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THE OVARY
Adekunle A.O. 1
MALIGNANT TUMOURS OF THE
OVARY
ENABLING OBJECTIVES
Mention the incidence of malignant ovarian
tumours, and aetiology including genetic
factors;
Classify ovarian tumours;
Describe the essential features of each type;
Discuss the clinical staging of ovarian
tumours;
Discuss the diagnosis and management of
malignant ovarian tumours.
Adekunle A.O.
2
Malignant Tumours of the Ovary
The incidence of carcinoma of the ovary is
increasing steadily.
It is a leading cause of cancer deaths in
women being surpassed only by cancer of
the breast, cervix, lungs, colon and rectum.
Ca ovary is unusual before the age of 20, but
it increases steadily thereafter.
The average age at which it is diagnosed is
about 50.
It occurs somewhat more often in whites
than un blacks.
Adekunle A.O.
3
Malignant Tumours of the Ovary
The lesions are far advanced and impossible
to cure when the patient first seeks
treatment.
She may have had a mild GIT disturbance,
which she attributes to “indigestion,” and
perhaps a slight increase in girth but no
other symptom.
She often presents only after she feels a
mass in the abdomen or has an attack of
pain.
Less than 25% of women with ovarian cancer
are alive after 5 years.
Adekunle A.O.
4
Aetiological Factors
Epithelial tumours are most frequently
associated with:
Nulliparity
Early menarche
Adekunle A.O.
7
Classification of Ovarian Tumours
Primary ovarian tumours are divided into:
Epithelial type
Implying an origin from surface epithelium
elements.
Germ cell type
Metastatic tumours
Adekunle A.O.
8
Simplified Histological
Classification of Ovarian Tumours
A. Common
B. Sex Cord Stromal
Epithelial Tumours
(Benign, boderline or Tumours
malignant) Granulosa
Serous tumour stroma cell
Mucinous tumour tumour
Endometroid Androblastoma:
tumour Sertoli-Leydig
Clear cell cell tumour
(mesonephroid) Gynandroblasto
tumour ma
Brenner tumour
Undifferentiated
carcinomas Adekunle A.O.
9
Histological Classification of
Ovarian Tumours (Contd.)
C. Germ Cell D. Metastatic Tmours
Tumours
Dysgeminoma
Endodermal sinus
tumour
Choriocarcinoma
Teratoma
Mixed tumours
Adekunle A.O.
10
Pathology of Epithelial Tumours
Well-differentiated epithelial ca. tend to be more
often associated with early stage disease, but
the degree of differentiation does not correlate
with survival (except in most advanced stages).
Diploid tumours tend to be associated with
earlier stage disease and a better prognosis.
Cell type is not itself prognostically significant;
There is no difference in survival between
different epithelial types although mucinous and
endometrial lesions are likely to be associated
with earlier stage and lower grade than serous
cystadenocarcinoma.
Adekunle A.O.
11
Serous Carcinoma
Most 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.
Occassionally, glandular structures may be
present to enable diagnosis of
adenocarcinoma to be made.
Adekunle A.O.
12
Mucinous Carcinoma
Malignant mucinous tumours account for
10% of the malignant tumours of the ovary.
Usually multioccular, thin-walled cysts with a
smooth external surface containing
mucinous fluid.
They are amongst the largest tumours of the
ovary and may reach enormous dimensions;
A cyst diameter of 25 cm is quite common.
Adekunle A.O.
13
Endometroid Carcinoma
These are ovarian tumours that resemble
endometrial carcinomas.
Most are cystic, often unilocular, and contain
turbid brown fluid;
Five to 10% are seen in continuity with
recognizable endometriosis;
15% are associated with endometrial ca. in the
body of the uterus. In most cases, these are 2
separate primary tumours.
Ovarian adenoacanthoma account for 50% of
some series of endometroid tumours.
Adekunle A.O.
14
Clear Cell carcinoma (Mesonephroid)
Least common of the malignant epithelial
tumours of the ovary;
Accounts for 5 – 10% of ovarian ca.
The appearance from which the tumour derives
its name is the clear cell pattern;
However, some areas show a tubulo-cystic
pattern with the characteristic ‘hob-nail’
appearance of the lining epithelium.
There is very strong association between clear
cell tumours of the ovary and ovarian
endometriosis and they often co-exist.
