Endometrial cancer Flashcards
what is the fourth most common cancer among american women
endometrial (breast, bowel and lung are ahead)
what is the most commonly encountered gynecological malignancy in the US
endometrial
favorable survival profile because majority are dx early
what % of women with endometrial cancer are diagnosed at stage I
72%–surgical staging is thus usually curative
why are most endometrial cancers caught early
early symptoms and accurate diagnosis modalities
what are the risk factors for endometrial cancer
obesity chronic anovulation nulliparity late menopause unopposed estrogen use hypertension DM
what are the two distinct pathogenic etiologies of endometrial cancer
Type I–> most common (80%); occurs in women with history of chronic estrogen exposure unopposed by progestin (estrogen dependent neoplasms); more favorable prognosis
Type II–> (20%); estrogen independent; not related to unopposed estrogen stimulation or endometrial hyperplasia; often occur within a background of ATROPHIC endometrium or polyps; often have high grade nuclear atypia with SEROUS or CLEAR CELL histology; many assoc with p53
how do type I endometrial cancers start
as atypical endometrial hyperplasia and progress to carcinomas
tend to be well differentiated (endometroid type) with lower grade nuclei and usually more favorable prognosis
what type of histology is associated with type II
clear cell or serous
many associated with p53 tumor suppressor gene
what is an important component of staging and prognosis of endometrial cancer
depth of myometrial invasion
prognosis worsened when cancer has invaded more than one half of the thickness of the myometrium
what are the 4 primary routes of spread of endometrial cancer
direct extension–most common
–towards cervix or outward through the myometrium and serosa
lymphatic–when there is significant myometrial penetration, spread to pelvic or para-aortic lymph nodes
transtubally–via exfoliated cells, to the ovaries, parietal peritoneum, and omentum
hematogenous–less frequent, can result in mets to liver, lungs, bones
what is the most common type of endometrial cancer
endometroid adenocarcinoma (75-80%)
what are the other (non endometroid) types of endometrial cancer
mucinous carcinoma (5%)
clear cell carcinoma (5%)
papillary serous carcinomas (4%)
squamous carcinomas (1%)
these types tend to be more aggressive
what does invasive adenocarcinoma usually result from
proliferation of the glandular cells of the endometrium in a back-to-back fashion without intervening stroma
what is the most important prognostic factor for endometrial carcinoma
histologic grade
poorly differentiated tumours have a higher grade and a higher percentage of solid (non glandular) growth –> have a poorer prognosis due to likelihood of proliferation outside of the uterus
histologic type of the carcinoma also affects prognosis
define grade 1 endometrial cancer
5% or less of the tumour shows a solid growth pattern –> highly differentiated
define grade 2 endometrial cancer
6-50% of the tumour shows solid growth pattern–> moderately differentiated
define grade 3 endometrial cancer
more than 50% of the tumour shows a solid growth pattern–> poorly differentiated
list the major independent risk factors for endometrial cancer
age depth of myometrial invasion histologic grade histologic type surgical stage peritoneal cytology tumour size lymphovascular invasion pelvic lymph node mets
what age group is most likely to get endometrial cancer
post menopausal women (75% versus 25% in premenopausal)
what is the average age of dx of endometrial cancer
61–largest affected group is between 50-59
what % of women who receive estrogen replacement therapy without progesterone will develop endometrial hyperplasia within a year?
