Transcript Ovarian neoplasms.

Ovarian neoplasms.
Ovarian neoplasms. Anita Chudecka - Głaz
• Human ovarian neoplasms (especially
epithelial ovarian cancer) presents a major
challenge to oncological research , because
they are frequently diagnosed late and show
poor prognosis and low survival despite the
apparent success of chemotherapy in
achieving remission with no evidence of
disease.
Ovarian neoplasms. Anita Chudecka - Głaz
Epithelial ovarian cancer is the fourth most
common cause of death from cancer in
Epithelial ovarian cancer is the fourth
women
and the most lethal of gynaecologic
most common cause of death from cancer in women
neoplasms.
and the most lethal of gynaecologic neoplasms.
Ovarian neoplasms. Anita Chudecka - Głaz
• The most important positive prognostic
feature continues to be diagnosis at an early
stage.
• BUT EARLY STAGE OVARIAN
CANCERS DON’T PRODUCE
SYMPTOMS !!!
Ovarian neoplasms. Anita Chudecka - Głaz
• The incidence of ovarian cancer is relatively
high in Scandinavian (15/100000)
countries , lower in western Europe and
North America ( 10/100000 ) and low in
Japan (3/100000).
Ovarian neoplasms. Anita Chudecka - Głaz
ETIOLOGY
• Two hypotheses have been proposed to
explain the biological mechanisms that
increase the risk of ovarian cancer :
 genetics
gonadotropin hypothesis
Ovarian neoplasms. Anita Chudecka - Głaz
ETIOLOGY
The involvement of gonadotropins in human
ovarian carcinoma is backed by a number of
epidemiological and experimental studies
showing:
increase occurrence of disease with
exposure to high levels of LH , FSH during
menopause , after ovariectomy or during
fertility treatment
Ovarian neoplasms. Anita Chudecka - Głaz
ETIOLOGY
 reduced risk of cancer associated with
multiple pregnancies, oral contraceptives ,
breast - feeding
LH and hCG receptors are expressed in
40% of epithelial ovarian cancer
LHRH receptors are expressed in almost
80% of EOC
Ovarian neoplasms. Anita Chudecka - Głaz
ETIOLOGY
 deficit of cases of ovarian cancer among
women with diagnosis of alcoholism in
animals ovarian cancer may be induced by
gonadal radiation or chemical toxins that
cause premature oocyte death , but
hypophysectomized animals do not develop
ovarian tumours after oocyte depletion
which suggests a specific role of
gonadotropins
Ovarian neoplasms. Anita Chudecka - Głaz
ETIOLOGY
other risk factors:
diet
talc
pelvic irradiation
viruses
age
Ovarian neoplasms. Anita Chudecka - Głaz
ETIOLOGY
other risk factors:
PID
endometriosis
blood group
legal status
education
Ovarian neoplasms. Anita Chudecka - Głaz
SYMPTOMS
EOC
EOC oftenest are asymptomatic
until
oftenest
are stage
asymptomatic
until
advancedisstage
advanced
, when the
prognosis
poor,
the prognosis
is 40%.
poor
and 5 yearwhen
survival
less then
and 5 year survival less then 40%.
Ovarian neoplasms. Anita Chudecka - Głaz
SYMPTOMS
Irrespective of histology , most ovarian
neoplasms when they have large size in
advanced stage cause symptoms by exerting
pressure on contiguous structures (urinary
frequency, pelvic discomfort and
constipation).
Ovarian neoplasms. Anita Chudecka - Głaz
SYMPTOMS
The most common :
abdominal swelling
fatigue
abdominal pain
Ovarian neoplasms. Anita Chudecka - Głaz
SYMPTOMS
Upper abdominal metastases or ascites cause
nausea, heart burn , bloating , weight loss
and anorexia.
Acute abdominal pain secondary to
haemorrhage , rupture or torsion can all
result from tumour growth.
Ovarian neoplasms. Anita Chudecka - Głaz
SYMPTOMS
Biologically active hormones , including
estrogen, progesterone, testosterone ,
corticosteroids and hCG can be produce by
a variety of ovarian neoplasms and cause
the predicted symptoms associated with
each compound.
