Female Genital System and Gestational Pathology

Question 1

What is the epithelium of the vulva?

Answer 1

Squamous epithelium

Question 2

Bartholin cyst

Answer 2

cystic dilation of barthoin gland (on each side of the vaginal canal)

arises from inflammation and obstruction of gland

presents as a unilateral, painful cystic lesion at the lower vestibule adjacent to the vaginal canal

Question 3

Condyloma

Answer 3

warty neoplasm of vulval skin, often large

most commonly due to HPV 6+11 (condyloma characterized by koilocytes), secondary syphilis (condyloma latum) is a less common cause

Question 4

Lichen sclerosis

Answer 4

characterized by thinning of the epidermis and fibrosis (sclerosis) of the dermis

presents as a white patch (leukoplakia) with parchment-like vulvar skin

commonly seen in postmenopausal women; possible autoimmune etiology

benign but associated with slightly increased risk for squamous cell carcinoma

Question 5

Lichen simplex chronicus

Answer 5

hyperplasia of the vulvar squamous epithelium

leukoplakia with thick, leathery vulvar skin

associated with chronic irritation and scratching

benign; no increased risk of squamous cell carcinoma

Question 6

vulvar carcinoma

Answer 6

carcinoma arising from squamous epithelium lining the vulva

rare

leukoplakia

HPV (types 16 &18) or non HPV related (long-standing lichen sclerosis - chronic inflammation and irritation eventually lead to carcinoma)

Question 7

extramammary paget disease

Answer 7

malignant epithelial cells in the epidermis of the vulva

presents as erythematous, pruritic, ulcerated vulvar skin

represents carcinoma in situ, usually with no underlying carcinoma

Paget disease of the nipple is also characterized by malignant epithelial cells in the epidermis of the nipple, but it is almost always associated with an underlying carcinoma

Must be distinguished from melanoma: paget cells are PAS+ (marking mucus - only epithelial cells make mucus), karatin +, and S100 - )

Question 8

What is the epithelium lining the vagina?

Answer 8

non-keratinizing squamous epithelium

Question 9

Adenosis

Answer 9

Focal persistence of columnar epitheliumin the upper vagina

during development, squamous epithelium from the lower 1/3 of the vagina (derived from the UG sinus) grows upward to replace the columnar epithelium lining of teh upper 2/3 of the vagina (derived from Mullerian ducts)

increased incidence in females exposed to DES in utero

Question 10

clear cell adenocarcinoma

Answer 10

Malignant proliferation of glands with clear cytoplasm

complication of DES-associated vaginal adenosis

Question 11

Embryonal rhabdomyosarcoma

Answer 11

malignant mesenchymal proliferation of immature skeletal muscle - rare

bleeding and a grape-like mass protruding from the vagina or penis of a child; also known as sarcoma botryoides

the characteristic cell - rhabdomyoblast - exhibits cytoplasmic cross-striations and positive immunohistochemical staining for desmin and myogenin

Question 12

Vaginal carcinoma

Answer 12

carcinoma from squamous epithelium lining the vaginal mucosa

related to high risk HPV

precursor lesion is vaginal intraepitheliel neoplasia (VAIN)

lymph node spread - lower 1/3 of vagina through inguinal nodes, upper 2/3 cancer through regional iliac nodes

Question 13

High risk HPV types

Answer 13

16,18,31,33

Question 14

Low risk HPV types

Answer 14

6 + 11

Question 15

Cervical Intraepithelial Neoplasia

Answer 15

Koilocytic change - disordered cellular maturation, nuclear atypia, and increased mitotic activity within the cervical epithelium

Question 16

Grades of cervical intraepithelial neoplasia

Answer 16

CINI - <2/3 thickness of epithelium - reverses 33% of time

CINIII - slightly less than entire thickness of epithelium - very rarely reverses

CIN classicallyprogresses in a stepwise fashion through CINI, CINII, CINIII and CIS to become invasive squamous cell carcinoma

Question 17

Cervical Carcinoma

Answer 17

Invasive carcinoma arising from the cervical epithelium

Most commonly seen in middle-aged women

postcoital vaginal bleeding

risk factor = high risk HPV, smoking, immunodeficiency

Both squamous cell carcinoma dn adenocarcinoma

advnced tumors often invade through the anterior uterine wall into the bladder, blocking the ureters. Hydronephrosis with postrenal failure is a common cause of death in advanced cervical carcinoma

Question 18

goal of screening

Answer 18

to catch dysplasia (CIN - cervical intraepithelial neoplasm) before it develops into carcinoma

Question 19

colposcopy

Answer 19

visualization of cervix with a magnifying glass

Question 20

What types of HPV does the vaccine cover?

