Pathology Of The Uterus

Front 1

Histology and hormones of days 1-5

Back 1

progesterone drops. Functionalis layer degenerates/sheds. Bleeding into stroma (fibrin, RBC's, inflammatory cells). Stromal breakdown.

Front 2

Day 5-Day 14 is called the ____________.

Back 2

Proliferative phase (estrogenic)

Front 3

Proliferative phase--what happens

Back 3

Rapid growth of glands and stroma from deeper basalis-->new functionalis.

Front 4

Proliferative phase histology

Back 4

glands are straight, tubular structures

regular tall, pseudostratified columnar cells w/ basal nuclei

No mucus secretion or vacuolization.

Numerous mitotic figures in glands and stroma

Front 5

When does proliferative phase end?

Back 5

Ovulation (Day 14)

Front 6

Secretory phase (luteal phase) marked by which hormone?

Back 6

progesterone (made by corpus luteum in the ovary)

Front 7

Early secretory phase:

Back 7

secretory subnuclear vacuoles (day 16-17)

Front 8

What happens days 18-24

Back 8

glands dilate--maximum secretion

Front 9

What would you see week 4?

Back 9

Tortuous and serrated or "saw-toothed" glands (due to secretory exhaustion & gland shrinkage)

Front 10

What happens to the vacuoles during week 3 of the cycle? (still early secretory phase)

Back 10

subnuclear vacuoles migrate and become supranuclear

Front 11

What happens in the late secretory phase?

Back 11

stromal changes. Prominent spiral arterioles. Increased edema.

Front 12

What happens day 23-24

Back 12

predicidual change: stromal cell hypertrophy, increased cytoplasmic eosinophilia, and resurgance of stromal mitoses

Front 13

Decidualized cells are high in glycogen and lipid (why?)

Back 13

early nutrient supply for the blastocyst and developing fetus

Front 14

Abnormal uterine bleeding definition

Back 14

Uterine bleeding that lacks an underlying organic (structural) abnormality

Front 15

AUB most commonly stems from what?

Back 15

hormonal disturbance

(hypothalamic/pituitary/ovarian axis)

Front 16

What is the most common cause of AUB?

Back 16

anovulatory cycle

Front 17

Anovulatory cycle occurs in which ages?

Back 17

adolescence, reproductive age, perimenopausal

Front 18

Why does anovulatory cycle cause bleeding?

Back 18

Failure of ovulation results in excessive endometrial stimulation by estrogens that is unopposed by progesterone

Front 19

I which ages would anatomic lesions (carcinoma, hyperplasia, and polyps) be most common?

Back 19

perimenopausal and postmenopausal. (reproductive age possible but less likely)

Front 20

What are the 3 most common causes of anovulatory cycle?

Back 20

Generalized metabolic probs: obesity, malnutrition, other chronic dz

Endocrine: thyroid, adrenal, pituitary

Ovarian lesions: functioning tumors, PCOS

Front 21

Obesity causes what hormone state?

Back 21

hyperestrogenic

Front 22

What would not be present on endometrial biopsy of somebody with anovulatory cycle?

Back 22

No subnuclear or supranuclear vacuoles because no secretory phase (progesterone driven) ex: day 22 may look like proliferative phase

Front 23

Young pt w/ infertility, increased irregular bleeding & sometimes amenorrhea). You notice inadequate progesterone during post-ovulatory period. EMB shows secretory endometrium that doesnt correspond with cycle day. Diagnosis?

Back 23

Inadequate Luteal Phase

Front 24

When would you see acute endometritis?

Back 24

After deivery/abortion/miscarriage. (Retained products of conception (POC) is substrate for infection--nutritious!)

Front 25

What are the most common infectious agents of acute endometritis?

Back 25

Group A hemolytic streptococci, staphylococci, others. Give abx & curettage

Front 26

Which is more common, chronic or acute endometritis?

Back 26

Chronic

Front 27

When does chronic endometritis occur?

