LM 9.1: Endometrial/Uterine Cancers

Question 1

what is the most common gynecologic malignancy in the US?

Answer 1

endometrial cancer

typically in postmenopausal women

majority are diagnosed in early stages due to abnormal bleeding

Question 2

what are the types of endometrial carcinomas?

Answer 2

type 1 and type 2

type 1 risk factors are related to excess estrogen states –> excess unopposed estrogen leads to overgrowth of endometrium

type 2 isn’t associated with estrogen excess

Question 3

what are the risk factors for endometrial cancer?

Answer 3

1. older age
2. living in north america
3. higher level of education or income
4. white race
5. nulliparity
6. infertility
7. mensrual irregularities

Question 4

what is Lynch syndrome?

Answer 4

syndrome characterized by germline mutation of one of the mismatch repair genes

increased colon cancer, ovarian cancer, and type 1 endometrial cancer

AD

prophylactic hysterectomy with bilateral salpingo-oophorectomy is recommended when affected women reach 35 to 40 after childbearing is complete

Question 5

who should get genetic screening for Lynch syndrome?

Answer 5

patients with endometrial or colorectal cancer and tumor evidence of: 
1. microsatellite instability or

2. DNA mismatch repair protein loss

first-degree relative with endometrial or colorectal cancer who was diagnosed: 
1. before age 60 years or

2. is at risk for Lynch syndrome based on personal and medical history

Question 6

what is simple vs complex hyperplasia without atypic?

Answer 6

simple: glandular and stromal cell elements proliferate excessively –> glands are modestly crowded and typically display normal tubular shape or mild gland-shape abnormalities
complex: abnormal proliferation of primarily glandular elements – some specimens show architectural abnormalities such as papillary infolding

Question 7

what does simple and complex hyperplasia with atypia look like histologically?

Answer 7

simple: glands are only mildly crowded – occasional glands show nuclear atypia characterized by nuclear rounding and visible nucleoli
complex: glands are markedly crowded and some have papillary infoldings – nuclei show variable atypia

Question 8

what is the cancer risk associated with hyperplasia without atypia?

Answer 8

low chance of progression to cancer

may spontaneously regress without therapy

treatment is typically using synthetic progestins

Question 9

how do you treat hyperplasia without atypia?

Answer 9

treatment is typically using synthetic progestins which:

1. alter enzymatic pathways to convert estradiol into weaker estrogens
2. decrease number of estrogen receptors in endometrial glandular cells
3. stimulation of progesterone receptors leads to thinning of the endometrium and stromal decidualization

Question 10

what is hyperplasia with atypia?

Answer 10

aka endometrioid intraepithelial neoplasia

significant numbers of glandular elements

exhibit cytologic atypia and disordered maturation

precursor to endometrial adenocarcinoma

Question 11

how do you treat hyperplasia with atypia?

Answer 11

hysterectomy

can attempt high-dose progestin therapy for those wishing to preserve fertility and poor surgical candidates

Question 12

what are endometrial polyps?

Answer 12

focal, accentuated, benign hyperplastic process composed of endometrial glands, fibrous stroma, and surface epithelium

most common presenting symptom is abnormal bleeding

most frequently in perimenopausal or immediately postmenopausal women

malignant transformation occurs in approximately 5%

Question 13

what are the types of endometrial cancer?

Answer 13

1. endometriod adenocarcinoma

2. non-endometrioid adenocarcinoma

Question 14

what is endometriod adenocarcinoma?

Answer 14

type 1 endometrial cancer

endometrioid adenocarcinomas are composed of neoplastic glands resembling those of the normal endometrium

cells are typically tall columnar with mild to moderate nuclear atypia – they form glands that are abnormally crowded or “back-to-back”

gland cribriforming, confluence and villous structures with disappearance of intervening stroma distinguish well-differentiated endometrioid adenocarcinoma from complex hyperplasia

subtypes: endometrioid, endometrioid with squamous differentiation, villoglandular, secretory endometrioid

this is the most common type (80%)

“estrogen-dependent” risk factors

Question 15

what is non-endometriod adenocarcinoma?

Answer 15

type 2 endometrial cancer

subtypes: serous, clear cell, mucinous, squamous, transitional cell, menonephric, undifferentiated

high grade with poorer prognosis than type 1 cancer

“estrogen independent” risk factors

occurs spontaneously characteristically in thin, postmenopausal women with an atrophic endometrium rather than hyperplastic

Question 16

what do clear cell adenocarcinomas look like histologically?

Answer 16

type 2 endometrial cancer

composed of cells with clear to eosinophilic granular cytoplasm

cells are arranged in papillae, sheets, tubulocystic structures, or most often, some combination of these

eosinophilic hyaline globules are common

Question 17

what is a common presenting history that’s associated with endometrial cancer?

Answer 17

most (98%) patients come in with abnormal uterine bleeding

in more advanced disease, patient may have pelvic discomfort or pressure

between 5-20% of women found to have endometrial cancer are asymptomatic

Question 18

what pap smear result should make you worried about endometrial/cervical neoplasia?

