L40- Female GUT Pathology I (uterus)

Question 1

list the endometrium phases

Answer 1

(Menstrual Cycle)
Day 1-13: proliferation, estrogen (days 1-4 = menstruation)

Day 14: ovulation

Day 15-28: secretory, progesterone

Question 2

describe the key feature of the endometrium during:

• (1) proliferative phase
• (2) early secretory phase
• (3) late secretory phase
• (4) menstration

Answer 2

1- mitoses, straight glands, single/double layer of cuboidal to tall cells (pseudostratification), dense stroma, compact cells, round glands

(coiled glands / single layer tall cells with vacuoles, edematous stroma, plump cells, conspicuous arterioles)
2- subnuclear (clear mucinous) vacuoles, inc vascularization
3- pre-decidual changes, apical vaculoes, serrated glands, inc vascularization

4- stromal breakdown, blood

Question 3

list the many Uterus Sxs

Answer 3

• Amenorrhea- primary or secondary
• Menorrhagia: excess bleeding (cyclical)
• Metrorrhagia (epimenorrhea)- irregular non-cyclical bleeding

Dysmenorrhea (pain with menses):

• primary at menarche (nerve/muscle activity abnormality)
• secondary after menarche

Infertility- congenital anomalies, neoplasms, endometrial disease

Mass- palpable when large

Question 4

Amenorrhea:

• (1) definition
• (2) primary causes
• (3) secondary causes

Answer 4

1- absence of menstruation

2- (never menarche) hypoplastic uterus, imperforate hymen, endocrine problems

3- (after menarche) pregnancy, lactation, endocrine problems, stress

Question 5

list the uterine / cervical disease evaluation techniques

Answer 5

Pelvic Exam: speculum, colposcopy, US, CT scan

Pap smear: infection, CIN, neoplasia

Biopsy- cervix, endometrium

D&C- dilatation and curettage

Question 6

DUB = (1):

-(2) describe cycle / hormone status that may cause DUB

Answer 6

1- dysfunctional uterine bleeding (abnormal endometrial cycle)

2:

• unopposed estrogen effect
• exogenous progesterone effect
• inadequate luteal phase
• persistent luteal phase

Question 7

Unopposed Estrogen: list causes of anovulatory cycles

Answer 7

• extremes of reproductive life (most common)
• PCOD (Stein-Leventhal Syndrome)
• endocrine disorders (thyroid, adrenal)
• Obesity, emotional stress
• excess physical activty

Question 8

Unopposed Estrogen in abnormal endometrial cycle may develop from (1) disease and has the (2) as net effects

Answer 8

1- estrogen producing neoplasms: granulosa cell tumor in ovary, adrenal cortcal adenoma (glomerulosa)

2- persistent proliferation –> irregular bleeding breakdown (DUB), endometrial hyperplasia, endometrial carcinoma

Question 9

Exogenous Progesterone Effect:

• (1) is the primary cause
• (2) is the descriptive result with (3) as features

Answer 9

1- contraceptive pills with progesterone

2- ‘Pill endometrium’

3:

• abundant stroma, plump cells (pseudodecidualized), edema
• small atrophic glands (lack of priming by estrogen)

Question 10

Inadequate Luteal Phase:

• (1) common cause
• (2) net effects
• (3) labs

Answer 10

1- inadequate corpus luteum function (dec progesterone)

2:

• irregular ripening
• irregular breakdown (DUB)
• poorly developed secretory endometrium, lacks secondary characteristics

3- low progesterone, low FSH, low LH

Question 11

Persistent Luteal Phase:

• (1) perpetuates normal menstruation
• (2) is the abnormality of (1) here
• (3) is the main change via (2)
• (4) is evident on biopsy

Answer 11

1- abrupt cessation of progesterone secretion of corpus luteum

2- continued corpus luteum secretion of low levels of progesterone

3- regular periods, but excess bleeding and prolonged (10-14 days)

4- persistent secretory appearance 5 days post-menstruation

Question 12

Endometriosis:

• (1) definition and (2) locations
• (3) is endometrial tissue w/in uterine wall
• (4) Sxs

Answer 12

1- endometrial tissue outside of uterus

2- ovaries, uterine ligaments, rectovaginal septum, cul-de-sac / pouches, GIT, appendix, laparotomy scars

