Conditions of the Female Reproductive Tract

Question 1

cervix - anatomy/histology

Answer 1

*divided into the exocervix (visible on vaginal examination) and endocervix
*exocervix = squamous epithelium
*endocervix = glandular/columnar epithelium
*junction between the exocervix & endocervix = transformation zone
*transformation zone is where disease (dysplasia/malignancy) develops

Question 2

human papillomavirus (HPV) - characterstics

Answer 2

*small DNA virus
*non-enveloped, environmentally stable
*more than 200 distinct human types

Question 3

human papillomavirus (HPV) - warts

Answer 3

*benign hyperplasia of dry or mucosal epithelium
*common, flat, palmo-plantar, genital, laryngeal
*flat / colored skin (epidermodysplasia verruciformis)
*usually caused by strains 6 and 11

Question 4

human papillomavirus (HPV) - cancer

Answer 4

*associated with “high risk” types (16, 18, 31, 33)
*cervical carcinoma: classically associated with HPV strains 16 and 18
*head and neck cancer: classically associated with strain 16 > 18
*skin carcinoma in individual with EV: types 5 and 8 most commonly

Question 5

human papillomavirus (HPV) - oncoproteins

Answer 5

1. E6: causes dysregulation in tumor suppressor p53
2. E7: causes dysregulation in tumor suppressor E2F and Rb
   *overall effect: increased proliferation of cells → increased risk of tumor development

Question 6

cervical intraepithelial neoplasia (CIN) - overview

Answer 6

*koilocytic change, disordered cellular maturation, nuclear atypia, and increased mitotic activity within the cervical epithelium
*divided into grades based on extent of epithelial involvement by immature, dysplastic cells
*the higher the grade of dysplasia (CIN), the more likely it is to progress and less likely it is to regress

Question 7

cervical intraepithelial neoplasia (CIN) - grades

Answer 7

*CIN1: 90% chance of regression
*CIN2: 70% chance of regression
*CIN3: more likely to develop into cancer/invasive disease

Question 8

vaccination against HPV - recommedations

Answer 8

*recommended ages 11-12 (starting as early as age 9)
*2 doses if vaccine given prior to age 15 (3 doses if after age 15)
*up to age 27, but covered up to age 45

Question 9

immunization against HPV - types

Answer 9

*quadrivalent vaccine: covers HPV types 6, 11, 16, and 18
*bivalent vaccine covers HPV types 16 and 18
*ideally, administered before sexual debut
*does not replace need for screening

Question 10

screening for HPV/cervical cancer

Answer 10

*goal = identify dysplasia (CIN) prior to development of carcinoma
*techniques = PAP smear and HPV testing
*screening begins at age 21, initially performed every 3 years
*abnormal screen leads to colposcopic directed biopsies and potential treatment

Question 11

cervical carcinoma - risk factors

Answer 11

*HPV infection (early age of sexual debut, multiple sexual partners, etc)
*immunosuppression
*tobacco use
*OCP use

Question 12

cervical carcinoma - subtypes

Answer 12

*squamous cell cervical carcinoma = most common (80%)
*adenocarcinoma (15%)

Question 13

cervical carcinoma - treatment

Answer 13

*early-stage disease: radical hysterectomy
*advanced-stage disease: chemo / radiation

Question 14

endometrial hyperplasia - overview

Answer 14

*proliferation of endometrial glands relative to stroma
*usually due to increased estrogen relative to progesterone
*classically presents as postmenopausal bleeding
*can progress to endometrial cancer

Question 15

endometrial hyperplasia - histology

Answer 15

*classified based on:
1. architectural growth pattern (simple vs. complex)
2. presence or absence of cellular atypia
*risk of progression of hyperplasia to invasive adenocarcinoma correlates with degree of hyperplasia:
penny, nickel, dime, quarter:
-simple = <1% chance of turning into cancer
-complex = 4-5% chance
-simple with atypia = 10-12% chance
-complex with atypia = 10-20% chance

