Szabolcs Máté M.D.

I st. Dept. of OB/GYN

Semmelweis University

OVARIAN NEOPLASMS

PATHOLOGY, DIAGNOSIS AND TREATMENT

Principles

Neoplasm

• Abnormal mass of tissue as a result of neoplasia

• Neoplasia (new growth in Greek) is the abnormal proliferation of cells

• The growth is uncoordinated

• May be benign, pre-malignant or malignant

Malignant tumour

• Uncontrolled growth

• Invasion

• Metastasis

A benign tumour

• Tumour that lacks all three of the malignant properties of a cancer

Symptoms of adnexal mass

• Lower abdominal pain, crumpling

• Compression of pelvic organs• Urinary bladder- frequency• Bowel- altered bowel habits, nausea, constipation, dyshesia• Veins- oedema, thrombosis, varicose vein

• Endocrine• Bleeding, irregular cycles, hyperandrogenism

Differential diagnosis of pelvic mass

Organ Cystic Solid

Ovary Functional cyst Neoplasm(benign/malignant)

Neoplastic cyst (benign/malignant)

Endometriosis

Fallopian tube Tubo-ovarian abscess Tubo-ovarian abscess

Hydrosalpinx Ectopic pregnancy

Parovarian cyst Neoplasm

Uterus Intrauterine pregnancy in bicornate uterus Pedunculated or interligamentous myoma

Bowel Sigmoid or coecum distended with gas or feces

Diverticulitis

Ileitis

Appendicitis

Colonic cancer

Miscancellaneous Distended bladder Abdominal wall haematoma or abscess

Pelvic kidney Retroperitoneal neoplasm

Urachal cyst

Ovarian massFUNCTIONAL CYSTS Follicular cyst

Corpus luteum cyst

Theca-lutein cyst Due to overstimulation (hCG)

Pregnancy luteoma Vs. hCG dependent non-neoplastichyperplasia during pregnancy, regress after delivery

Endometriosis cyst Endometrial epithelium,Endometrial-type stroma, Hemosiderin-laden macrophages in cyst wall

Neoplasm benign/borderline/malignant

Management-Physical examination

• Abdominal, trans-vaginal, rectal examination• Benign

• smooth walled, • mobile,• cystic,

• unilateral,

• smaller than 8 cm

• Malignant

• solid or semisolid• bilateral• irregular • fixed• associated with nodules in the cul-de-sac• ascites

Management-Ultrasound

• Benign CYST• Unilocular• Thin-walled • Sonolucent• Smooth, regular borders

• Malignant• Irregular borders• Papulations• Solitary thick septa• Excrescences • Ascites, distant metastasis

• Doppler flowmetry

• High Pulsatility index (PI)

• Low Resistance (RI)

• (not specific)

Management- CT, MRI, PET-CT

(Rieber A., et.al.: AJR Am J Roentgenol. 2001, 177(1):1239)

Management-LabsTumor markers

• Epithelial: • CA 125, elevated in 80%

• Also elevated in many benign conditions

• Elevated only 50% in stage I

• HE4 (Human epidimidis protein 4)• Produced by the ovary

• More specific

• ROMA score• HE4+CA-125+menopausal status (pre/post)

• Higher predictive value than each alone

• Malignant germ cell tumors: • β-hCG, LDH, AFP

• Embryonal carcinoma: • AFP, β-hCG

• Endodermal Sinus tumor: • AFP

• Granulosa cell tumors: • Inhibin β

Risk assessment

• Prediction of dignity

• Ultrasound morphology

• RMI score• Ultrasound morphology• CA-125• Menopausal status

• ROMA score• CA-125• HE4• Menopausal status

Biopsy

• Cytology• Ascites• Hydrothorax• FNAB

(fine needle aspiration biopsy)

• Tissue sample• CORE / true cut biopsy (Ultrasound guided)• Laparoscopic biopsy

• Don’t puncture a cyst in case there is no sign for disseminated disease!!!

