Ovary

Question 1

Normal anatomy of the ovary

Answer 1

Consists of STROMAL INTERSTITIAL CELLS (hilus cells) and SUPPORTING CELLS (theca and granulosa) that function to support the growing ovum

Theca –> respond to LH for follicular maturation; Theca cells produce adrostenidione which is given to granulosa cells

Granulosa –> respond to FSH for follicular maturation; (convert androstenidione to estradiols (via aromatase) before ovuation, then progesterone after)

As the ovum develops it will progress from primordial follicle –> primary follicle –> secondary follicle –> mature (Graffian or Vesicular) follicle

When ovulation occurs and the ovum is release, the follicle DEGRADES to the progesterone releasing CORPUS LUTEUM and regresses to the CORPUS ALBICANS (similar to scar tissue)

Question 2

The ovary is a CYST!!!

Answer 2

Normal ovary is cystic! Under the influence of hormones each month, follicle grows until surrounding area becomes so filled with fluid that it RUPTURES, releasing an ovum into the fallopian tube

Question 3

Pathological Cysts – Follicular, Cystic follicles, and Corpus Luteum Cysts

Answer 3

Follicular Cysts (> 2.5 cm) and Cystic Follicles (< 2.5 cm)

Most common cause of ovarian cysts; arise from GRAFFIAN (Late stage) FOLLICLES

Only difference is their size

ESTROGEN SECRETING –> can cause PRECOCIOUS PUBERTY or METORRHAGIA (irregular periods), or hyperplasia (right?); most common ovarian mass in young women!

Corpus Luteum Cysts –> very similar, except they arise from the CL –> CL arises after the egg has released from the ovary, so only occur around the time of menstruation –> doesn’t occur in women over 50

Question 4

Polycystic Ovarian Syndrome

Answer 4

Occurs when there are MULTIPLE CYSTIC FOLLICLES in the ovary, along with marked STROMAL HYPERPLASIA

Ovary appears LARGE and FIBROTIC

Characterized by oligomenorrhea, infertility and hirsutism (abnormal hair growth)

Appears to be an issue with secretion of gonadotropes from the pituitary –> leads to abnormally high LH and abnormally low FSH

Excess LH acts on thecal cells surrounding the follicles –> extremely high androgen formation in the ovary –> converted to ESTROGEN by adipocytes in the periphery –> negative feedback on the hypothalamus and pituitary –> ANOVULATORY CONDITION –> suppression of sex hormones!!!

Question 5

ENDOMETRIOSIS

Answer 5

Very common condition, cause by ECTOPIC PRODUCTION OF BENIGN ENDOMETRIAL TISSUE, and usually involves the ovaries

Because it is the endometrial tissue from the uterus, it will respond to hormones the same way as it would in the uterus –> MONTHLY SLOUGHING

Pain as the cystic endometrium hemorrhages into the peritoneum

Blood that is released is pro-inflammatory –> macrophages –> look brown on microscopic examination (hemosiderin from RBCs)

Results in ENDOMETRIAL (CHOCOLATE) CYSTS

Treat with oral contraceptives!

Question 6

Causes of endometriosis?

Answer 6

Menstrual Implantation? Involves migration of endometrial tissue through the fallopian tube to the ovary during menses

Lymphatic or hematogenous spread? Involves dissemination of endometrial cells through the lymph nodes or blood

Coelemic metaplasia? Occurs when peritoneal epithelium undergoes metaplasia to endometrial epithelium (associated with an increased risk of certain ovarian cancers)

Question 7

Ovarian cancer overview

Answer 7

Second most common carcinomas in the female reproductive system (behind endometrial/uterine, cervical #3)

HIGHEST mortality rate because the peritoneal cavity is LARGE and COMPRESSIBLE so the tumors can get HUGE before the patient realizes anything!!!

Question 8

Risk Factors for Ovarian Cancer

Answer 8

Race –> Japanese have lower, Europeans higher

BRCA1/2 Mutations –> Strongly associated with ovarian cancer (also a more common mutation in Ashkenazi Jews)

Number of ovulations –> more chances to mess it up and have an oncogenic mutation –> “Nun” theory (more ovulatory cycles cause they don’t have kids!)

