Female Reproductive System Outline Ovaries Disorders of Gestation

Female Reproductive System Outline

• Ovaries

• Disorders of Gestation

Polycystic Ovary Disease

•Formerly Stein-Leventhal syndrome

• affects 3% to 6% of reproductive-age women

•. The central pathologic abnormality is numerous cystic follicles

•often associated with oligomenorrhea: persistent anovulation, obesity (40%), hirsutism (50%), and, rarely, virilism

Polycystic Ovary Disease

Morphology The ovaries are usually twice

normal size and have a smooth, gray-white outer cortex studded with subcortical cysts 0.5 to 1.5 cm in diameter. On histologic examination, there is a thickened, fibrotic superficial cortex beneath which are innumerable follicle cysts associated with hyperplasia of the theca interna (follicular hyperthecosis

Polycystic Ovary Disease

Etiology Unclear, due to dysregulation of several enzymes involved in androgen synthesis

• Increased secretion of luteinizing hormone may contribute to excessive production of androgens by the theca lutein cells. The excessive androgens are converted to estrone .

• Insulin resistance is an additional features usually seen.

• Treatment: of the insulin resistance sometimes results in resumption of ovulation.

Ultra sound “ Strings of pearl”

Ovarian Tumours

Divided into:•The surface müllerian epithelium

• The germ cells• The sex cord-stromal cells.

Surface epithelial tumors

• Cystadenoma• Cystadenocarcinoma• Brenner tumor

Germ cell tumors

• Teratoma • Dysgerminoma• Yolk sac tumor• Choriocarcinoma

• Granulosa-theca cell tumor• Sertoli-Leydig cell •tumor

Sex cord-stromal tumors

Origin of Ovarian Tumors

Ovarian Tumours

Ovarian epithelial tumors are divided into Serous, mucinous and endometriod types based on histology. These are further divided based on extent of epithelial proliferation into:

• Benign, Borderline ,Malignant• Benign tumors in younger age group• Borderline and Malignant in older age

group

• 90 % of ovarian tumors

• 80% are benign

Ovarian Tumours

Ovarian epithelial tumors are divided into Serous, mucinous and endometriod types based on histology. These are further divided based on extent of epithelial proliferation into:

• Benign, Borderline ,Malignant• Benign tumors in younger age group• Borderline and Malignant in older age

group• 80% are benign• The malignant epithelial derived

tumors constitute more than 80% of all malignant ovarian tumor.

Ovarian Tumours

Serous tumorMost common histologic type(tall cilliated columnar epithelium with watery secretions(fallopian tube like epitheliu)

• Bilateral tumors are relatively common

• BRCA-1 ,BRCA2,P53 BRAF,KRAS mutations

• Benign Serous adenoma, Serous cystadenoma,

• Malignant Serous cystadenocarcinoma(most common malignant ovarian tumor ,40%)

• Omental and peritoneal spread =>ascites

Ovarian TumoursMucinous Tumors• KRAS mutation• Most are unilateral tumors• Areas of solid growth correlate with

increase chances of malignancy• Tall ,columnar, mucin secreting

epithelial lining(endocervical like epithelium).

• Huge tumors(larger than serous tumors)More likely benign than malignant.

• Dissemination into the peritoneum may lead to pseudomyxoma peritonei.

• Note that metastatic spread from appendiceal tumor may also present with P.Myxoma Peritonei.

Ovarian Tumours

Endometriod tumors• Glandular epithelium similar to

uterine endometrium• Most are

carcinomas(malignant)• Associated with PTEN,B-

catenin pathway mutation and p53 mutation

• 20% 0f cases coexist with endometriosis,15-30% have an associated endometrial carcinoma.

Ovarian Tumours

Endometriod tumors• Glandular epithelium similar to

uterine endometrium• Most are carcinomas• Associated with PTEN,B-

catenin pathway mutation and p53 mutation

• 20% 0f cases coexist with endometriosis,15-30% have an associated endometrial carcinoma.

Ovarian Tumours

Brenner tumors• Adenofibromas of the ovary

• Fibrous stroma and epthelial component that shows a transitional type differentation(Bladder like epithelium)

• Most are benign and non functional.

Ovarian Tumours;Diagnosis and clinical features

• Most ovarian tumors present late• CA125 is marker present in 80%

of Ovarian CA. It lacks specificity and may be elevated in other conditions of ovarian inflammation such as endometriosis.

• CA 125 is more useful for monitoring tumor remission in patient undergoing treatment.

• OCPS and bilateral tubal ligation has shown remarkable reduction in ovarian CA risk.

Ovarian Cancer Clinical

Symptoms• feeling of fullness or bloating

• pelvic pain

• back pain

• abnormal menses

Risk factors• nulliparity

• family history (BRCA gene mutation)

• NOT using oral contraceptives!