Therefore, it has been suggested that clear cell
tumour may be a variant of endometrial tumour.
Adekunle A.O.
15
Borderline Epithelial Tumours
Ten percent of all epithelial tumours of the ovary
are of borderline malignancy;
These show:
Varying degrees of nuclear atypia;
the stroma
Most borderline tumours remain confined to the
ovaries and this may account for their much
better prognosis.
Adekunle A.O.
16
Metastatic Spread – Direct and
Lymphatic Spread
The peritoneum and other pelvic organs become
involved by direct spread;
The peritoneal fluid, flowing to lymphatic
channels on the undersurface of the diaphragm,
carries malignant cells to:
The omentum and the liver,
Peritoneal surface of small and large bowels,
The parietal peritoneal surface throughout the
abdominal cavity and on the surface of the
diaphragm.
Metastasis on the undersurface of the
diaphragm may be found in what otherwise
seems to be stage I – II disease.
Adekunle A.O.
17
Metastatic Spread – Lymphatic and
Haematogenic Spread (Contd.)
Lymphatic spread commonly involves the:
Pelvic and para-aortic nodes;
May also occur to the nodes in the neck or
inguinal region.
HAEMATOGENIC SPREAD
Usually occurs late in the course of the disease.
The main areas involved are:
Liver and lungs
Adekunle A.O.
18
CLINICAL STAGING – FIGO staging for
primary ovarian carcinoma
STAGE I Stage Ic
Growth limited to the ovaries Tumour either
Note that:
Clinical staging is an important prognostic
indicator;
Peritoneal deposits on the surface of the
liver do not make the patient Stage IV, the
parenchyma must be involved;
Similarly, the presence of a pleural effusion
is insufficient to put the patient in Stage IV
status unless malignant cells are found on
cytological examination of the pleural fluid.
Adekunle A.O.
21
DIAGNOSIS
Abdominal pain or ON EXAMINATION
discomfort – A hard abdominal mass
commonest presenting arising from the pelvis
complaint is highly suggestive,
especially in the
Distension or Feeling a presence of ascites.
lump – next most
frequent A fixed, hard, irregular
pelvic mass is usually
Other complaints:
felt best by combined
Indigestion vaginal and rectal
Urinary frequency examination.
Weight loss Examine the neck and
Abnormal menses or groin for enlarged
postmenopausal nodes.
bleeding - rarely Adekunle A.O.
22
DIAGNOSIS (Contd.)
HAEMATOLOGICAL INVESTIGATIONS
Full Blood Count
Urea and electrolytes
Liver function tests
RADIOLOGICAL
A chest x-ray is essential
LAPAROTOMY
Most women are diagnosed at laparotomy –
undertaken on the basis that there is a large
mass that needs to be removed regardless of
its nature. 24
Adekunle A.O.
MARKERS FOR EPITHELIAL TUMOURS
Ca125 is the only marker in common clinical
use but can also be raised in benign
conditions such as endometriosis.
It is useful for monitoring women receiving
chemotherapy to assess response:
A persistent rise in Ca125 may precede
clinical evidence of recurrent diseases, in
some cases, by several months.
However, the values can be normal even in
the presence of small tumour deposits.
Adekunle A.O.
25
SCREENING FOR OVARIAN CANCERS
Most patients present with advanced disease
because Ca. ovary tend to be asymptomatic in
the early stages.
As yet, no tumour marker has become available
which is truly specific and suitable for early
detection of epithelial tumours.
Ultrasound is not suitable as a primary
screening tool because it is too expensive and
has a high false-positive rate
The most promising approach is a combination
of Ca125 with ultrasound for those women with
persistent raised values.
At this moment, screening the general
population is neither useful or safe.
Adekunle A.O.
26
TREATMENT - SURGERY
Surgery is the mainstay of both diagnosis and
the treatment of ovarian cancer.
A vertical incision is required for an adequate
exploration of the upper abdomen.
The therapeutic objective of surgery is the
removal of all tumours.
While this is achieved in the majority of Stage I
and Stage II cases, it is usually impossible in the
more advanced diseases.
A sample of ascitic fluid or peritoneal washings
with normal saline should be taken for cytology.
The pelvis and abdomen are explored carefully
to identify metastatic disease.
Adekunle A.O.
