Download Malignant-Diseases-Of-The-Ovary

‫بسم هللا الرحمن‬
‫الرحيم‬
MALIGNANT OVARIAN
TUMOURS
Prof.Osman Donia
• Malignant epithelial
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tumours:
Serous adenocarcinoma
Mucinous adenocarcinoma
Endometrioid adenocarcinoma
undifferentiated adenocarcinoma
• Malignant germ cell tumours:
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Dysgerminoma
Endodermal sinus tumour
Choriocarcinoma
Solid teratoma
• Malignant sex cord stromal tumours:
• Granulosa cell tumour
• Sertoli-Leydig cell tumour
I. EPITHELIAL OVARIAN
CANCER
Incidence:
• Primary ovarian epithelial cancer
forms 60-70% of all ovarian tumours.
• 90% of all ovarian malignancies.
• It is the third common malignancy of
female genital organs.
Aetiology:
Possible factors include:
1. Reproductive factor:
Nulliparous or infertile women are more
liable to develop it.
2. Hereditary 'Genetic' factor:
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5- 10% of epithelial ovarian cancer occur in women
with hereditary predisposition.
A particular feature of familial cancer is that it
tends to occur at a younger age.
Hereditary predisposition is due to a defective gene
in their families, which is tumour suppression gene
BRCA, BRCA2 .i.e. gene mutation.
Three types of familial ovarian
cancer are identified:
– Site specific ovarian cancer syndrome
(15%)
– Hereditary breast / ovarian cancer
syndrome (75%)
– Hereditary non polyposis colorectal
cancer syndrome with endometrial,
breast, or ovarian cancer (10%).
Risk factors for epithelial cancer:
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Age
Nulliparity & infertility
White race
Prior history of endometrial or breast
cancer
– Family history of ovarian cancer
PATHOLOGY OF PRIMARY EPITHELIAL
OVARIAN CANCER
Macroscopic appearance:
• Usually solid but may be partially cystic
partially solid.
• Unilateral or bilateral
• The size is extremely variable
• The substance of the tumour is the seat
of extensive haemorrhage and necrosis.
Microscopic picture: It is an
Adenocarcinoma
Which might be either :
– Serous cystadenocarcinoma
– Mucinous cystadenocarcinoma.
– Endometrioid cystadenocarcinoma.
Which could be either :
a. Well differentiated (Gr I)
b. Moderately differentiated (Gr II)
c. Undifferentiated (Gr III)
N.B. Border line epithelial tumours
MALIGNANT GERM CELL
TUMOURS
• The incidence of germ cell tumours
is only 20-30% of all ovarian
tumours.
• Five per cent of germ cell tumours
are malignant.
Classification of malignant germ cell
tumours:
1. Dysgerminoma
2. Endodermal sinus tumour (yolk sac
tumour)
3. Choriocarcinoma
4. Malignant teratoma
• Benign cystic teratoma with
malignant transformation
• Malignant solid teratoma
Special Features of Germ Cell Tumours:
They differ from epithelial ovarian cancer by
the following points:
1. Lower age incidence
2. The commonest tumours of abnormal
gonads and in sex chromatin negative
females.
3. tend to grow rapidly resulting in pelvic
pain and pressure symptoms occurring
early tend to grow rapidly resulting in
pelvic pain and pressure symptoms
occurring early.
4. Most tumours produce substances in the
circulation that can be used as tumour
markers;
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Dysgerminoma: alkaline phosphatase & lactic acid
dehydrogenase.
Endodermal sinus tumour : alpha feto proteins.
Choriocarcinoma :hCG
5. Radiosensitive, chemotherapy in some of
them gives excellent results in stage Ia.
6. Conservative surgery in the form of
salpingoopherectomy is the first line of
treatment.
A) Dysgerminoma:
• The commonest malignant germ cell
tumour accounting for about 3040% of all malignant germ cell
tumours.
• Represents 1-3% of all ovarian
tumours.
• Tends to occur at a younger age
(10-20 years).
• May secrete alkaline phosphatase
Pathology:
• Solid ovarian tumour, usually of small
or moderate size
• Bilateral in only 10% of cases.
• Greyish with lobulated surface with
tendency to haemorrhage and
necrosis.
Microscopically:
• Consists of gem cells arranged in alveoli
or nests separated by fibrous tissue
septa heavily infiltrated with
lymphocytes.
• Cells are round, large, with abundant
cytoplasm and a large irregular nucleus.
Treatment:
• Surgery:
– Unilateral salpingoophorectomy,
– TAH&BSO
• Radiotherapy
B) Endodermal Sinus Tumour “EST”
• Prevalent in a young age (median age
of 16-18 years).