Adnexal mass: Indication for surgery

• Ovarian cystic structure >5cm • has been observed 6-8 weeks without regression

• Any solid ovarian lesion

• Any ovarian lesion with papillary vegetation on the cyst wall

• Any adnexal mass >10cm in diameter

• Ascites

• Palpable adnexal mass • Pre-menarchel• POST-menopausal

• Torsion or rupture suspected

Classification of ovarian tumors

• EPITHELIAL• Serous• Endometrioid• Mucinous• Clear-cell• Transitional• Undifferenciated

• GERM-CELL

• SEX-CORD STROMAL

• METASTATIC OVARIAN TUMORS

Classification of Epithelial Ovarian neoplasm

• Histologic type• Serous 50-70% (the worst prognosis) • Endometrioid 15-20%• Mucinous 10%• Clear-cell 4-10%• Transitional• Undifferentiated 6-10%

• Biologic behavior• Benign• Low malignant potential/ Borderline ovarian neoplams• Malignant (Epithelial ovarian carcinoma (EOC))

• Low grade• High grade

Classification of Epithelial Ovarian Carcinoma (EOC)

• Borderline ovarian Tumor• Malignant cells• No invasion• Implantation rather than metastasis• 10 year survival ~90%• Can recur after long time as malignant Low-grade cancer

• Low-grade carcinoma• usually diagnosed at early stage• indolent behavior• precancerous stage is BORDELRINE OVARIAN CANCER• BRAF + KRAS oncogenes mutation 28-35%, • PTEN + CTNNB1 tumor suppressor genes mutation

• High-grade carcinoma• usually locally-advanced stage III• aggressive biological behavior• early metastases • p53 tumor suppressor gen mutation

Origin of high grade serouscarcinoma

High grade serous ovarian cc. pathogenesis• Traditional theory

• Originates from the ovarian surface epithelium

• Serous intraepithelial neoplasia / carcinoma(TIN/TIC)• Thorough pathological examination of fallopian tubes

from Prophylactic adnexectomies (BRCA1, BRCA2 pos.)

• TIC is frequent in the distal tubal epithelium• (Piek et al., 2001).

• 50% besides serous ovarian cc.• 47% Primary peritoneal carcinoma

• (Kindelberger et al., 2007). • (Carlson et al.,2008).

High grade serous ovarian cc. pathogenesis

• Genetics

• Characteristic p53 mutation (‘p53 signatures’) • TIC

• Invasive high grade serous ovarian cc.

Low grade serous ovarian cc. pathogenesis

• Morphologic and immune phenotypic studies of the ovaries• Ovarian surface epithelium

• 96% mesothelial phenotype (calretinin+/PAX8-/tubulin-)

• Low proliferative index (0.012%),

• 4% tubal phenotype (calretinin-/PAX8+/tubulin+).

• Inclusion cyst• 78% tubal phenotype

• Significantly higher proliferative index, than the surface epithelium

•

Low grade serous ovarian cc. pathogenesis

• Low-grade serous carcinoma• 10% of all ovarian serous carcinomas

• Development

• KRAS and BRAF mutations

Ovarian inclusion cyst

Serouscystadenoma

Serousborderline

tumor

Low grade carcinoma

Epithelial Ovarian CancerEpidemiology

Globally 7th most incident and lethal cancer

• Leading cause of cancer death of gynecologic origin in the developed countries

• Overall 5-year survival rate is 45%

• The “silent killer”: asymptomatic in early stages

• 75% diagnosed with advanced stage disease

Epithelial Ovarian CancerEpidemiology

• In adulthood • 90% of malignant ovarian tumors are epithelial

• Peek incidence 64 years

• Sporadic (90%)

• 5-10% is inherited

Etiology of sporadic EOC

• Unknown, but

• Environmental factors could be the major cause• Highest rates in highly industrial countries (except for Japan)

• Fat, alcohol, smoking

• Azbest, talcum

• The role of ovulation• Term pregnancies

• OAC RR (relative risk) < 0,5%!

• Ovulation induction drugs increase RR!

Inherited forms

• Sporadic• No epithelial ovarian cancer among relatives• Relative risk 1,4% (1 in 70)

• Familiar • At least 1 close relative has epithelial ovarian cancer• RR 3,6 x 1,4%=5%!