Answer 20

6,11,16,18

antibodies generated against types 6 and 11 protect against condylomas

antibodies generated against 16 and 18 protect against CIN and carcinoma

Question 21

Endometrium and myometrium

Answer 21

endometrium is the mucosal lining of the uterine cavity

myometrium is the smooth muscle wall underlying the endometrium

endometrium is hormonally sensitive

• growth of endometrium is estrogen driven (proliferative phase)
• preparation of the endometrium for implantation is progesterone driven (secretory phase)
• Shedding occurs with loss of progesterone support (menstrual phase)

Question 22

Asherman syndrome

Answer 22

secondary amenorrhea due to loss of the basalis (regenerative layer) and scarring

Result of overaggressive dilation and curettage (D&C)

Question 23

Anovulatory Cycle

Answer 23

lack of ovulation

Estrogen-driven proliferative phase without a subsequent progesterone driven secretory phase

proliferative glands break down and shed resulting in uterine bleeding

Common cause of dysfunctional uterine bleeding, especially during menarche and menopause

Question 24

Acute endometritis

Answer 24

bacterial infection of the endometrium

usually due to retained products of conception (e.g. after delivery or miscarriage); retained products act as a nidus for infection

Presents as fever, abnormal uterine bleeding, pelvic pain

Question 25

Chronic endometritis

Answer 25

chronic inflammation of the endometrium characterized by lymphocytes and plasma cells plasma cells are necessary for diagnosis of chronic endometritis given that lymphocytes are normally found in the endometrium cuases = retained products of conception, chronic pelvic inflammatory disease (Chlamydia), IUD, TB Presents as abnormal uterine bleeding, pain, and infertility

Question 26

Endometrial polyp

Answer 26

hyperplastic protrusion of endometrium Presents as abnormal uterine bleeding Side effect of tamoxifen, anti-estrogenic effects on the breast but weak pro-estrogenic effects on the endometrium

Question 27

Endometriosis

Answer 27

Endometrial glands and stroma outside of the uterine endometrial lining Due to retrograde menstruation with implantation at an ectopic site Presents as dysmenorrhea (pain during menstruation) and pelvic pain; may cause infertility - endometriosis cycles just like normal endometrium

Question 28

Most common site of involvement of endometriosis

Answer 28

Ovary - classically results in formation of 'chocolate cyst' Uterine ligaments - pelvic pin Pouch of Douglas - pain with defecation Bladder wall - pain with urination Bowel serosa - abdominal pain and adhesion Fallopian tube mucosa - scarring increases risk for ectopic tubal pregnancy Implants appear as yellow-brown 'gun-powder' nodules Involvement with uterine myometrium called adenomyosis

Question 29

Is there an increased risk of carcinoma at the site of endometriosis?

Answer 29

Yes, especially the ovary

Question 30

Endometrial hyperplasia

Answer 30

Hyperplasia of endometrial glands relative to stroma A consequence of unopposed estrogen (obesity, polycystic ovary syndrome, estrogen replacement) Presents as postmenopausal uterine bleeding Presence of cellular atypia = most important predictor for progression to carcinoma - simple hyperplasia with atypia often progresses to cancer, complex hyperplasia without atypia rarely does

Question 31

Endometrial carcinoma

Answer 31

Malignant proliferation of endometrial glands Most common invasive carcinoma of the female genital tract Postmenopausal bleeding Arises via hyperplasia and sporadic

Question 32

Hyperplasia pathway of endometrial carcinoma

Answer 32

75% of cases, carcinoma arises from endometrial hyperplasia risk factors related to estrogen exposure and include early menarche/late menopause, nulliparity, infertility with anovulatory cycles, and obesity Average age of presentation is 60 Histology is endometrioid (i.e., normal endometrium-like)

Question 33

Sporadic pathway of endometrial carcinoma

Answer 33

carcinoma arises in an atrophic endometrium with no evident precursor lesion average age = 70 histology usually serous and characterized by papillary structures with psammoma body formation; p53 mutation common and tumor exhibits aggressive behavior

