2/21 Cancers of Female Repro Tract - Corbett Flashcards
cervical cancer
risk factors
- multiple sexual factors (incr poss exposure to HPV)
- start sexual intercourse at young age
- smoking
- HIV infection
anatomy of cervix
endocervix: simple columnar epithelium, produces mucus
transition zone
ectocervix: stratified squamous epithelium
change in vaginal epithelium during puberty
exposed columnar epi cells undergo metaplasia
transition zone
esp susceptible to HPV infection
HPV and invasive cervical cancer
progression numbers?
higher risk of progression?
histo connection
viral factors
higher risk if
- HPV phenotype/course
- high risk HPV type (16 - 60%, 18 - 10%; - also 31, 33) - more likely to integrate into host genome
- persistent infection
- immunocompromised state (5x if HIV+)
- environmental factors (smoking, vit deficiency)
histologically: KOILOCYTES = HPV
HPV oncoproteins: resp for viral transformation
-
E7 : binds to Rb protein → release/activation of E2F tf → cells enter S phase
- also binds p21 and other cyclins
- E6 : binds to p53, causes its degradation → prevents cell growth check
HPV oncoproteins
CERVICAL INTRAEPITHELIAL NEOPLASIA
region of dysplasia extends further and further
assoc with failure of maturation
incr variabliilty in cell and nuclear size
invasive carcinoma of cervix
all linked to HPV
- 80% squamous cell carcinoma
- 15% adenocarcinoma (hard to detect w pap smear)
- 5% neuroendocrine tumor
peak indicence: 45
presentation: cervical cancer
- abnormal pap smear (but most women are asymp)
- post-coital vaginal bleeding
- vag discomfort
- malodorous discharge
- dysuria
in advanced disease…
- invasion of bladder and rectum
- constipation, hematuria, fistula, ureteral obst (w, wout hydronephrosis)
- triad suggesting pelvic wall: leg edema, pain, hydronephrosis
- distant metastasis possible
cervical cancer screening/vaccine
screen at 21 or w/in first 3yr of sexual activity
- cytology/pap smear + HPV testing 3yr-ly
- neg? testing Q 5yr
- pos? cervical cytology every 6-12mo
vaccination protects against HPV 16, 18
endometrium
two layers
-
functional layer
- most affected by changes in blood levels of estrogen/progesterone & spiral aa blood supply
- partly/totally lost during menstruation
- basal layer
- not affected by changes in blood levels of estrogen/progesterone
- blood supply is from basal aa
- not lost after menstruation → basal-fx layer boundary will serve as point of regeneration for fx layer after menstruation
changes in endometrium through menstrual cycle
tumors of myometrium
- benign (leiomyoma)
- malignant (leiomyosarcoma)
leiomyoma
LEIOMYOMA
- estrogen-sensitive
- often multiple: sharply circumscribed, discrete, round, firm gray white tumors
- commonly asymp but can also present w
- abnl uterine bleeding
- urinary sx
- pelvic pain
risk factors
- race (AfAm)
- estrogen (low parity, premenopausal, large in preg)
- fam hx
- obesity
leiomyosarcoma
rare tumor from stroma/smooth muscle
LEIOMYOMAS ARE NOT PRECURSOR LESIONS FOR LEIOMYOSARCOMA → have distinct karyotypes and gene mutations
pathologically:
- nuclear atypia
- mitotic index
clinical presentation:
- bleeding
- pelvic pain/pressure
- pelvic mass
subtypes of endometrial cancer
endometrial cancer type 1 (80)
- endometrioid
- mimic proliferative endometrial glands
- precursor lesion: endometrial hyperplasia
-
key risk factor:
- unopposed extrogen exposure (tamoxifen or endog)
- obesity, chronic anovulation, nulliparity
- DM
- HTN
endometrial cancer type 2
- occurs in setting of endometrial atrophy in older women in 70s
- poorly differentiated
- all high grade
- 90% have p53 mutation
-
serous: papillary architecture resembling serous carcinoma of ovary
