CC#5: Management of Endometrial Intraepithelial Neoplasia or Atypical Endometrial Hyperplasia Flashcards

1
Q

Why is EIN clinically significant?

A

Precursor lesion to endometrial adenocarcinoma

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2
Q

Two-tiered classification system for endometrial hyperplasia

A

1) Hyperplasia w/o atypia (benign endometrial hyperplasia)
2) EIN-AEH

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3
Q

Essential histologic criteria for EIN-AEH (2)

A

Crowded glandular architecture, altered epithelial cytology distinct from surrounding endometrium and/or entrapped neoplastic glands

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4
Q

Desirable IHC criteria for EIN-AEH

A

Loss of immunoreactivity for PTEN/PAX2/MMR proteins

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5
Q

What does unopposed estrogenic stimulation lead to at level of endometrium?

A

Proliferative glandular epithelial changes/hyperplasia

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6
Q

Is benign hyperplasia a precursor to EIN-AEH/endometrial adenocarcinoma?

A

No, they are biologically distinct

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7
Q

What type of cancer is EIN-AEH a precursor lesion to?

A

Type I endometrial adenocarcinoma

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8
Q

Mortality risk among Black pts w/ endometrial cancer compared to White pts w/ endometrial cancer

A

55% higher 5-year mortality risk

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9
Q

One reason that Black individuals have higher mortality rate w/ endometrial cancer

A

More likely to be diagnosed w/ nonendometrioid (aggressive) histologies, though this alone does not account for mortality disparities

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10
Q

Difference between Asian/Pacific Islander pts compared to White pts regarding endometrial cancer presentation

A

Asian/Pacific Islanders more likely to present w/ advanced disease

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11
Q

What percentage of pts diagnosed with/ EIN-AEH who undergo hyst will have endometrial cancer in the hyst specimen?

A

~30-50%

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12
Q

What must be done if fertility-sparing tx is pursued for EIN-AEH?

A

Underlying/Occult endometrial cancer must be excluded via hysteroscopic uterine sampling

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13
Q

Primary objective in management of pt w/ EIN-AEH (2)

A

R/o endometrial cancer, design tx plan that can prevent/delay progression to endometrial cancer

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14
Q

Risk per year of EIN-AEH progressing to endometrial cancer

A

~8% per year

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15
Q

Advantages of hyst for tx of EIN-AEH (2)

A

Definitive assessment for poss concurrent carcinoma, effective tx of premalignant lesions that require no further therapy or f/u for EIN-AEH

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16
Q

Factors to consider when deciding on concomitant oophorectomy in premenopausal pts (2)

A

Risk of underlying endometrial cancer, risk of surgical menopause

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17
Q

Is supracervical hyst appropriate in tx of EIN-AEH, why or why not?

A

No, 2/2 inability to assess lowest extent of lesions (which may involve LUS/upper endocervix)

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18
Q

Intraop consideration when performing hyst for EIN-AEH

A

Intraop path assessment for occult carcinoma, as detection may require additional surgical management

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19
Q

How should morcellation be performed if EIN-AEH (if needed)?

A

Within contained environment (ie surgical bag) to prevent spillage

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20
Q

Downside of morcellation for EIN-AEH

A

Will likely make path interpretation more difficult

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21
Q

Is endometrial ablation appropriate tx for EIN-AEH?

A

No

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22
Q

Percentage of pts w/ EIN-AEH or grade 1 adenocarcinoma that demonstrated initial response to progestins; percentage of pts that demonstrated complete response (resolution) of EIN-AEH

A

86%; 66%

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23
Q

Overall rates of EIN-AEH disease regression shown w/ progestin therapy

A

50-90%

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24
Q

Routes of progesterone administration available (3)

A

PO, IU, combined

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25
Q

Is continuous PO progestin therapy more effective than cyclical therapy?

A

Yes

26
Q

Adverse effect more likely w/ IU progestin methods; adverse effect more likely w/ PO progestin methods

A

VB; nausea

27
Q

Recommended LNG-IUD device for management of EIN-AEH; delivery rate of this device

A

52-mg device; 20mcg/day

28
Q

Progestational agent options for tx of EIN-AEH (4)

A

Megestrol acetate, medroxyprogesterone acetate, LNG-IUD, LNG-IUD + PO progestin

29
Q

Which progestational tx method has higher regression rate?