Ovarian neoplasms. Anita Chudecka - Głaz
DIAGNOSIS
1. Physical examination-bimanual rectovaginal pelvic
examination
2. Ultrasound investigation
3. Tumour markers
4. Ascites puncture
5. Biopsy the tumour
6. Laparoscopy
7. CT
8. NMR
9. Chest X ray
Ovarian neoplasms. Anita Chudecka - Głaz
ULTRASONOGRAPHY
ULTRASONOGRAPHY
abdominal
transvaginal TVS
colour Doppler CDI
Ovarian neoplasms. Anita Chudecka - Głaz
TUMOR MARKERS
CA 125
CA 19-9 CEA
epithelial ovarian cancer
Ovarian neoplasms. Anita Chudecka - Głaz
TUMOR MARKERS
AFP
endodermal sinus tumors
embryonal carcinomas
mixed germ cell tumors
rarely immature teratoma and polyembryoma
Ovarian neoplasms. Anita Chudecka - Głaz
TUMOR MARKERS
hCG
chorioncarcinoma
embryonal carcinoma
mixed germ cell tumors
polyembryoma
Ovarian neoplasms. Anita Chudecka - Głaz
TUMOR MARKERS
ESTRADIOL
adult granulosa cell tumors
thecomas
Ovarian neoplasms. Anita Chudecka - Głaz
TUMOR MARKERS
INHIBIN
adult granulosa cell tumors
Ovarian neoplasms. Anita Chudecka - Głaz
PREMENOPAUSAL OVARIAN MASS
EXCLUDE NON-GYNAECOLOGICAL PROBLEM
Simple on US
AND
< 6 cm
AND
Normal CA 125
Solid or complex
on US
OR
> 6 cm
OR
Elevated
AFP/hCG/LDH
OR
Elevated CA 125
Observation for 6-8 weeks
and
Gonadotrpopin suppression
Peristent on US
Surgical evaluation
POSTMENOPAUSAL OVARIAN MASS
EXCLUDE NON-GYNAECOLOGICAL PROBLEM
Asymptomatic
AND
Simple on US
AND
< 3 cm
AND
Normal CA 125
Observe with
Follow up
US
Symptomatic
OR
Complex on US
OR
> 3 cm
OR
Elevated CA 125
Surgical
Evaluation
DIFFERENTIAL DIAGNOSIS
 gynaecologic
tuboovarian abscess
ectopic pregnancy
leiomyoma
fallopian tube neoplasia
luteal or follicular cysts
Ovarian neoplasms. Anita Chudecka - Głaz
DIFFERENTIAL DIAGNOSIS
 gynaecologic
ovarian hyperthecosis
pregnancy luteoma
theca-lutein cysts
endometrioma
simple cysts
Ovarian neoplasms. Anita Chudecka - Głaz
DIFFERENTIAL DIAGNOSIS
 nongynaecologic
diverticular disease
appendiceal abscess
Crohn’s disease
primary nongynaecological malignancy
pelvic kidney
Ovarian neoplasms. Anita Chudecka - Głaz
CLASSIFICATION
1. Epithelial ovarian tumours - 70% of all
ovarian neoplasms
2. Sex cord stromal tumours 5-10%
3. Germ cell tumours 15-20%
4. Metastatic 5 %
5. Other
Ovarian neoplasms. Anita Chudecka - Głaz
Epithelial ovarian neoplasms
malignant
benign
borderline
Ovarian neoplasms. Anita Chudecka - Głaz
EOC
(malignant, borderline, benign)
serous
mucinous
endometrioid
clear cell
Brennertransitional cell
mixed mesodermal
undifferentiated
unclassified
Ovarian neoplasms. Anita Chudecka - Głaz
SEX CORD STROMAL TUMOURS
1. Granulosa stromal cell
 granulosa cell
 thecoma-fibroma
2. Sertoli stromal cell
3. Lipid cell tumours
4. Gynanandroblastoma
Ovarian neoplasms. Anita Chudecka - Głaz
GERM CELL TUMOURS
1. Dysgerminoma
2. Endodermal sinus tumour
3. Embryonal carcinoma
4. Polyembryoma
5. Chorioncarcinoma
6. Teratomas
7. Mixed forms
8. Gonadoblastoma
Ovarian neoplasms. Anita Chudecka - Głaz
STAGE I
Growth limited to the ovaries
Ovarian neoplasms. Anita Chudecka - Głaz
STAGE II
Growth involving one or both ovaries with
pelvic extension
Ovarian neoplasms. Anita Chudecka - Głaz
STAGE III
Tumour involving one or both ovaries with
peritoneal implants outside the pelvis and/or
positive retroperotoneal or inguinal nodes;
superficial liver metastasis ; tumour is
limited to the true pelvis but with
histologically proven malignant extension
to small bowel or omentum
Ovarian neoplasms. Anita Chudecka - Głaz
STAGE IV
Tumour involving one or both ovaries with
distant metastases; if pleural effusion is
present , there must be positive cytology to
allot a case to stage IV
Ovarian neoplasms. Anita Chudecka - Głaz
Five - year survival rates for epithelial ovarian
cancer
Stage
IA
IB
IC
IIA
IIB&IIC
III
IV
82,3%
74,9%
67,7%
60,6%
53,8%
22,7%
8 %
Ovarian neoplasms. Anita Chudecka - Głaz
PREDICTORS OF SURVIVAL
 stage
 grade
 age
 residual disease
 max. cytoreductive surgery
 histopathology
 others ( protein p53, CA 125, EGF-R)
Ovarian neoplasms. Anita Chudecka - Głaz
TREATMENT
• surgical
• chemotherapy
• radiotherapy
• hormonal treatment
Ovarian neoplasms. Anita Chudecka - Głaz
postoperative
procedures
SURGICAL TREATMENT
cytoreductive operation:
 hysterectomy
 bilateral oophorectomy
 omentectomy
 appendectomy
 lypmphadenectomy ??
