15

OVARIAN CANCER

Di Wen, M.D.,Ph.D

2003-10-27 Ovarian Cancer 2

Definition Ovarian tumors may arise at any age, but

are commonest between 30 and 60. 1.Ovarian tumors are particularly liable to be

or to become malignant.2.In their early stages they are asymptomatic

and painless.3.They may grow to a large size and tend to u

ndergo mechanical complications such as torsion and perforation.

OVARIAN TUMOURS


Definition

In developed countries ， women have a lifetime risk of developing ovarian cancer of about 1.4% ， which is slightly greater than the risk of cervical or endometrial cancers, but well below the 7% average risk of breast cancer ．

CARCINOMA OF THE OVARY


Risk Factor Genetic factor are sometimes involved 、

as in the Lynch Syndrome of familial breast colorectal and ovarian cancer ． Ovulation induction with Clomiphene over more than year carries a l0-fold increased risk of ovarian cancer, Long-term ora1 contraceptive use reduces the incidence of ovarian cancers ．



Incidence Nearly 25% of all ovarian neoplasm

are malignant ． Approximately 80 ％ of them are primary growths of the ovary 、 the remainder being secondary ，usually carcinomata ．



Primary Carcinoma of the Ovary 80 ％ of all cases of primary carcin

oma of the ovary arise in serous or mucinous cysts.



Solid Carcinoma of the Ovary This accounts for 10% of primary carcino

ma. It is arise commonly bilateral but one tumor is usually larger than the other. The ovarian shape is retained for a time and there is a well-marked pedicle but soon the tumors become fixed. Secondary deposits occur in the omentum and ascites develops.



Symptoms due to Size Lack of any specific symptoms, ovarian tumors are often large by the time the doctor is consulted.

CLINICAL FEATURES OF OVARIAN TUMOURS


Menstrual function is seldom upset, and any irregularity is attributed to the patient’s ‘time of life’.


She may have noticed that her clothes are getting tight ant attributed this to weight gain or, if the abdominal swelling has coincided with amenorrhea she may believe herself to be pregnant.


Pressure Symptoms These are commonly increased frequency

of micturition, gastro-intestinal symptoms and a dull pain in the lower abdomen. Very large tumors may cause respiratory embarrassment and edema or varicosities in the legs, and a characteristic ‘ ovarian cachexia’ develops, due perhaps to interference with alimentary function.



General rule An experienced examiner will

recognize an ovarian tumor mainly because ovarian tumor is, in the circumstances, the most likely diagnosis. All abdominal swellings should be subjected to ultrasound and X-ray examination.

DIFFERENTIAL DIAGNOSIS


ASCITES

A fluid thrill may be elicited from an ovarian cyst, and ascites and tumor may coexist; but as a rule the distinction should be easily made.



Uterine Fibroids

A large midline intramural fibroid may be impossible to distinguish from a solid ovarian tumor until the abdomen is opened and an entirely different surgical problem encountered.



Complications of Ovarian Tumors

This is the commonest complication and may occur with any tumor except those with adhesions. The thin-walled veins of the pedicle are obstructed first while the arterial supply continues. As a result there is hemorrhage into the tumor and into the peritoneum, and if not treated gangrene will occur. Very rarely the pedicle atrophies and the tumor obtains a new blood supply through its adhesions to surrounding viscera (parasitic tumor).

TORSION of the PEDICLE


Clinical FeaturesSubacute The patient complains of recurrent a

bdominal pain which passes off as the pedicle untwists. There is a rise in pulse and temperature during the bleeding; and over a period anemia develops.



Clinical Features Acute The signs and symptoms are those of an ac

ute abdominal condition. The problem becomes one of differential diagnosis to exclude those conditions in which laparotomy is not needed and laparoscopy may be useful.

Pain tends to be intense and continuous.



Clinical FeaturesDifferential Diagnosis ‘Surgical Conditions’ (i.e. those conditio

ns commonly seen and dealt with by a general surgeon.)

Acute appendicitis Meckel’s diverticulitis Obstruction of bowel Diverticulitis



Ruptured Cyst This may occur alone or in

conjunction with torsion. Rupture is not particularly upsetting to the patient unless the contents are irritant.



RUPTURE OF OVARIAN CYST


RUPTURE OF OVARIAN CYST RUPTURE OF OVARIAN CYST



PSEUDOMYXOMA PERITONEI This rare condition occasionally but no

t inevitably follows mthe rupture of a mucinous cystadenoma. The epithelial cells implant on the peritoneum and continue to secrete a gelatinous pseudomucin which is not absorbed, or secretion is faster than absorption. The abdominal cavity is eventually filled with the jelly, while the secreting cells spread over the parietal and visceral peritoneum.



