L40- Female GUT Pathology I (uterus) Flashcards
list the endometrium phases
(Menstrual Cycle)
Day 1-13: proliferation, estrogen (days 1-4 = menstruation)
Day 14: ovulation
Day 15-28: secretory, progesterone
describe the key feature of the endometrium during:
- (1) proliferative phase
- (2) early secretory phase
- (3) late secretory phase
- (4) menstration
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
list the many Uterus Sxs
- 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
Amenorrhea:
- (1) definition
- (2) primary causes
- (3) secondary causes
1- absence of menstruation
2- (never menarche) hypoplastic uterus, imperforate hymen, endocrine problems
3- (after menarche) pregnancy, lactation, endocrine problems, stress
list the uterine / cervical disease evaluation techniques
Pelvic Exam: speculum, colposcopy, US, CT scan
Pap smear: infection, CIN, neoplasia
Biopsy- cervix, endometrium
D&C- dilatation and curettage
DUB = (1):
-(2) describe cycle / hormone status that may cause DUB
1- dysfunctional uterine bleeding (abnormal endometrial cycle)
2:
- unopposed estrogen effect
- exogenous progesterone effect
- inadequate luteal phase
- persistent luteal phase
Unopposed Estrogen: list causes of anovulatory cycles
- extremes of reproductive life (most common)
- PCOD (Stein-Leventhal Syndrome)
- endocrine disorders (thyroid, adrenal)
- Obesity, emotional stress
- excess physical activty
Unopposed Estrogen in abnormal endometrial cycle may develop from (1) disease and has the (2) as net effects
1- estrogen producing neoplasms: granulosa cell tumor in ovary, adrenal cortcal adenoma (glomerulosa)
2- persistent proliferation –> irregular bleeding breakdown (DUB), endometrial hyperplasia, endometrial carcinoma
Exogenous Progesterone Effect:
- (1) is the primary cause
- (2) is the descriptive result with (3) as features
1- contraceptive pills with progesterone
2- ‘Pill endometrium’
3:
- abundant stroma, plump cells (pseudodecidualized), edema
- small atrophic glands (lack of priming by estrogen)
Inadequate Luteal Phase:
- (1) common cause
- (2) net effects
- (3) labs
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
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
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
Endometriosis:
- (1) definition and (2) locations
- (3) is endometrial tissue w/in uterine wall
- (4) Sxs
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
list the 2 theorized pathogenic mechanisms of endometriosis
- metastatic pathogenesis, metaplasia of coelomic epithelium
- inflammatory cascade- PGs, estrogen
list the changes seen in endometriosis (3 main ones)
Endometrium: glands and stroma undergo cyclical bleeding, hemosiderin deposition, fibrosis, adhesions
Ovary- chocolate cysts
Fallopian Tubes: tubal Scars –> infertility
Endometriosis:
- (1) time of occurrence
- (2) is the common presentation, (3) is seen at higher disease progression
- (4) when regression may occur
1- reproductive phase of life
2- asymptomatic
3- dysmenorrhea, menorrhagia, infertility
4- after pregnancy, oral contraceptives
Endometriosis:
- cyclical bleeding is observed in (1)
- fibrosis may lead to the following- (2)
1- urinary tract, rectum, umbilicus, surgical scars
2:
- infertility (tubes), risk of tubal pregnancy
- urinary obstruction
- intestinal obstruction
Acute Endometritis definition and causes
-active inflammation
Postpartum: offensive lochia (puerperal sepsis, Strep/Staph spp.)
Ascending gonococcal / chlamydia
Pyometrium- os obstruction by neoplasm, fibrosis
Chronic Endometritis causes
(15% nonspecific)
- chronic PID
- postpartum / post-abortion (retained products)
- IUDs
- TB
- chlamydia
Endometrial Polyp:
- (1) size
- (2) developmental association
- (3) presentation
- (4) possible complication
1- 0.5-3 cm
2- certain drugs- Tamoxifen
3- asymptomatic or metrorrhagia
4- malignant transformation
Endometrial Hyperplasia:
- (1) and (2) are main causes
- (3) are other causes
- (4) is genetic association
- (5) Tx
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)
list the forms of endometrial hyperplasia and the risks for carcinoma development
Simple hyperplasia:
- w/o atypia –> 1%
- w/ atypia –> 8%
Complex hyperplasia:
- w/o atypia –> 3%
- w/ atypia –> 24-48%
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
1- PTEN (tumor suppressor)
2- MLH1
3- KRAS, MSI
4- ARID1A, PIK3CA, CTNNB1, FGFR2
list the criteria needed to consider endometrial hyperplasia as atypical
- nuclear enlargement (x2-3 bigger than RBC)
- pleomorphisms
- vesicular change
- chromatin irregularity
- loss of polarity
- prominent nucleoli
- cellular stratification
______ is the most common invasive carcinoma of female genital tract
endometrial carcinoma: type I > type II
-biopsy needed for Dx
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
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)
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
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
Endometrial CA:
- (1) mass description
- (2) describe metastasis
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
briefly describe Endometrial CA grading
I- confined to uterus (corpus)
II- involves uterine corpus and cervix
III- outside uterus, still w/in pelvis
IV- outside pelvis, involves rectum, bladder
Malignant Mixed Mullerian tumor, aka (1):
- (2) age group
- (3) origin –> prefixes
- (4) aggressiveness / prognosis
- (5) gross appearance
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
Leiomyoma:
- (1) prevalence and definition
- (2) age group
- (3) key property, in relation to growth
- (high/low) malignant potential
1- 25% of women, benign smooth muscle tumor
2- 20-40 y/o
3- estrogen dependent growth (regression with menopause)
4- NO potential
Leiomyoma:
- (single/multiple) in (2) location related to layers of uterus
- (3) nodule description
1- multiple
2- subserosal, intramural, submucosal
3- circumscribed whorled nodules, resembles normal smooth muscle with fibrosis
Leiomyoma:
- (1) Sxs
- (2) Tx
1:
- asymptomatic
- menorrhagia, metrorrhagia, infertility
- mass effects (compression)
- acute pain –> red degeneration, especially in pregnancy
2: laproscopic resection, hysterectomy
list leiomyoma variants
- atypical / symplastic
- cellular
- benign metastasizing leiomyoma
- disseminated peritoneal leiomyomatosis
describe the aspects of smooth muscle tumors of the uterus that are evaluated upon investigation / biopsy and how they influence DDx and further investigation
1) nuclear atypia
2) tumor necrosis
i) absent –> **leiomyoma (skip 3)
ii) present –> step 3
3) mitotic count > 10 –> **leiomyosarcoma
(T/F) leiomyosarcomas result from malignant transformations of leiomyomas
F- de novo derivation
-leiomyomas have NO malignant potential
Leiomyosarcoma:
- (1) age group
- (2) gross appearance
- (3) microscopic appearance
- (good/poor) prognosis
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%
Endometrial tumors with stromal differentiation:
- aka (1)
- resembles (2) tumor
- (3) age group
- (high/low) malignancy
- (5) genetic association
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
briefly describe the types of Endometrial tumors with stromal differentiation
(stromal tumors)
i) benign stromal nodule- endometrial stromal cells, well circumscribed
ii) endometrial stromal sarcoma- low grade (infiltrative edge + lymphovascular invasion) or high grade
In the ovarian follicle, (1) produces the androgens and (2) converts it to estrogens
1- theca cells
2- granulosa cells
