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MALIGNANT TUMOURS OF

THE OVARY

Professor Adeyemi O. Adekunle


Department of Obstetrics and Gynaecology
College of Medicine, University of Ibadan
University College Hospital,
Ibadan, Nigeria.

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.
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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

 Late age at menopause

 A long estimated number of years of ovulation

 Oral contraceptive use reduces the risk four-


fold.
 Even without oral contraceptives, increasing age
at first birth reduces the risk of ovarian cancer.
 This and other anomalies cast doubt upon the
“incessant ovulation” theory.
Adekunle A.O.
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Aetiological Factors - Genetic
 There is family history in between 5 and 10% of
women with epithelial ovarian cancers – usually
serous adenocarcinomas.
 A woman with one affected relative has a
lifetime risk of 2.5%, which is twice the risk in
the general population.
 With two affected relatives, the lifetime risk
increases to 30 – 40 per cent.
 Most of these families also have cases of breast
or colorectal cancer in the family.
 The defective gene in the breast/ovary families is
most commonly the tumour suppressor gene
BRCA1 (81%).
 BRCA2 is defective in about 14 per cent.
Adekunle A.O.
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Classification of Ovarian Tumours
 Ovarian tumours may be:
 Solid or
 Cystic

 They may be:


 Benign
 Malignant, and in addition,
 Borderline – i.e., those while having some
features of malignancy, lack any evidence
of stromal invasion.

Adekunle A.O.
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Classification of Ovarian Tumours
Primary ovarian tumours are divided into:
 Epithelial type
 Implying an origin from surface epithelium

 Sex gonadal type


 Also known as sex cord stromal type, or

Sex cord mesenchymal type


 Originating from sex cord mesencymal

elements.
 Germ cell type
 Metastatic tumours
Adekunle A.O.
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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.
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Histological Classification of
Ovarian Tumours (Contd.)
C. Germ Cell D. Metastatic Tmours
Tumours
 Dysgeminoma

 Endodermal sinus

tumour (yolk sac


tumour)
 Embryonal cell

tumour
 Choriocarcinoma

 Teratoma

 Mixed tumours

Adekunle A.O.
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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.
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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.
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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.
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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.
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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.
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Borderline Epithelial Tumours
 Ten percent of all epithelial tumours of the ovary
are of borderline malignancy;
 These show:
 Varying degrees of nuclear atypia;

 An increase in mitotic activity;

 Multilayering 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.
Adekunle A.O.
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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.
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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

 Bone and brain (sometimes)

Adekunle A.O.
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CLINICAL STAGING – FIGO staging for
primary ovarian carcinoma
STAGE I  Stage Ic
 Growth limited to the ovaries  Tumour either

 Stage Ia: Stage 1a or 1b


 Growth limited to one ovary; but tumour on
the surface of
 No ascites;
one or both
 No tumours on external ovaries; or
surfaces with ascites
 Capsule intact present
containing
 Stage Ib malignant
 Growth limited to both cells.
ovaries STAGE 2
 No ascites;
 Growth involving
 No tumours on external
one or both
surfaces; ovaries with
 Capsule intact pelvic extension
Adekunle A.O.
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CLINICAL STAGING – FIGO staging for
primary ovarian carcinoma (Contd.)

STAGE III STAGE IV

 Growth involving one


 Growth involving one
or both ovaries with or both ovaries with
peritoneal implants in distant metastases
the pelvis or positive  If pleural effusion is
retroperitoneal or present, there must
inguinal nodes. be positive cytology
to allot a case to
 Superficial liver Stage IV;
metastases equals
Stage III
 Parenchymal liver
metastasis equals
Stage IV.
Adekunle A.O.
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CLINICAL STAGING – FIGO staging for
primary ovarian carcinoma (Contd.)

