Malignant ovarian tumours

Lectures on Gynecology

Dr Magda Helmi

The process of malignant change is associated with reproduction and

ovulation, there are two main theories:

I -Incessant ovulation theory: his relates to

continuous ovulation causing repeated trauma to the

ovarian epithelium leading to genetic mutation and

development of a cancer. This is supported by an

increased incidence of “EOC in nulliparous women,

women with early menarche or late menopause and a

reduction in incidence of EOC in multiparous women

and in women who have used oral contraception.

2 -Excess gonadatrophin secretions: This

promotes higher levels of oestrogen which in turn leads

to epithelial proliferation and malignant transformation

of the ovarian epithelium.

Decreased risk of

ovarian cancer

Increased risk of

ovarian cancer

Multiparty Nulliparty

Oral contraceptive

Pill

Intrauterine device

(RR reduced by 20

% per 5 years use)

(RR 1 76)

Tubal Ligation Endometrioses

Hysterectomy Cigarette smoking

(mucinous tumours

only)

Obesity

Risk factors in ovarian cancer

1 Epithelial ovarian tumours (80%) Serous

Mucinous

Endometroid

Clear cell

Undifferentiated

2 Sex cord stromal tumours (10%) Granulosa cell

Sertoli-Leydig

Gynandroblastoma

3 Germ cell tumours ( 10%) Dysgerminoma

Endodermal sinus (yolk sac)

Teratoma

Choriocarcinoma

Mixed4 Metastatic (including Krukenberg tumours)

Classification of malignant ovarian tumours

Epithelial tumours of the ovary can be

benign, malignant or borderline.

Approximately 10 per cent of epithelial

tumours are classified as borderline

tumours.

These tumours are well differentiated

with some features of malignancy but are

characterized by not invading the

basement membrane; borderline

tumours can spread to other structures

(peritoneum, omentum) and rarely recur

following initial surgery.

Staging of ovarian cancerStage Figo definition

I Growth limited to ovaries.

IA Limited to one ovary: no external tumour, capsule intact, no ascites

IB Limited to both ovaries: no external tumour, capsule intact, no ascites

IC Either IB or IB, but tumour on surface of ovary or with capsule ruptured or with ascites positive

for tumour cells

II Growth limited to pelvis

IIA Extension and or metastases to uterus or tubes

IIB Extension to other pelvic organs

IIIC As IIA or IIB, but tumour on surface of ovary or with capsule ruptured or with ascites positive

for tumour cells

III Growth limited to abdominal peritoneum or positive retroperitoneal or inguinallymph nodes

IIIA Tumour grossly limited to pelvis with negative nodes, but histologically confirmed microscopic

peritoneal implants

IIIB Abdominal implants <2 cm in diameter

IIIC Abdominal implants >2 cm diameter or positive retroperitoneal or inguinal lymph nodes

IV Growth involving one or both ovaries with distant metastases, Must have positive cytology on

pleural effusion, liver parenchyma.

EpidemiologyInternationally, the incidence is 3.1 cases per 100,000 women in Japan and 21 cases per 100,000 women in Sweden. Around the world, more than 200,000 women are estimated to develop ovarian cancer every year and about 100,000 die from the disease. Epithelial ovarian cancer occurs most commonly in white women in the industrialized countries of northern and western Europe and North America and least commonly in India and Asia. Asian women have low risk unless they relocate to North America or Europe. Scandinavian and Norwegian women have the highest risk.

Prognosis

Five-year-survival rate for LMP tumors by FIGO stage (survival percentages

rounded to nearest

for epithelial ovarian carcinoma by FIGO stage are as follows:

Stage IA - 87%

Stage IB - 71%

Stage IC - 79%

Stage IIA - 67%

Stage IIB - 55%

Stage IIC - 57%

Stage IIIA - 41%

Stage IIIB - 25%

Stage IIIC - 23%

Stage IV - 11%

Overall survival rate – 46%

For tumors of low malignant potential by FIGO are as follows:

Stage IA - 93%

Stage IB - 90%

Stage IC - 91%

Stage IIA - 88%

Stage IIB - 86%

Stage IIC - 100%

Stage IIIA - 29%

Stage IIIB - 75%

Stage IIIC - 62%

Stage IV - 30%

Overall survival rate - 86%

Carriers of mutations may be detected through laboratory analysis of the genetic structure of white blood cells.Physical findings are uncommon in patients with early

disease. Patients with more advanced disease may

present with ovarian or pelvic mass, ascites, pleural effusion, or abdominal mass or bowel obstruction.