Nowotwory jajnika. Anita Chudecka - Głaz
CHEMOTHERAPY
•
•
•
CT
PC
PAC
I LINE CHEMOTHERAPY
• Vepesid or
Ifosfamid with CDDP as II LINE CHT.
•
Hycamptin or Gemzar as III LINE CHT.
Ovarian neoplasms. Anita Chudecka - Głaz
SURGICAL TREATMENT - EOC
 benign
In young women conservative surgery usually including
cystectomy or oophorectomy. In postmenopausal women
TAH/BSO should be considered to avoid the risk of cancer
in the future.
 borderline
In young women conservative surgery oophorectomy or USO
can be performed. In women who have completed their
child bearing a TAH/BSO/Omentectomy is appropriate
always with very precise surgical staging.
Ovarian neoplasms. Anita Chudecka - Głaz
SURGICAL TREATMENT - EOC
 malignant
In all cases we have to carry out cytoreductive
surgery. It includes TAH/BSO complete
omentectomy with resection of any metastatic
lesions. In some cases bowel resection and
retroperitoneal lymphadenectomy are necessary in
order to obtain optimum cytoreduction. Optimum
cytoreduction is achieved when the largest
residual tumour mass measures less then 1,5 cm.
Ovarian neoplasms. Anita Chudecka - Głaz
POSTOPERATIVE TREATMENT - EOC
 chemotherapy
Platinum-based combination with paclitaxel
chemotherapy is now the standard postoperative
treatment for patient with ovarian cancer
 radiation therapy
It is useful method especially in patient who have
positive second-look laparoscopy or laparotomy
after chemotherapy treatment but the residual
mass are less than 2 cm.
 hormonal treatment
Ovarian neoplasms. Anita Chudecka - Głaz
FOLLOW - UP
 second-look laparoscopy every year during
first 5 year to detect early microscopic
relapse
 CA 125 every 3 to 4 month
 complete medical history
 physical examination
 rectovaginal pelvic examination
Ovarian neoplasms. Anita Chudecka - Głaz
SCREENING
Screening is recommended in women with
HOCS and HBOCS and include:
 rectovaginal pelvic examination
 CA 125 determination
 TVS
 prophylactic TAH/BSO
Ovarian neoplasms. Anita Chudecka - Głaz
MALIGNANT GERM CELL TUMOURS
 Dysgerminoma most common germ cell
malignancy , in 10-15% is bilateral , survival rate for
early stage is 95% and even in advanced stage grater
then 80% when appropriate adjuvant therapy is given.
LDH is useful tumour marker. hCG levels is elevated in
small number of patients. In young women and stage I
unilateral oophorectomy is recommended with
inspection and biopsy of opposite ovary and staging
with retroperitoneal lymphadenectomy. In other
women TAH/BSO. Adjuvant therapy should be given
in all patients radiotherapy and/or chemotherpy.
Ovarian neoplasms. Anita Chudecka - Głaz
MALIGNANT GERM CELL TUMOUR
Embryonal carcinoma is quite rare , rarely
bilateral and trends to spread intraperitoneally ,
survival is slightly better then with EST using the same
platinum based chemotherapy regiments . Both AFP
and hCG can serve as tumour markers. Surgical
treatment depend on age and stage . Adjuvant therapy (
chemotherapy) is recommended in all cases.
Ovarian neoplasms. Anita Chudecka - Głaz
MALIGNANT GERM CELL TUMOURS
Immature teratoma represents approximately
20% of all malignant germ cell tumours and 25 % in
girls under 10. After grade surgicopathologic stage is
the most prognostic factors. Fortunately most patient
are diagnosed with early stage. Occasionally immature
carcinoma produce AFP as tumour marker but hCG is
never produced. Surgical treatment depend on age and
stage. Chemotherapy is kind of adjuvant therapy but
only in immature teratoma of all malignant germ cell
tumours chemotherapy in stage IA grade I does not
benefit.