• Herediter• Multiple family members are affected over several generations

Inherited forms

• Herediter ovarian cancer syndrome (10-15%)

• BRCA 1, 2 mutation carrier• Herediter ovarian and breast cancer syndrome

• Double strand DNA repair

• Life-time risk for ovarian cc. (65-75%)

• Lynch sy. • Mutation of Mismatch repair genes

• MSH2, MLH1…

14%

7%

21%

BRCA mutation

Germ line BRCA mutation Somatic BRCA mutation

Normal cells

Allele copies 1 normal, 1 mutant 2 normal

Function BRCA function intact BRCA function intact

Cancer cells

Allele copies 1 inherited mutation + 1 acquired (LOH)

2 acquired BRCA mutation

Function LOST BRCA function LOST BRCA function

BRCA mutáció- szövettani típus

Lynch syndrome

• Early onset

• Various malignant tumors• Colorectal

• Endometrial

• Ovarian

• Small intestine, stomach

• Cholecyst, pancreas

• Ureter, pyelon

• Glioblastoma

Lifetimerisk (%)

Average age(years)

LS / all(%)

Endometrial cc. 40-60 48–62 2,3%

Colorectal cc 40-60 45 2-5%

Ovarian cc. 10-12 42.5

Screening of EOC

• Ultrasound

• CA-125

• No evidence that they can be used effectively for widespread screening to reduce mortality from EOC

• Result in unnecessary surgery with associated risk!

Ovarian Cancer Risks

• Increase Risk• Age

• most important independent risk factor• Family history• BRCA1 (60x increased risk), BRCA2 (30x), Lynch sy.(13x)• Null parity, infertility, endometriosis

• Decrease Risk• Prophylactic oophorectomy

• Prophylactic salpingectomy

• Oral contraceptive pills

Prophylactic Salpingectomy

• Prophylactic salpingectomy• It’s risk reducing effectivity is not known• No prospective randomised studies going to show this in the near

future• Easy procedure• No known negative side affects

• Several guidelines included prophylactic salpingectomy• Hysterectomy • Sterilisation

• In case of high cancer risk (BRCA1, BRCA2 mutation)• The proven effective salpingo-oophorectomy should be performed

Risk reducing salpingooophorectomy(RRSO)

• BRCA1 and BRCA2 mutation• 95% of the hereditary ovarian tumors• 15% to 60% lifetime risk for ovarian cc.

• Prophylactic salpingo-oophorectomy• Proven effectiveness

• Reduces the risk of BRCA related gynec. tumors by 96%• If done premenopausal, it reduces the risk of breast cc by 50-80%

• Primer peritoneal cc 0,8% -1% (after RRSO)

• Transvaginal sonography + CA125 yearly screening• Is not efective in this population

Symptoms of EOC

• No early sign!

• Advanced stage (St III) • Local

• Tumor (if size is more than > 10 cm.)

• Meteorism, • Pelvic pain• Compression on the ureters• Obstipation

• Symptoms of disseminated disease• Ascites, Hydrothorax, Upper abdominal disease

• Increased abdominal circumference• Dyspepsia, reflux, • Subcostal pain• Dyspnoea

Dissemination of EOC

• Intraperitoneal dissemination• Following the movement of peritoneal fluid• Parietal- and visceral peritoneum• Douglas-pouch (coul-de-sac)• Omentum major• Carcinosis peritonei ascites

• Direct (local) infiltration • Tubes, uterus, bladder, sigmoid bowel, rectum

• Lymphogen spread• Infundibulopelvic lig.

• Paraaortic lymph nodes

• Lig. latum• Art. iliaca int.+ext.

