Download Epithelial ovarian neoplasm

Ovarian Neoplasm
卵巢肿瘤
Chen Xiaojun
2011.09
Chen Xiaojun
Ob&GynHospital
Hospital Fudan Uniiversity
Obstetrics &Gynecology
Fudan University
1
• One single disease or a group of diseases?
– A group of diseases
• Benign or malignant disease?
– Benign, borderline and malignant
• Cancer or sarcoma?
– Cancer, sarcoma, germ cell tumor… …
2
 What we are going to discuss
– General principles of ovarian neoplasm
– Benign 良性
– Malignant 恶性
– Epithelial ovarian neoplasm 上皮性卵巢肿瘤
– Nonepithelial ovarian neoplasm 非上皮性
3
• Key points in the session
– Pathological classification of ovarian tumor
– Spread pattern and staging of ovarian cancer
– Differential diagnosis of benign and malignant ovarian
neoplasm
– The use of tumor markers in diagnosis of ovarian
neoplasm
– Principles of primary operation and chemotherapy for
ovarian cancer
4
• What is ovarian neoplasm?
Epithelial tumor
Germ cell tumor
Metastatic tumor
20-40%
Sex cordstromal tumor
50-70%
上皮性肿瘤
生殖细胞肿瘤
5%
转移性肿瘤
性索间质肿瘤
5-10%
5
• Epidemiology
– Almost 1/3 of invasive malignancies of the female genital organs
– The fifth most common cause of death from malignancy in
women.
– A woman's risk at birth of having ovarian cancer sometime in her
life is 1% to 1.5%, and that of dying from ovarian cancer almost
0.5%
– 5 year survival rate : 90% for malignant germ cell tumor; 30-40%
for epithelial ovarian cancer
6
• Age distribution of ovarian neoplasm
• Epithelial ovarian neoplasm
50-60 y
绝经后妇女
• Germ cell neoplasm
Under 30 y
育龄年轻妇女
Epithelial ovarian cancer
7
• Brief description
– Benign-borderline-malignant
– Mostly sporadic, 5-10% hereditary for
malignancies
– Hard to be detected in early stage, often
advanced when symptom appeared
– Operations being the most effective treatment
– Chemotherapy greatly improved prognosis of
ovarian cancer
8
Etiology & Risk factors
--Epithelial ovarian cancer
– Most benign and malignant ovarian neoplasm
is sporadic, with familial or hereditary patterns
accounting for 5% to 10% of all epithelial
ovarian cancer.
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Etiology & Risk factors
--Epithelial ovarian cancer
 Sporadic ovarian cancer 散发性卵巢癌
– Continuous ovulation 持续排卵
– Early menarche and late menopause
– Low parity and infertility
• Damage –repair process leading to mutation
– Environment
• Pollution
• Diet
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Etiology & Risk factors
--Epithelial ovarian cancer
 Hereditary ovarian cancer 遗传性卵巢癌（5-10% ）
− Hereditary ovarian cancers occur 10 years younger than those with
nonhereditary tumors
− BRCA1, BRCA2 mutation (ovarian and breast cancer)
− Hereditary non-polyposis colorectal cancer遗传性非息肉性结直肠癌
(HNPCC) Syndrome (Lynch II syndrome) (multiple site
adenocarcinoma)
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Etiology & Risk factors
--Epithelial ovarian cancer
Hereditary ovarian cancer
– BRCA1 gene mutation + high-risk families= 28% to 44% lifetime
risk of ovarian cancer
– BRCA2 gene mutation + high-risk families= 27% lifetime risk of
ovarian cancer
– BRCA1 or BRCA2 mutation= 56% to 87% risk of breast cancer
12
Symptoms----nonspecific 非特异症状
 Benign and early stage malignancy
– Always found during physical examination when the mass is small
– Benign and Early stage-vague and nonspecific symptoms
• Ovary dysfunction -- irregular menses
• Mass compression -- urinary frequency or constipation because of
mass compression
• Mass compression -- Lower abdominal distention, pressure, or pain,
such as dyspareunia
• Acute symptoms -- pain secondary to rupture or torsion, are unusual
13
Symptoms
Advanced-stage malignancy
• symptoms related to the presence of ascites, omental
metastases, or bowel metastases
• abdominal distention, bloating, constipation, nausea,
anorexia 厌食, or early satiety 早饱
• Cachexia 恶病质
• irregular or heavy menses
• 70% had abdominal or gastrointestinal symptoms, 58%
pain, 34% urinary symptoms, 26% pelvic discomfort
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Signs
 Benign
– Pelvic mass with smooth wall
 malignant
– solid, irregular, fixed pelvic mass
– Pelvic floor nodules
– upper abdominal mass or ascites
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Diagnosis
–
–
–
–
–
–
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History
Physical examination
Imaging study
Laboratory examination
Cytological examination
Laparoscopic examination and biopsy
Other auxiliary examination needed
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Diagnosis
History
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–
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Use of oral contraceptives
Pregnancy and breast-feeding history
Previous gynecologic surgery : tubal ligation or hysterectomy
History of ovarian tumor in the family
Previous cancer history
smoking habits
exposures to harmful occupational or environmental substances
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Diagnosis
Pelvic examination
• If the mass is larger than 5cm, is
solid rather than cystic, or is bilateral ,
ovarian cancer may be present.