• Most EST secrete alpha-fetoproteins
that are used as a tumour marker.
Pathology:
• Small solid tumours which are almost
always unilateral.
Microscopically:
• EST have a characteristic microscopic
picture; Shiller-Duval bodies. These are
cystic spaces in which projects a glomerulouslike structure with a central vascular core.
Treatment:
• Surgery :
– unilateral salpingoophorectomy
– TAH&BSO
• Chemotherapy: the tumour is
chemosensitive
MALIGNANT SEX-CORD
STROMAL TUMOURS
Sex-cord stromal tumours may arise from
non- functioning or functioning stroma
of the ovary.
• Functioning sex–cord tumours may be:
– Estrogenic: as granulosa cell tumour.
– Androgenic: as Sertoli-leydig cell tumours
– Both estrogenic and androgenic effect
(very rare): as in Gynandroblastoma.
• Non- functioning stroma may very
rarely give rise to fibrosarcoma of the
ovary.
A) Granulosa Cell Tumours:
• Usually unilateral, solid, yellow or yellow-grey
in colour.
• Some are functioning secreting oestrogen,
while most appear to secrete inhibin.
• Associated with endometrial carcinoma in 510% of cases, and with endometrial
hyperplasia in 25-50% of cases.
• They may cause irregular bleeding or
precocious puberty (before puberty),
menstrual irregularities or post menopausal
bleeding.
Microscopically:
• The tumour is formed of granulosa cells
arranged in different patterns. CallExner bodies are pathognomonic, but
are present in only 50% of cases. These
are cystic spaces surrounded by
granulosa cells arranged in a rosettelike shape.
Treatment:
• Unilateral salpingoophorectmy:
• TAH BSO:
• No place for irradiation or
B) Sertoli-Leydig Cell Tumours:
• They are very rare representing < 0.2%
of all ovarian tumours.
• They are usually small, unilateral, solid
tumours, of low grade malignancy.
• Many are functioning producing
androgens.
• Treatment: Either unilateral
salpingoopherectmy if the patient is
young or TAH&BSO.
PATTERNS OF SPREAD
OF OVARIAN CANCER
Primary methods of spread of ovarian
cancer are:
• Direct extension
• Lymphatic spread
• Transcoelomic spread
• Haematogenous spread
Metastatic Ovarian
Cancer
Metastatic ovarian cancer forms about 56% of all ovarian tumours. The primary
may be:
– Genital tumours: From the endometrium,
cervix, tube, and contralateral ovary.
– Extragenital tumours: From the stomach,
colon, breast, biliary tract, and thyroid
gland.
Krukenberg Tumour:
• It accounts of 30-40% of metastatic cancer
to the ovary.
• The primary is usually in the pylorus, less
commonly in colon, breast or biliary tract.
• They are bilateral solid ovarian tumour
retaining the shape of the ovary.
• The main interest is in its histogenesis, the
most acceptable theory is that malignant cells
reached both ovaries by retrograde lymphatic
spread.
Prognosis:
Bad, most patients die within one
year because most of the lesions are
not discovered until the primary
disease is advanced.
CLINICAL PICTURE OF
PRIMARY MALIGNANT
OVARIAN TUMOURS
•
This is a disease of late decade of life: 55–
65 years of age in the majority of cases.
• It is more common in industrial countries.
SYMPTOMS:
A. Early stage disease: are mostly
asymptomatic.
• may be associated with non specific GIT
symptoms in the form of dyspepsia,
indigestion, and anorexia. Pressure symptoms
as urinary frequency, and constipation may
be present, with or without pelvic pain.
B. Late stage disease: may present
with:
• Abdominal pain and cachexia,
abdominal swelling.
• Abnormal uterine bleeding, and
especially postmemnopausal
bleeding.
• Rarely ascites may be the first
clinical presentation.
PHYSICAL SIGNS:
• The most important physical sign is the
palpation of a pelvic mass.
• If the patient is lucky this pelvic mass is
discovered during routine pelvic
examination.
• In late cases a pelviabdominal fixed solid
mass is felt.
• Bilateral solid fixed masses are always
suspicious of malignant ovarian tumour.
CLINICAL FEATURES
SUGGESTING MALIGNANCY
INOVARIAN TUMOURS
A) History:
• Age, especially extremes of age
(before puberty, or > 40-60 years).
• Rapid growth of the tumour.
• Pain and loss of weight are always
late symptoms.
• Post menopausal bleeding and
symptoms of virilisation, are
suspicious.
B) General examination:
• Malignant Cachexia (with marked and rapid
weight loss and dehydration)
• Palpable supraclavicular lymph nodes
especially on the left side, (Virchows
glands).