• Round lig. • inguinal lymph nodes

• Haematogen spread• liver, lungs, brain

Ovarian Cancer Staging

I/A tumor confined to the ovary (capsule is intact)I/B both ovaries are involved, but capsule is intactI/C ascites or capsule is involved

Ovarian Cancer Staging

II/A either uterus or adnexis are involvedII/B other pelvic organs are involvedII/C II/A or II/B + ascites

Ovarian Cancer Staging

III/A microscopical metastases on peritoneumIII/B macrocopical metastases on the peritoneum

<2cm

Ovarian Cancer Staging

III/C macrocopical metastases on the peritoneum >2cm /positive retroperitoneal or inguinal lymph nodes

IV distant metastases(liver, lung or cancer cells in the pleural fuid)

Therapy- Surgical

Aim: Removal of all macroscopic tumor + staging

Staging laparotomy – (Small tumor)

Midline incision

Trans abdominal hysterectomy (TAH)

Bilateral Salpingo oophorectomy (BSO)

Omentectomy

Samples from peritoneal fluid/ washings,

Peritoneal biopsies

Debated: retroperitoneal lymph node dissection

(Aviod rupture of cyst!)

Therapy- Surgical

Aim: Removal of all macroscopic tumor + staging

Debulking or cytoreductiv operation (Griffiths, 1975)

Remove macroscopic tumor

„optimal” cytoreduction : no gross residual disease should be the goal of primary

cytoreductive surgery

Previously

1 cm cutoff point to differentiate optimally vs. suboptimally cytoreduced

patients”

0%

25%

50%

75%

100%

0 12 24 36 48 60 72 84 96 108 120 132 144

% P

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1-10 mm

> 10 mm

HR (95%CI)

1-10 mm vs. 0 mm: 2.52 (2.26;2.81)

>10 mm vs. 1-10 mm: 1.36 (1.24;1.50)

log-rank: p < 0.0001

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25%

50%

75%

100%

0 12 24 36 48 60 72 84 96 108 120 132 144

% O

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HR (95%CI)

1-10 mm vs. 0 mm: 2.70 (2.37; 3.07)

>10 mm vs. 1-10 mm: 1.34 (1.21; 1.49)

log-rank: p < 0.0001

The Impact of Residual Tumor: What Is Optimal Debulking?

Generated from 3 prospective Phase III trials (OVAR 3,5, & 7)

N = 3126 pts

DuBois, Cancer (2009)115:1234

Therapy of early stage EOC

Stage I/A-I/B

• Young pts. St. I/A

• Fertility sparing surgery

• Unilateral salpingoophorectomy

• + Staging Procedure

• resection of omentum + samples from peritoneal fluid

• peritoneum + pelvic lymph node sampling

In case of stage I/A low grade cc, adjuvant chemotherapy is not recommended!

• Patient more than 40 years / no fertility desire

• Proper Staging operation

Therapy of advanced EOC

Cytoreduktive or debulking surgery

• Extended operations

• Upper abdominal procedures

• Bowel resection• Bladder resection • Splenectomy• Peritonectomy• Diaphragm peritonectomy• Diaphragm resection• Thoracic surgery

+ CHEMOTHERAPY

Adjuvant therapy of EOC

• Chemosensitive tumor Response Rate

• 60-s and 70-s alkilating agents (cyclophosphamid) RR=20%

• 80-s introduction of platinium (polychemotherapy) RR=40%

• Cyclophosphamid + Adriamycin + CISPLATIN

• 90-s taxanes RR=70-75%

• Paclitaxel - Cisplatin PACLITAXEL - CARBOPLATIN

• XXI. Century targeted therapy Bevacizumab- (Avastin)

• VEGF Ab

• Paclitaxel – Carboplatin + Bevacizumab

Therapy of EOC

Classic strategy

• Upfront surgery

Laparotomy

Adjuvant/

First line chemotherapy

6x TAX/CBP ± BEV

Therapy of EOC

Neoadjuvant chemo + delayed debulking surgery

• Preoperatively predicted• No optimal operation is possible

• Advanced Stage III- Stage IV

• Poor patient condition

BiopsyNeo-adjuvant

3-4x TAX/CBPDelayed

debulkingAdjuvant

3x TAX/CBP • FNAB

• Core biopsy

• Laparoscopic biopsy

• (explorative laparotomy)

Neoadjuvant chemo-delayed debulking surgery

• Why?• Almost Equally effective

• Less perioperative complications

• Easier operation (better chance for optimal debulking)

