Endometrium Pathology

Question 1

Describe how the endometrium is affected by the menstrual cycle

Answer 1

Endometrial growth in the functional layer is stimulated during the follicular phase of the menstrual cycle by estrogen (via LH) and then by porgesterone from the corpus luteum in the luteal phase of the menstrual cycle. If not fertilization occurs, the functional layer loses its stimulation from the CL and is sloguhed off during menses. Note that the basal layer of the endometrium remains in tact during menses

Question 2

Describe the layers of the uterus as seen below

Answer 2

The body of the uterus is composed of three layers, the inner most endometrium (which is sloughed during menses), the muscular myometrium, and the outer perimetrium. Circled in this picture is the basal layer of the endometrium

Question 3

What does the endometrium look like during the proliferative phase of the menstrual cycle

Answer 3

The glands are round, proliferative, and contain mitotic figures (not curly)

Question 4

What does the endometrium look like during the secretory phase of menstruation?

Answer 4

In the early phase, secretions inside the glands start to be seen and they become corkscrew shaped and sub-nuclei vacoules that eventually secrete into the lumen of the glands

Question 5

What does the endometrium look like during the menses phase of menstruation?

Answer 5

Tissue begins to almost ball up to be sloughed and hemorrhage can be seen

Question 6

What are the common causes of dysfunctional uterine bleeding (bleeding from the uterus in the absence of an organic uterine lesion) in pre-pubertal children?

Answer 6

precocious puberty

Question 7

What are the common causes of dysfunctional uterine bleeding in adolescence?

Answer 7

Anovulatory cycle, coag disorders

Question 8

What are the common causes of dysfunctional uterine bleeding in reproductive age women?

Answer 8

complications of pregnancy (abortion, ectopic preg)

Anatomic lesiosn (leiomyoma, endometrial hyperplasia, carcinoma)

Anovulatory cycle

Ovulatory dysfunctional bleeding (e.g. inadequate luteal phase)

Question 9

What are the common causes of dysfunctional uterine bleeding in peri-menopausal women?

Answer 9

anovulatory cycle

Anatomic tumors/lesions

Question 10

Why would an anovulatory cycle be associated with bleeding?

Answer 10

Failure to ovulate leads to unopposed estrogenic stimulation of the endometrium with low progesterone which causes it to overproliferate and dilate and eventually the top layer breaks down and sheds. The endometrial glands may develop cystic changes and appear disorderly, while the endometrial stroma may be scarce (b/c it requires progesterone to grow)

Biopsy will read as a “disordered proliferative pattern with shedding’

Question 11

Anovulatory cycles result from subtle hormonal imbalances and are most common when?

Answer 11

at menarche and in the perimenopausal period.

Question 12

Less commonly, anovulation is the result of:

Answer 12

• Endocrine disorders , such as thyroid disease, adrenal disease, or pituitary tumors
• Ovarian lesions , such as a functioning ovarian tumor (granulosa cell tumors) or polycystic ovaries
• Generalized metabolic disturbances , such as obesity, malnutrition, or other chronic systemic diseases

Question 13

What is this?

Answer 13

Endometrial polyps are localized overgrowth of endometrial glands and stroma that present as a pedunculated mass typically as a result of unopposed estrogen. These typically dont turn malignant

Question 14

Patients taking ______ are more likely to get endometrial polyps

Answer 14

tamoxifen (because tamoxifen has weak pro-estrogenic effects in the endometrium.). Hormone replacement and obesity can also increase the risk

Question 15

T or F. Most endometrial polyps are unresponsive to progesterone

Answer 15

T. A few are hyperfunctional

Question 16

Question 17

POC= product of conception (below- chorionic villi)

Question 18

Look for plasma cells!!

Answer 18

Infection with an IUD, think actinomyces

Question 19

What is Endometriosis?

Answer 19

the presence of endometrial glands and stroma outside the endomyometrium. It occurs in as many as 10% of women in their reproductive yrs and nearly 50% of women with infertility

Question 20

Where is endometriosis most commonly seen?

Answer 20

Most often pelvic structures (ovaries, pouch of Douglas, uterine ligaments) and less frequently distant areas of the periotoneal cavity and rarely even lungs, heart, and bone.

Question 21

What causes endometriosis?

Question 22

Is the displaced endometrial tissue in endometriosis normal or abnormal?

Answer 22

Abnormal in the sence that it exhibits increased levels of inflammatory mediators, particularly prostalandin E2, and increased estrogen production due to higher aromatase activity. These factors enhance this tissue’s ability to survive outside the uterus and can explain the beneficial effects of COX-2 inhibitors and aromatase inhibitors in tx.

Question 23

When is adenomyosis?

Answer 23

the growth of the basal layer of the endometrium down into the myometrium between muscle bundles that commonly causes the myometrium to hypertrophy.

Question 24

How mihgt adenomyosis present?

Answer 24

May produce menorrhagia, dysmenorrhea, and pelvic pain before the onset of menses

Question 25

How does endometriosis presnet?