• Pleural effusion, however it may be
present in Meig’s syndrome.
• Associated breast mass, on breast
examination
• Unilateral leg & edema (unilateral pressure
by tumour with venous and lymphatic
obstruction).
C) Abdominal Examination:
• Inspection: Abdominal enlargement,
over lying skin showing peau d’orange.
• Palpation: Tumour which is solid (or
partially solid), fixed especially if
bilateral.
• Percussion: Presence of ascites
(except with ovarian fibroma in
Meig’s syndrome).
D) Pelvic examination:
• Nodules in Douglas pouch in the
presence of a non tender adnexal
mass.
• Bilateral, especially if solid adnexal
masses are very presumptive.
• Fixed pelvic masses especially if
amalgamated with pelvic organs
(frozen pelvis).
At Laparotomy:
• Ascites, especially if altered blood stained
ascites.
• Bilaterality, fixation, and invasion of the
capsule.
• Extracystic papillae, and adhesions to
surrounding structures.
• Peritoneal nodules or secondary deposits in
omentum, intestine or liver
• Variable consistency with a cut section of the
tumour shows haemorrhage and necrosis.
SPECIAL INVESTIGATIONS
FOR OVARIAN CANCER
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Pelvic ultrasound
Endometrial curettage
Chest X-Ray
Plain X-Ray abdomen
Barium meal and/or enema
Upper and/or lower G.I. Endoscopy
I.V.P.
Paracentesis.
CT & MRI.
Tumour markers:
• CA 125 (n < 35 u/ml):
• This the most important marker used.
• However it may be elevated in some benign
conditions; as endometriosis and chocolate cysts.
• It can be used also to monitor response to
chemotherapy (decreasing levels denote good
response).
• Other markers include; serum B-hCG
(choriocarcinoma), alpha fetoprotein (EST), serum
alkaline phosphatase, and lactic acid
dehydrogenase (dysgerminoma).
SCREENING for Ovarian Cancer:
• Routine yearly pelvic examination in
premenopausal and postmenopausal
women.
• Periodic TVS coupled with a serum
CA-125 in those with an enlarged
ovary
DIFFERENTIAL DIAGNOSIS
of ovarian masses
• Pelvic masses: as
– adnexal masses.
– uterine enlargement (myomata &
pregnancy).
– colonic masses.
– retroperitoneal masses (pelvic kidney,
retroperitoneal sarcoma, ...)
• Abdominal masses as
– liver or pancreatic tumour.
– tense ascites.
EXPLORATORY LAPAROTOMY IN
OVARIAN CANCER
The final diagnosis of ovarian cancer
can only be made at exploratory
laparotomy, which will serve not only
for diagnosis but also for surgical
staging and primary surgical
treatment.
STAGING OF OVARIAN
CANCER
Clinical staging
For a malignant ovarian tumour will
always
be short of important items that will
affect
the prognosis and line of treatment,
surgical
staging is therefore the only standard
method.
Surgical staging of primary
ovarian cancer:
entails a mid line subumbilical suprapubic
exploratory laparotomy in which the following is
performed:
• Exploration of the pelvic and peritoneal cavity
• Aspiration of any fluid in cul de sac (ascites), or
perform peritoneal washings for Cytology.
• Performing an infracolic omentectomy.
• Pelvic and paraaortic lymph node sampling
• Resection of any visible enlarged nodules or
masses.
• The complete procedure will then be
a TAH BSO (or debulking of the
malignant tumour), omentectomy,
lymph node sampling or resection,
removal of any pelvic or extrapelvic
tumour masses >2.0 cm, and
cytology to peritoneal fluid.
FIGO surgical staging for
primary epithelial ovarian
carcinoma
Stage
FIGO definition (simplified)
Stage Growth limited to ovaries
I
Ia
Growth limited to one ovary
No ascites; No tumour on external
surfaces; capsule intact
Ib
Growth limited to both ovaries
No ascites; no tumour on external
surfaces; capsule intact
FIGO surgical staging for
primary epithelial ovarian
carcinoma (ctd)
Ic
Stages Ia, or Ib with tumour
on surface of one or both
ovaries, capsule ruptured, or
presence of ascites containing
malignant cells or +ve
peritoneal washings
FIGO surgical staging for
primary epithelial ovarian
carcinoma (ctd)
Stage Growth involving one or both
II
ovaries with pelvic extension to
IIa
uterus and tubes
IIb
IIc
other pelvic tissues
stages IIa, or IIb with tumour on
surface of one or both ovaries,
capsule ruptured, or presence of
ascites containing malignant cells or
+ve peritoneal washings
FIGO surgical staging for
primary epithelial ovarian
carcinoma (ctd)
Stage
III
IIIa
Growth involving one or both ovaries with
peritoneal implants outside the pelvis or
positive retroperitoneal or inguinal nodes
tumour grossly limited to the true pelvis
with –ve nodes
IIIb
tumour with implants < 2.0 cm on abdominal
peritoneal surface. Nodes are -ve
IIIc
tumour with implants > 2.0 cm or Nodes are
+ve
N.B.; superficial liver metastases is included
in stage III c.