27
SURGERY FOR EPITHELIAL
OVARIAN CANCER (1)
PRIMARY SURGERY
To determine diagnosis and remove
tumour.
Requires:
total hysterectomy,
bilateral salpingo-oophorectmy, and
infracolic omentectomy
Adekunle A.O.
28
SURGERY FOR EPITHELIAL OVARIAN
CANCER (2)
CONSERVATIVE SURGERY
(In young, nulliparous women with Stage Ia
disease and no ascites)
Unilateral salpingo-oophorectomy may be
justifiable after:
Careful exploration to exclude metastatic
disease and
Curettage of the uterine cavity to exclude a
Adekunle A.O.
34
CHEMOTHERAPY
For Stages II to IV, and possibly Stage Ic.
Chemotherapy is given both to:
Prolong clinical remission and survival, and
For palliation in advanced and recurrent disease.
It is commenced as soon as possible after surgery
and is usually given for five or six cycles at three-
to four-weekly intervals.
The platinum drugs, cisplatin and its analogue,
carboplatin, are considered to be the most
effective drugs in general use for Rx of ovarian ca.
There are the most widely used cytotoxic drugs
either alone or in combination.
Adekunle A.O.
35
CHEMOTHERAPY - Cisplatin
Cisplatin and Carboplatin are heavy metal
compounds that cause cross-linkage of DNA
strands in a similar fashion to alkylating agents.
Cisplatin is a very toxic drug.
Severe nausea and vomiting, sometimes lasting
several days, were serious problems before the
advent of 5HT antagonists (ganestron and
ondasetron).
Permanent renal damage will occur unless
cisplatin is given with adequate hydration with
intravenous fluids.
Peripheral neuropathy and hearing loss are
reported with increasing cumulative doses.
Adekunle A.O.
36
CHEMOTHERAPY - Carboplatin
As effective as cisplatin in the treatment of
ovarian cancer;
Causes less nausea and vomiting;
Has no significant renal toxicity, therefore no
need to give carbplatin with intravenous
hydration.
Neurotoxicity is rare and hearing loss is
subclinical.
The dose is calculated in relation to the
glomerular filteration rate.
Adekunle A.O.
37
CHEMOTHERAPY – Paclitaxel (Taxol)
Now considered to be part of the standard
treatment for ovarian ca. given in combination
with cisplatin or carboplatin.
Paclitaxel is derived from the bark of the Pacific
yew tree (taxus brevifolia) and has a mechanism
of action which is unique among cytotoxic
drugs.
Causes sensory neuropathy and neutropenia in
high doses.
Loss of body hair is total, irrespective of dose
schedule.
Nausea and vomiting is mild.
Adekunle A.O.
38
TREATMENT RESULTS –
Borderline Epithelial Tumours
Those confined to the ovaries have a good
long-term prognosis with very few women
dying from their disease.
Adekunle A.O.
39
TREATMENT RESULTS – Invasive
Epithelial Ovarian Cancer
Survival for epithelial ovarian cancer is
dependent on:
Stage
Size of the tumour at the end of initial
surgery, and
Grade of tumour
The 5-year survival rate ranges from 60 – 70
per cent for women with Stage I disease to
10% for Stages III – IV.
Adekunle A.O.
40
NON-EPITHELIAL TUMOURS
Non-epithelial tumours constitute approximately
10 per cent of all ovarian cancers.
Because of their rarity and their sensitivity to
intensive chemotherapy, it is especially appro-
priate to refer these patients for specialist care.
They include:
Sex cord stromal tumours
Granulosa and theca cell tumours
Sertoli-Leydig cell tumours
Germ cell tumours
Disgerminomas
Teratomas
Adekunle A.O.
41
SEX CORD STROMAL TUMOURS –
Granulosa and Theca Cell Tumours
The most common sex cord tumours are the
granulosa and theca cell tumours.
They often produce steroid hormones, in
particular estrogens, which can cause
postmenopausal bleeding in older women and
sexual precocity in prepubertal girls.
Granulosa cell tumours usually secrete inhibin.
This can be used to monitor the effects of
treatment.
Theca cell tumours are usually benign.
Granulosa cell tumours occur at all ages, but are
found predominantly in postmenopausal
women.
Adekunle A.O.