20-50%
what is tamoxifen
a selective estrogen receptor modulator (SERM)–can act as a source of exogenous estrogen
works to block estrogen stimulation of breast tissue in women with estrogen-progesterone sensitive breast cancer
BUT in endometrium, it acts as a partial agonist/weak estrogen to stimulate endometrial proliferation
why is obesity a risk factor for endometrial cancer
increased endogenous estrogen due to peripheral conversion of androgens to estrone and estradiol in adipocytes
also have lower sex hormone binding globulin levels
many are anovulatory
why do women with PCOS have higher risk for endometrial cancer
chronic anovulation/PCOS typically have more central obesity and therefore more estrogens
also have relative lack of progesterone in luteal phase due to anovulatory cycles
(may also explain higher rates of endometrial cancer in nulliparous women)
why are DM and HTN independent risk factors for endometrial cancer
possible the presence of hyperinsulinemia, insulin resistance and insulin-like growth factors may lead to abnormal endometrial proliferation
what is a syndrome that is assoc with increased risk of endometrial cancer
lynch II syndrome in the family
what is Lynch II syndrome
herediatary nonpolyposis colorectal cancer (HNPCC)
genetic predisposition to breast, ovarian, colon and endometrial cancers
specific germline gene mutations are responsible for the cancers in the majority of these women
what is the risk of endometrial cancer in simple endometrial hyperplasia without atypia
1% if untreated
what is the risk of endometrial cancer in complex endometrial hyperplasia with atypia
29% if untreated
are there any effective screening mechanisms for endometrial cancer
no
what are some protective factors for endometrial cancer
those that decrease lifetime estrogen exposure
combined OCPs
progestin containing contraceptives
combo estrogen-progesteron hormone replacement
high parity
pregnancy
physical activity
smoking (increased hepatic metabolism of estrogen)
is smoking a risk factor for endometrial cancer
no its actually protective as it increases hepatic metabolism of estrogen
how protective is exercise for endometrial cancer
women who exercise have a one half risk of endometrial cancer compared to those who dont
are there any identifiable risk factors for type II endometrial cancer
no
classic history for endometrial cancer
90% have either postmenopausal vaginal bleeding or some form of abnormal vaginal bleeding (menorrhagia, postcoital spotting, intermenstrual bleeding)
10% may present with bloody vaginal discharge
these are EARLY symptoms
pelvic pain, mass and weight loss are seen in women with more advanced disease
classic physical exam for endometrial cancer
obesity acanthosis nigricans HTN stigmata of DM (pleural effusion, ascites, hepatosplenomegaly, general LAD, abdo masses) typically normal pelvic exam
in more advanced stages, cervical os may be patulous, cervix may be firm and expanded
uterus may be or normal size or enlarged
adnexae should be carefully examined for evidence of extrauterine mets
ddx for premenopausal abnormal uterine bleeding
uterine fibroids endometrial polyps adenomyosis endometrial hyperplasia ovarian cysts thyroid dysfunction (endometrial cancer)
ddx for postmenopausal abnormal uterine bleeding
endometrial atrophy (60-80%)
exogenous estrogens/HRT (15-25%)
endometrial cancer (10-15%) –> the older the patient and the more years since menopause, the higher the likelihood of malignancy (amount of bleeding does not correlate with risk of malignancy)
endometrial or cervical polyps (2-12%)
endometrial hyperplasia (5-10%)
other (10%)
what is the diagnostic method of choice for evaluating irregular bleeding
office endometrial biopsy (EMB)–> has an accuracy of 90-98% without the need for anesthesia and operative time (was previously D&C)
what test can you use to evaluate postmenopausal bleeding
transvaginal US–> can distinguish between suspicious lesions and atrophy (most common source of bleeding)
what endometrial thickness is suggestive of low risk of malignancy
4mm or less–> do not require EMB unless bleeding is persistent ot recurrent or they are at high risk for malignancy
what do you do if there are suspicious findings on EMB
D&C
what is the initial workup for a patient with abnormal bleeding beyond biopsy?
TSH
prolactin level (if oligomenorrheic)
FSH and estradiol (to see if menopausal)
CBC (rule out anemia preop)
CA-125 level–> if very high, suggestive of spread beyond uterus–> can follow post op to assess success of tx
up to date pap
pelvic US to look for polyps, fibroids, adenomyosis, endometrial hyperplasia
what % of women with HNPCC will develop endometrial cancer before colon cancer
50%–thus should have yearly EMB beginning at age 35
what is the treatment for stage I and II endometrial cancer
total abdominal hysterectomy and bilateral salpingo-oophrectomy (TAH-BSO), pelvic washings, pelvic and para-aortic lymph node resection and complete resection of visible tumour for all stages –> “complete surgical staging”
exceptions: young women with grade 1 endometroid ca who desire future fertility or women with high mortality risk with surgery
may require radiation therapy in addition if there are poor prognostic factors
treatment for stage III and IV endometrial cancer
when has spread to uterine serosa or beyond, patients also require pelvic radiation
define stage I endometrial cancer
Ia–> Ic ranges from limited to endometrium with no myometrial involvement to invasion greater than one half of myometrium
define stage II endometrial cancer
IIa–> spread to endocervical glands only
IIb–> spread to cervical stroma
define stage III endometrial cancer
ranges from tumor invades serosa and/or positive peritoneal cytology to positive para-aortic/pelvic nodes
define stage IV endometrial cancer
tumor invasion of bladder or bowel mucosa//distant mets
what is the overall 5 year survival of endometrial cancer
65%
87% stage 1–> 18% stage IV
what are the high risk features for endometrial cancer
more than 50% myometrial involvement
papillary serous or clear cell
grade 3
large (over 2 cm or filling cavity)
spread beyond uterine fundus
lymph involvement
follow up for endometrial cancer
physical (rectovaginal and speculum) every three months for three years followd by biannual for subsequent 2 years—annually after that if all normal
risk of recurrence greatest in first three years
treatment for recurrent endometrial cancer
radiation
chemo
high grade progestin therapy
