Endometrial Disorders + Cancer B&B Flashcards
what is the effect of of estrogen vs progesterone on the endometrium?
estrogen stimulates growth (drives proliferative phase)
Progesterone stimulates secretary activity (drives secretory phase, progesterone withdraw = menstruation)
What is the most common cause of dysfunctional uterine bleeding?
abnormal menstrual bleeding not due to a structural cause (“functional”)
Most commonly caused by an anovulatory cycle - no corpus luteum formation, therefore, no switch from estrogen to progesterone secretion… unopposed growth from estrogen leads to irregular bleeding
what is acute endometritis caused by?
aka pregnancy-related endometritis: caused by bacterial infection after delivery or miscarriage
C-section is key risk factor (prophylactic antibiotics given)
presents with fever, abdominal pain, uterine tenderness
how is acute endometritis classically treated?
aka pregnancy-related endometritis: caused by bacterial infection after delivery or miscarriage (higher risk with C-section)
classic tx: clindamycin + gentamycin (broad-spectrum because it can be caused by almost any bacteria)
Following a cesarean section at-home delivery (with no medical personnel present), a woman presents to her physician with fever, abdominal pain, and uterine tenderness. What is the most likely cause of her symptoms?
acute/pregnancy-related endometritis: caused by bacterial infection after delivery or miscarriage
C-section is key risk factor (prophylactic antibiotics given)
tx: clindamycin + gentamycin
how does RPOC (retained products of conception) present?
placental/fetal tissue remaining in uterus after delivery causes uterine bleeding and pelvic pain as tissue becomes necrotic
Prone to infection by flora from the service or vagina —> leads to acute endometritis (fever, abdominal pain, uterine tenderness)
what are the usual causes of pelvic inflammatory disease (PID)? (2)
chlamydia or gonorrhea
cause ascending infection that can involve uterus (chronic endometritis), fallopian tubes (salpingitis), and ovaries (oophoritis)
what is the biopsy hallmark of chronic endometritis?
plasma cells - not normal finding, indicates chronic inflammation
what are endometrial polyps caused by?
hyperplastic growth of glands/stroma that project from endometrium (“exophytic mass”)
usually benign + asymptomatic, may cause painless uterine bleeding - can be surgically removed (prevent infection, small chance of malignancy)
common near menopause, associated with tamoxifen use - associated with unopposed estrogen
hyperplastic growth of glands/stroma that project from endometrium (“exophytic mass”)
endometrial polyps: usually benign + asymptomatic, may cause painless uterine bleeding - can be surgically removed (prevent infection, small chance of malignancy)
common near menopause, associated with tamoxifen use - associated with unopposed estrogen
explain why tamoxifen is associated with endometrial polyps
tamoxifen: SERM (selective estrogen receptor modulator) that is competitive antagonist in breast but agonist in bone/uterus
unopposed estrogen activity can lead to endometrial polyps (hyperplastic growth of glands/stroma)
may lead to endometrial cancer
where does endometriosis commonly occur?
endometriosis: endometrial tissue outside of the uterus (glands and stroma)
commonly in ovary/fallopian tubes, uterosacral ligaments, rectovaginal septum, or pelvic peritoneum (these structures are all near the uterus)
what are some of the theories regarding why endometriosis occurs?
endometriosis: endometrial tissue outside of the uterus, etiology unknown but theories:
retrograde flow - movement of menstrual tissue through the fallopian tubes
metastasis - endometrial tissue spreads via venous/lymphatics
metaplasia - coelomic epithelium (lines organ/body cavities) develops into endometrial tissue
What are the symptoms of endometriosis and why do these occur?
endometriosis: endometrial tissue outside of the uterus which is hormone sensitive (grows with estrogen, atrophies with progesterone withdrawal)
—> cyclic pelvic pain
—> dysmenorrhea/menorrhagia (painful & heavy bleeding of ectopic tissue)
—> infertility (due to ovarian/fallopian lesions)
—> dyspareunia (painful intercourse), dyschezia (painful defecation), dysuria
How is endometriosis diagnosed?