A

LNG-IUD (though continuous PO progestins have been shown to be nearly as effective as LNG-IUD)

30
Q

Regression rate seen w/ combined IU and PO progestins; regression rate seen w/ LNG-IUD alone

A

85%; 55%

31
Q

Clinical benefits of LNG-IUD over PO progestins (3)

A

Lower rates of adverse events, higher rates of pt adherence, improved pt-reported health status scores (ie physical functioning, energy levels) over time

32
Q

Recommended surveillance following total hyst w/o coexisting endometrial carcinoma

A

Not recommended, as surgery eliminates risk of disease progression

33
Q

When is histologic reassessment recommended if EIN-AEH managed w/ progestational agents?

A

3-6 months

34
Q

Poss outcomes seen on repeat endometrial sampling (4)

A

Resolution (complete response), regression, persistence, progression

35
Q

Definition of resolution on repeat endometrial sampling

A

Atrophic/Secretory/ Proliferative endometrium w/o hyperplasia

36
Q

Definition of regression on repeat endometrial sampling

A

Hyperplasia, but w/o atypia

37
Q

Definition of persistence on repeat endometrial sampling

A

No change in histology at time of sampling

38
Q

Definition of progression on repeat endometrial sampling

A

Cancer

39
Q

Next step if no response or some regression during initial 3-6 months of progestin therapy

A

Consider additional 3-6 months of therapy

40
Q

Next step if no response after 9-12 months of progestin therapy

A

Consider other management options (ie surgery)

41
Q

Median time to complete resolution in pts w/ EIN-AEH managing w/ progestational agents

A

6 months (w/ range of 1 month to 18 months)

42
Q

Factor associated w/ lack of response after 3 months of progestin tx

A

Failure to detect exogenous progesterone effect

43
Q

Factor associated w/ nonresponse after 6 months of tx w/ LNG-IUD

A

Increased uterine diameter

44
Q

Can repeat endometrial sampling be performed w/ IUD in place?

A

Yes

45
Q

Method w/ some initial benefit demonstrated in predicting relapse after progestin therapy

A

Pre-tx hormone receptor expression (PR-A and PR-B) testing

46
Q

Frequency/Duration for which repeat endometrial sampling should occur in pts using progestational agents

A

q3-6 months x2 years

47
Q

Is recurrence rate of EIN-AEH elevated after initial response to progestational agents?

A

Yes

48
Q

Recurrence rate for pts w/ EIN-AEH treated w/ progestational agents; median time to recurrence

A

~23%; 24 months

49
Q

When can surveillance biopsies be discontinued in pts being treated w/ progestational agents?

A

After 2 years in pts w/o evidence of persistent/ recurrent/progressive disease and if asymptomatic w/o VB

50
Q

When should therapy be continued long-term in pts being treated w/ progestational agents?

A

Pts who remain at risk for development of endometrial cancer

51
Q

Risk factors for endometrial cancer (8)

A

Increasing age, late menopause, nulliparity, chronic anovulation, high-risk genetic conditions (ie Lynch syndrome, Cowden syndrome), use of unopposed estrogen therapy, obesity, T2DM

52
Q

Risk of progression from EIN-AEH to carcinoma among pts receiving Megace tx through 4 years; cumulative risk of progression at 19 years after index bx

A

8.2%; 27.5%

53
Q

Pregnancy rates among premenopausal pts w/ EIN-AEH managed w/ progestational agents

A

26-3-41.0%

54
Q

Live-birth rate among EIN-AEH pts using ART; live-birth rate among EIN-AEH pts attempting spontaneous pregnancy

A

39.4%; 14.9%

55
Q

Is IVF s/p fertility-sparing management of EIN-AEH or grade 1 endometrial adenocarcinoma associated w/ increased risk of recurrence?

A

No

56
Q

Referral to consider in EIN-AEH pts interested in pregnancy

A

REI, as many pts also have conditions that can adversely affect fertility (ie PCOS, obesity, DM)

57
Q

Percentage of endometrial cancer survivors who have obesity

A

> 75%

58
Q

Lifestyle modification found to have positive effects on health outcomes, including endometrial cancer risk

A

Weight loss of 7-10% of TBW

59
Q

Referral to consider for obese pts w/ endometrial hyperplasia

A

Bariatric surgery

60
Q

Positive outcome associated w/ >10% weight loss from TBW

A

Such pts nearly 4x more likely to respond to LNG-IUD