Answer 18

atypical glandular cells found on Pap test carry higher risks for underlying cervical or endometrial neoplasia and requires further evaluation with colposcopy and endocervical curettage for endometrial sampling

Question 19

if someone is presenting with pelvic pain, when must you do an endometrial biopsy to rule out carcinoma?

Answer 19

1. patient is over 45
2. patient is under 45 but with risk factors

D&C with hysteroscopy and directed endometrial biopsy can be performed if outpatient endometrial biopsy is unable to be completed

transvaginal ultrasound may also be used as an adjunct for evaluating endometrial thickness and looking for polyps, leiomyomas, and structural abnormalities of the uterus

endometrial thickness of >4mm in postmenopausal patient is an indication for further evaluation with endometrial biopsy

Question 20

how does CA-125 levels play a role in endometrial cancer diagnosis and treatment?

Answer 20

pre-operative measurement of CA-125 level may be appropriate for assisting in predicting treatment response or in post-treatment surveillance but is not used for screening purposes

Question 21

what are the grades of endometrial cancer?

Answer 21

G1: well-differentiated adenomatous carcinoma

G2: moderately differentiated adenomatous carcinoma

G3: poorly differentiated or undifferentiated

Question 22

what are the stages of endometrial cancer?

Answer 22

I: tumor confined t the corpus uteri

IA: no or less than 1/2 myometrial invasion

IB: invasion equal to or more than half of the myometrium

II: tumor invades cervical stroma but does not extend beyond the uterus

II: local and/or regional spread of the tumor

IIIA: tumor invades the serosa of the corpus uteri and/or adnexae

IIIB: vaginal and/or parametrical involvement

IIIC: metastases to pelvic and/or paraaortic lymph nodes

IIIC1: positive pelvic nodes

IIIC2: positive paraaortic lymph nodes with or without positive pelvic lymph nodes

IV: tumor invasion of bladder and/or bowel mucosa and/or distant metastases

IVA: tumor invasion of bladder and/or bowel mucosa

IVB: distant metastases including intraabdominal metastases and/or inguinal lymph nodes

Question 23

what are the poor prognostic variables in endometrial cancer?

Answer 23

1. advanced surgical stage
2. older age
3. histologic type: UPSC or clear cell adenocarcinoma
4. advanced tumor grade
5. presence of myometrial invasion
6. presence of lymphovascular space invasion
7. peritoneal cytology positive for cancer cells
8. increased tumor size
9. high tumor expression levels of ER and PR

Question 24

how do you treat endometrial cancer?

Answer 24

hysterectomy with complete surgical staging including bilateral salpino-oophorectomy, lymph node dissection, and peritoneal washings

women wishing to preserve fertility with G1 endometroid adenocarcinoma may be treated with high dose progestin and monitoring with serial endometrial sampling

women who are poor surgical candidates may be treated with therapeutic radiation and continuous chronic progestin treatment or levonorgesterel-releasing IUD, though results are suboptimal.

Question 25

which patients are good candidates for conservative treatment of endometrial cancer?

Answer 25

1. a well-differentiated, grade 1, endometrioid endometrial carcinoma
2. no myometrial invasion
3. no extrauterine involvement (no synchronous ovarian tumor or metastases, no suspicious retroperitoneal nodes)
4. strong desire for fertility sparing
5. no contraindications for medical management
6. patient understands and accepts that data on cancer-related and pregnancy-related outcomes are limited (informed consent)

Question 26

when would you use postoperative radiation for endometrial cancer?

Answer 26

postoperative radiation is used for known metastatic disease, positive lymph nodes, and cases of recurrence

women with intraperitoneal disease are treated with surgery followed by chemotherapy, radiation, or both

Question 27

how do you do surveillance after treating endometrial cancer?

Answer 27

speculum and rectovaginal examinations every 3-4 months for 2-3 years then twice a year to detect recurrent disease, particularly in the vagina, for women who do not receive radiation therapy

serum CA-125 levels and CT or MRIs may be indicated for more advanced cancers that require radiation or chemotherapy

recurrent vaginal disease has better prognosis than pelvic recurrence

may respond to high-dose progestin therapy if estrogen-dependent cancer

Question 28

what is a uterine sarcoma?

Answer 28

sarcomas originate from the myometrium or stromal components of endometrium

these tumors are very aggressive and are more likely to spread hematogenously

symptoms include progressive uterine enlargement, abnormal uterine bleeding, pelvic pain, increase in unusual vaginal disease

rare gynecologic malignancy accounting for approximately 3% of all cancers involving body of uterus and 0.1% of all myomas

Question 29

how do you diagnose and treat uterine sarcomas?

Answer 29

diagnosis through surgical removal

treatment is hysterectomy with surgical staging

radiation and chemotherapy provide little survival advantage but can decrease recurrence rate