Back 27

Chronic PID

retained gestational tissue

IUD

TB

Front 28

How can pelvic TB present? (hint: 3rd world countries have way higher rates)

Back 28

Both fallopian tubes involved

Tuberculous endometritis=50%

Tuberculosis of cervix= 5%

Ovaries=only surface involvement

Front 29

Do women with genital tuberculosis have TB elsewhere? (ex: lungs)

Back 29

yes. 38%

Front 30

Pt presents w/ abnormal bleeding, pain, discharge. You note an infection and diagnose chronic endometritis. Which organism?

Back 30

Chlamydia (ascending infection)

15% of cases show no apparent cause

Front 31

How do you diagnosis chronic endometritis histologically?

Back 31

plasma cells: cells w/ perinuclear hoth or clearing

Front 32

Endometriosis definition

Back 32

ectopic endometrial tissue outside of the uterus

Front 33

Adenomyosis definition

Back 33

endometrial tissue w/in myometrium (2-3mm below the basalis layer)

Front 34

What patient population shows endometriosis?

Back 34

reproductive age, 3rd & 4th decade

6-10% of women affected

Front 35

Most common sites of endometriosis (3)

Back 35

1. Ovaries

2. Uterine ligaments

3. Rectovaginal septum (GI sx)

Front 36

Endometriosis on ovary. Theory?

Back 36

Regurgitation theory

Front 37

Endometriosis in amenorrhea. Theory?

Back 37

Metaplastic theory (in pelvis or abdomen)

Front 38

Endometriosis in men on hormones for prostate cancer. Theory?

Back 38

Stem cell theory

Front 39

Endometriosis in brain, lung, bone. Theory?

Back 39

Benign metastasis theory

Front 40

Do ectopic endometrium and intrauterine endometrium have the same requirements?

Back 40

No. ectopic needs more estrogen & a new blood supply (VEGF) & proinflammatory components (PGE2)

Front 41

How does ectopic endometrium get the increased estrogen needed?

Back 41

High levels of aromatase from stroma

Epigenetic alterations increase response to estrogen & decrease response to progesterone

Front 42

The proinflammatory portion of endometriosis is associated w/ what?

Back 42

scarring, PID, ultimately infertility

Fibrous adhesions (bowel obstruction)

Front 43

Red/blue to yellow/brown nodules on or beneath the mucosa or serosa (powder burn marks) seen in?

Back 43

Endometriosis

Front 44

Ovarian endometriosis (common) presents as

Back 44

cysts filled w/ brown fluid-->chocolate cyst AKA endometrioma. ovaries can look distorted and cystic

Front 45

Cancer risk w/ ovarian endometriosis?

Back 45

Lining can be atypical--increased risk of cancer.

3 fold increased risk of ovarian cancer of the endometroid and clear cell types

Front 46

Shared mutations in genes (__________ and ___________) in endometriotic cysts, atypical ndometriosis, and associated carcinomas.

Back 46

PTEN

ARID1A

Front 47

Common presenting complaints w/ endometriosis?

Back 47

Pelvic pain & Infertility

Front 48

What populations are at risk for endometrial polyps?

Back 48

Reproductive age, perimenopausal, postmenopausal

Front 49

Sessile or pedunculated exophytic masses of varying size presenting in a patient w/ abnormal uterine bleeding

Back 49

Endometrial polyps

Front 50

Endometrial polyps are associated w/ which drug?

Back 50

Tamoxifen (estrogen blocker) used in breast cancers (has a pro-estrogenic effect in the endometrium)

Front 51

What's the greatest risk of an endometrial polyp?

Back 51

May become malignant-->adenocarcinoma

can present looking like a miscarriage when passed

Front 52

Perimenopausal or postmenopausal woman w/ AUB, first differential should be what?

Back 52

Endometrial hyperplasia

Front 53

What is of greatest concern concerning endometrial hyperplasia?

Back 53

progression to adenocarcinoma

Front 54

How is endometrial hyperplasia diagnoses histologically?

Back 54

Increased glands: stroma ratio compared to normal proliferative endometrium

Front 55

What causes endometrial hyperplasia?