• Why not?• Probably more platinum resistance

• Some data on worse oncologic outcome

Recurrent EOC• Recurrent EOC is basicly not Cureable! Palliative

treatment

• Platinium-sensitive EOC (recurrence after 6 months)• reinduction (cisplatin, carboplatin+paclitaxel)

• Platinium-resistant (recurrence 0-6 months)• pegylated liposomal doxorubicin (Caelyx)

• topotecan (Hycamtin),

• gemicitabine (Gemsar),

• etoposide (Vepesid)

• SURGERY• In case optimal operation is possible

• Palliative interventions (passage, paracentesis)

Recurrance medical therapy

Recurrance

< 1 month Refracter Protocoll change TopotecanPegylated lyposomal doxorubicin (PLD)

< 6 months Resistent Non platinum agents TopotecanPegylated lyposomal doxorubicin (PLD)Mono TAX

+ bevacizumab+ bevacizumab+ bevacizumab

6-12 months Partialyplatinumsenisitve

Non platinum agents / Platinum reinduction

Trabectedin +PLD

>12 months Platinumsensitive

Platinum reinduction Gemcitabine + CBP Paclitaxel + CBPCyclophosphamid+Adriamycin+Cisplatin(CAP)Mono CBP

+ bevacizumab

Ovarian Cancer: Natural History

Symptoms

Diagnosis

Chemotherapy #1

Staging

Evaluation

Recurrence /Progression

Chemo #2 Chemo #3+

SupportiveCare

Death

SecondarySurgery

Maintenance

Duration

Progression-Free Survival(12-28 mos)

Post Progression Survival(12-38 mos)

BevacizumabOlaparib

Prospect for the future

• Targeted therapy

• Antibodies

• Thyrosin kinase inhibitors

• Anti-VEGF (Bevacizumab)

• Olaparib

• Sorafenib

• EGF, EGFR, and HER2/neu inhibitors (Erlotinib)

• Approximately 30% of EOC overexpress HER2/neu (Trastuzumab)

• Inhibition of PI3K/AKT pathway (CCI 779, RAD 001)

• Inhibition of Alpha-folinate Receptor

Low malignant potential/

Borderline EOC

15% EOC

Younger population

10-year survival rate St I 90%

Recurrence, death can occur decades after therapy

Grossly similar to benign cystadenomas Papillary projections Bilaterality is more common

Histologic criteria Epithelial pleiomorphism Atypicality Mitotic activity No stromal invasion

Serous, mucinous, endometrioid (transitional, clear cell)

Low malignant potential/ borderline malignant EOC

• Spread• Implantation on the peritoneum

• (invasive implants bad prognostic factor)

• Lymph node involvement

• Therapy• Complete tumor reduction• TAH+BSO+staging (lymphadenectomy)• St. Ia• Fertility spearing-USO + staging• Adjuvant chemoth.- No evidence of benefit• Completion of surgery after finishing childbearing (TAH+ contralateral SO)

Classification of ovarian tumors

• EPITHELIAL

• GERM-CELL

• Dysgerminoma,

• Gonadoblastoma,

• Embryonal carcinoma,

• Polyembryoma,

• Teratoma (cysta dermoides),

• Endodermalis sinus tumor,

• Choriocarcinoma

• SEX-CORD STROMAL

• METASTATIC OVARIAN TUMORS

Germ cell ovarian tumors

• Classified according to degree of differentiation

• Undifferentiated:• Dysgerminoma• Gonadoblastoma

• Differentiated:• Extraembyonic:

• Choriocarcinoma

• Endodermal sinus tumor

• Embryonal tumors• Embryonal carcinoma

• Polyembryoma

• Teratoma

• mature – mono-, bi-, tridermal

• immature

• Histologically pure or mixed • The most aggressive histologic subtype determines the behavior

Germ cell ovarian tumors

• Usually diagnosed in childhood or early adulthood

• 97% is benign 3% is malignant

• Rapidly growing, usually palpable

• Chief symptom is pelvic pain, rupture of capsule and haemoperitoneum may occur

• Unilateral in 90%

• Typically diagnosed at Stage Ia

• Spread: Peritoneal, more common lymphatic and haematogen than EOC

• Significant improvement in chemotherapy recently

• Most common germ cell tumor: teratoma (usually benign)