normal uterus size, uterus may be retroverted (tipped backwards), chocolate cyst in ovary (blood filled)
biopsy of lesion for definitive diagnosis
+/- nodules in posterior fornix or ovarian mass
how is endometriosis typically treated?
definitive: surgical removal of ectopic tissue (reserved for severe symptoms)
NSAIDs to reduce inflammation
first line: oral contraceptive pills (progestin suppress ovarian function and endometrial growth)
leuprolide
GnRH agonist, binds receptors in pituitary —> down-regulation of GnRH receptors & pituitary desensitization —> decreased LH/FSH —> decreased estrogen production from ovaries
can be used to treat endometriosis
danazol
steroid with weak androgen and progesterone activity —> inhibits LH surge and suppresses ovarian function (anovulation)
can be used to treat endometriosis, but rarely used due to side effects - high androgens, low estrogen (hot flashes), pseudotumor cerebri (intracranial HTN)
What is the cause of adenomyosis and how does it present?
hyperplasia of basal endometrium into myometrium
presents with globular/diffusely enlarged uterus and heavy/painful menstruation
often co-exits with endometriosis (can treat the same), definitive treatment is hysterectomy
Pt is a 42yo F presenting with heavy and painful periods. Laparoscopy reveals a globular, diffusely enlarged uterus. A biopsy is done which reveals basal endometrium within the myometrium. What is the diagnosis, and how will you treat her?
adenomyosis: hyperplasia of basal endometrium into myometrium
often co-exits with endometriosis and can be treated the same
definitive treatment is hysterectomy, but this depends if the woman has completed childbearing
Benign tumor of myometrium that occurs in pre-menopausal woman due to growth stimulated by estrogen
leiomyoma, aka fibroid - usually presents with multiple tumors and resolves at menopause (decreased estrogen production)
discrete/round/firm tumors, histology shows smooth muscle cell proliferation
usually asymptomatic, may cause irregular bleeding
Pt is a 49yo F (pre-menopause) presenting with irregular bleeding which has been heavier and longer than normal. Otherwise she is asymptomatic. PE is notable for several palpable pelvic masses. A biopsy is taken which shows proliferation of smooth muscle cells. What is the most likely diagnosis?
leiomyoma, aka fibroid: benign tumor of myometrium due to growth stimulated by estrogen
usually resolves at menopause (decreased estrogen production)
contrast leiomyoma and leiomyosarcoma
leiomyoma: aka fibroid, benign tumor of myometrium, presents in pre-menopausal women with multiple tumors
leiomyosarcoma: malignant tumor of myometrium, presents in post-menopausal women as a single large mass, arises de novo (NOT progression of fibroids)
Pt is a 63yo F (post-menopause) presenting to her OBGYN for an annual exam. A single large pelvic mass is palpated and a biopsy is taken, which reveals smooth muscle proliferation of the myometrium. What is the likely diagnosis?
leiomyosarcoma: malignant tumor of myometrium, presents in post-menopausal women as a single large mass, arises de novo (NOT progression of fibroids)
What is the cause of endometrial hyperplasia and in which patients does it usually occur?
absence of progesterone allows for unopposed estrogen stimulation of the endometrium (pre-malignant to endometrial carcinoma)
usually occurs in peri/postmenopausal woman
PTEN inactivation in ~50% of high-risk lesions
how do each of the following cause endometrial hyperplasia?
a. Obesity
b. PCOS.
c. Tamoxifen.
d. Ovarian granulosa cell tumor.