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.
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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.
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DIAGNOSIS (Contd.)
HAEMATOLOGICAL INVESTIGATIONS
 Full Blood Count
 Urea and electrolytes
 Liver function tests
RADIOLOGICAL
 A chest x-ray is essential

 Sometimes, it is advisable to carry out a barium


enema or colonoscopy to
 Differentiate between an ovarian and colonic
tumour and
 To assess bowel involvement from the ovarian
tumour itself
 An IVP (Intravenous urogram) is occasionally
useful. Adekunle A.O.
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DIAGNOSIS (Contd.)
ULTRASONOGRAPHY
 May help to confirm the presence of a pelvic
mass and detect ascites before it is clinically
apparent.
 In conjunction with Ca125 estimation- may be
used to calculate a “risk of malignancy
score”

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.
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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.
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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.
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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.
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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

synchronous endometrial tumour.


 If the tumour is subsequently found to be
poorly differentiated or if the washings are
positive, a second operation to clear the
pelvis will be necessary.
Adekunle A.O.
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SURGERY FOR EPITHELIAL OVARIAN
CANCER (3)
INTERVAL DEBULKING SURGERY
 When bulky disease remains after initial
surgery, a second laparotomy may be
performed on those who respond after 2 to 4
courses of chemotherapy.
 The chemotherapy is then resumed as soon
as possible after the second operation.
 This is called “Interval debulking.”
 May improve the survival at 3 years from 10
to 20 per cent.
Adekunle A.O.
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SURGERY FOR EPITHELIAL OVARIAN
CANCER (4)
SECOND-LOOK SURGERY
 Defined as a planned laparotomy at the end of
chemotherapy.
 The objectives are:
 To determine the response to previous therapy

in order to document accurately its efficacy and


to plan subsequent management, and
 To excise any residual disease.
 Evidence suggests that neither the surgical
resection nor the opportunity to change treatment
has any effect on patient’s survival.
 Therefore, second-look procedures have no place
outside clinical trials at the present time.
Adekunle A.O.
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SURGERY FOR EPITHELIAL
OVARIAN CANCER (5)
BODERLINE TUMOURS
 Usually presents as Stage Ia tumour confined
to one ovary.
 It is often not recognized as malignant.
 Ovarian cystectomy or oophorectomy is
adequate in young women.
 Hysterectomy and bilateral salpingo-
oophorectomy in older women who have no
wish to have children.
Adekunle A.O.
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ADJUVANT THERAPY FOR
EPITHELIAL OVARIAN CANCER
 Women with Stage Ia or Ib disease
and well- or moderately differentiated
tumours may not require further
treatment.
 The benefit of adjuvant therapy for
women with Stage Ic remains
uncertain, but many oncologists will
recommend chemotherapy;
 All other patients with invasive
ovarian carcinoma require adjuvant
therapy.
 There is no evidence that adjuvant
therapy affects the outcome in
women with borderline Adekunle
tumours.
A.O.
33
RADIOTHERAPY
 Radiotherapy is now almost never used in
the routine management of ovarian cancer.
 A potential exception is radio-immunoassay
in which radioactive Ytrium is linked to a
monoclonal antibody which recognizes an
antigen found on most ovarian cancers.
 Given intraperitoneally.
 Remains an experimental treatment.

Adekunle A.O.
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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.
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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.
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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.
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TREATMENT RESULTS –
Borderline Epithelial Tumours
 Those confined to the ovaries have a good
long-term prognosis with very few women
dying from their disease.

 Even with extra-ovarian spread, the 15-year


survival for serous borderline epithelial
tumours is around 90 per cent.

 For Stage III mucinous tumours, the 15-year


survival rate is only 44 per cent.

Adekunle A.O.
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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.
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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

 Yolk sac (endodermal sinus) tumours

 Teratomas

Adekunle A.O.
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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.
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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.
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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.
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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

 Hysterectomy and BSO in older patients.

 Women are suitable for conservative surgery if


they have:
 Encapsulated tumour

 No ascites

 No evidence of abnormal lymph nodes at surgery

 Negative CT scan of the para-aortic nodes

Adekunle A.O.
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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.
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