• Most common malignant germ-cell ovarian tumor is dysgerminoma

Comparing EOC and germ-cell ovarian tumors

EOC GERM CELL TUMORS

IN ADULTHOOD 90% OF MALIGNANT OVARIAN TUMORS ARE EPITHELIAL

IN CHILDHOOD 90% OF OVARIAN TUMORS ARE GERM-CELL TUMORS

AVERAGE AGE IS 60 YEARS AVERAGE AGE IS 20 YEARS

ARISES FROM OVARIAN SURFACE EPITHELIUM

ARISES FROM GERM CELLS OF OVARIES

ETIOLOGY IS UNKNOWN ETIOLOGY IS UNKNOWN

90% IS SPORADIC 5-10% IS INHERITED 100% IS SPORADIC

Staging

• Like EOC

• Surgical • Vertical midline incision

• Ascites sampling/ cell washings

• Random biopsies of omentum, and peritoneum

• Lymph node sampling of suspicious nodes

Treatment-Surgery

• Childbearing has been completed• Hysterectomy + bilateral salpingo-oophorectomy + staging

• Fertility desired: • Unilateral salpingo-oophorectomy• Careful inspection of contralateral ovary

• If abnormal biopsy• Normal – Don’t biopsy

• Second-look laparotomy/laparoscopy• For patients who had incompletely resected tumor may give

benefit

Treatment-Chemotherapy

• Tremendous advances have been made

• even advanced germ cell tumors has an excellent chance at long term control or cure• Adjuvant

• with surgery alone 20% recur• except for Stage Ia dysgerminoma, Stage Ia grade 1 immature teratoma

• VAC- vincristine, actinomycin, cyclophosphamid• VBP- vinblastine, bleomycin, cisplatin• BEP- bleomycin, etoposide, cisplatin

• Side affects• Little on fertility• Pulmonary toxicity-bleomycin• Secondary AML etoposide

Dysgerminoma

Undifferentiated, solid

Bilateral in 20% (only bilat. germ cell tu.)

50% of malignant germ-cell tumors

Elevated LDH, β-hCG may be present

Chemosensitive and radiosensitive

Tend to spread lymphatic way (paraaotic)

75% is diagnosed in early stage (ST-I)

May develop in gonadal dysgenesis- gonadoblastoma

Common recurrences

Endodermal sinus tumor (yolk sac tumor)

• Second most common malignant germ c.t.

• Median age 19 years

• Most rapidly growing tumor in human

• Large

• Pain, pelvic mass, torsion, rupture hemorrhage

• Highly malignant, extensive intra abdominal growth, early metastasis

• Produce AFP

• Not sensitive to radiotherapy

• VAC, VBP, BEP effective

Teratoma

Mature cystic (95%) 15% of all ovarian tumors Tissue of ecto-, meso-, endodermal origin Skin, hair, sebaceous or swet gland, tooth Only ectodermal- true dermoid cyst Slow-growing, often accidentally diagnosed Compression, torsion Malignant degeneration is rare

Mature solid- uncommon

Immature (1%) Tree germ layers Immature or embryonal structures (neural elements) determines grade 0-3 Malignant Adjuvant chemoth (VAC) except for St Ia grade 1

Other Germ-cell tumors

• Embryonal cc.• Rare, but one of the most malignant ovarian tumors• Mean age 15• AFP, hCGHormonal abnormalities

• Precociuos puberty, irregular uterine bleeding, amenorrhoea, hirsrutism

• Polyembryoma• Highly malignant, rare, usually mixed

• Choriocarcinoma• Rare, highly malignant• Gestational-non gestational• β-hCGprecocious puberty, ut. bleeding, signs of EUG• Methotrexat combination chemoth (MAC, EMACO)

• Gonadoblastoma• Germ cells+stroma cells• Sexual dysgenesis• Virilization• Excellent prognosis• Dysgerminoma may develop

Classification of ovarian tumors

• EPITHELIAL

• GERM-CELL

• SEX-CORD STROMAL • Granulosa cell tumors• Thecal cell tumours• Sertoli-Leydig tumors• Gynandroblastoma• Fibroma

