Pathology of the Uterus

Question 1

What is the endometrium?

Answer 1

• mucosal lining of the uterine cavity

* it is hormonally sensitive

Question 2

What is the myometrium?

Answer 2

• smooth muscle wall underlying the endometrium.

Question 3

What hormones are directly active on the endometrium?

Answer 3

• estrogen drives its growth (proliferative/follicular phase).
• progesterone drives preparation for implantation (secretory/luteal phase).
• withdrawal of progesterone causes shedding (menstrual phase).

Question 4

What is Asherman syndrome?

Answer 4

• secondary amenorrhea (lack of menstrual cycles) due to LOSS of BASALIS (regenerative layer/stem cells of the endometrium) and scarring.
• result of overaggressive dilation and curettage; scrape away the uterine wall (D&C)

Question 5

What is an anovulatory cycle?

Answer 5

• lack of ovulation. Woman goes through estrogen-driven proliferative/follicular phase, but WITHOUT a subsequent progesterone-driven secretory/luteal phase.
• common cause of dysfunctional uterine bleeding (especially during menarche and menopause; puberty and later in life).

Question 6

What is ACUTE endometritis? (PICMONIC)

Answer 6

• bacterial infection of the endometrium, usually due to retained products of conception (e.g. after deliver or miscarriage); retained products act as a nidus for infection.
• presents as fever, abnormal uterine bleeding, and pelvic pain.

Question 7

What characterizes CHRONIC endometritis?

Answer 7

• chronic inflammation of endometrium characterized by lymphocytes and PLASMA CELLS.
• presents with abnormal uterine bleeding, pain, and infertility.

Question 8

What could cause chronic endometritis?

Answer 8

• retained products of conception, chronic PID (especially from Chlamydia), IUD, and TB (would see granulomas with TB).

Question 9

*** What is an endometrial polyp?

Answer 9

• hyperplastic protrusion of endometrium.
• presents as abnormal bleeding.
• can arise as a side effect of TAMOXIFEN (anti-estrogenic effects on breast BUT weakly PRO-ESTROGENIC on the endometrium).

Question 10

*** What is endometriOSIS? (PICMONIC)

Answer 10

• ABNORMAL PLACEMENT of both endometrial GLANDS and STROMA outside of the uterine endometrial lining.
• presents with DYSMENORRHEA (pain with uterine cycle) and PELVIC PAIN; may cause INFERTILITY.

Question 11

Does endometriosis cycle just like normal endometrium?

Answer 11

YES

Question 12

What are the 3 theories of causes for endometriosis?

Answer 12

1. retrograde menstruation theory= menstrual products go backward instead of out, and implant at an ectopic site.
2. metaplastic theory= metaplasia of endometrium during development from the mullerian duct.
3. lymphatic dissemination theory (benign metastasis theory)= endometrium spreads through lymphatics (explains how you can get endometrial tissue in lungs, heart, or brain).

Question 13

*** What is the most common site of endometriosis involvement?

Answer 13

• OVARY, resulting in formation of a “CHOCOLATE” CYST.

Question 14

What are some other common sites of endometriosis involvement?

Answer 14

• uterine ligaments= pelvic pain.
• pouch of Douglas= pain with defecation.
• bladder wall= pain with urination.
• bowel serosa= abdominal pain and ADHESIONS.
• fallopian tube mucosa= SCARRING and FIBROSIS that increases risk for ECTOPIC tubal pregnancy.

Question 15

What does endometriosis look like when it involves soft tissues?

Answer 15

• red-blue to yellow-brown “GUN-POWDER” NODULES

Question 16

*** Can endometriosis involve the myometrium?

Answer 16

YES, called ADENOMYOSIS= growth of endometrial basal layer into the myometrium.
*remember this is benign.

Question 17

Does endometriosis increase the risk of carcinoma?

Answer 17

YES at the site of endometriosis (especially the ovary).

