Endometrial Disorders + Cancer B&B

Question 1

what is the effect of of estrogen vs progesterone on the endometrium?

Answer 1

estrogen stimulates growth (drives proliferative phase)

Progesterone stimulates secretary activity (drives secretory phase, progesterone withdraw = menstruation)

Question 2

What is the most common cause of dysfunctional uterine bleeding?

Answer 2

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

Question 3

what is acute endometritis caused by?

Answer 3

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

Question 4

how is acute endometritis classically treated?

Answer 4

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)

Question 5

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?

Answer 5

acute/pregnancy-related endometritis: caused by bacterial infection after delivery or miscarriage

C-section is key risk factor (prophylactic antibiotics given)

tx: clindamycin + gentamycin

Question 6

how does RPOC (retained products of conception) present?

Answer 6

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)

Question 7

what are the usual causes of pelvic inflammatory disease (PID)? (2)

Answer 7

chlamydia or gonorrhea

cause ascending infection that can involve uterus (chronic endometritis), fallopian tubes (salpingitis), and ovaries (oophoritis)

Question 8

what is the biopsy hallmark of chronic endometritis?

Answer 8

plasma cells - not normal finding, indicates chronic inflammation

Question 9

what are endometrial polyps caused by?

Answer 9

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

Question 10

hyperplastic growth of glands/stroma that project from endometrium (“exophytic mass”)

Answer 10

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

Question 11

explain why tamoxifen is associated with endometrial polyps

Answer 11

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

Question 12

where does endometriosis commonly occur?

Answer 12

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)

Question 13

what are some of the theories regarding why endometriosis occurs?

Answer 13

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

Question 14

What are the symptoms of endometriosis and why do these occur?

Answer 14

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

Question 15

How is endometriosis diagnosed?

Answer 15

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

Question 16

how is endometriosis typically treated?

Answer 16

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)

Question 17

leuprolide

Answer 17

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

Question 18

danazol

Answer 18

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)

Question 19

What is the cause of adenomyosis and how does it present?

Answer 19

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

Question 20

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?

Answer 20

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

Question 21

Benign tumor of myometrium that occurs in pre-menopausal woman due to growth stimulated by estrogen

Answer 21

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

Question 22

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?

Answer 22

leiomyoma, aka fibroid: benign tumor of myometrium due to growth stimulated by estrogen

usually resolves at menopause (decreased estrogen production)

Question 23

contrast leiomyoma and leiomyosarcoma

Answer 23

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)

Question 24

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?

Answer 24

leiomyosarcoma: malignant tumor of myometrium, presents in post-menopausal women as a single large mass, arises de novo (NOT progression of fibroids)

Question 25

What is the cause of endometrial hyperplasia and in which patients does it usually occur?

Answer 25

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

Question 26

how do each of the following cause endometrial hyperplasia? a. Obesity b. PCOS. c. Tamoxifen. d. Ovarian granulosa cell tumor.

Answer 26

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

Question 27

How is low risk versus high-risk endometrial hyperplasia treated?

Answer 27

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*

Question 28

what is the most common gynecological cancer and in which patients does it most often present?

Answer 28

*endometrial carcinoma* - typically post-menopausal women (~60yo) because anovulation increases estrogen exposure often preceded by endometrial hyperplasia presents with *abnormal uterine bleeding*

Question 29

With what type of hysterectomy is endometrial carcinoma typically treated?

Answer 29

*total abdominal hysterectomy* most common gynecological carcinoma, presents in postmenopausal women with abnormal uterine bleeding

Question 30

Contrast the two types of endometrial carcinoma

Answer 30

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)

Question 31

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?

Answer 31

*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)

Question 32

what is the most common non-colon malignancy that occurs in patients with HNPCC?

Answer 32

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*

Question 33

menorrhagia vs metrorrhagia

Answer 33

menorrhagia = profuse/prolonged menstrual bleeding metrorrhagia = irregular bleeding between menses

Question 34

what are the differential diagnosis for uterine bleeding? (hint, mnemonics!)

Answer 34

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

Question 35

how does endometrial hyperplasia appear histologically?

Answer 35

increased proliferation of endometrial glands relative to stroma

Question 36

what is the number one risk factor for type 1 endometrial cancer?

Answer 36

Type I, endometriod: estrogen-dependent hyperplasia, resembles endometrium #1 risk factor is *unopposed estrogen exposure* - exogenous (tamoxifen), obesity (high aromatase activity), PCOS (chronic anovulation), nulliparity (no pregnancies) oral contraceptives are protective (source of progesterone) *30-80% have silenced PTEN gene*

Question 37

how does type 1 endometrial cancer spread, and where does it typically metastasize to?

Answer 37

Type I, endometriod: estrogen-dependent hyperplasia, resembles endometrium (85% are adenocarcinomas - glandular) spread via direct *myometrial invasion*, metastasizes to *lungs, bone, liver*

Question 38

describe the histology of type 2 endometrial cancer

Answer 38

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!

Question 39

what molecular genetics are associated with type 1 versus type 2 endometrial cancer?

Answer 39

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*

Question 40

how should abnormal uterine bleeding be evaluated?

Answer 40

pelvic exam necessary but findings may be normal (normal cervix/ uterine size) *evaluation of endometrium* is necessary - trans-vaginal ultrasound, endometrial biopsy