Lecture 8
النسائية
د
. سجى
Carcinoma of the ovary
Page 1 of 9
Carcinoma of the ovary
o Carcinoma of the ovary is most common in the wealthy
nations of the world. There are just under 6000 cases each year in the UK.
o While the incidence of ovarian cancer is similar to that of endometrium
and of cervix, more women die from ovarian cancer than from carcinoma
of the cervix and body of the uterus combined
Aetiology
1-'Incessant ovulation' theory
o Epithelial tumours are most frequently associated with nulliparity, an
early menarche, a late age at menopause and a high estimated number of
years of ovulation
o Oral contraceptive use reduces the risk fourfold, However, even without
oral contraceptives, increasing age at first birth reduces the risk OF
ovarian cancer
2-Subfertility treatment
o Subfertility, especially when it is unexplained, is associated with both
ovarian and endometrial cancer.
o However, case-controlled studies have suggested that there might possbly
be a link between ovarian cancer and prolonged attempts at induction of
ovulation
3-Genetic factors
Familial ovarian cancer
o There is a family history in between 5 and 10 per cent of women with
eithelial ovarian cancers – usually serous adenocarcinomas, A woman
with one affected close relative has a lifetime risk of 2.5 per cent, twice
the risk in the general population. With two affected close relatives, the
lifetime risk increases to 30-40 per cent, A particular feature of familial
cancers is the relatively early age at which they occur
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Lecture 8
النسائية
د
. سجى
Carcinoma of the ovary
Page 2 of 9
o Most of these families also have cases of breast or colorectal cancer in the
family. The defective gene in the breast/ovary famil ies is most commonly
the tumour-supp ressor gene BRCAI (81 per cent).
o BRCA2 is defective in about 14 per cent
o Familial ovarian cancer is rare - 5-10%
o Suggestive history:
At least two first-degree relatives with ovarian, breast or colorectal
carcinoma
Cases usually diagnosed before 50 years of age
o Defective genes include BRCA 1 and BRCA2
o The risk of ovarian cancer (40%) in these families is
o less than the risk of breast cancer (80%)
o Genetic testing cannot guarantee to detect all defective genes
Classification of ovarian tumours
Ovarian tumours can be solid or cystic. They may be benign or malignant
and in addition there are those that, while having some of the features of
malignancy, lack any evidence of stromal invasion. These are called
borderline tumours.
Simplified histological classification of ovarian tumours
I- Common epithelial tumors (benign, borderline or malignant)
A. Serous tumour
B. Mucinous tumour
C. Endometrioid tumour
D. Clear cell (mesonephroid) tumour
E. Brenner tumour
F. Undifferentiated carcinomas
II Sex cord stromal tumours
A. Granulosa stroma cell tumour
B. Androblastoma: Sertoli-Leydig cell tumour
C. Gynandrobl'astoma
Lecture 8
النسائية
د
. سجى
Carcinoma of the ovary
Page 3 of 9
III Germ cell tumours
A. Dysgerminoma
B. Endodermal sinus tumour (yolk sac tumour)
C. Embryonal cell tumour
D. Choriocarcinoma
E. Teratoma
F. Mixed tumours
IV Metastatic tumours
Pathology of epithelial tumours
o Well-differentiated epithelial carcinomas tend to more often associated
with early-stage disease
o Mucinous and endometrioid lesions are likely to be associated with an
earlier stage and lower grade than Serous cystadenocarcinomas
Borderline epithelial tumours
Ten per cent of all epithelial tumours of the ovary are of borderline
malignancy.
These show:
1. Varying degrees of nuclear atypia
2. An increase in mitotic activity,
3. Multi-layering of neoplastic cells
4. Formation of cellular buds,
5. But no invasion of the stroma
6. Most borderline tumours remain confined to the ovaries and this
may account for their much better prognosis
Serous carcinoma
o Most serous carcinomas have both solid and cystic elements but some
may be mainly cystic.
o They often affect both ovaries.
Lecture 8
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. سجى
Carcinoma of the ovary
Page 4 of 9
o Well-differentiated tumours have a papillary pattern with stromal
invasion.
o Psammoma bodies (calcospherules) are often present.
Mucinous carcinoma
o Malignant mucinous tumours account for 10 per centof the malignant
tumours of the ovary. They are usually multilocular, thin-walled cysts
with a smooth external surface containing mucinous fluid
o Mucinous tumours are amongst the largest tumours of the ovary and may
reach enormous dimensions. A cyst diameter of25 cm is quite common
Endometrioid carcinoma
o These are ovarian tumours that resemble endometrial carcinomas. Most
are cystic, often unilocular, and contain turbid brown fluid. Five to 10 per
cent are seen in continuity with recognizable endometriosis
o It is important to note that 15 per,_ cent of endometrioid carcinomas of
the ovary are associated with endometrial carcinoma in the body ofthe
uterus.
o In most cases these are two separate primary tumours
Clear cell carcinoma (mesonephroid)
o These are the least common of the malignant epithelial tumours of the
ovary, accounting for 5-10 per cent of ovarian carcinomas
o The appearance from which the tumours derive their name is the clear cell
pattern but, in addition, some areas show a tubulo-cystic pattern with the
characteristic 'hob-nail' appearance of the lining epithelium.
Natural history
o Some two-thirds of patients with ovarian cancer present with disease that
has spread beyond the pelvis.
o This is probably due to the insidious nature of the signs and symptoms of
carcinoma of the ovary, but may sometimes be due to a rapidly growing
Lecture 8
النسائية
د
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Carcinoma of the ovary
Page 5 of 9
tumour.