Back 55

Excessive estrogenic states including:

Obesity, menopause, PCOS, functioning granulosa cell tumors of ovary, excessive ovarian cortical function (cortical stromal hyperplasia), exogenous estrogen therapy

Front 56

Perimenopausal patient w/ AUB. Markedly increased gland: stroma ratio on biopsy w/ an ovarian mass. Most likely Dx?

Back 56

Functioning granulosa cell tumors of the ovary (increased estrogen production)

Front 57

What is the tumor suppressor gene found to be inactivated in both endometrial hyperplasia & endometrial cancer?

Back 57

PTEN ( Phosphate & tensin homologue)

Front 58

Pt w/ benign cutaneous tumors along w/ endometrial & breast cancer. Dx? What would you see on molecular study?

Back 58

Answer: Cowden syndrome

Inactivation of PTEN

Front 59

What happens w/ loss of PTEN?

Back 59

Overactivation of the PI3K/AKT pathway.

Stimulates estrogen dependent gene expression. Upregulates estrogen reception in endometrium & breast

Front 60

What are the classifications of endometrial hyperplasia?

Back 60

Non-atypical hyperplasia

Atypical hyperplasia (endometrial intraepithelial neoplasia)

Front 61

What is the histologic & clinical picture of non-atypical endometrial hyperplasia?

Back 61

Increased gland-stroma ratio (>50:50)

Can be back to back glands, but usually intervening stroma remains.

Rarely progresses to cancer (1-3%)

Front 62

What happens in non-atypical hyperplasia post menopause?

Back 62

Since estrogen is withdrawn, it evolves into cystic atrophy

Front 63

How does atypical hyperplasia (EIN) present histologically and clinically?

Back 63

complex patterns of proliferating glands displaying nuclear atypia.

glands back to back and branching.

Nucleolus***

Looks like well differentiated cancer

Front 64

How to treat reproductive age women w/ endometrial hyperplasia?

Back 64

Give progesterone. If doesn't want kids then hysterectomy

Front 65

Most common invasive cancer of the female genital tract?

Back 65

Endometrial Carcinoma

Front 66

What is the patient picture of endometrial carcinoma? (Note: there is type 1 & 2)

Back 66

Peak age 55-65 (postmenopausal) <40 uncommon. Bleeding earliest sign.

Front 67

Ages for Type I and Type II endometrial carcinomas

Back 67

T1: 55-65

T2: 65-75

Front 68

Which is more common T1 or T2 endometrial carcinoma?

Back 68

Type 1 (80%)

Front 69

Which type of endometrial cancer is well differentiated and can mimic proliferative endometrial glands?

Back 69

Endometroid carcinoma (assoc w/ T1)

Front 70

Which type of endometrial carcinoma arises in the setting of hyperplasia?

Back 70

Type 1

Front 71

Which type of endometrial carcinoma arises w/ obesity, hypertension, & diabetes?

Back 71

Type 1

Front 72

What are the mutations seen in type 1 endometrial carcinoma?

Back 72

PTEN

DNA MMR defects in 20% (MLH1)

KRAS

LOF in ARID1A

TP53 only in poorly differentiated

Front 73

What molecular finding could you expect in a pt w/ T1 endometrial carcinoma and HNPCC?

Back 73

DNA MMR defects

Also called lynch syndrome

Front 74

ARID1A, PIK3CA, CTNNB1, and FGFR2 may effect which quality of the neoplasm?

Back 74

They may be responsible for invasion

Front 75

3 histologic grades for endometroid carcinoma.

Back 75

1: well differentiated. Almost entirely well formed glands

2. Moderately diff: features of both

3. Poorly diff: 50% solid pattern

Front 76

Type 2 (serous) endometrial carcinoma is seen in which patients mainly?

Back 76

African Americans aged 65-75 years old

Front 77

Which type of endometrial carcinoma arises in the setting of endometrial atrophy and is poorly differentiated?

Back 77

Type 2

Front 78

Other than serous, what are the additional types of Type 2 endometrial carcinoma?

Back 78

Clear cell, Mixed Mullerian tumor (aka carcinosarcoma)

Front 79

What are the mutations associated w/ T2 endometrial carcinoma?