• Nodules on the floor of the pelvis
indicate ovarian cancer.
Malignant
benign
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Diagnosis
Image studies
•
•
•
•
Ultrasonography--most ovarian mass>1cm can be found
– low resistance and pulsatile indexes suggest the presence of a
cancerous tumor.
X-ray—mature teratoma with bones and teeth
CT scan
MRI
benign
malignant
19
Diagnosis
 Laboratory Tests
– Serum tumor markers
• CA125 epithelial ovarian cancer
• AFP Yolk sac tumor; other germ cell tumor
• hCG ovarian choriocarcinoma
– Sex hormones sex cord stromal tumor
– Tests for genetic mutations
– Microscopic examination of ovarian cancer cells from
ascites or pleural effusion
20
Diagnosis
CA125---epithelial cancer marker
– 85% of women with clinically apparent ovarian cancer have
increased levels of CA125 (> 35 U/ml).
– CA125 is not a specific tumor marker
– as the protein also is increased during other conditions
– Some ovarian cancers may not produce enough CA125 to cause
a positive test result
21
Differential diagnosis
benign
malignant
history
Long term, grow slowly
Short term, grow fast
mass
Unilateral, cystic, smooth and
movable
Bilateral, solid or partially solid, irregular
surface, unmovable and solid mass in cul-desac
ascites
negative
malignant cells found in ascites
General condition
well
Lost of weight, cachexia
Ultrasonography
Unilocular, thin-walled,
no papillae, no solid areas
Multilocular, thick walls, papillae present,
mixed echogenicity due to solid areas
CA125(>50y)
<35U/ml
>35U/ml
22
Differential diagnosis
 Benign ovarian tumor
–
–
–
–
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Physilogical ovarian cyst: follicular cyst; corpus luteum cyst
Inflammatory cyst
Uterine myoma
pregnancy
Ascites
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Differential diagnosis
 Malignant ovarian neoplasms
–
–
–
–
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Endometriosis
Tuberculous peritonitis
Chronic pelvic inflammatory disease
Metastatic ovarian tumor 哑铃状
Tumor from other pelvic organs
What metastatic
ovarian cancer
might look like
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Pattern of spread
• Transcelomic 腹腔内扩散
– The most common and earliest mode of dissemination is by
exfoliation of cells than implant along the surfaces of the
peritoneal cavity.
• Lymphatic 经淋巴转移
– retroperitoneal ( pelvic and paraaortic ) LN spreading is common
in advanced- stage disease.