3- adenomyosis, 20% uteri

4- pelvic pain, dysmenorrhea, infertility

Question 13

list the 2 theorized pathogenic mechanisms of endometriosis

Answer 13

• metastatic pathogenesis, metaplasia of coelomic epithelium

- inflammatory cascade- PGs, estrogen

Question 14

list the changes seen in endometriosis (3 main ones)

Answer 14

Endometrium: glands and stroma undergo cyclical bleeding, hemosiderin deposition, fibrosis, adhesions

Ovary- chocolate cysts

Fallopian Tubes: tubal Scars –> infertility

Question 15

Endometriosis:

• (1) time of occurrence
• (2) is the common presentation, (3) is seen at higher disease progression
• (4) when regression may occur

Answer 15

1- reproductive phase of life

2- asymptomatic

3- dysmenorrhea, menorrhagia, infertility

4- after pregnancy, oral contraceptives

Question 16

Endometriosis:

• cyclical bleeding is observed in (1)
• fibrosis may lead to the following- (2)

Answer 16

1- urinary tract, rectum, umbilicus, surgical scars

2:

• infertility (tubes), risk of tubal pregnancy
• urinary obstruction
• intestinal obstruction

Question 17

Acute Endometritis definition and causes

Answer 17

-active inflammation

Postpartum: offensive lochia (puerperal sepsis, Strep/Staph spp.)

Ascending gonococcal / chlamydia

Pyometrium- os obstruction by neoplasm, fibrosis

Question 18

Chronic Endometritis causes

Answer 18

(15% nonspecific)

• chronic PID
• postpartum / post-abortion (retained products)
• IUDs
• TB
• chlamydia

Question 19

Endometrial Polyp:

• (1) size
• (2) developmental association
• (3) presentation
• (4) possible complication

Answer 19

1- 0.5-3 cm
2- certain drugs- Tamoxifen
3- asymptomatic or metrorrhagia
4- malignant transformation

Question 20

Endometrial Hyperplasia:

• (1) and (2) are main causes
• (3) are other causes
• (4) is genetic association
• (5) Tx

Answer 20

1- excess unopposed estrogen effect
2- perimenopausal metrorrhagia
3- obesity, PCOD, menopause, estrogen replacement therapy, estrogen tumor (granulosa tumor), adrenal disorder

4- PTEN, tumor suppressor
5- hysterectomy, progesterone therapy (small number of patients)

Question 21

list the forms of endometrial hyperplasia and the risks for carcinoma development

Answer 21

Simple hyperplasia:

• w/o atypia –> 1%
• w/ atypia –> 8%

Complex hyperplasia:

• w/o atypia –> 3%
• w/ atypia –> 24-48%

Question 22

name the genetic changes related to the following:

• (1) development into non-atypical endometrial hyperplasia
• (2) change while in non-atypical hyperplasia
• (3) progression from non-atypical to atypical
• (4) progression from atypical to grade I carcinoma

Answer 22

1- PTEN (tumor suppressor)

2- MLH1

3- KRAS, MSI

4- ARID1A, PIK3CA, CTNNB1, FGFR2

Question 23

list the criteria needed to consider endometrial hyperplasia as atypical

Answer 23

• nuclear enlargement (x2-3 bigger than RBC)
• pleomorphisms
• vesicular change
• chromatin irregularity
• loss of polarity
• prominent nucleoli
• cellular stratification

Question 24

______ is the most common invasive carcinoma of female genital tract

Answer 24

endometrial carcinoma: type I > type II

-biopsy needed for Dx

Question 25

Type I endometrial CA: - (more/less) prevalent than type II - (2) age group - (3) key clinical history feature - (4) risk factors - (5) genetic associations - (6) types - (fast/slow) - (8) precursor

Answer 25

``` 1- more 2- 55-65 y/o 3- nulliparous 4- unopposed estrogen, obesity, DM, HTN 5- PTEN, KRAS, MSI 6- endometrioid (only) 7- slow, indolent 8- complex hyperplasia with atypia (endometrium) ```

Question 26

Type II endometrial CA: - (more/less) prevalent than type I - (2) age group - (3) key clinical history feature - (4) risk factors - (5) genetic associations - (6) types - (fast/slow) - (8) precursor

Answer 26