Ovarian Cancer• 23,000 new cases / 15,000 deaths in 2007

• 5th commonest, 5th most deadly cancer in women

• Danger: no definitive signs until advanced

• Peak age: 50

• Most are cystadenocarcinomas and sometimes shows Psamomma bodies.

• Risk of malignancy increases with

:Bilaterality,Increase in solid areas,presence of of complex atypia and endometriod histology.

Papillary cystadenocarcinoma

Ovarian Cancer

• Treatment: surgery, radiation, chemotherapy

• Prognosis depends on stage• cancer confined to the ovary: 5y survival 70%

• cancer through ovarian capsule: 5y survival 13%

Patient with ovarian cystadenoma

Ovarian cystadenoma

Ovarian cystadenoma

Surface epithelial tumors

• Cystadenoma• Cystadenocarcinoma• Brenner tumor

Germ cell tumors

• Teratoma • Dysgerminoma• Yolk sac tumor• Choriocarcinoma

• Granulosa-theca cell tumor• Sertoli-Leydig cell •tumor

Sex cord-stromal tumors

Origin of Ovarian Tumors

Ovarian tumors

• Ovarian germ Cell Tumors• Similar to MGT, Germ cell

tumors• Patients are younger compared

to epithelial tumor(reproductive age)

• Most common is Benign teratomas

• Malignant germ cell tumors account for 5% of all ovarian cancers.

Teratoma

Benign tumor with differentiation along all three germ cell layers (ectoderm, endoderm, mesoderm)

• Usually cystic, with skin inside (“dermoid cyst”)

• Sebaceous material, matted hair, teeth, bone…

• Malignant variant has immature tissues(immature neuroepithelium)

• Monodermal teratoma includes struma ovarii and ovarian carcinods.

• Rarely teratomas undergo malignant transformation(squamous, thyroid carcinoma)

Teratoma Benign tumor with differentiation along all three germ

cell layers (ectoderm, endoderm, mesoderm)

• Usually cystic, with skin inside (“dermoid cyst”)

• Sebaceous material, matted hair, teeth, bone…

• Malignant variant has immature tissues(immature neuroepithelium),uncommon,seen in prepurtal

• Monodermal teratoma includes struma ovarii and ovarian carcinods.

• Rarely teratomas undergo malignant transformation(squamous, thyroid carcinoma)

Teratoma

Teratoma

Dysgerminoma

•Analogous to Seminoma in males

•Always malignant but variable degree of aggressiveness

•Chemo and radio sensitive(>80% survival)

•Morphology: large cell cells with clear cytoplasm dispersed in sheets of or cords with scanty fibrous stroma.

Yolk Sac Tumor

• Similar to the male counterpart

• Alpha feto protein and alpha-1 antitrypsin may be positive

• Extra embryonic differentiation• Malignant tumor children and

young women.• Morphology; Schiller duval bodies

,(central blood vessel enveloped by germ cells within a space lined by germ cells.(said to resemble primitive looking glomerulus)

Schiller –Duval Body

Choriocarcinoma

• Most are mixed tumors

• Trophoblastic differentiation of germ cells

• Poorer response to chemotherapy compared to Gestational Choriocarcinoma

• Elevated Beta HCG

Surface epithelial tumors

• Cystadenoma• Cystadenocarcinoma• Brenner tumor

Germ cell tumors

• Teratoma • Dysgerminoma• Yolk sac tumor• Choriocarcinoma

• Granulosa-theca cell tumor• Sertoli-Leydig cell •tumor

Sex cord-stromal tumors

Origin of Ovarian Tumors

Ovarian stroma tumors

• Granulosa –Theca cell tumor

• Fibro-Thecomas

Granulosa –Theca cell tumor

Estrogen producing tumors, may lead to uterine hyperplasia, precocious puberty

• Risk of malignancy 5-25 %• 2 components granulosa and

theca,the granulosa component is responsible for estrogen as well as the risk of malignancyy

• Cells recapitulating ovarian follicles, Call -Exner bodies may be seen.

• The tumor produces Inhibin.

Granulosa –Theca cell tumor

Estrogen producing tumors, may lead to uterine hyperplasia, precocious puberty

• Risk of malignancy 5-25 %• 2 coponents granulosa and

theca,the granulosa component is responsible for estrogen as well as the risk of malignancyy

• Cells recapitulating ovarian follicles, Call -Exner bodies may be seen.

• The tumor produces Inhibin.

Call-Exner Bodies

Fibrothecomas

Composed of fibroblasts or lipid producing cells

Common,4 % of ovarian tumors.