Tumor marker used in ovarian carcinoma

Tumor

marker

Tumor type Uses

Ca 125 Epithelial ovarian cancer (serous), borderline ovarian

tumours

Pre operative, follow

up

Ca 19-9 Epithelial ovarian cancer (mucinous), borderline ovarian

tumours

Pre operative, follow

up

Inhibin Granulosa cell tumours follow up

B-hCG Dysgerminoma, choriocarcinoma Pre operative, follow

up

AFP Endo dermal yolk sack, teratoma Pre operative, follow

up

Decreased risk of ovarian

cancer

Increased risk of ovarian cancer

Multiparty Nulliparty

Oral contraceptive Pill Intrauterine device

(RR reduced by 20 % per 5

years use)

(RR 1 76)

Tubal Ligation Endometrioses

Hysterectomy Cigarette smoking (mucinous

tumours only)

Obesity

Risk factors in ovarian cancer

BiopsyFine-needle aspiration (FNA) or percutaneous biopsy of an adnexal mass is not routinely recommended

Mucinous ovarian carcinoma

Micrograph of serous carcinoma

Imaging

Routine imaging is not required in all patients in whom ovarian cancer is highly suggested. If diagnostic uncertainty is present, a pelvic ultrasound or CT scan of the abdomen and pelvis is warranted.

Chest radiographs are common and considered routine

MRI can increase the specificity of imaging evaluation in cases where the ultrasound appearance of the lesion is indeterminate.

SurgeryIs the initial treatment of choice,

provided patients are medically fit.

Patients who are not fit for surgery may

be given chemotherapy and considered

for surgery later. The aim of surgery is to

confirm the diagnosis, define the extent

of disease, and resect all visible tumors.

Surgical StagingThe staging procedure should include the following:•Peritoneal cytology•Multiple peritoneal biopsies•Omentectomy•Pelvic and para-aortic lymph node sampling.

Cytoreductive SurgeryThis should be performed by a gynecologic oncologist at the time of initial laparotomy, Patients with advanced ovarian cancer are classified in 3 groups as follows, based on the postoperative residual tumor:•Good risk - Microscopic disease outside the pelvis (stage IIIa) or macroscopic disease less than 2 cm outside the pelvis (stage IIIb)•Intermediate risk - Macroscopic disease less than 2 cm outside the pelvis only after surgery•Poor risk - Macroscopic disease more than 2 cm after surgery or disease outside the peritoneal cavity

Interval DebulkingInterval debulking can be performed in patients who were not adequately debulked at the time of initial surgery. It should also be considered in those patients in whom an initial debulking surgery was not attempted.

Choosing Appropriate Surgery

Appropriate surgery depends on whether or

not disease is visible outside the ovaries.

Surgery for patients with stage IV disease

should be individualized, particularly when

disease is in the liver and above the

diaphragm. Patients who are in stage IV

because of small-volume disease in the

liver, abdominal wall, or lung should undergo

cytoreductive surgery if medically fit.

Laparoscopic SurgeryAccording to guidelines developed

by the American College of

Obstetricians and Gynecologists,

laparoscopy may be used for

diagnostic purposes in a patient

with low risk for ovarian cancer and

to remove cystic masses. The mass

must be 10 cm or smaller as viewed

by a sonogram

Secondary SurgerySecondary cytoreductive surgery is safe and effective in patients with platinum-sensitive recurrent ovarian cancer. The surgery is most beneficial in patients who had remained disease free for more than 24 months after primary treatment and in those who achieved optimal cytoreduction.

Chemotherapy RegimensOnly a small percentage of women with epithelial ovarian cancer can be treated with surgery alone. These include patients with stage IA grade 1 and stage IB grade 1.Patients not treated with chemotherapy should be monitored closely at regular intervals, Standard therapy for all patients with advanced disease following surgery is a taxane/platinum combination, usually carboplatin and either paclitaxel or docetaxel for a minimum of 6 courses; however, this may be changing soon. Adding pazopanib, a kinase inhibitor, to the standard postsurgical chemotherapy regimen has shown promise for progression-free survival in advanced ovarian cancer. Patients receiving adjuvant intraperitoneal chemotherapy are more likely to have recurrences outside the abdominal cavity, Postoperative chemotherapy is indicated in all patients with ovarian cancer except those who have surgical-pathologic stage I disease

Intraperitoneal chemotherapyNeoadjuvant chemotherapyMaintenance chemotherapySecond-line chemotherapyHyperthermic intraperitoneal chemotherapyRadiation Therapy.Estrogen Replacement TherapyExperimental Medications

Ovarian adenocarcinoma deposit in the mesentery of the small

bowel

and the omentum

An enlarged ovary with a papillary serous carcinoma on the

surface

Epithelial tumors are found as partially cystic lesions with solid components. The surface may be smooth or covered in papillary projections (see the image below), and the cysts contain fluid ranging from straw-colored to opaque brown or hemorrhagic.

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