Question 16

type 1 endometrial cancer - overview

Answer 16

*age: 50s-60s (around time of menopause)
*risk factors: unopposed estrogen exposure, hyperplasia is a precursor
*grade: low
*smoking: decreases risk
*histopathologic subtypes: endometrioid; well-differentiated
*behavior: stable
*treatment: surgery
*outcome: favorable

Question 17

type 2 endometrial cancer - overview

Answer 17

*age: 60s-70s (older patients)
*risk factors: unknown but occurs in atrophic endometrium
*grade: high
*smoking: increases risk
*histopathologic subtypes: serous, clear cell
*behavior: aggressive
*treatment: radical surgery + chemotherapy
*outcome: less favorable

*includes clear cell carcinoma of the uterus and UPSC

Question 18

endometrial cancer - overview

Answer 18

*malignant proliferation of endometrial glands
*presents as postmenopausal/abnormal uterine bleeding
*diagnosed by endometrial biopsy (office pipelle or D&C)
*treatment is surgical staging
*stage and grade determine prognosis/therapy

Question 19

leiomyosarcoma - overview

Answer 19

*malignant proliferation of smooth muscle arising from the myometrium
*do NOT arise from leiomyomas (fibroids)
*histological features (2+): increased mitotic activity (> 10 mitoses/hpf), cellular atypia, necrosis
*often diagnosed incidentally after hysterectomy for “fibroids”
*rare, aggressive guarded prognosis

Question 20

ovary - overview

Answer 20

*follicle is functional unit; it consists of an oocyte surrounded by granulosa and theca cells
*after ovulation, the residual follicle becomes the corpus luteum
*hemorrhage into a corpus luteum can result in a hemorrhagic cyst
*degeneration of follicles results in follicular cysts

Question 21

epithelium tumors/neoplasms of the ovaries

Answer 21

*derived from epithelium that lines the ovary/fallopian tube
*produces the epithelial lining of the fallopian tubes (serous), endometrium and endocervix (mucinous cells)
*can be benign, “borderline,” or malignant
*BRCA mutation carriers have an increased risk for serous ovarian/tubal cancer

Question 22

benign tumors of the ovaries

Answer 22

*serous and mucinous cystadenomas
*single cyst with a simple, flat lining
*single layer of benign, columnar tubal type epithelium
*mucinous fluid is secreted by the epithelium and contained within the cystic mass
*most commonly arise in pre-menopausal women

Question 23

malignant tumors of the ovaries

Answer 23

*serous cystadenocarcinoma = most common
*complex cysts
*atypical serous cells form sheets
*most commonly arise in postmenopausal women
*most common type of ovarian cancer

Question 24

BRCA gene

Answer 24

*tumor suppressor genes
* > 1000 mutations reported in each
*most BRCA mutations result in truncated protein product
*proclivity for breast/ovarian cancer may be related to hormonal interactions

Question 25

BRCA gene - function

Answer 25

*important for double-stranded DNA repair:
1. homologous recombination (high fidelity)
2. NHEJ (low fidelity)

Question 26

diagnosis of epithelial ovarian cancer

Answer 26

*reliable (but common) symptoms but often ignored by patient/provider: abdominal pain, changes in GU/GI habits, increasing abdominal girth, early satiety
*CA-125, pelvic sonogram, and CT scans are helpful
*internal mass architecture = single most reliable predictor of malignancy “complexity”
*surgical intervention is recommended for suspicious masses
*most ovarian cancers at caught late (avg. stage 3)

Question 27

treatment of epithelial ovarian cancer

Answer 27

*early-stage disease: surgical staging +/- chemotherapy
*advanced/metastatic disease: surgical debulking + IV chemotherapy
*recurrence rate for patients with advanced disease = 75%+
*chemotherapy is mainstay of treatment for recurrent disease

Question 28

germ cell tumors in females - overview

Answer 28

*usually occur in women of reproductive age (<30 years)
*produce reliable tumor markers (LDH, AFP, beta-hCG)
*treatment = fertility-sparing surgery and chemotherapy
*prognosis is more favorable than epithelial ovarian cancer
*large cohort of survivors who have had successful pregnancies