Question 34

Leiomyoma

Answer 34

Benign neoplastic proliferation of smooth muscle arising from myometrium Related to estrogen exposure - common in premenopausal women - often multiple - enlarge during pregnancy; shrink after menopause Gross exam shows multiple, well-defined white, whorled masses that may distort the uterus and impinge on pelvic structures Usually asymptomatic; when present, symptoms include abnormal uterine bleeding, infertility, and a pelvic mass

Question 35

Leiomyosarcoma

Answer 35

Malignant proliferation of smooth muscle arising from the myometrium Arises de novo; leiomyosarcomas do not arise from leiomyomas Usually seen in postmenopausal women Gross exam often shows a single lesion with areas of necrosis and hemorrhage; histological features include necrosis, mitotic activity, and cellular atypia

Question 36

LH

Answer 36

Acts on theca cells to induce androgen production

Question 37

FSH

Answer 37

Stimulates granulosa cells to convert androgen to estradiol (drives the proliferative stage of the endometrial cycle)

Question 38

What surge leads to ovulation?

Answer 38

Estradiol surge leads to LH surge, which leads to ovulation

Question 39

Corpus luteal cyst Follicular cyst

Answer 39

Hemorrhage into a corpus luteum can result in a hemorrhagic corpus luteal cyst, especially during early pregnancy Degeneration of follicles results in follicular cysts - small numbers of follicular cysts are common in women and have no clinical significance

Question 40

Polycystic Ovarian Disease

Answer 40

Multiple ovarian follicular cysts due to hormone imbalance Increased LH induces excess androgen production (from theca cells) resulting in hirsutism (excess hair in a male distribution) androgen is converted to estrone in adipose tissue Estrone feedback decreases FSH resulting in cystic degeneration of follicles High levels of circulating estrone increase risk for endometrial carcinoma Some patients have insulin resistance and may develop type 2 diabetes mellitus

Question 41

Surface Epithelial Tumors of the Ovary

Answer 41

Most common type of ovarian tumor derived from coelomic epithelium that lines the ovary (serous cells and mucinous cells) most common types of surface epithelial tumors are serous (watery) and mucinous (mucus-like)

Question 42

Ovarian Cystadenoma (mucus or serous)

Answer 42

composed of a single cyst with a simple, flat lining, commonly arise in premenopausal women

Question 43

Ovarian Cystadenocarcinoma (mucus or serous)

Answer 43

Composed of complex cysts with a thick, shaggy lining; most commonly arise in postmenopausal women (30-40 yo)

Question 44

Borderline Ovarian Tumor (mucus or serous)

Answer 44

Features in between benign and malignant tumors Better prognosis than clearly malignant tumors, but still carry metastatic potential

Question 45

What gene carries an increased risk for serous carcinoma of the ovary and fallopian tube?

Answer 45

BRCA1

Question 46

Endometrioid surface epithelial tumor

Answer 46

composed of endometrial-like glands and are usually malignant May arise from endometriosis

Question 47

Brenner tumor

Answer 47

composed of bladder-like epithelium and are usually benign (urothelium)

Question 48

What do surface tumors present with and what is their prognosis?

Answer 48

Surface tumors present late with vague abdominal symptoms (pain and fullness) or signs of compression (urinary frequency) Prognosis is generally poor for surface epithelial carcinoma (worst prognosis of female genital tract cancers) Epithelial carcinomas tend to spread locally, especially to the peritoneum CA-125 is a useful serum marker to monitor treatment response and screen for recurrence

Question 49

Germ cell ovarian tumor

Answer 49

2nd most common type of ovarian tumor usually occurs in women of reproductive age Tumor subtypes mimic tissues normally produced by germ cells: fetal tissue - cystic teratoma and embryonal carcinoma Oocytes- dysgermination Yolk sac- endodermal sinus tumor Placental tissue - choriocarcinoma

Question 50

Cystic teratoma | GST

Answer 50

cystic tumor composed of fetal tissue derived from two or three embryologic layers (e.g., skin, hair, bone, cartilage, gut, and thyroid) most common germ cell tumor benign, but presence of immature tissue (usually neural) or somatic malignancy (usually squamous cell carcinoma of skin) indicates malignant potential Struma ovarii is a teratoma composed primarily of thyroid tissue

Question 51

Dysgerminoma | GST

Answer 51

Tumor composed of large cells with clear cytoplasm and central nuclei. Most common malignant germ cell tumor Testicular counterpart is called seminoma, which is relatively common germ cell tumor in males Good prognosis; responds to radiotherapy Serum LDH may be elevated