- psammoma bodies in 60%
- marked nuclear atypia in 100%
- clear cell
- tumor exfoliates, often spread beyond uterus at dx
MUST KNOW
postmenopausal bleeding and cancer
20% of postmenopausal bleeding is due to cancer
- MUST ELIMINATE CANCER IN THESE PTS
ovary review
plus a few more review pics
ovarian cancer
risk factors
- BRCA1, BRCA2 (8-10% of all ovarian cancers)
- NHPCC
- incr estrogen exposure
- nulliparity
- delayed menopause
symptoms
(triad) and others
symptom triad (43% if they had all 3)
- bloating
- incr abdominal girth
- urinary sx
- bloating/abd distention
- early satiety
- pressure effects on bladder/rectum
- SOB/fatigue
origins of ovarian tumors
memorize
- surface epithelium x5
- 90% malignancy
- 65-70% benign
- germ cells x5
- sex cord-stroma x6
surface epithelial cell tumors
serous tumors
70% benign: serous CYSTadenomas
- younger women
- simple cysts w cuboidal epithelium
30% malignant: serous cystadenocarcinomas
- postmenopausal women
- proliferative cyst lining “shaggy”
- spread via diffuse peritoneal seeding (85% extra-ovarian at dx)
- common assoc with ascites
commonly bilateral
psammoma bodies (though not specific)
mucinous tumors
- 90% benign, low malignant potential
- less likely to involve ovary surface
- 5% bilat
- LARGE and multilobulated and filled with gelatinous fluid
- assoc with K-Ras mutations
- solid areas of growth? → malignancy
endometrioid tumors
- marked by tubular glands bearing close resemblance to benign or malignant endometrium
- 15-20% arise in setting of endometriosis
- 15-30% of ovarian endometriod carcinoms occur with endometrial carcinoma
- usually young women
- microsatellite instability (DNA MMR mutations, ex. Lynch syndrome)
transitional cell tumors
Brenner tumors
mostly benign
uncommon
solid, encapsulated, unilateral
abundant stroma containing nests of transitional-type epithelium
ovarian cancers summary
surface epitheilum-stroma
germ cell tumors
-
“embryo-like”
- teratoma: mature (BENIGN) & immature
- dysgerminoma (immature germ cells) → LDH
- bHCG → embryonal carcinoma
-
“placenta-like”
- yolk sac → AFP
- bHCG → choriocarcinoma
generally younger women (10-30y)
- 70% of ovarian neoplasms in this age group
- malignant OGCNs more freq among Asian/Pacific Islander, Hispanic women
teratomas
15-20% of all benign ovarian neoplasms
most common ovarian tumor in women in 20s/30s
most likely in younger women (under 20)
over 95% are benign cystic teratomas
- contain mature tissue from all three germ cell layers, lined by epidermis
- can undergo malignant transformatoin → squamous cell carcinoma (usually)
- 90% unilat (R > L)
specialized teratomas
struma ovarii
carcinoid
struma ovarii
- mature thyroid tissue
- can be fxal → 30% of pts will have clinical hyperthyroidism
carcinoid
- can cause carcinoid syndrome if large (even w/out hepatic metastases)
germ cell origin + metastases to ovary
summary
sex cord stromal tumors
derived from ovarian stroma (sex cords of embryonic gonad)
undifferentiated gonadal mesenchyme…
- male (Sertoli, Leydig) : secrete androgens → VIRILIZING
- female (granulosa, theca) : secrete androgens → FEMINIZING
granulosa cell tumors
mostly in adults
presence of gland-like structures: Call-Exner bodies
may pump out lots of estrogen → dysfx uterine bleeding, 10-15% develop endometrial cancer
inhibit: tumor marker
97% have mutation in FOXL2 gene: imp to granulosa cell devpt
Sertoli-Leydig cell tumors
often androgen-secreting: recap testicular Sertoli cells
peak: 20-30y
unilateral
over 50% have mutation sin DICER1 (microRNA processing)
can lead to “defeminization” or virilization
- breast atrophy
- amenorrhea
- hair loss
- infertility
all ovarian cancer cancers