Question 9

Classifying Ovarian Tumors

Answer 9

Grading and staging – not only benign and malignant, but also “tumors of low malignancy potential” - LMP has pathologic features of both benign and malignant; might be more benign than previously though, but still more deaths than purely benign lesions

Bilaterality –> particularly in women who want to maintain fertility; some cancer types have higher risk of being bilateral than others

Tumors with a high risk of bilaterality should be REMOVED ON BOTH SIDES NO MATTER WHAT

Histology – described the ORIGIN of the tumor (can be from surface epithelium, from germ cells - oocytes - from supporting cells - theca, granulosa - or from stroma cells) — or obviously metastases

Question 10

Surface Epithelial Tumors - SEROUS

Answer 10

Serous tumors are the MOST COMMON TYPE, comprising 30% of all ovarian cancers; cystic, filled with CLEAR, SEROUS fluid

60% BENIGN (Serous Cystadenoma) 25% of which are bilateral, 5 year survival 100%

30% are LMP –> 30% bilateral; papillary folds, begin to show some atypia but don’t invade –> 5 yr 90%

15% are MALIGNANT –> Serous Cystadenoma –> 65% are bilateral; Invasion with atypic, high mitotic activity, glandular complexity; much lower survival

Question 11

Surface Epithelial Tumors - MUCINOUS

Answer 11

Comprise 25% of ovarian tumors; cysts filled with MUCIN

80% are benign –> Mucinous Cystadenoma; 5% bilateral; columnar mucin-secreting goblet cells with a PICKET-FENCE conformation and no atypic

LMP – 10% with 10% of those being bilateral; atypia, some stromal invasion; less necrosis than malignant, 70% 5 yr survival

MALIGNANT – Mucinous Cystadenocarcinoma –> 10% with 20% of those being bilateral; more necrosis, layering greater than 4 cells thick; 35% 5 yr survival

MUCINOUS tend to be larger than SEROUS and are more likely to have multiple cystic compartments

Harder to tell difference between LMP and Malignant

These also have a generally low bilaterality risk, so single oophorectomy is possible for younger women

Question 12

Surface Epithelial Tumors - ENDOMETRIOID

Answer 12

These comprise 20% of all ovarian tumors, and 99% of endometrioid tumors are MALIGNANT!!!!!

Endometrioid Adenocarcinoma –> mimic endometrial carcinoma; papillary and cystic regions as well as areas of hemorrhagic, solid tumors

Typically smaller than mucinous or serous – 15-30% are associated with ENDOMETRIAL CARCINOMA, 15% with ENDOMETRIOSIS; majority are DE-NOVO

15-30% are BILATERAL; prognosis is GENERALLY BETTER THAN SEROUS OR MUCINOUS! Despite being malignant, they tend to be WELL DIFFERENTIATED

Worse prognosis if co-existing endometrial carcinoma

Question 13

Ovarian CLEAR CELL CARCINOMA

Answer 13

Uncommon ovarian tumor (5%)

ALWAYS MALIGNANT and AT LEAST GRADE 3 in SEVERITY

Primarily solid tumors with necrosis

Cytoplasm filled with glycogen and lipids

BILATERALITY –> 10%

5 yr survival 50%

Question 14

BRENNOR TUMORS

Answer 14

Rare –> 2% of total ovarian tumors

Benign, Older patients

Biphasic (Stromal AND epithelial elements) –> RESEMBLES THE TRANSITIONAL EPITHELIUM OF THE BLADDER

Sometimes there will be a CYSTIC DELINEATION within a solid mass –> concurrent mucinous cystadeoma

VERY RARELY TURNS MALIGNANT

Question 15

Tumors of GERM CELL ORIGIN – MATURE TERATOMAS!