Question 52

Endodermal sinus tumor | GST

Answer 52

Malignant tumor that mimics the yolk sac; most common germ cell tumor in children Serum AFP is often elevated Schiller-Duval bodies (glomerulus-like structures) are classically sen on histology

Question 53

Choriocarcioma | GST

Answer 53

Malignant tumor composed of cytotrophoblasts and syncytiotrophoblasts; mimics placental tissue, but villi are absent Small, hemorrhagic tumor with early hematogenous spread High Beta hCG is characteristic (produced by syncytiotrophoblasts); may lead to thecal cysts in the ovary Poor response to chemotherapy

Question 54

Embryonal carcinoma | GST

Answer 54

Malignant tumor composed of large primitive cells Aggressive with early metastasis

Question 55

Sex Cord-Stromal Tumors

Answer 55

tumors that resemble sex cord-stromal tissues of the ovary

Question 56

Granulosa-theca cell tumor | SCST

Answer 56

neoplastic proliferation of granulosa and theca cells Often produces estrogen; presents with signs of estrogen excess prior to puberty-precocious puberty reproductive age-menorrhagia or metrorrhagia postmenopause (most common setting for granulosa-theca cell tumors) - endometrial hyperplasia with postmenopausal uterine bleeding malignant, but minimal risk for metastasis

Question 57

Sertoli-Leydig cell tumor | SCST

Answer 57

Composed of Sertoli cells that form tubules and leydig cells (between tubules) with characteristic Reinke crystals May produce androgen; associated with hirsutism and virilization

Question 58

Fibroma | SCST

Answer 58

Benign tumor of fibroblasts Associated with pleural effusions and ascites (Meigs syndrome); syndrome resolves with removal of tumor

Question 59

Krulenberg Tumor

Answer 59

A metastatic mucinous tumor that involves both ovaries; most commonly due to metastatic gastric carcinoma (diffuse type) Bilaterality helps distinguish metastases from primary mucinous carcinoma of the ovary, which is usually unilateral

Question 60

Pseudomyxoma peritonei

Answer 60

massive amounts of mucus in the peritoneum sue to a mucinous tumor of the appendix, usually with metastasis to the ovary

Question 61

Placenta previa

Answer 61

Implantation of the placenta in the lower uterine segment; placenta overlies cervical os (opening) Presents as third-trimester bleeding Often requires delivery of fetus by caesarian section

Question 62

PLacental abruption

Answer 62

Separation of placenta from the decidua prior to delivery of the fetus Common cause of still birth Presents with third-trimester bleeding and fetal insufficiency

Question 63

Placenta Accreta

Answer 63

improper implantation of placenta into the myometrium with little or no intervening decidua Presents with difficult delivery of the placenta and postpartum bleeding Often requires hysterectomy

Question 64

Preeclapsia

Answer 64

Pregnancy-induced hypertension, proteinuria, and edema, usually arising in the third trimester; seen in approx 5% of pregnancies hypertension may be severe, leading to headache and visual abnormalities resolves with delivery

Question 65

Eclampsia

Answer 65

Preeclampsia with seizures

Question 66

HELLP

Answer 66

preeclampsia with thrombotic microangiopathy involving the liver; characterized by Hemolysis, Elevated Liver enzymes, and Low Platelets Eclampsia and HELLP warrant immediate delivery

Question 67

Hydatidiform mole

Answer 67

Abnormal conception characterized by swollen and edematous villi with proliferation of trophoblasts Uterus expands as if a normal pregnancy is present, but the uterus is much larger and beta hCG much higher than expected for date of gestation presents in the second trimester as passage of grape-like masses through the vaginal canal With prenatal care, moles are diagnosed by routine ultrasound in the early first trimester. Fetal heart sounds are absent,and a 'snowstorm; appearance is classically seen on ultrasound Treatment is suction curretage - beta hCG monitoring is important to ensure adequate mole removal and to screen for the development of choriocarcinoma Choriocarcinoma may arise as a complication of gestation (spontaneous abortion, normal pregnancy, or hydatidiform mole) or as a spontaneous germ cell tumor Choriocarcinomas that arise from the gestational pathway respond well to chemotherapy; those that arise from the germ cell pathway do not

Question 68

Look up table comparing complete and partial moles

Answer 68

do it