HYDROTHORAX Hydrothorax may accompany ascite

s due to any cause, or may occur as an accompaniment of a lung tumor. The so-called Meigs’ syndrome describes the specific condition of ascites and hydrothorax in conjunction with benign ovarian fibroma.



Features suggestive of malignancy 1.Age. If the patient is over 50 the chance

of malignancy is over 50% as opposed to less than 15% in premenopausal women. Tumors in childhood are usually malignant.

2.Rapid growth.3.Ascites.


Features suggestive of malignancy4.Solid tumours, especially when bilateral.5.Multilocular cysts with solid areas. (At least

10% of cysts are malignant).6.Pain. Pressure pain can occur with any tumo

r; but referred pain suggests malignant involvement of nerve roots.

7.Tumor markers, such as CA125, may be measured in the blood, but a normal level does not exclude malignancy.


Histological Classification Most tumors arise from the ovarian s

troma and germinal epithelium. The embryonic coelom from which that epithelium develops also gives rise to the Mullerian duct from which develop the structures of the genital tract, and it is this common origin which explains the great variety of epithelial patterns which are met with.

OVARIAN TUMOURS


PRIMARY EPITHELIAL TUMOR1.Mucinous cystadenoma or cystadencarcino

ma (of. Cervical epithelium).2.Serous cystadenoma or cystadenocarcinom

a (of . tubal epithelium).3.Endometrioma or Endometrioid carcinoma

(of. Endometrium).4.Clear cell carcinoma.5.Brenner tumour.

OVARIAN TUMOURS


STROMATOUS TUMOURS GERM CELL TUMOURS.Fibroma or sarcoma..Dysgerminoma..Teratoma..Gonadoblastoma..Yolk sac tumour..Carcinoid.Thyroid tumour Choriocarcinoma

OVARIAN TUMOURS


HORMONE-PRODUCING TUMORSEstrogen-producing:Estrogen-producing:

Granulosa cell tumour.Thecoma.

Androgen-prodicing:Androgen-prodicing:Sertoli-Leydig cell tumour (Arrhenoblastoma).Hilar cell tumour.Lipoid cell tumour.

OVARIAN TUMOURS


krukenberg tumour There is one well-known secondary

tumour of the ovary, the krukenberg tumour, a secondary of a stomach carcinoma.

OVARIAN TUMOURS


Definition A unilocular or multilocular cyst of

ovary lined by tall columnar epithelium resembling that of the cervix or large intestine. It is usually large and may reach immense proportions, occupying the whole peritoneal cavity and compressing other organs. It may occur at any age.

OVARIAN TUMOURS --MUCINOUS CYSTADENOMA


signs and symptoms

The signs and symptoms are those generally associated with any non-functioning ovarian tumor. Rupture may occur and seeding of the epithelium on the peritoneal surface may cause pseudomyxoma peritonei.



Definition This is only a third as common as the

serous variety. Malignancy in a mucinous cyst is characterised by the formation of areas of solid carcinoma in the wall. The cells are columnar, show mitoses and tend to form glandular structures.

OVARIAN TUMORS --MUCINOUS CYSTADENOCARCINOMA


Definition

A unilocular or multilocular cyst lined by epithelium similar to the fallopian tube. They are the most common benign epithelial tumors and form 20% of all ovarian neoplasm. In 10% of cases they are bilateral. It is uncommon to find them large than a fetal head.

OVARIAN TUMORS --SEROUS CYSTADENOMA


OVARIAN TUMORS --SEROUS CYSTADENOMA


Definition This is by far the commonest primary carc

inoma, accounting for 60% of all cases, and in over half the cases it is bilateral. The cysts are always of papillary type and the epithelium burrowing through the capsule produces papillary processes on the serous surface. Extension of the growth to the pelvis and adjacent organs fixes the tumor. Ascites is always present.

OVARIAN TUMORS --SEROUS CYSTADENOCARCINOMA


Endometrioid Carcinoma of the Ovary It is now recognized that carcinoma of the

ovary may be of endometrial type, sometimes arising in endometrioma. Attacks of pain, unusual with ovarian cancer, are common. Sometimes there is uterine bleeding in post-menopausal cases.



Endometrioid Carcinoma of the Ovary

Usually the lesion is cystic and chocolate brown in color. If such a cyst ruptures spontaneously, malignancy should be suspected. The histology varies as in uterine carcinoma. It may be a well-differentiated adenocarcinoma, an adeno-acanthoma, mucinous adenocarcinoma or clear-celled carcinoma.