• Hematogenous 血行转移
– uncommon, lungs and liver is the most common sites
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26
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Stage I
• Tumor limited to ovary
– Ia limited to one ovary
– Ib limited to both ovary
– Ic Ia or Ib +tumor on
ovarian surface; tumor
rupture; tumor cell (+） in
peritoneal fluid or washing
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Stage II
• With pelvic extension
– IIa to uterus or fallopian
tube
– IIb to other pelvic tissue
– IIc IIa or IIb +tumor on
ovarian surface; tumor
rupture; tumor cell (+） in
peritoneal fluid or washing
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Stage III
• Peritoneal implants outside
pelvic; LN (+); superficial liver
metastasis
– IIIa microscopic abdominal
seeding
– IIIb abdominal
implants≤2cm
– IIIc abdominal
implants>2cm; LN(+)
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Stage IV
• With distant metastasis
– Tumor cell (+) in Pleural
effusion
– parenchymal liver
metastasis 肝实质转移
31
Complications
•
•
•
•
Torsion 扭转
Rupture 破裂
Infection 感染
Malignant transformation 恶性变
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Acute Complications
– Torsion 扭转
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•
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Tumor with long pedicel
Middle sized
Without adhesion
Content not evenly distributed
Sudden occurrence of pain after changing of position, defecation or
urination
Complicated with nausea or vomiting, even shock
Tenderness of the pelvic mass, most prominent at the pedicle site
Emergent operation is needed
Tumor should be moved with clapping the root of the pedicle
Torsion should not be released before clapping the pedicle
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Acute Complications
– Tumor rupture 肿瘤破裂
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•
•
•
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Spontaneous or exogenesis mechanical reasons
Mild or severe abdominal pain
Symptoms and signs of peritoneal irritation
Intraperitoneal bleeding
Preexisted Pelvic mass cloud not be felt or became smaller
on pelvic examination
• Emergent operation is needed
34
Management
 Benign ovarian neoplasm
– Cystectomy or salphingo-oophorectomy
 Malignant ovarian neoplasm
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–
–
–
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Complete staging surgery
Fertility preservation surgery for young women
Cytoreductive surgery for advanced stage
Chemotherapy
Radiotherapy
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Management
• Complete staging surgery
– Laporotormy--A midline or paramedian
abdominal incision is recommended to allow
adequate access to the upper abdomen
– Laparoscopic operation-- only for early
stage ovarian cancer
•
·
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Management
complete staging surgery 完全分期手术
•
Exploration
1. Free fluid or peritoneal washings for cytological evaluation
2. Systematic exploration of all the intra-abdominal surfaces
and viscera—clock wise
3. Biopsy any suspicious areas or adhesions on the peritoneal
surfaces; and Random peritoneal biopsy including diaphragm
37
Management
complete staging surgery
•
Operation
4. Total hysterectomy+ bilateral salpingectomy &
oophorectomy (Keep and encapsulated mass intact during
removal)
5. Unilateral salpingo – oophorectomy when fertility
preservation is desired in selected patients
6. Omentectomy
7. Aortic & pelvic lymph node dissection
8. Appendectomy when mucinous cancer
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Management
• Indication for fertility preserving operation 保留生育
功能手术
The uterus and the contralateral ovary can be preserved when
– Young and desires fertility
– Stage Ia
– Low grade (1 or 2)
– No evidence of spread beyond the ovary after a thorough staging
laparotomy
40
Management
• Cytoreductive surgery 肿瘤细胞减灭术
– Staging surgery
– Maximal efforts should be made to remove all gross
diseases
– Optimal cytoreduction: residual disease <1cm
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Management
• Treatment for borderline ovarian tumor
交界性卵巢肿瘤
– Stage I
• Hysterectomy + bilateral salpingo-oophorectomy
• Unilateral salpingo – oophorectomy when fertility
preservation is desired
– Stage II-IV complete staging surgery
42
Pregnancy complicated with ovarian neoplasm
妊娠合并卵巢肿瘤
– Mostly benign
• Teratoma
• Cystic adenoma
– Diagnosed by
• Pelvic examination during early pregnancy
• Ultrasonography after mid-term pregnancy
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Pregnancy complicated with ovarian neoplasm
– Complication
•
•
•
•
•
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Abortion
Torsion
Rupture
Abnormal fetal growth
Birth tract obstruction
Fast progression of malignant tumor
– Management
• Operation after 3 months of pregnancy
• Surgery when C-S if found during late term pregnancy
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Prevention and Screening 预防与筛查
 Sporadic ovarian cancer
– Prevention
• Child bearing
• Oral contraceptive pills
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Prevention and Screening
 Sporadic ovarian cancer
– Screening
• Ultrasonography + CA125 every 6 months for high risk women
• Surgery if tumor >5cm
• High alert if enlarged ovary before menarche, after menopause or oral
contraceptive pills is taken regularly
• Consider laparoscope or laparotomy if pelvic mass can not be
diagnosed clearly or no effect after treatment
46
Prevention and Screening
 Hereditary ovarian cancer
– Genetic counseling and genetic testing for BRCA1and BRCA2.