Ovarian neoplasms. Anita Chudecka - Głaz
MALIGNANT GERM CELL TUMOURS
Endodermal sinus tumour
also known as
“yolk sac tumour” is an extremely aggressive
malignancy. Almost never is bilateral. Intraperitoneal
and hematogenous spread is common. Commonly
patients present with acute abdomen secondary to
spontaneous rupture and haemorrhagiae. Platinum
based chemotherapy significantly improves the
survival. AFP is useful tumour marker.
Ovarian neoplasms. Anita Chudecka - Głaz
MALIGNANT GERM CELL TUMOURS
Chorioncarcinoma nongestational is extremely
rare , 50% is diagnosed in prepuberatal females ,
produced hCG as tumour marker . Although
gestsational chorioncarcinoma is treated successfully in
most patients with platinum based chemotherapy ,
remission is less common in patients with
nongestational type.
Polyembryoma
 Mixed
Ovarian neoplasms. Anita Chudecka - Głaz
BENIGN GERM CELL TUMOURS
 Gonadoblastoma is almost always found in patients
with gonadal dysgenesis associated with chromosome Y. In 50%
coexist with malignant germ cell tumours
 Teratomas 25-40% of all ovarian neoplasms. The most
common is cystic teratoma - “dermoid cysts”. Most cases
diagnosed in premenopausal women . Most patients are
asymptomatic and often dermoids are diagnosed by usg. This
tumours can be bilateral in 15%. The risk of malignancy is 1-2%
and most commonly occurs in postmenopausal women.
 Struma ovarii it is dermoid where thyroid tissue
comprises greater than 50% of teratomas. This is unusual and
accounts for only 2,7% of ovarian teratomas.
Ovarian neoplasms. Anita Chudecka - Głaz
SEX CORD STROMAL TUMOURS
 Adult granulosa cell tumours (GCTs)
excess estrogen production is often found causing
precocious puberty and menometrorrhagia in
menstruating or postmenopausal. Endometrial
hyperplasia or carcinoma is at 60% in patients with
this tumour.50% occur in postmenopausal women and
only 5% in prepubertal girls. It is interestin that this
king of tumour may relapse after many years ( even
above 20 ) after primary diagnosis. Estardiol and in
nowadays inhibin are useful tumour marker.
Ovarian neoplasms. Anita Chudecka - Głaz
SEX CORD STROMAL TUMOURS
Juvenile granulosa cell tumours in 50% occur
in prebubertal girls , rare relapse after many years from
diagnosis , typically is early recurrence. Rarely lethal as
GCTs.
Fibroma unilateral , diagnosed in 5 decade of life.
Hormone production is unusual , eventually estrogen. It is
benign tumour, when 1 to 3 mitoses are present is called
cellular fibroma, if greater then 3 it is considered as
fibrosarcoma.
Thecoma very similar to fibroma but more commonly
produce etsrogen which causes postmenopausal bleeding ,
menorrhagia, endometrial hyperplasia or cancer.
Ovarian neoplasms. Anita Chudecka - Głaz
SEX CORD STROMAL TUMOURS
 Sertoli stromal cell tumours 1 % of all ovarian
neoplasms , many of these tumours androgen producing ,
many are hormonally inert and some occasionally may
produce estrogen. Diagnosed of pure Sertoli tumours is
unlikely in the presence of virilization. Rarely is malignant.
 Sertoli-Leydig cell tumours are the most
common in these group , 40% have evidence of estrogen or
androgen production, unilateral and occur in 3 decade of
life. Rather frequently is malignant.
 Sex cord tumour with annular tubules
(SCTAT) in 30% associated with Peutz-Jegers
syndrome.
Ovarian neoplasms. Anita Chudecka - Głaz
SEX CORD STROMAL TUMOURS
Lipid cell tumour are typically virilizing with
increased serum levels of testosteron and androstendione.
Occasionally produce estrogen, estron and cortisol and in
10% cases Cushing Syndrom in found. In 20 % develop
metastases.
 Gynanroblastoma is rare ovarian tumours which
contain granulosa stromal cell and Sertoli stromal cell
tumours.
Leydig cell tumours mean age is 50 and almost
always behaves in benign fashion. Testosterone is commonly
produced resulting in mild virilization.
Ovarian neoplasms. Anita Chudecka - Głaz