Download Carcinoma of the ovary

Carcinoma of the ovary
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.
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
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
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
Subfertility, especially when it is unexplained, is
associated
with both ovarian and endometrial cancer.
However, case-controlled studies have
suggested that there might possibly be a link
between ovarian cancer
and prolonged attempts at induction of
ovulation
3-Genetic factors
Familial ovarian cancer
There is a family history in between 5 and 10 per cent
of women with epithelial 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
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).
BRCA2 is defective in about 14 per cent
Familial ovarian cancer
• Familial ovarian cancer is rare - 5-10%
• Suggestive history
• At least two first-degree relatives with ovarian,
breast or colorectal carcinoma
• Cases usually diagnosed before 50 years of age
• Defective genes include BRCA 1 and BRCA2
• The risk of ovarian cancer (40%) in these families is
less than the risk of breast cancer (80%)
• 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 epith elial tumours (benign,
borderHne or ma'lignant)
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
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
Well-differentiated epithelial carcinomas tend to
more often associated with early-stage
disease
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
*varying degrees of nuclear atypia
*an increase in mitotic activity,
*multi-layering of neoplastic cells
*formation of cellular buds,
*but no invasion of the stroma
*Most borderline tumours remain confined to the
ovaries and this may account for their much better
prognosis
Serous carcinoma
*Most serous carcinomas have both solid and cystic
elements but some may be mainly cystic.
*They often affect both ovaries.
*Well-differentiated tumours have a papillary pattern
with stromal invasion.
*Psammoma bodies (calcospherules) are often
present.
Mucinous carcinoma
Malignant mucinous tumours account for 10 per
cent
of the malignant tumours of the ovary. They are
usually
multilocular, thin-walled cysts with a smooth
external
surface containing mucinous fluid
Mucinous
tumours are amongst the largest tumours of the
ovary and may reach enormous dimensions. A
cyst
diameter of25 cm is quite common
Endometri oid carcinoma
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
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.
In most cases these are two separate primary
tumours
Clear cell carcinoma (mesonephroid)
These are the least common of the malignant
epithelial
tumours of the ovary, accounting for 5-10 per
cent
of ovarian carcinomas
The appearance from which
the tumours derive their name is the clear cell
pattern
but, in addition, some areas show a tubulocystic
pattern with the characteristic 'hob-nail'
appearance of
the lining epithelium.
Natural history
Some two-thirds of patients with ovarian cancer
present with disease that has spread beyond the
pelvis.
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
tumour.
Diagnosis symptoms
*Abdominal pain or discomfort are~he commonest
presenting complaints
*distension or
*feeling a lump the next most frequent.
*Patients may complain of indigestion,
*urinary frequency,
*weight loss r
*rarely, abnormal menses or postmenopausal
bleeding
signs
*A hard abdominal mass arising from the pelvis is
highly suggestive, especially in the presence of
ascites.
*A fixed, hard, irregular pelvic mass is usually felt best
by combined vaginal and rectal examination
*The neck and groin should also be examined
for enlarged nodes.
investigations
*Haematological investigations include a full blood
count, urea, electrolytes and liver function tests.
*A chest X-ray is essential.
* 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
An intravenous pyelogram (IVP) is occasionally
useful. Ultrasonography may help to confirm the
presence of a pelvic mass and detect ascites
before it is
clinically apparent. In conj unction with CA 125
estimation,
it may be used to calculate a 'risk of malignancy
score
Markers for epithelial tumours
CA 125 is the only marker in common clinical use.
It can also be raised in benign conditions such as
endometriosis. 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
FIGO
definition
I
Growth limited to ovaries
II
Growth involving one or both ovaries with
pelvic extension
Growth involving one or both ovaries with
peritoneal implants outside the
pelvis or positive retroperitoneal or inguinal
nodes
Superficial liver metastases equals Stage III
III
IV
Growth involving one or both
ovaries with distant metastases 1
If pleural effusion is present, there
must be positive cytology to allot a
case to Stage IV
Parenchymal liver metastasis equals
Stage IV
treatment
• Depends on
– Staging
– Tumor type
– Age
– Desire for future fertility
• Include surgery, chemotherapy and/or
radiation therapy
Surgery for epithelial ovarian cancer
Primary surgery -to determine diagnosis and
remove tumour
• Total abdominal hysterectomy
• Bilateral salpingo-oophorectom
• Infracolic omentectomy
Conservative primary surgery
• Young, nulliparous woman with Stage la
disease
• No evidence of synchronous endometrial
cancer
• Unilateral salpingo-oophorectomy
Interval debulking surgery
• Women with bulky disease after primary surgery
• Must respond after two to four courses of
chemotherapy
• Chemotherapy resumed after surgery
Second-look surgery
• At the end of chemotherapy
• No place in current management
Borderline tumours
• Ovarian cystectomy or oophorectomy
adequate in
young women
• Hysterectomy and bilateral salpingooophorectomy in
older women
Non-epithelial tumours
• Sex-cord stromal tumour •
• Granulosa cell tumour
• Theca cell tumour
• Sertoli-Leydig tumour
• Germ cell tumour
• Dysgerminoma
• Yolk sac (endodiermal sinus) tumour
• Teratoma
Sex-cord stromal tumour
Granulosa and theca cell tumours
The most common sex cord stromal tumours are
the granulosa and theca cell tumours.
They often produce steroid hormones, in
particular oestrogens, which can cause
*postmenopausal bleeding in older
women
*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.
Sertoli-Leydig cell tumours
Half of these rare neoplasia produce male
hormones
which can cause virilization.
The prognosis for the majority who have
localized disease is good
Germ cell tumours
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
Dysgerminomas are solid tumours which have a
smooth or nodular, bosselated external surface
They may reach a considerable size: the mean
diameter
is 15 cm. 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
Yolk sac (endodermal sinus) tumours
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.
The tumour is usually
well encapsulated and solid.
It often
secretes AFP, which can be used to monitor treatment
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
Cancer from other sites may metastasize to the
overies,there may be microscopic surface
deposits or gross solid or cystic enlargement
of the ovary.
Endometrial carcinoma may spread to the ovary
& other common primary sites are the
colon,stomach&breast.
Krukenberg tumor
Is secondary growth from a mucus-secreting
carcinoma arising in stomach or colon,in
which both ovaries usually involved .
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.
METASTATIC TUMOR FROM GASTRIC CANCER
(Krukenberg )
gastric carcinoma of the fundus, with secondary
ovarian tumor (Mucus-secreting signet-ring cells)
Krukenberg
Tumor:
METASTATIC TUMOR FROM BREAST
CANCER
both ovaries replaced by pale, rather nodular tumor,
with breast cancer cells arranged in long lines
perpendicular to the surface of the ovarian cortex