Answer 15

Mature (BENIGN) –> 95% of teratomas, occur most frequently in children; predominantly SOLID; can include cells from ALL THREE GERM CELL LAYERS

Gooey! Filled with dermoid material (sebum, keratin, fat)

Can include any type of tissue – HAIR, TEETH, BRONCHI, CARTILAGE, SMOOTH MUSCLE, GI TISSUE, FAT

Also called DERMOID CYSTS

1% undergo MALIGNANT TRANSFORMATION

Question 16

Tumors of GERM CELL ORIGIN – IMMATURE and MONODERMAL TERATOMAS

Answer 16

Immature (MALIGNANT) - found more frequently in PRE-PUBERTAL ADOLESCENTS and YOUNG WOMEN (18 y.o.)

Resemble embryonal and immature fetal tissue –> mesodermal and neurogenic cells most common

Grading depends on the amount of immature tissue present

HIGH GRADE IMMATURE TERATOMAS (lots of embryonal tissue) have a POOR PROGNOSIS

MONODERMAL TERATOMAS –> extremely rare; come from JUST ONE GERM LAYER
STRUMA OVARII –> consists Strictly of THYROID TISSUE and thus can present as HYPERTHYROIDISM!!!!

Question 17

Tumors of the SEX CORD or STROMA (Supporting Cells) —> GRANULOSA CELL TUMORS

Answer 17

Granulosa Cell Tumors –> consist of varying degrees of theca/granulosa cells and are BILATERAL 5% of the time

55% women of child-bearing age; 40% in post-menopausal; 5% in children

ALWAYS MALIGNANT

Usually associated with hyperestrinism –> manifests as isosexual precocious puberty, metorrhagia in adults (irregular periods) and postmenopausal hemorrhage in the elderly

Partially solid and partially cystic –> exhibit CALL-EXNER bodies (Rosettes that mimic immature follicles; coffee bean crease in the nuclei)

Generally of LOW-GRADE MALIGNANCY (somewhat indolent) but are RECURRENT even after 10-15 years

Question 18

Tumors of the SEX CORD or STROMA –> THECOMAS or FIBROMAS

Answer 18

Comprise 4% of all ovarian tumors; 10% are bilateral

Solid tumors with some FOCAL CALCIFICATIONS

Pure fibromas are ACELLULAR with high collagenization

Pure Thecomas have SIGNIFICANT amounts of STROMA and are HORMONALLY active (produce lots of estrogen) –> pure forms of each are RARE, mainly come as FIBROTHECOMAS

Both of the tumors present similarly to ovarian adenocarcinomas

Benign fibromas/thecomas are associated with ASCITES or PLEURAL EFFUSION (40%; disappear with removal)

Question 19

Tumors of the SEX CORD or STROMA –> SERTOLI-LEYDIG CELL TUMORS

Answer 19

Very uncommon tumors that are ANDROGEN PRODUCING and often called Androblastomas

Commonly produce MASCULINIZATION or at least DEFEMINIZATION

Can be associated with MUCINOUS GLANDS, BONE, and CARTILAGE

Unilateral –> Decent prognosis

Question 20

Ovarian Tumors via METASTASIS

Answer 20

7% of ovarian cancers arise from metastasis, and 50% are bilateral

KRUKENBERG TUMOR – Bilateral multinodular enlargement of the ovary with hyperplastic stroma

Contain characteristic SIGNET-RING cells which have lots of MUCIN in the CYTOPLASM and they SECRETE THIS MUCIN

Usually come from the GASTRIC MUCOSA though they can arise from the LARGE BOWEL, APPENDIX, BREAST, UTERUS, LUNG and SKIN

Question 21

Other Germ Cell Tumors that aren’t Teratomas

Answer 21

o Dysgerminomas are primarily in young women and morphologically identical to testicular seminomas. They respond well to radiation therapy.

o Yolk sac tumors are rare tumors that are alpha-fetoprotein+ and contain extraembryonic tissue found in the normal yolk sac. They have a poor prognosis (13% 3-year survival).

o Choriocarcinomas are extremely rare tumors when they’re primary, but they are more often found as secondary tumors originating post-partum from remnants of the placenta.