• METASTATIC OVARIAN TUMORS

Sex-cord stromal ovarian tumours

• 5% of all ovarian carcinomas

• Granulosa-cell tumours (70%)

• Found in all age groups

• 90% hormonally active

• Indolent growth- benign / low malignant potential

• 10-year survival St I 90%, St III 0-22%

Comparing epithelial and sex-cord stromal ovarian tumors

EOC

• In adulthood 90% of malignant ovarian tumors are epithelial

• Etiology is unknown

• Average age is 60 years

• 90% is sporadic

• 5-10% is inherited

• Fast recurrence

SEX-CORD STROMAL TUMOR

• Very rare both in childhood and adulthood

• Arises form the sex-cord stroma

• Etiology is unknown

• Average age is 52 years

• Familiar forms

(Gorlin-sy.: herediter fibroma+basalioma)

• Recurrence after long time

Comparing stage at diagnosisepithelial and sex-cord stromal ovarian tumors

• Epithelial ovarian carcinoma 10-15% St I

70-75% St III

10-15% St IV

• Sex-cord stromal ovarian tumors (SCT) 60-70% St I

25-30% St III

Treatment of sex-cord stromalovariumtumors

• Young pts. (less, than 40 years)

USO + staging laparotomy + D & C(endometrial hyperplasia due to oestrogen production)

• After 40 years

TAH + BSO+ staging

• Stage I/C- Stage III adjuvant chemo is required (BEP 3 x)

• Recurrence after long interval (long follow-up)

• In case of recurrence either surgery or chemotherapy (TBEP, VBP, VAC) or irradiation

Granulosa-cell ovarian tumors

• Incidence 0,9/100,000 females

• Average age 52 years

• Intra-tumor hemorrhage

• Low malignant potential

• Majority estrogen producing

(Associated with endometrial ca. in 10%)

• Classification based on age (juvenile and adult types)

• Tumor marker• Oestrogen• Inhibin-B• MIF

Granulosa-cell ovarian tumors

• Adult granulosa-cell ovarian tumors• 95% of granulosa cell tumors• Typically postmenopausal pts.• Most common estrogen producing tumors• Chief symptom: uterine bleeding• 2-3% hyperandrogenism, virilisation• 25-50% associated with endometrial hyperplasia• Lab. diagnosis: elevated estrogen level• 95% unilocular• Mainly early stage (ST-I 5-year survival >90%)

• Juvenile type• Estrogen, progesterone, androgens sexual precocity, irregular

bleeding• Less well differentiated than the adult type• Cure rate is also high

Sertoli-Leydig cell tumour

• Very rare 0,1-0,5%

• Usually between 20-30 years 10% postmenopausal

• 99% unilateral 80% St I

• 80-85% benign, 10-15% malignant

• 70-80% androgen producing tumor

• Some estrogen production

• Chief symptom is virilisation• oligomenorrhoea, amenorrhoea, breast atrophy, acne, hirsutismus, deepening of the voice

Other Sex-cord stroma tumors• Gynandroblastoma

• Rare• Containing both testicular and ovarian tissues• Virilization and/or feminization• Low malignant potential

• Fibroma• Solid• Benign• Hormonally not active• Gorlin sy. Inherited predisponance to ovarian fibroma,

basal cell carcinoma etc.• Fibroma + ascites +hydrothrorax – Meigs sy.

• Thecoma• 1%-of ovarian tumors• Benign• Mostly occur in postmenopausa• First sign can be postmenopausal bleeding• Steroid producing tumor endometrial hyperplasia /ca. (25%)

Classification of ovarian tumors

• EPITHELIAL

• GERM-CELL

• SEX-CORD STROMAL

• METASTATIC OVARIAN TUMORS

Metastatic ovarian tumor

• Origin• Gynaecologic

• Endometrial adenocarcinoma• Cervical carcinoma

• Non-gynaecologic• Breast• Gastro-intestinal

• Kruckenberg• Primary usually stomach• Signet ring cells on pathology

• Evaluation

• Bilateral

• Immunhistochemistry

• Treatment• According to the primary tumour

• Basically no extended operation is advised

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