Uterus, placenta Flashcards
normal weight of uterus
50g
uterus division
corpus uteri with myometrium and endometrium
lower uterine segment
cervix
normal size of uterus
8x6x3 cm
two major components of the uterus
myometrium
endometrium
endometrium- functionalis
horomone responsive upper zone
how much is shed in the functionalis at the start of the cycle?
upper half to 2/3
surface epithelium covering the endometrial mucosa
compacta layer
most hormonaly sensitive layer of the functionalis
spongiosa layer
hormonally sensitive endometrial layer
basalis layer
most common disorders of the uterus result from
endocrine imbalances
complication in pregnancy
neoplastic proliferation
clinical usefulness of endometrial dating
assess hormonal status
document ovulation
determine cause of endometrial bleeding- most important indication
for infertility workup
1st half of the endometrial cycle is characterized by
proliferation of both endometrial glands and stroma to build up then shedding from previous menstruation
which part of the endometrial cycle is variable among women?
1st half of the cycle
the 2nd half of the endometrial cycle aka
post ovulatory phase or secretory phase
2nd half of the cycle is controlled by
progesterone
clinical significance of post ovulatory or secretory phase
14day period: can be used to date the endometrium for monitoring of abnormal bleeding and part of infertility work up
granulosa cells produce estrogen effect on basalis layer
proliferation: extremely rapid growth of both glands and stroma
proliferative phase is at
day 1-14
proliferative phase histo features
straight, tubular glands
pseudostratified columnar, nonvacuolated lining epithelia
pencil like nucleus- elongated and slender
mitotic figures
increase in number of cells
compact spindly stroma
proliferative is dictated by
FSH
proliferative phase is interrupted by
ovulation ➡️rupture of Graafian follicle
if no fertilization, Graafian follicle becomes
corpus luteum
early secretory phase histo features
subnuclear or supranuclear vacuoles in the lining cells of the gland
luminal position of the nuclei
cease of mitotic activity
during early secretory phase, the corpus luteum produces
progesterone
estrogen
when basal vacuoles becomes prominent
3rd week of the menstrual cycle
midsecretory histo features
accumulation of intraluminal secretions within the lumen of the glands
loosed stroma due to edema
glands tortuous and coiled
secretions are discharged into the gland lumens by the
4th week
late secretory phase histo features
pre decidual stroma
round and plump stromal cells
serrated saw tooth appearance
days 21-22 of the endometrial cycle
development of spiral arterioles
days 23-24 of the endometrial cycle
increase in ground substance and edema
accumulation of cytoplasmic eosinophilia
mitoses
days 24-28 of the endometrial cycle
neutrophils and lymphocytes
disintegration of the functionalis layer
signaling by estrogen and progesterone on local production of molecules
autocrin
paracrine
much of the effect of estrogen in glandular proliferation occurs via
stromal cells
estrogen on stromal cells cause production of
ILGF-1
EGF
progesterone in the secretory phase
inhibits proliferation in both the glands and stroma
promotes differentiation of the glands
cause profound alteration of the stroma
disintegration, fissuring of the functional layer leads to
menstrual shedding
menstrual shedding (day24-28) begins with
dissolution of the corpus luteum
sudden withdrawal of estrogen and progesterone
characterized by short or long menstrual period or period of bleeding in between the normal cycle
abnormal uterine bleeding
most common clinical presentation of different diseases of endometrium
bleeding
dysfunctional in DUB means
not associated with pathologic condition of the uterus
50% with DUB are
> 45
30% of DUB px are
in reproductive years
20% of DUB px are
adolescents
DUB cause in prepuberty
precocious puberty
DUB cause in adolescence
anovulatory cycle
coagulation disorder
DUB cause in reproductive age
pregnancy complication
organic lesions
ovulatory dysfunction
DUB cause in perimenopausal age group
anovulatory cycle
irregular shedding
organic lesion
DUB cause in postmenopausal age group
organic lesions
endometrial atrophy
most common form of DUB dt hormonal imbalance
anovulatory bleeding or cycle
hormonal imbalance in anovulatory bleeding is due to
excess estrogen production
prolinged estrogen stimulation without ovulation
two possible mechanisms of anovulatory bleeding
- unopposed estrogen stimulation due to persistence of follicles without ovulation
