Malignant ovarian tumors

MALIGNANT Ovarian TumorDr KanupriyaDr Rajeev

EpidemiologyRisk factorsPathology and pathogenesisDiagnosisScreeningStagingPrognosisManagement

Ovarian malignancies represent the greatest challenge of all the malignancies because of its high mortality.

Ovarian cancers -6% of all cancers among women

Approximately 27% of gynecologic cancers are of ovarian origin

About 53% of all the deaths of gynecological cancers are of ovarian origin (highest fatality to case ratio)

American cancer society incidence

Incidence of ovarian cancers are highest in Sweden (19.6/100000) united states (15.4/100,000) and lowest in Japan (10.1/100,000)

Incidence in India 0.9 to 8.4 per 100,000

The silent killer: asymptomatic in early stages

75% diagnosed with advanced stage disease; 5-year survival only 10-28%

Womans lifetime risk of developing sporadic epithelial ovarian cancer is 1%-1.5% in developed nations and 0.75% in India.dying from ovarian cancer is 0.5%

AgeRare before 40yrs, increases steadily thereafter, peaks at 65-75yrs.Reproductive historyearly menarche, nulliparity or age >30 at first child-bearing, and late menopause Nulliparity is the most important non genetic factor.Fertility drugsprolonged use especially without achieving pregnancy

Personal history of breast cancerHormone replacement therapy > 10 yearsMay be associated with 30% increased riskTalcum powderSome studies have shown slightly increased risk in women who use talc powder on genital area

American Cancer Society 2001

Hereditary breast-ovarian cancer syndrome (HBOC) Hereditary site specific ovarian cancer syndrome (HSSOC) Hereditary nonpolyposis colon cancer syndrome (HNPCC) * Inherited - 10% of ovarian cancers while 90% sporadic* Mode of inheritance is autosomal dominant *Occurs 10 years younger than sporadic

Lifetime risk of ovarian cancer is estimated - 39 % of BRCA 1 mutations11% with BRCA2 mutations

Life time probability of ovarian cancer 1.6 % without family history5% if one relative is affected7% if two relatives affected

~7% of hereditary ovarian cancer cases

Responsible genes: mutation in mismatch repair genes (MMR) including MLH1, MSH2, and MSH6

Predominance of early onset proximal colon cancer, ca ovary and endometrium.Estimated lifetime risk of ovarian cancer 10-12%.

10

Multiparity: First pregnancy before age 30 Oral contraceptives: decreases approx 11% per year of use. Max of 46% after 5 years of use . Tubal ligation Hysterectomy (Salpingectomy/ Fimbriectomy) Bilateral oopherectomy - risk by 80% to 95% Lactation

Role of ovulation in the pathogenesis of the malignancy.

Risk is related directly to the number of uninterrupted ovulatory cycles.

As repair follows multiple ovulations, the surface epithelium of the ovary often extends into the ovarian stroma to form inclusion glands and cysts.

Incessant ovulation

Retrograde menstruation hypothesis.

Retrograde transportation of carcinogens from lower genital tract.

Exposure of ovarian epithelium to persistently high levels of pituitary gonadotropins.

Te Linde's

Very recently, Lee et al. have proposed many high-grade serous carcinomas actually arise in the mucosa of the fimbriated end of the fallopian tube.

THEORY TO IMPLICATE FTOvary has no cells of Mullerian origin.FT has cells of mullerian origin i.e. tall mucuos secreting ciliated columnar cells.SOC are cells of mullerian origin i.e. columnar epithelium.HGSOC express mullerian marker PAX8.

The epithelium, via neoplastic transformation, may exhibit differentiation toward a variety of mllerian-type cells

Serous fallopian tubal lining MucinousIntestinal gastrointestinal mucosaMllerian endocervix

Endometrioid endometrial glands

Brenner/transitional bladder

Clear cell mesonephric (renal cell)

PRIMARY(80%)1)Surface epithelial 80-90% 2)Non-epithelial Germ cell tumors 15-20% Sex cord stromal 5-8%SECONDARY(20%) 1) Typical 2) Atypical (Krukenberg)

Dutta Gynae

Serous (tubal) ----75-80%Mucinous (endocx & intestinal)-----8-10%Endometrioid-----10%Transitional cell Brenner-------