Back 79

TP53 (90% of serous carcinomas)

PI3K

PP2A

Front 80

Which type of endometrial carcinoma is usualy associated w/ no glands, but rather papillary structures w/ marked cytologic atypia.

Back 80

Type 2

Front 81

What is the precursor lesion for type 2 endometrial carcinoma?

Back 81

Serous EIN (endometrial intraepithelial neoplasm) stains w/ p53

Front 82

Which type of endometrial carcinoma has a propensity for extrauterine spread (via lymphatics or tubes)

Back 82

Type 2

Front 83

Which population has 2x mortality w/ T2 endometrial carcinoma?

Back 83

African American women

Front 84

Stage 1-Stage 4

Back 84

1. in corpus uteri

2. corpus + cervix

3. outside uterus

4. outside pelvis or + rectum/bladder

Front 85

What is carcinosarcoma?

Back 85

Malignant mixed mullerian tumor (MMMT) made of malignant glandular and mesenchymal elements

Front 86

Mutations seen in MMMT?

Back 86

Same as others. TP53, PTEN, PIK3CA.

NOTHING SPECIFIC

Front 87

What is a tumor showing stromal sarcoma or leiomyosarcoma(mesenchymal) + bone, fat, muscle, cartilage(sarcomatous)?

Back 87

MMMT (malignant glands AND stroma)

Front 88

Older Woman w/ postmenopausal bleeding. bulky polypoid mass w/ EMB showing adenocarcinoma mixed w/ malignant mesenchymal elements. Metastasis is noted but contains only the epithelial components. Dx & signs of worse prog?

Back 88

MMMT. Invasion & heterologous components=worse outcome.

Front 89

Endometrial stroma tumors are common/rare?

Back 89

Rare (5% of endometrial cancers)

Front 90

Adenosarcoma

Back 90

benign glands & malignant stroma

Front 91

Pure stromal tumors

Back 91

Just malignant stroma. stromal nodule vs stromal sarcoma

Front 92

Malignant glands benign stroma

Back 92

Endometrial cancer

Front 93

FYI. Younger pt (30-50), polypoid mass can protrude through os. Low grade. HIgh recurrence

Back 93

Adenosarcoma

Front 94

Which fusion genes seen in low grade stromal sarcoma?

Back 94

JAZF1 and SUZ12

Front 95

What is the risk w/ stromal sarcomas?

Back 95

50% recur

Distant mets decades later

Front 96

What is the main tumor of the myometrium?

Back 96

Leiomyoma (fibroids) 70% of women.

Single or multiple

Front 97

Both benign (leiomyomas) and malignant (leimyosarcomas) present w/ which gene mutations?

Back 97

HMGIC & HMGIY

MED12 (uncontrolled division)

Front 98

Gross features of leiomyoma

Back 98

Well circumscribed. Firm white-gray mass.

Front 99

Where would a leiomyoma cause abnormal intrauterine bleeding?

Back 99

Leiomyoma located below the endometrium

Front 100

Microscopic features of leiomyoma

Back 100

bundles of smooth muscle cells (whorled)

uniform size/shape of cells

***RARE MITOSIS

can degenerate

Front 101

Most common presentation of leiomyoma

Back 101

uterine bleeding, infertility, spontaneous abortion, breech delivery, uterine inertia

Front 102

Disseminated peritoneal leiomyomatosis

Back 102

multiple small peritoneal nodules from pedunculated leiomyoma that broke free

Front 103

Lymphangioleiomyomatosis

Back 103

Associated w/ lung disease & tuberous sclerosis (TSC2)-->pulmonary dz. Don't confuse w/ repro

Front 104

Where can leiomyomas be mitotically active?

Back 104

young or pregnant patients

Front 105

Leiomyosarcoma presentation & risk

Back 105

uncommon. (peak 40-60)

more than half metastasize

if >10cm then assume leiomyosarcoma

Front 106

Key histological features of leiomyosarcoma?

Back 106

Nuclear atypia

***Mitotic index (10 or >/10hpf=malignant)

**Zonal necrosis

Front 107

Most common place of metastasis?

Back 107

lung-->d/t venous drainage