These are all sources of estrogen
a. Obesity - increased conversion of androgens to estrogens (estrone)
b. PCOS - obesity/anovulation
c. Tamoxifen - estrogen agonist
d. Ovarian granulosa cell tumor - secretes estrogen
unopposed estrogen stimulation of endometrium causes endometrial hyperplasia
How is low risk versus high-risk endometrial hyperplasia treated?
absence of progesterone allows for unopposed estrogen stimulation of the endometrium (pre-malignant to endometrial carcinoma)
low risk —> progestins (opposes estrogen, reverses hyperplasia and improves bleeding)
high risk (complex, atypical histology) —> hysterectomy
what is the most common gynecological cancer and in which patients does it most often present?
endometrial carcinoma - typically post-menopausal women (~60yo) because anovulation increases estrogen exposure
often preceded by endometrial hyperplasia
presents with abnormal uterine bleeding
With what type of hysterectomy is endometrial carcinoma typically treated?
total abdominal hysterectomy
most common gynecological carcinoma, presents in postmenopausal women with abnormal uterine bleeding
Contrast the two types of endometrial carcinoma
classified histologically
Type I, endometriod (80%): estrogen-dependent hyperplasia, resembles endometrium
Type II, serous/sporadic: estrogen-independent, arises from atrophic endometrium post-menopause (65-75yo), 90% with p53 mutation, undifferentiated, poor prognosis (more aggressive)
Pt is a 71yo F (post-menopause) undergoing a biopsy for a suspicious uterine mass. Biopsy shows undifferentiated pink, serous material that is negative for estrogen but positive for a p53 mutation. What is the most likely diagnosis?
Type II, serous/sporadic endometrial carcinoma: estrogen-independent, arises from atrophic endometrium post-menopause, 90% with p53 mutation
pink/serous biopsy, undifferentiated, poor prognosis (more aggressive)
what is the most common non-colon malignancy that occurs in patients with HNPCC?
HNPCC = hereditary non-polyposis colorectal cancer / Lynch Syndrome
due to germ-line mutation in DNA mismatch repair genes
lifetime risk up to 70% for endometrial cancer
menorrhagia vs metrorrhagia
menorrhagia = profuse/prolonged menstrual bleeding
metrorrhagia = irregular bleeding between menses
what are the differential diagnosis for uterine bleeding? (hint, mnemonics!)
structural issues: PALM
Polyps
Adenomyosis
Leiomyoma (fibroids)
Malignancy* and hyperplasia
functional issues: COIN
Coagulopathy
Ovulatory dysfunction
Endometrial
Iatrogenic
Not yet classified
*15-20% of post-menopausal bleeding is due to cancer, therefore must always be ruled out
how does endometrial hyperplasia appear histologically?
increased proliferation of endometrial glands relative to stroma
what is the number one risk factor for type 1 endometrial cancer?
1 risk factor is unopposed estrogen exposure - exogenous (tamoxifen), obesity (high aromatase activity), PCOS (chronic anovulation), nulliparity (no pregnancies)
Type I, endometriod: estrogen-dependent hyperplasia, resembles endometrium
oral contraceptives are protective (source of progesterone)
30-80% have silenced PTEN gene
how does type 1 endometrial cancer spread, and where does it typically metastasize to?
Type I, endometriod: estrogen-dependent hyperplasia, resembles endometrium (85% are adenocarcinomas - glandular)
spread via direct myometrial invasion, metastasizes to lungs, bone, liver
describe the histology of type 2 endometrial cancer
Type II, serous/sporadic: estrogen-independent, arises from atrophic endometrium post-menopause, p53 mutation, poor prognosis
papillary architecture resembling serous/clear cell carcinoma, psammoma bodies (calcifications) often present, marked nuclear atypia, always undifferentiated
all type 2 EC are considered high grade!
what molecular genetics are associated with type 1 versus type 2 endometrial cancer?
Type I, endometriod: estrogen-dependent hyperplasia, associated with PTEN silencing and Lynch Syndrome (HNPCC)
Type II, serous/sporadic: estrogen-independent, arises from atrophic endometrium post-menopause, associated with p53 mutation and aneuploidy
how should abnormal uterine bleeding be evaluated?
pelvic exam necessary but findings may be normal (normal cervix/ uterine size)
evaluation of endometrium is necessary - trans-vaginal ultrasound, endometrial biopsy