Answer 25

Extensive scarring of the oviducts and ovaries can often produce discomfort in the lower abdominal quadrants and eventually sterility. Rectal wall involvement can produce pain on defecation, or possible dysparenuria if the bladder is involved. Almost all cases involve dysmenorrhea

Question 26

T or F. In contrast with adenomyosis, endometriosis almost always contains functioning endometrium

Answer 26

T. So it undergoes cyclic bleeding. And becuase blood can collect in these abnormal areas, they usually appear grossly red. When the ovaries are involved, the lesions may form large, blood filled cysts that turn brown (Chocolate cysts) as the blood ages and possible even fibrosis if the blood organizes (possible sealing the ovarian tubes)

Question 27

What is menorrhagia?

Answer 27

profuse or prolonged bleeding at the time of a period

Question 28

What is metorrhagia?

Answer 28

irregular bleeding between periods

Question 29

What are the most common proliferative lesions of the uterine wall?

Answer 29

Endometrial hyperplasia

endometrial carcinoma

polyps

smooth muscle tumors

Question 30

What induces endometrial hyperplasia?

Answer 30

Typically a prolonged excess of estrogen relative to progestin can cause this to occur which is important because hyperplasia is a precursor of endometrial carcinoma!

Question 31

What are some potential causes of estrogen excess?

Answer 31

• Failure of ovulation (common in perimenopause)
• prolonged admin of estrogen
• estrogen producing ovarian lesions (such as polycystic ovary disease and grnaulosa-theca cell tumors of the ovary)
• obesity

Question 32

How is endometrial hyperplasia categorized?

Answer 32

Primarily by cellular crowding (simple vs. complex) and the presence or absence of cytologic atypia (which is more closely related to the risk of transformation to carcinoma)

Question 33

Endometrial hyperplasia (and the eventual transformation to carcinoma) is associated with what mutations?

Answer 33

PTEN tumor suppressor gene

Question 34

Answer 34

When you start to not see any stroma in between the glands (i.e. the glands are back-to-back, that is more suggestive of transformation to a carcinoma)

Question 35

Things to look for: cellular atypia is diagnosed via cytology and is characterized by high N/C ratio, appearance of nucleoli, loss of polarity, and course chromatin

Answer 35

Higher power to show atypia

Question 36

What is the most common tumor of the female genital tract?

Answer 36

endometrial carcinoma. This most commonly presents in post-menopausal women (around 60 yo) and needs to be considered if you see bleeding in postmenopausal women

Question 37

Endometrial carcinom includes what cancer types?

Answer 37

endometriod and serous carcinoma of the endometrium

Question 38

How do endometrioid cancers arise?

Answer 38

They arise in association with estrogen excess and endometrial hyperplasia in perimenopausal women (type I), whereas serous cancers arise in the setting of endometrial atrophy in older postmenopausal women (type II)

Question 39

Endometrioid cancers are the most common of the two. What are the risk factors?

Answer 39

obesity, diabetes, HTN, infertility, breast carcinoma, and exposure to unopposed estrogen (exogenous or from an ovarian carcinoma) (most lead to more estrogen causing endometrial hyperplasia)

Question 40

What mutations are common in endometriod cancers of the endometrium?

Answer 40

mutations in PTEN (Cowden syndrome is due to the germline mutation- can be spontaneous) and MSI

•***Defects involving DNA mismatch repair genes are found in about 20% of sporadic tumors and are particularly prevalent in endometrial carcinomas arising in women from families with hereditary nonpolyposis colorectal carcinoma (HNPCC-lynch syndrome)****

Question 41

What mutations are common in serous cancers of the endometrium?

Answer 41

TP53

Question 42

Which type of endometrial carcinoma is more aggressive?

Answer 42

serous are aggressive and tend to spread via lymph and intraperitoneal while endometriod are indolent (and also spread via lymph)

Question 43

Question 44

Question 45

What is leukorrhea?

Answer 45

a whitish or yellowish discharge of mucus from the vagina.

Question 46

How do endometrial carcinomas present?

Answer 46

usually with leukorrhea and irregular bleeding, often in postmenopausal women. With progression, the uterus can become affixed to surround tissue as the cancer spreads. These tumors are usually slow to met usually, however.

Question 47

What is the prognosis of endometrial carcinomas?

Answer 47

With therapy, the 5 yr survival is 90% in early-stage tumors

Question 48

Question 49

Look for the medusa head cellular appearance

Question 50

Both the glandular and stroma components are malignant

Question 51

Leiomyomas are aka?

Answer 51

fibrinoids because of their hardness

Question 52

When are leiomyomas common?

Answer 52

Mostly in reproductive age and more common in black women

Question 53

How do leiomyomas present?

Answer 53

They are often asymptomatic, being discovered incidentally on routine pelvic exam OR presenting with menorrhagia. Leiomyomas almost never transform into sacromas, and the presence of multiple lesions does not increase risk of malignancy

Question 54

Leiomyosarcomas

Answer 54

arise de novo from mesenchymal cells of the myometrium, not from preexisting leiomyomas. They are almost always solitary (leiomyomas are more often multiple) and most commmonly occur in post-menopausal women

Seeding of these tumors is very common!