carcinoma of the body of the uterus.
Clear cell carcinoma (mesonephroid): The least common of ovarian carcinoma, has characteristic "hob-nail" appearance of the lining epithelium.
Borderline epithelial tumours: these have some features of malignancy but they lack stromal invasion. They constitute 10% of epithelial ovarian tumours. They show varying degrees of nuclear atypia & increased mitotic activity, multilayring of neoplastic cells& formation of cellular buds but no stromal invasion. Most of them confined to the ovaries & therefore have much better prognosis. Most borderline tumours are serous or mucinous in type.
Natural history: two third of patients present with the disease has spread beyond the pelvis. This is due to the insidious onset of signs & symptoms although some times it is due the rapidly growing tumour. Also because of non-specific nature of symptoms & sign, the diagnosis is reached when the cancer is in advanced stage.
Metastatic spread: The pelvic peritoneum & other pelvic organs are involved by direct spread. Peritoneal fluid, flowing to lymphatic channels on the undersurface of the diaphragm, carries malignant cells to all intra-abdominal structure surfaces. Lymphatic spread involve pelvic & para-aortic lymph nodes, nodes in the neck & inguinal region. Haematogenous spread occurs late in the course of disease involving liver & lung, sometimes bone & brain.
Clinical staging:
Stage Figo definition
I growth limited to ovaries
Ia growth limited to one ovary, no ascites, no
tumour on external surface, capsule intact
Ib growth limited to both ovaries, no ascites, no
tumour on external surfaces, capsule intact
Ic tumour either stage Ia or Ib but tumour on surface of one or both ovaries or with capsule rupture or with ascites present containing malignant cells or with positive peritoneal washing
II growth involving one or both ovaries with pelvic extension
IIa extension &/or metastasis to the uterus or tubes
IIb extension to other pelvic tissues
IIc tumour either stage IIa or IIb but tumour on surface of one or both ovaries or with capsule rupture or with ascites containing malignant cells or with positive peritoneal washing
III growth involving one or both ovaries with peritoneal implants outside the pelvis or positive retroperitoneal or inguinal nodes
Superficial liver metastasis equals stage III
IIIa tumour grossly limited to the true pelvis with negative nodes but with histologically confirmed microscopic seeding of abdominal peritoneal surfaces
IIIb tumour with histologically confirmed implants on abdominal peritoneal surfaces, non-exceeding 2 cm in diameter, nodes are negative
IIIc abdominal implants > 2cm in diameter or positive retroperitoneal or inguinal nodes
IV growth involving one or both ovaries with distant metastasis, if pleural effusion is present, there must be positive cytology to allot a case to stage IV
parenchymal liver metastasis equal stage IV.
Presentation: abdominal pain & discomfort, feeling of a lump, indigestion, urinary frequency, weight loss, abnormal menses or postmenopausal bleeding. A hard mass arising from the pelvis is highly suggestive of malignancy especially in the presence of ascites. A fixed, hard, irregular mass may be felt. The neck & groin should be examined for enlarged nodes.
Haematological investigations include FBC, urea, electrolyte, & LFT. Ultrasonography, chest X-ray & barium enema or colonoscopy are all important.
Surgery: is the mainstay for both diagnosis & treatment. Therapeutic objective is to remove all the tumour. While surgery alone is curative in many stage I cases, additional therapy is required in most of the remainder. Surgery includes total hysterectomy, bilateral salpingo-oophorectomy & infracolic omentectomy. In young nulliparous woman with unilateral tumour & no ascites, unilateral salpigo-oophorectomy may be justified after exploration to exclude metastatic disease & curettage of the uterine cavity to exclude synchronous endometrial tumour. If the tumour is subsequently found to be poorly differentiated or the washing is positive, a second operation to clear the pelvis will be necessary. When bulky disease remains after initial surgery, chemotherapy should be given in two to four courses then a second laparotomy is performed after which chemotherapy is resumed as soon as possible. This is called interval debulking surgery.
In borderline tumours ovarian cystectomy or oophorectomy are adequate in young women while hysterectomy & bilateral salpingo-oophorectomy is advisable for older women.
Chemotherapy: is indicated for those with stage II-IV & possibly stage Ic. Chemotherapy is given to prolong clinical remission & survival, & for palliation in advanced & recurrent disease.It is usually commenced soon after surgery & is given for 5 or 6 cycles at 3-4 weeks intervals. The platinum drugs, cisplatin & its analogue carboplatin are heavy metal compounds which cause cross-linkage of DNA strands. They are the most effective & widely used in the management of ovarian carcinoma. Cisplatin is very toxic, side effects include persistant nausea & vomiting, permanent renal damage if not given with adequate hydration, peripheral neuropathy & hearing loss & electrolyte disturbance, marrow toxicity is unlikely.
Carboplatin is as effective as cisplatin but with lesser side effects.
Paclitaxel is given in combination with cisplatin or carboplatin as first-line treatment. Side effects include sensory neuropathy & neutropenia, myalgia & arthralgia, hair loss is usually total.
Prognosis:
Borderline tumours: excellent long term prognosis in most cases.
Invasive tumours: 5-year survival rate is 90% for stage Ia & Ib well or moderately differentiated tumours, 10% for stage III.
Non-epithelial tumours:
Sex cord stromal tumours:
Granulosa & theca cell tumours: they often produce steroid hormones. The staging system is the same as for epithelial tumours. Most present as stage I. they are mostly solid. The cut surface is yellow because of neutral lipid related to sex steroid production.
Treatment: surgical treatment is the same as for epithelial tumours. Unilateral oophorectomy is indicated in young women with stage Ia disease. The 5-year survival is 80% overall but recurrence is associated with high mortality.
Sertoli-leydig cell tumours: half of these tumours produce male hormones causing virilization. Prognosis is good for early stage disease, treatment is the same as for granulosa cell tumours.
Germ cell tumours:
Dysgerminoma: usually occur in women < 30 years old. Serum alpha-fetoprotein & beta-hCG must be assayed to exclude the ominous presence of elements of choriocarcinoma, endodermal sinus tumour or teratoma. Pure dysgerminoma have good prognosis as they are usually stage Ia.
Dysgerminoma are solid with smooth or nodular, bosselated surface. They are soft or rubbery in consistency. Elements of immature teratoma, yolk sac tumour or choriocarcinoma can be found in 10% of cases which are more malignant.
Yolk sac (endodermal sinus) tumors: It may present as an acute abdomen due to rupture of the tumour following necrosis & haemorrhage. The tumour is well encapsulated & solid. It often secretes AFP, which can be used to monitor treatment.
Immature Teratoma: composed of wide variety of tissues. They are solid with smooth surface.
Treatment: Early disease is treated by surgery. In young women with stage Ia, unilateral oophorectomy may suffice, but in older patients hysterectomy & bilateral salpingo-oophorectomy is recommended. Stage I malignant teratoma & dysgerminoma may be followed up closely without further treatment. For the remainder, chemotherapy is required with good prognosis.