Question 18

*** What is endometrial hyperplasia?

Answer 18

• hyperplasia of endometrial GLANDS relative to the stroma due to UNOPPOSED ESTROGEN (obesity causes androgens to get converted to estrone in adipose tissue, PCOS, and estrogen replacement).
• presents as postmenopausal uterine bleeding.
• has MALIGNANT POTENTIAL

Question 19

** What is the most important predictor for progression to endometrial carcinoma? (BOARD QUESTION)

Answer 19

CELLULAR ATYPIA

Question 20

** What are the 2 types of HISTOLOGICAL hyperplasia classification?

Answer 20

• SIMPLE (with or without cellular atypia).
• COMPLEX (with or without cellular atypia)= increased number and size of glands.
• neither rarely progresses to carcinoma WITHOUT atypia. However, WITH atypia, then either is likely to progress to carcinoma.

Question 21

What is endometrial carcinoma?

Answer 21

• malignant proliferation of endometrial glands.

- presents as POSTmenopausal bleeding (aka in older women).

Question 22

** What are the 2 pathways for endometrial carcinoma? (KNOW PICTURES)

Answer 22

1. HYPERPLASIA (type I)= unopposed estrogen leading to endoMETRIOID histology because it looks a lot like the endometrium (age 50-60).
2. SPORADIC (type II)= ATROPHIC endometrium (no evident precursor lesion) driven by p53 MUTATION leading to SEROUS histology characterized by PAPILLARY structures (age greater than 70). Think “S” for Sporadic and Serous.

Question 23

What is the most common INVASIVE carcinoma of the female genital tract?

Answer 23

endometrial carcinoma

Question 24

*** What can form as a result of the SPORADIC pathway to endometrial carcinoma?

Answer 24

PSAMOMMA BODIES= concentrically layered calcifications of the papillary structures

Question 25

** In what other tumors will you see psammoma bodies? (HIGH YIELD BOARD QUESTION)

Answer 25

• papillary carcinoma of the thyroid.
• meningioma
• papillary serous carcinoma (THIS ONE)
• MESOTHELIOMA

Question 26

*** What is the most common tumor in females?

Answer 26

• Leiomyoma (Fibroids)= BENIGN proliferation of SMOOTH MUSCLE, arising from myometrium.
• associated with MED 12 gene mutations

Question 27

What causes leiomyoma of myometrium?

Answer 27

• estrogen exposure in PREmenopausal women.
• often multiple
• enlarge during pregnancy; shrink after menopause.

Question 28

** What do leiomyomas look like? (HIGH YEILD)

Answer 28

• MULTIPLE, well-defined WHITE WHORLED MASSES.

Question 29

*** Are leiomyomas usually asymptomatic?

Answer 29

YES

*if symptomatic, then abnormal uterine bleeding, infertility, or pelvic mass.

Question 30

** How does leiomyoSARCOMA differ from leiomyoma of the myometrium?

Answer 30

• malignant proliferation of smooth muscle arising from the myometrium.
• arises DE NOVO
• POSTmenopausal women
• SINGLE lesion with NECROSIS and HEMORRHAGE.

Question 31

** Can leiomyomas become leiomyosarcomas? (HIGH YIELD)

Answer 31

NO NO NO

*leiomyosarcomas arise DE NOVO (aka on their own).

Question 32

What would happen if the corpus luteum failed to mature or regressed prematurely?

Answer 32

relative lack of progesterone leading to dysfunctional uterine bleeding.

Question 33

Will endometriosis activate the inflammatory cascade and upregulate estrogen?

Answer 33

YES

*estrogen due to high levels of aromatase, which is absent in normal endometrial stroma.

Question 34

What are some epigenetic changes that could lead to endometriosis?

Answer 34

• steroidogenic factor 1 and estrogen receptor beta, leading to overproduction of estrogen and prostaglandin, with subsequent resistance to progesterone action.

Question 35

*** What is a common genetic alteration found in endometrial hyperplasia leading to endometrial carcinoma?

Answer 35

inactivation of PTEN tumor suppressor gene. This leads to uninhibited AKT phosphorylation= stimulated protein synthesis, cell proliferation, and inhibited apoptosis.

Question 36

What is a malignant mixed mullerian tumor (carcinosarcoma)?

Answer 36

• mixture of carcinomatous and sarcoma-like elements usually seen in POSTmenopausal women.
• uterine bleeding and large soft polypoid growths
• highly aggressive.