1 Obstetrics &Gynecology Hospital Fudan University 2011.09 Chen Xiaojun Ovarian Neoplasm 卵巢肿瘤 Chen Xiaojun Ob&Gyn Hospital Fudan Uniiversity

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Obstetrics &Gynecology Hospital

Fudan University

2011.09Chen Xiaojun

Ovarian Neoplasm

卵巢肿瘤

Chen XiaojunOb&Gyn Hospital Fudan Uniiversity

http://www.art-com.co.kr/online/ppt_gallery_1.htm

• 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… …

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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

• 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

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• What is ovarian neoplasm?

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Epithelial tumor

50-70%

上皮性肿瘤

Germ cell tumor

20-40%

生殖细胞肿瘤

Sex cord-stromal tumor

5%

性索间质肿瘤

Metastatic tumor

5-10%

转移性肿瘤

• 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

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• Age distribution of ovarian neoplasm

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• 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

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• 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

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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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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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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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

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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

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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

– History– Physical examination– Imaging study– Laboratory examination– Cytological examination– Laparoscopic examination and biopsy– Other auxiliary examination needed

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Diagnosis

– Use of oral contraceptivesUse of oral contraceptives– Pregnancy and breast-feeding historyPregnancy and breast-feeding history– Previous gynecologic surgery : tubal ligation or hysterectomy Previous gynecologic surgery : tubal ligation or hysterectomy – History of ovarian tumor in the familyHistory of ovarian tumor in the family– Previous cancer history Previous cancer history – smoking habits smoking habits – exposures to harmful occupational or exposures to harmful occupational or environmental substancesenvironmental substances

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History

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Pelvic examination• If the mass is larger than 5cm, is If the mass is larger than 5cm, is

solid rather than cystic, or is solid rather than cystic, or is bilateral , ovarian cancer may be bilateral , ovarian cancer may be present.present.

• Nodules on the floor of the pelvis Nodules on the floor of the pelvis indicate ovarian cancer.indicate ovarian cancer.

benignMalignant

Diagnosis

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Image studies• Ultrasonography--Ultrasonography--most ovarian mass>1cm can be found

– low resistance and pulsatile indexes suggest the presence of a low resistance and pulsatile indexes suggest the presence of a cancerous tumor.cancerous tumor.

• X-rayX-ray—mature teratoma with bones and teeth• CT scanCT scan• MRIMRI

benign malignant

Diagnosis

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Laboratory Tests – Serum tumor markersSerum 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 mutationsTests for genetic mutations– Microscopic examination of ovarian cancer cells from Microscopic examination of ovarian cancer cells from

ascites ascites or pleural effusion

Diagnosis

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CA125---CA125---epithelial cancer markerepithelial cancer marker – 85% of women with clinically apparent ovarian cancer have 85% of women with clinically apparent ovarian cancer have

increased levels of CA125 (> 35 U/ml).increased levels of CA125 (> 35 U/ml).– CA125 is not a specific tumor markerCA125 is not a specific tumor marker– as the protein also is increased during other conditionsas the protein also is increased during other conditions– Some ovarian cancers may not produce enough CA125 to Some ovarian cancers may not produce enough CA125 to

cause a positive test result cause a positive test result

Diagnosis

Differential diagnosis

benign malignanthistory 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-de-sac

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

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Benign ovarian tumor– Physilogical ovarian cyst: follicular cyst; corpus luteum cyst – Inflammatory cyst– Uterine myoma– pregnancy– Ascites

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Malignant ovarian neoplasms– Endometriosis– Tuberculous peritonitis – Chronic pelvic inflammatory disease– Metastatic ovarian tumor 哑铃状– Tumor from other pelvic organs

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What metastatic ovarian cancer might look like

• 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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Pattern of spread

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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

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• Torsion 扭转• Rupture 破裂• Infection 感染• Malignant transformation 恶性变

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Complications

– Torsion 扭转• 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• 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

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Acute Complications

Management

Benign ovarian neoplasm– Cystectomy or salphingo-oophorectomy

Malignant ovarian neoplasm– 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

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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. Omentectomy7. Aortic & pelvic lymph node dissection8. 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

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• 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

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Management

– 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妊娠合并卵巢肿瘤

– Complication• 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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Pregnancy complicated with ovarian neoplasm

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

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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

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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

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Epithelial ovarian neoplasm

Serous 浆液性

Mucinous 黏液性

Endometriod 内膜样Clear-cell 透明细胞Brenner 勃勒纳

Undifferentiated未分化

endosalpingeal

endocervical

endometrial

mullerian

transitional

anaplastic

Epithelial ovarian neoplams

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Grade 1 Highly differentiated

Grade 2 Moderately differentiated

Grade 3 Poorly differentiated

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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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Serous cystadenoma

浆液性囊腺瘤

Borderline serous cystademona

Serous cystadenocarcinoma

浆液性囊腺癌


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Mucinous cystadenoma黏液性囊腺瘤

Borderline mucinous cystadenoma

Mucinous cystadenocarcinoma黏液性囊腺癌


• 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

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• Serous tumor most common in ovarian neoplasm, than mucinous

• Mucinous cystadenoma– 5-10% develop into malignancy– myxoma peritonei 腹膜假粘液瘤

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Epithelial ovarian neoplams• Pseudo-Myxoma-Peritonei 腹膜假粘液瘤

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• 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

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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)

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prognosis61

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

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• 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– Also named Endodermal sinus tumor 内胚窦瘤– Highly malignant– Affect young women and girls– Tumor marker: AFP

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• 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

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• 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

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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

stroma mesenchyme

normal female Granulosa cell Theca cell

male Sertoli cell Leydig cell

tumor female Granulosa cell tumor Thecoma Fibroma

male Sertoli-Leydig cell tumor

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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

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• 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

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• 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

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• 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

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• 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)

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• 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

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Documents

1 Obstetrics &Gynecology Hospital Fudan University 2011.09 Chen Xiaojun Ovarian Neoplasm 卵巢肿瘤 Chen Xiaojun Ob&Gyn Hospital Fudan Uniiversity