Question 29

mature cystic teratoma (“dermoid”) of the ovary

Answer 29

*most common germ cell tumor in women
*cystic tumor composed of fetal tissue derived from 2 or 3 embryologic layers (skin, hair, bone, cartilage, thyroid)
*BENIGN
*presence of immature tissue (ie. neural tissue) indicates malignancy = immature teratoma

Question 30

dysgerminoma - overview

Answer 30

*most common MALIGNANT germ cell tumor in women (commonly adolescent patients)
*tumor composed of large cells with clear cytoplasm & central nuclei; “fried egg appearance”
*serum LDH may be elevated

Question 31

markers secreted by germ cell and sex cord-stormal tumors of the ovary

Answer 31

germ cell tumors:
*dysgerminoma = LDH
*embryonal = hCG
*choriocarcinoma = hCG
*endodermal sinus = AFP
*immature teratoma = NONE

sex cord-stromal tumors:
*granulosa cell = inhibin

Question 32

granulosa cell tumor

Answer 32

*often produces estrogen and presents with signs of estrogen excess
*Call-Exner bodies are identified by their rosette appearance
*malignant
*treatment = surgery + chemotherapy
*bimodal distribution (young kids + older women)

Question 33

vulva - overview

Answer 33

*anatomically includes the skin and mucosa of the female genitalia external to the hymen
*lined by squamous epithelium

Question 34

condyloma (female) - overview

Answer 34

*warty neoplasm of vulvar skin, often large
*most commonly due to HPV 6 and 11
*condylomas are characterized by koilocytes (hallmark of HPV-infected cells)
*koilocytes = nuclear enlargement and peri-nuclear halos
*rarely progress to invasive cancer

Question 35

Lichen sclerosis - overview

Answer 35

*thinning of the epidermis and fibrosis of the dermis
*presents as a white patch with parchment-like skin
*most common in postmenopausal women
*autoimmune etiology
*benign; slight increased risk for SCC
*treatment = topical steroids

Question 36

Paget’s disease of the vulva (female) - overview

Answer 36

*malignant epithelial cells of the epidermis & vulva
*erythematous, pruritic vulvar skin
*represents CIS usually with no underlying carcinoma
*treatment = wide local excision

Question 37

vulvar carcinoma - overview

Answer 37

*etiology may be HPV (usual
-type VIN) or non-HPV (differentiated VIN)
*generally seen in elderly women
*risk factor = tobacco use
*diagnosis = biopsy
*treatment = radical vulvectomy +/- groin LND

Question 38

vulvar cancer - subtypes

Answer 38

1. squamous cell (non-HPV vs. HPV related)
2. melanoma
3. basal cell
4. other (rare) types:
   -Bartholin gland carcinoma
   -sarcoma
   -Paget’s disease

Question 39

presenting symptoms of vulvar cancer

Answer 39

*PRURITIS (itching)
*mass of vulva/groin
*pain/burning
*dysuria
*bleeding
*ulceration
*DISCHARGE

Question 40

gestational trophoblastic disease (hydatidiform mole)

Answer 40

*abnormal conception characterized by swollen and edematous villi with proliferation of trophoblasts
*uterus expands as if normal pregnancy is present, but uterus is much larger and beta-hCG is much higher than expected for date of gestation
*classified as partial or complete
*treatment = suction curettage

Question 41

partial mole - features

Answer 41

*genetics: normal ovum fertilized by 2 sperm (or one sperm that duplicates chromosomes)
*number of chromosomes: 69 XXX, XXY, or XYY
*fetal tissue: +
*villous edema: +/-
*trophoblastic proliferation: focal around hydropic villi
*risk for GTN (gestational trophoblastic neoplasia): ~4%

Question 42

complete mole - features

Answer 42

*genetics: empty ovum fertilized by 2 sperm (or one sperm that duplicates chromosomes)
*number of chromosomes: 46 XX, 46XY
*extremely high hCG levels
*fetal tissue: -
*villous edema: +
*trophoblastic proliferation: diffuse
*risk for GTN (gestational trophoblastic neoplasia): ~20%