– Screening by transvaginal ultrasonography every 6 months for
women wishing to preserve their reproductive capacity
– Oral contraceptives for young women before they embark on an
attempt to have a family.
– Prophylactic bilateral salpingo-oophorectomy for women who do
not wish to maintain their fertility
47
Prevention and Screening
 Hereditary ovarian cancer
– Annual mammographic screening beginning at age 30 years for
women having strong family history of breast or ovarian cancer
– HNPCC syndrome: be treated as above and undergo periodic
screening mammography, colonoscopy,and endometrial biopsy
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Epithelial ovarian neoplasm
上皮性卵巢肿瘤
49
Epithelial ovarian neoplasm
Serous 浆液性
endosalpingeal
Mucinous 黏液性
endocervical
Endometriod内膜样
endometrial
Clear-cell 透明细胞
mullerian
Brenner 勃勒纳
transitional
Undifferentiated
anaplastic
未分化
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Epithelial ovarian neoplams
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Epithelial ovarian neoplasm
Grade 1
Highly differentiated
Grade 2
Moderately differentiated
Grade 3
Poorly differentiated
The higher the grade, the poorer the prognosis.
病理级别越高，恶性程度越高，预后越差！
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Epithelial ovarian neoplasm
Serous cystadenoma
浆液性囊腺瘤
Borderline serous
cystademona
Serous
cystadenocarcinoma
浆液性囊腺癌
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Epithelial ovarian neoplasm
Mucinous
cystadenoma
黏液性囊腺瘤
Borderline
mucinous
cystadenoma
Mucinous
cystadenocarcinoma
黏液性囊腺癌
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Epithelial ovarian neoplasm
• Peak incidence of invasive epithelial ovarian cancer : 56 to 60 years
• Average age is 46 years for borderline tumors
• Benign ovarian tumor
– Unilateral
– Ball-like with smooth wall
– Single or multiple foci
• Borderline ovarian tumor
–
–
–
–
low malignant potential
lesions tend to remain confined to the ovary for long periods
occur predominantly in premenopausal women
good prognosis
55
Epithelial ovarian neoplasm
• Serous tumor most common in ovarian neoplasm, than
mucinous
• Mucinous cystadenoma
– 5-10% develop into malignancy
– myxoma peritonei 腹膜假粘液瘤
56
Epithelial ovarian neoplams
• Pseudo-Myxoma-Peritonei 腹膜假粘液瘤
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Epithelial ovarian neoplams
• Endometrioid tumor 内膜样肿瘤
– ≠ovarian endometriosis
• Endometriod carcinoma 内膜样癌
– 15-20%Complicated with endometrial cancer
• Clear cell cancer 透明细胞癌
– Always complicated with endometriosis
– All high grade( Grade 3)
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Epithelial ovarian neoplasm
• Brenner tumor 勃勒纳瘤
– Differentiate into transitional cells
• Undifferentiated carcinoma 未分化癌
– 9-43 y (average 24)
– 70% complicated with hypercalcemia
– Highly progressive
– Mortality rate 90% within 1 year
59
Epithelial ovarian neoplasm
 Treatment
– Benign
• Surgery
– Malignant
• Complete staging surgery
• Chemotherapy
– All epithelial ovarian cancer except for stage Ia-Ib grade 1
– TP regimen Taxane紫杉烷 / carboplatin 卡铂 IV or IP for 6-9
courses (3 weeks per course)
60
Epithelial ovarian neoplams
prognosis
61
Nonepithelial ovarian neoplasm
非上皮性肿瘤
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Nonepithelial ovarian neoplasm
• Ovarian germ cell tumor 卵巢生殖细胞肿瘤
– Derived from the primordial germ cells of the ovary
– Affect mostly in young women and girls
• 60-90% before menarche
• 4% after menopause
– Highly sensitive to chemotherapy
– Fertility can be preserved for most patients
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Ovarian germ cell tumor