42
Granulosa and Theca Cell Tumours
Most present as Stage I.
Bilateral tumours are present in only 5% of
cases.
PATHOLOGY
Granulosa cell tumours are normally solid but
cystic spaces may develop when they become
large.
Some are predominantly cystic.
Like most tumours in this group, the cut surface
is often yellow because of neutral lipid related to
sex steroid hormone production.
Areas of haemorrhage are also common. 43
Adekunle A.O.
Granulosa and Theca Cell
Tumours - Treatment
The surgical treatment is the same as for
epithelial tumours.
The effect of adjuvant therapy is difficult to
assess as granulosa cell tumours can recur
up to 20 years after the initial diagnosis.
Radiotherapy has been largely replaced by
chemotherapy in advanced or recurrent
cases.
The five-year survival is around 80% overall
but recurrence is associated with a high
mortality.
Adekunle A.O.
44
Sertoli-Leydig Cell Tumours
(Androblastoma)
Rare tumour;
Half of these neoplasia produce male
hormones which cause virilization.
Rarely, estrogens are secreted.
The prognosis for the majority with
localized disease is good.
Treatment is the same as for
granulosa cell tumours.
Adekunle A.O.
45
Germ Cell Tumours -
Dysgerminomas
Disgerminomas account for 2 – 5% of all
primary malignant ovarian tumours.
Nearly all occur in women less than 30 years
old;
They spread by lymphatics.
PATHOLOGY
They are solid tumours that have a smooth or
nodular, bosselated external surface.
Soft or rubbery in consistency, depending on
the proportion of fibrous tissue contained in
them.
Adekunle A.O.
46
Germ Cell Tumours –
Dysgerminomas (Contd.)
They may reach a considerable size, the
mean diameter is 15 cm.
Approx. 10% are bilateral; they are alone
among malignant germ tumours in having a
significant incidence of bilaterality.
Elements of immature teratoma, yolk sac
tumour or choriocarcinoma are found in
about 10% of dysgerminomas.
Presence of these more malignant cell
elements indicates a worse prognosis.
Adekunle A.O.
47
Germ Cell Tumours:
Dysgerminomas - Treatment
DIAGNOSIS
Chest x-ray
Computerized Tomography (CT) scan
Serum alpha-fetoprotein (AFP) and βhCG must
be assayed to exclude the omnious presence of
elements of choriocarcinoma, endodermal sinus
tumour or teratoma.
PROGNOSIS
Pure dysgerminomas have a good prognosis as
they are normally Stage I tumours (75%), most
being Stage Ia.
Adekunle A.O.
48
Germ Cell Tumours: Yolk Sac
(endodermal sinus) Tumours
Second most common malignant germ cell
tumour of the ovary, making up 10 – 15% over all
and reaching a higher proportion in children.
May present as an acute abdomen due to
rupture following necrosis and haemorrhage;
Usually well-encapsulated and solid.
Areas of necrosis and haemorrhage are often
seen, as are small cystic spaces.
Its consistency varies from soft to firm and
rubbery; cut surface slippery and mucoid.
Secretes AFP, which can be used to monitor
treatment. 49
Adekunle A.O.
Germ Cell Tumours: Teratomas
Mature teratomas are benign, the most
common being the cystic teratoma or dermoid
cyst;
Found at all ages but particularly in the third
and fourth decades;
Immature teratomas are composed of a variety
of tissues and comprise about 1% of all
ovarian teratomas.
They are unilateral in almost all cases and
appear as solid masses that have smooth and
bosselated surfaces.
Not all solid tumours are of immature type.
Adekunle A.O.
50
Teratomas – Treatment
Suspect a germ cell tumour prior to surgery if a
young woman has what appears to be
predominantly solid tumour on ultrasound
examination.
Early disease is treated by surgery:
Oophorectomy in young women
No ascites
Adekunle A.O.
51
Teratomas – Adjuvant Treatment
Stage I malignant teratomas and
dysgerminomas may be followed up closely
without further treatment.
For the remainder, chemotherapy has
replaced radiotherapy, particularly when
there is wish to preserve fertility;
Short courses of cisplatin chemotherapy
given in combination with bleomycin and
etoposide (BEP) is curative in 90% of
patients without adverse features.
More intensive regimens are used for
patients with adverse features.
Adekunle A.O.
52