• Most are unilateral tumors and are benign

• Meigs syndrome(Ascites ,right sided hydrothorax ,ovarian tumor)

• Gorlin syndrome(Basal cell nevus syndrome)

Sertoli-Leydig (Androblastomas)

Causes masculinizaton due to excessive androgen

Hirsuitism,breast atrophy,masculine voice,(defeminization)

Embryogensis is unclear

Secondary tumors

Mullerian derived tumors(uterus, fallopian tube, pelvic peritoneum)

Krukenberg tumors from gastric(signet ring type),sometimes breast

Pseudo myxoma peritonei from appendiceal tumors(rare)

Diseases of Pregancy

• Gestational Trophoblastic diseases

Gestational Trophoblastic Disease

1. Complete mole2. Partial mole 3. Invasive mole

4. Gestational Choriocarcinoma

Hydatidiform mole

A hydatidiform mole is an abnormality of fertilization

It is the result of fertilisation of anucleated ovum ( has no chromosomes) with a sperm which will

duplicate giving rise to 46 chromosomes of paternal

origin only.

It is the result of fertilisation of an

ovum by 2 sperms so the chromosomal

number is 69 chromosomes

COMPLETE MOLE PARTIAL MOLE

Complete mole:

(ii) Partial mole

Grapelike hydrropic chorionic villi

Hydatidiform Mole, complete mole. No maternal tissues.

Partial mole

• This is a partial mole that occurs when two sperms fertilize a single ovum. The result is triploidy (69 XXY). Only some of the villi are grape- like, and a fetus can be present, but rarely survives past 15 weeks.

S & S Hydatiform Mole

• Vaginal bleeding anemia

• uterus size, cramps• No FHT’s Nausea/Vomiting• Early PIH• Elevated B-hcg.

Hydatidiform Moles

• Risk of malignancy Complete Mole 2.5% increased risk of choriocarcinoma.

• No significant risk of choriocarcinoma in partial moles.

Hydatidiform MolesInvestigation:• B-Hcg• Histology : Complete mole; All or most of the villi

are involved. The chorionic villi are enlarged,shows central cavitations and lack well developed blood vessels)There is extensive proliferation of trphoblasts.

Partial mole; Villous enlargement ,architectural changes and trophoblast proliferation are seen in only portions of the chorionic villi.

Hydatidiform Moles

Investigation:

• P57 immunostaining may be used to differentiate complete from partial moles in equivocal cases. (+ve in partial moles but absent in complete moles).The p57 gene is present in maternal tissues but absent in paternally derived chromosomes due to genomic imprinting.

Invasive Mole

• Invasive hydatidiform moleInvasive hydatidiform mole (complete or partial) is common since molar trophoblast invades the myometrium in most cases.

• Confirmed both on ultrasound examination of the uterus and the hCG profile in patients following evacuation of the uterine cavity.

• May spread to lungs and brain but do not grow in these organs(not true metastasis)

• Elevated B-HCG• Irregular bleeding,and uterine

enlargement.• Chemotherapy..good cure rates.

Gestational Choriocarcinoma

•Choriocarcinoma is a tumour composed both of cyto-trophoblastic and syncitio-trophoblastic cells.

• Widespread intravascular dissemination to lungs, brain and other sites.

• Good response to chemotherapy compared to ovarian choriocarcinoma.

• The presence of paternal DNA is thought to elicit an immune reaction which contributes to elimination of the tumor

Gestational Chorio carcinoma

Origin:• 50% arise in complete

hydatidiform moles, • 25% in previous abortions,• 22% in normal pregnancies• 3% occurs following ectopic

pregnancy

Gestational Chorio carcinoma

Histology:• Mixed proliferation of syncytio

and cytotrophoblast without chorionic villi.

B-HCG elevation Choriocarcinoma>Invasive Mole>Complete mole>Partial mole>Normal pregnancy>Ectopic pregnancy

Hypertensive disease of Pregnanacy

Pre-eclampisa,Eclampsia and HEELP syndrome

Hypertensive disease of Pregnanacy

Pre-eclampisa:• Elevated blod pressure• Proteinuria• Pedal edema• 1st pregancies• 6% of pregnancies• Requires monitoring blood

pressure control and delivery ASAP

Hypertensive disease of Pregnanacy

Pathogenesis of Pre-eclampsia

• Thought to be caused by placenta ischemia

Hypertensive disease of Pregnanacy

Clinical

32nd weekHypertension,edema,proteinuria

,headeacheBed rest,anti-hypetensives and

delivery are the cureResolves within 2 weeks of

delivery.

Hypertensive disease of Pregnanacy

Eclampsia

• Syndrome of eclampsia with addition of seizures

• Carries a very high mortality rate

Hypertensive disease of Pregnanacy

HEELP syndrome• Hemolysis• Eclampsia• Elevated liver enzymes• Low Platelets