• Teratoma 畸胎瘤
– Mature teratoma 成熟性畸胎瘤
• Very common
– 10-20% of ovarian neoplasm
– 85-97% of ovarian germ cell tumor
– >95% of teratoma
• Content: fat, hair, bone, teeth
• Easily diagnosed by ultrasonography and X-ray
• Seldom highly differentiated: struma ovarii 卵巢甲状腺肿
• 2-4% become malignant
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Ovarian germ cell tumor
• Teratoma
– Immature teratoma 不成熟畸胎瘤
• malignant
• Average age of incidence 11-19y
• High recurrence and metastatic rate
• Mature transformation after
recurrence
65
Ovarian germ cell tumor
• Dysgerminoma 无性细胞瘤
–
–
–
–
Malignant solid tumor
Affect young women of teenage and reproductive age
Sensitive to radiotherapy
5 year survival rate 90% for pure dysgerminoma
• Yolk sac tumor 卵黄囊瘤
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–
–
–
Also named Endodermal sinus tumor 内胚窦瘤
Highly malignant
Affect young women and girls
Tumor marker: AFP
66
Ovarian germ cell tumor
• Embryonal Carcinoma 胚胎癌
– Multiple potential malignant tumor
• Choriocarcinoma of the ovary 卵巢绒毛膜细胞癌
–
–
–
–
Nongestational
Highly malignant
Poorer prognosis than gestational choriocarcinoma
Tumor marker: hCG
67
Ovarian germ cell tumor
• Treatment
– Operation
• Benign
– Tumor resection/ unilateral salpingo-oophorectmy/ hysterectomy +
bilateral salpingo-oophorectomy
• Malignant
– Complete staging surgery
– Fertility preserving surgery should be done for Stage Ia young patients
– Chemotherapy
• Sensitive to chemotherapy
• BEP (bleomycin 博来霉素, etoposide依托泊甙, cisplatin顺铂) 3-6 courses
(3weeks per course)
– Radiotherapy
• Dysgerminoma 无性细胞瘤most sensitive to radiotherapy
68
Ovarian sex cord stromal tumor卵巢性索间质肿瘤
– account for about 4.3% to 6% of all ovarian tumors malignancies
– derived from the primordial sex cords and mesenchyme: stroma
or mesenchyme
normal
tumor
stroma
mesenchyme
female
Granulosa cell
Theca cell
male
Sertoli cell
Leydig cell
female
Granulosa cell tumor
Thecoma
Fibroma
male
Sertoli-Leydig cell tumor
69
Ovarian sex cord stromal tumor
– Solid tumor
– Some can secrete sex hormones
– Manifested by symptoms of disturbed reproductive
endocrinology
– Sex hormone level be helpful for diagnosis
70
Ovarian sex cord stromal tumor
• Granulosa cell tumor 颗粒细胞瘤
– Adult granulosa cell tumor account for 95%
• low malignant
• 45-55 y
• Secret estrogen
• Might complicated with endometrial cancer
– Juvenile granulosa cell tumor account for 5%
• highly malignant
• teenage
71
Ovarian sex cord stromal tumor
• Thecoma 卵泡膜细胞瘤
– Benign ovarian tumor
– Can secret estrogen
– Might complicated with endometrial cancer
• Fibroma 纤维瘤
– Benign tumor
– Might complicated with ascites or hydrothorax—Meigs
syndrome
72
Ovarian sex cord stromal tumor
• Sertoli-Leydig cell tumor
–
–
–
–
–
Also named Androblastoma 卵巢男性细胞瘤
Affect women < 40y
70% are benign
Secret androgen
Seldom secret estrogen
73
Ovarian sex cord stromal tumor
• Treatment
– Operation
• Benign
– Tumor resection/ unilateral salpingo-oophorectmy/ hysterectomy +
bilateral salpingo-oophorectomy
• Malignant
– Complete staging surgery
– Fertility preserving surgery should be done for Stage Ia young
patients
– Chemotherapy
• Platinum based chemotherapy
• BEP (bleomycin, etoposide, cisplatin) 3-6 courses (3weeks per course)
74
• Key points in the session
–
–
–
–
–
Pathological classification of ovarian tumor
Spread pattern and staging of ovarian cancer
Differential diagnosis of benign and malignant ovarian neoplasm
The use of tumor markers in diagnosis of ovarian neoplasm
Principles of primary operation and chemotherapy for ovarian
cancer
75
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