Diagnosis
Symptoms
1. Abdominal pain or discomfort are the commonest presenting
complaints
2. Distension or
3. Feeling a lump the next most frequent.
4. Patients may complain of indigestion,
5. Urinary frequency,
6. Weight loss r
7. Rarely, abnormal menses or postmenopausal bleeding
Signs
1. A hard abdominal mass arising from the pelvis is highly suggestive,
especially in the presence of ascites.
2. A fixed, hard, irregular pelvic mass is usually felt best by combined
vaginal and rectal examination
3. The neck and groin should also be examined for enlarged nodes.
Investigations
1. Hematological investigations include a full blood count, urea, electrolytes
and liver function tests.
2. A chest X-ray is essential.
3. It is sometimes advisable to carry out a barium enema or colonoscopy to
differentiate between an ovarian and a colonic tumour and to assess bowel
involvement from the ovarian tumour itself
4. An intravenous pyelogram (IVP) is occasionally useful.
5. Ultrasonography may help to confirm the presence of a pelvic mass and
detect ascites before it is clinically apparent. In conjunction with CA 125
estimation, it may be used to calculate a 'risk of malignancy score
Lecture 8
النسائية
د
. سجى
Carcinoma of the ovary
Page 6 of 9
Markers for epithelial tumours
o CA 125 is the only marker in common clinical use.
o It can also be raised in benign conditions such asendometriosis. CA 125 is
useful for monitoring women receiving chemotherapy to assess response.
A persistent rise in CA 125 may precede clinical evidence of recurrent
disease by several months in some cases.
FIGO staging for primary ovarian carcinoma
Stage
FFIGO definition
I
o Growth limited to ovaries
II
o Growth involving one or both ovaries with pelvic
extension
III
o Growth involving one or both ovaries with peritoneal
implants outside the pelvis or positive retroperitoneal
or inguinal nodes
o Superficial liver metastases equals Stage III
IV
o Growth involving one or both ovaries with distant
metastases 1
o If pleural effusion is present, there must be positive
cytology to allot a case to Stage IV
o Parenchymal liver metastasis equals Stage IV
Treatment
Depends on
1. Staging
2. Tumor type
3. Age
4. Desire for future fertility
Include surgery, chemotherapy and/or radiation therapy
Surgery for epithelial ovarian cancer
Lecture 8
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Carcinoma of the ovary
Page 7 of 9
Primary surgery -to determine diagnosis and remove tumour
1. Total abdominal hysterectomy
2. Bilateral salpingo-oophorectom
3. Infracolic omentectomy
Conservative primary surgery
1. Young, nulliparous woman with Stage la disease
2. No evidence of synchronous endometrial cancer
3. Unilateral salpingo-oophorectomy
Interval debulking surgery
1. Women with bulky disease after primary surgery
2. Must respond after two to four courses of chemotherapy
3. Chemotherapy resumed after surgery
Second-look surgery
1. At the end of chemotherapy
2. No place in current management
Borderline tumours
1. Ovarian cystectomy or oophorectomy adequate in young women
2. Hysterectomy and bilateral salpingo-oophorectomy in older women
Non-epithelial tumours
Sex-cord stromal tumour
A. Granulosa cell tumour
B. Theca cell tumour
C. Sertoli-Leydig tumour
Germ cell tumour
A. Dysgerminoma
Lecture 8
النسائية
د
. سجى
Carcinoma of the ovary
Page 8 of 9
B. Yolk sac (endodiermal sinus) tumour
C. Teratoma
Sex-cord stromal tumour
A.
Granulosa and theca cell tumours
o The most common sex cord stromal tumours are the granulosa and theca
cell tumours.
o They often produce steroid hormones, in particular oestrogens, which can
cause:
1. Postmenopausal bleeding in older women
2. and sexual precocity in pre-pubertal girls.
Pathology
Granulosa cell tumours are normally solid, but cystic spaces may develop
when they become large, like most tumours of the sex cord stromal tumour
group, the cut surface is often yellow because of neutral lipid related to sex
steroid hormone production.
B.
Sertoli-Leydig cell tumours
o Half of these rare neoplasia produce male hormones which can cause
virilization.
o The prognosis for the majority who have localized disease is good
Germ cell tumours
A.
Dysgerminomas
Dysgerminomas account for 2-5 per cent of all primary malignant ovarian
tumours. Nearly all occur in young women less than 30 years old. They
spread mainly by lymphatics
Pathology
o Dysgerminomas are solid tumours which have a smooth or nodular,
bosselated external surface
o They may reach a considerable size: the mean diameter is 15 cm.
Lecture 8
النسائية
د
. سجى
Carcinoma of the ovary
Page 9 of 9
Approximately 10 per cent are bilateral Elements of immature teratoma,
yolk sac tumour or choriocarcinoma are found in about 10 per cent of
dysgerminomas.l
B.
Yolk sac (endodermal sinus) tumours
o Is the second most common malignant germ cell tumour of the ovary,
making up 10-15 per cent overall and reaching a higher proportion in
children.
o The tumour is usually well encapsulated and solid.
o It often secretes AFP, which can be used to monitor treatment
C.
Teratoma
Immature teratomas are composed of a wide variety of tissues and comprise
about 1 per cent of all ovarian teratomas, They are unilateral in almost all
cases and appear as solid masses
Metastatic Tumors of Ovary
o Cancer from other sites may metastasize to the overies,there may be
microscopic surface deposits or gross solid or cystic enlargement of the
ovary.
o Endometrial carcinoma may spread to the ovary & other common primary
sites are the colon, stomach & breast.
Krukenberg tumor
o Is secondary growth from a mucus-secreting carcinoma arising in
stomach or colon,in which both ovaries usually involved .
o The tumor histologically characterized by signet ring cells ,these have
accumulated mucoid substance in the cytoplasm so the nucleus is
displaced right to the edge of the cells.
By: Mu’taz Fathi