Conditions of the Female Reproductive Tract Flashcards
cervix - anatomy/histology
*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
human papillomavirus (HPV) - characterstics
*small DNA virus
*non-enveloped, environmentally stable
*more than 200 distinct human types
human papillomavirus (HPV) - warts
*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
human papillomavirus (HPV) - cancer
*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
human papillomavirus (HPV) - oncoproteins
- E6: causes dysregulation in tumor suppressor p53
-
E7: causes dysregulation in tumor suppressor E2F and Rb
*overall effect: increased proliferation of cells → increased risk of tumor development
cervical intraepithelial neoplasia (CIN) - overview
*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
cervical intraepithelial neoplasia (CIN) - grades
*CIN1: 90% chance of regression
*CIN2: 70% chance of regression
*CIN3: more likely to develop into cancer/invasive disease
vaccination against HPV - recommedations
*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
immunization against HPV - types
*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
screening for HPV/cervical cancer
*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
cervical carcinoma - risk factors
*HPV infection (early age of sexual debut, multiple sexual partners, etc)
*immunosuppression
*tobacco use
*OCP use
cervical carcinoma - subtypes
*squamous cell cervical carcinoma = most common (80%)
*adenocarcinoma (15%)
cervical carcinoma - treatment
*early-stage disease: radical hysterectomy
*advanced-stage disease: chemo / radiation
endometrial hyperplasia - overview
*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
endometrial hyperplasia - histology
*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
type 1 endometrial cancer - overview
*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
type 2 endometrial cancer - overview
*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
endometrial cancer - overview
*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
leiomyosarcoma - overview
*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
ovary - overview
*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
epithelium tumors/neoplasms of the ovaries
*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
benign tumors of the ovaries
*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
malignant tumors of the ovaries
*serous cystadenocarcinoma = most common
*complex cysts
*atypical serous cells form sheets
*most commonly arise in postmenopausal women
*most common type of ovarian cancer
BRCA gene
*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
BRCA gene - function
*important for double-stranded DNA repair:
1. homologous recombination (high fidelity)
2. NHEJ (low fidelity)
diagnosis of epithelial ovarian cancer
*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)
treatment of epithelial ovarian cancer
*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
germ cell tumors in females - overview
*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
mature cystic teratoma (“dermoid”) of the ovary
*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
dysgerminoma - overview
*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
markers secreted by germ cell and sex cord-stormal tumors of the ovary
germ cell tumors:
*dysgerminoma = LDH
*embryonal = hCG
*choriocarcinoma = hCG
*endodermal sinus = AFP
*immature teratoma = NONE
sex cord-stromal tumors:
*granulosa cell = inhibin
granulosa cell tumor
*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)
vulva - overview
*anatomically includes the skin and mucosa of the female genitalia external to the hymen
*lined by squamous epithelium
condyloma (female) - overview
*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
Lichen sclerosis - overview
*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
Paget’s disease of the vulva (female) - overview
*malignant epithelial cells of the epidermis & vulva
*erythematous, pruritic vulvar skin
*represents CIS usually with no underlying carcinoma
*treatment = wide local excision
vulvar carcinoma - overview
*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
vulvar cancer - subtypes
- squamous cell (non-HPV vs. HPV related)
- melanoma
- basal cell
- other (rare) types:
-Bartholin gland carcinoma
-sarcoma
-Paget’s disease
presenting symptoms of vulvar cancer
*PRURITIS (itching)
*mass of vulva/groin
*pain/burning
*dysuria
*bleeding
*ulceration
*DISCHARGE
gestational trophoblastic disease (hydatidiform mole)
*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
partial mole - features
*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%
complete mole - features
*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%