FIGO surgical staging for
primary epithelial ovarian
carcinoma (ctd)
Stage
IV
Growth involving one or both
ovaries with distant metastases.
•If pleural effusion is present
there must be +ve cytology to allot
a case to stage IV.
•Parenchymal liver metastasis
equals stage IV.
SURGICAL TREATMENT
OF OVARIAN CANCER
A) Early stage Ovarian Cancer:
• TAH BSO and infracolic
omentectomy is the standard
treatment for patients with disease
limited to the ovary (no gross
evidence for extension beyond the
ovaries Stage I-IIa). Surgical staging
is completed via peritoneal wash, and
lymph node sampling, for microscopic
assessment of the extent of the
disease.
• Occasionally, unilateral salpingooophorectomy may be done in selected cases
of stage Ia disease (tumour confined to one
ovary, with capsule intact, and –ve peritoneal
cytology), only when the patient is young and
fertility is desired. Such conditions are
mostly met with in some early epithelial
tumours (border line tumours), but more
commonly with malignant germ cell tumours
(dysgerminoma and EST), and malignant sex
cord stromal tumours (granulosa and Sertoli
Leydig cell tumours).
B) Advanced stage Ovarian Cancer:
• Primary Cytoreductive surgery (initial
Debulking)
• Interval Debulking
• Radical oophorectomy
Second-look Surgery in ovarian cancer:
•
Second look laparotomy or laparoscopy,
have been advocated to asses residual tumour
within the abdominal cavity after primary
surgery and chemotherapy, to decide on
further adjuvant therapy needed.
•
Nowadays modern imaging technique, as
spiral CT & MRI, together with serum CA125
tests have largely nullified the need for
second look surgery. At the present state its
only place is when a tumour marker is rising
apart from negative imaging for tumour
residues.
CHEMOTHERAPY IN
OVARIAN CANCER
Chemotherapy whether single or multiple
agents
has a major role in the management of
ovarian
cancer especially in advanced disease, and
mostly
with epithelial ovarian cancer:
1. Early stage disease: It has a limited
place only with poor prognostic factors as
Poorly differentiated tumours, ruptured
capsule, or +ve peritoneal wash (even in
stage I cases).
2. Advanced stage disease:
Chemotherapy is indicated in all
cases of stage II-IV disease.
a) All cases after primary cytoreductive
debulking surgery
b) Palliative therapy in patients with
irresectable tumours, or patients with
recurrent disease.
Types of chemotherapy used:
• Chemotherapy is usually
recommended as soon as possible
after surgery, and is given for five or
six cycles at 3-4 weekly intervals.
• The most frequently used
chemotherapeutic agents include:
Cisplatin or Carboplatin alone or in
combination with Paclitaxel (Taxol).
Toxicity from chemotherapy:
•
Chemotherapeutic agents are
highly toxic at therapeutic doses, and
therefore need close monitoring
during treatment cycles. Toxicity
includes; nausea, vomiting, myalgia
and arthralgia. In severe cases renal
damage, peripheral neuropathy,
hearing loss, dehydration and
electrolyte imbalance may occur.
RADIATION THERAPY IN
OVARIAN CANCER
Radiation therapy has little place in
epithelial
ovarian cancer. It may be used as an
adjuvant therapy following
cytoreductive
surgery in patients who refuse or are
not
good candidate for chemotherapy. Two
main forms are used:
• Intraperitoneal radioactive colloids
• Whole external beam abdominal
radiation.
PROGNOSIS IN OVARIAN
CANCER
The prognosis depends upon:
• Histopathological type of ovarian cancer
(epithelial or non epithelial ovarian cancer)
• Stage of ovarian malignancy: the best prognosis
is in stage Ia
• Optimal versus Suboptimal surgery (TAH BSO +
omentectomy, versus debulking)
• Histology and grading of the tumour. Well
differentiated tumours carry best prognosis,
while poorly differentiated and clear cell
carcinomas carry the worst prognosis.
• Response of the tumour to adjuvant therapy
(chemotherapy – irradiation).
• The 5-year survival rate in
epithelial ovarian cancer is as
follows:
• In stage I 85-90%
• In stage II 80%
• In stage III 15-20%
• In stage IV 5%
Thank you