Clear Cell Carcinoma It is doubtful if this exists as a distinct ent

ity. Clear cells may be seen in almost any variety of ovarian carcinoma, but occasionally a carcinoma, usually solid, consists almost entirely of polygonal cells with clear cytoplasm. It behaves in the same way as any other solid carcinoma and has the same prognosis.



Secondary Carcinoma of the Ovary

The ovary may be the site of secondary deposits from growths arising in other parts of the genital tract. These are usually overshadowed by the clinical manifestations of the primary growth.



Secondary Carcinoma of the Ovary

Ovarian metastases from extra-

genital tumors are not uncommon. The commonest sites of primary growth are breast, stomach and large intestine.



FIBROMA

This is composed of fibrous tissue and resembles fibromata found elsewhere. It is most common in the elderly and accounts for 4-5% of all ovarian neoplasm.

The fibroma is believed by many to be a thecoma which has undergone fibrous transformation. It is sometimes associated with Meig’s syndrome.



GERM CELL TUMOURS There are four main types of gern cell tu

mour:.Dysgerminoma;.Tumours of tissues found in the embryo or adult ---- the teratomata;.Tumours of dysgenetic gonads ---- commonly a gonadoblastoma;.Tumours of extra-embryonic tissues such as choriocarcinoma or yolk sac tumour.



Dysgerminoma This is the only solid ovarian tumor of cha

racteristic appearance. Usually ovoid with a smooth capsule, it is of rubbery consistency and greyish colour. It is commonest in younger age groups, under 30 years as a rule, and is often bilateral. Sometimes it is found in cases of intersex.



Yolk sac tumor This is a rare tumor found in children

and young adults. It has a variable histological structure and is highly malignant. The main interest lies in the fact that it produces alphafetoprotein and the blood levels can be used as a diagnostic test and as a means of monitoring response to treatment.



Estrogen-producing Tumors These belong to the granulosa-theca

cell group and are found at all ages. They account for 3% of all solid tumors of the ovary.



Estrogen-producing Tumors In childhood there is accelerated

skeletal growth and appearance of sex hair. 5% occur in children precocious puberty. 60% occur in child-bearing years

irregular menstruation. 30% occur in post-menopausal women

post-menopausal bleeding.



ANDOROGEN-PRODUCING TUMOURS

Three distinct types of masculinising ovarian tumor are recognised: a) Sertoli-Leydig cell tumor (Arrhenoblastoma), b) Hilar cell tumor, c) Lipoid cell tumor. All three cause amenorrhoea.



Direct The first spread is directly into neigh

bouring structures – peritoneum, uterus, bladder, bowel and omentum.

Spread of Ovarian Cancer


Lymphatics Ovarian drainage is to the para-aortic glan

ds, but sometimes to the pelvic and even inguinal groups. Cells seeded on to the peritoneum are drained via the lymphatic channels on the underside of the diaphragm into the subpleural glands and thence to the pleura.



Blood stream Blood spread is usually late, to

the liver and lungs.



General Principle1.To classify the growth according to its

extent of spread (staging) as accurately as possible.

2.To remove as much cancerous tissue as possible (‘surgical debulking’;’cyto-reductive treatment’).

SURGICAL PROCEDURES IN OVARIAN CANCER


General Rule Benign ovarian over 10 cm in diameter mu

st be removed, but clinical and ultrasonically diagnosed cysts under 10 cm (the size of a lemon) in women under 35 years may be reviewed in a few months if there is no suspicion of malignancy. A follicular or luteral cyst may resolve spontaneously.

SURGICAL TREATMENT OF OVARIAN TUMMOURS


General Principle Much attention is being directed

towards the treatment of epithelial ovarian cancer which is now the most frequent cause of death from gynecological malignancy. The principles of treatment are:

TREATMENT OF OVARIAN CANCER


General PrincipleOvarian carcinoma is staged surgically, so lap

arotomy is an essential part of management for most patients.

Surgical removal of as much malignant tissue as possible, even if this should call for resection of structures outside the normal field of the gynecologist.



General PrincipleFollow-up with intensive chemotherapy, usin

g various combinations of antineoplastic drugs. Taxanes, probably combined with platinum compounds, are an appropriate first choice.

A ‘second look’ laparotomy or laparoscopy operation (SLO), to determine the actual effectiveness of the chemotherapy and to decide whether it should be stopped does not affect prognosis, so should only be performed with informed consent in clinical trials.



Incision A vertical incision which can be exte

nded is essential to allow a full inspection. Reduction of a cyst by tapping and extraction through a suprapubic incision is not acceptable practice.



Cytology Before handling the tumour, take sp

ecimens of ascitic fluid or peritoneal saline washings for cytological examination, and a cytology smear from the underside of the diaphragm.


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