``` 1- less 2- 65-75 y/o 3- thin physique 4- endometrial atrophy (age) 5- p53 6- serous, clear cell, malignant mixed mullerian tumor 7- rapid / aggressive 8- endometrial intraepithelial carcinoma ```

Question 27

Endometrial CA: - (1) mass description - (2) describe metastasis

Answer 27

1) polyploid fungating mass in cavity, asymmetric enlargement of the uterus, back-to-back glands 2) - local: myometrium, cervix, vagina, rectum - peritoneum - lymphatics: iliac, para-aortic - blood: lung, liver

Question 28

briefly describe Endometrial CA grading

Answer 28

I- confined to uterus (corpus) II- involves uterine corpus and cervix III- outside uterus, still w/in pelvis IV- outside pelvis, involves rectum, bladder

Question 29

Malignant Mixed Mullerian tumor, aka (1): - (2) age group - (3) origin --> prefixes - (4) aggressiveness / prognosis - (5) gross appearance

Answer 29

1- mixed mesodermal tumor / carcinosarcoma 2- >55 y/o 3- epithelial, mesenchymal origin ==> leio-, rhabdo-, chondro-, osteo- 4- high grade, metastasis depends on epithelial component, poor prognosis 5- large, fleshy mass, hemorrhage, necrosis

Question 30

Leiomyoma: - (1) prevalence and definition - (2) age group - (3) key property, in relation to growth - (high/low) malignant potential

Answer 30

1- 25% of women, benign smooth muscle tumor 2- 20-40 y/o 3- estrogen dependent growth (regression with menopause) 4- NO potential

Question 31

Leiomyoma: - (single/multiple) in (2) location related to layers of uterus - (3) nodule description

Answer 31

1- multiple 2- subserosal, intramural, submucosal 3- circumscribed whorled nodules, resembles normal smooth muscle with fibrosis

Question 32

Leiomyoma: - (1) Sxs - (2) Tx

Answer 32

1: - asymptomatic - menorrhagia, metrorrhagia, infertility - mass effects (compression) - acute pain --> red degeneration, especially in pregnancy 2: laproscopic resection, hysterectomy

Question 33

list leiomyoma variants

Answer 33

- atypical / symplastic - cellular - benign metastasizing leiomyoma - disseminated peritoneal leiomyomatosis

Question 34

describe the aspects of smooth muscle tumors of the uterus that are evaluated upon investigation / biopsy and how they influence DDx and further investigation

Answer 34

1) nuclear atypia 2) tumor necrosis i) absent --> **leiomyoma (skip 3) ii) present --> step 3 3) mitotic count > 10 --> **leiomyosarcoma

Question 35

(T/F) leiomyosarcomas result from malignant transformations of leiomyomas

Answer 35

F- de novo derivation | -leiomyomas have NO malignant potential

Question 36

Leiomyosarcoma: - (1) age group - (2) gross appearance - (3) microscopic appearance - (good/poor) prognosis

Answer 36

1- 40-60 y/o, post-menopausal bleeding 2- large, bulky, hemorrhage, necrosis 3- hypercellular with atypia, >10 mitoses, coagulative necrosis 4- poor, 5yr ~40%

Question 37

Endometrial tumors with stromal differentiation: - aka (1) - resembles (2) tumor - (3) age group - (high/low) malignancy - (5) genetic association

Answer 37

1- adenosarcoma (benign epithelium + malignant stroma) 2- phyllodes tumor in breast 3- 30s-40s 4- low grade malignancy (decades for metastasis), but local recurrence [15% cases are fatal] 5- t(7;17) --> fusion of JAZF1 and JJAZ1

Question 38

briefly describe the types of Endometrial tumors with stromal differentiation

Answer 38

(stromal tumors) i) benign stromal nodule- endometrial stromal cells, well circumscribed ii) endometrial stromal sarcoma- low grade (infiltrative edge + lymphovascular invasion) or high grade

Question 39

In the ovarian follicle, (1) produces the androgens and (2) converts it to estrogens

Answer 39

1- theca cells 2- granulosa cells