- sudden regress of follicles causing reduction of estrogen production➡️withdrawal bleeding or estrogen breakthrough bleeding
hallmark of anovulatory bleeding
no ovulation and unopposed, prolonged estrogenic stimulation
endocrine disorders causing anovulatory bleeding or cycle
thyroid, adrenal disease
pituitary tumors
primary ovarian lesions causing anovulatory bleeding or cycle
granuloma-theca tumors
polycystic ovaries
generalized metabolic problem causing anovulatory bleeding or cycle
obesity
severe malnutrition
chronic systemic disease
anovulatory bleeding histo
cystic, irregular glandular architecture
stromal breakdown
morphologic patterns of anovulatory bleeding
normal proliferative weakly proliferative disordered proliferative glandulostromal breakdown ***hyperplasia
hyperplasia in Anovulatory bleeding
not a morphological pattern
due to prolonged estrogen stimulation
can lead to endometrial cancer in 20% cases
deficient progesterone secretion by corpus luteum either because of failure to develop normally or premature regression
Luteal Phase defect
clinical significance of luteal phase defect
menstrual abnormality
infertility
habitual 1st trimester abortion
diagnosis of luteal phase defect
at least 2 consecutive cycles
at least 2 biopsies showing delay in development of secretory changes
biopsy in mid secretory phase of px with luteal phase defect
normal looking glands
early secretory features: supra or subnuclear vacuoles, luminal nuclei
biopsy in secretory phase in px with luteal phase defect
normal glands
mid secretory feature: maximal stromal edema
inadequate luteal phase histo feature
normal secretory but out of date
lack of gland tortuosity
disassociation between glands of stromal development
rare cause of DUB
caused by persistence of corpus luteum function
irregular shedding syndrome
clinical features of irregular shedding syndrome
> 2 weeks bleeding
occurence in every menstruation
irregular shedding syndrome histo
star shaped secretory glands admixed with early proliferative glands
arias-stella
fibrin thrombi
glandular and stromal breakdown
which syndrome of luteal phase defect is due to increased progesterone?
irregular shedding syndrome
pill endometrium histo
small and inactive glands
poor stromal development
causes of inflammatory disease of the uterus
abortion retained products of conception ascending infection from cervix IUD systemic spread to uterus
nonspecific inflammatory response limited to the interstitium usually associated with pregnancy, abortion, miscarriage, perineal or cervial lacerations during delivery, instrumentation
acute endometritis
common causative agents of acute endometritis
strep
staph
clostridium
chronic endometritis hallmark
plasma cells
IUD associated with chronic endometritis is caused by
mycoplasma
chlamydia
actinomycosis
bacteria common in both acute and chronic endometritis
chlamydia
rare and usually a result of extension of tuberculous lesion in the uterine tubes
tuberculous endometritis
tuberculous endometritis generally found in
reproductive women
- infertile
- pelvic mass
- lower ab pain
tuberculousendometritis diagnosis
curettage sample during the late secretory or menstrual phase showing caseation necrosis
single and multiple exophytic mass
sessile
0.5 to 3 cm in diameter
large and pedunculated
endometrial polyp
breast cancer hormonal treatment causing endometrial polyp
tamoxifen
stromal cells in endometrial polyps contain
chromosome 6p21 rearrangements involving HMGIY gene
endometrial polyp is mostly encountered in
perimenopausal
menopausal women
occurence of carcinoma in endometrial polyps is
rare
most common clinical presentation of endometrial polyp
abnormal bleeding
endometrial polyp histo
covered on 3 sides by surface endometrium cystic glands estatic, thick-walled blood vessels fibrous stroma (*edematous in endocervical)
most commonly the glands of endometrial polyps are
atrophic or hyperplastic
endometrial polyp gland that demonstrate secretory changes
functional polyp
endometrial polyp that develop in association with generalized endometrial hyperplasia
responsive to estrogen
little or no progesterone response
hyperplastic polyp
presence of ectopic endometrial glands and stroma in the myometrium
adenomyosis
criteria for adenomyosis diagnosis
one low power field or more below the endomypmetrial junction
glands accompanied by stroma, no cyclical bleeding
etiology of adenomyosis
unknown
clinical features of adenomyosis
menorrhagea
dysmenorrhea
dyspareunia
pelvic pain during menstrual period
adenomyosis gross
globular thickend uterine wall
cigarette burnlike lesions
not well circumscribed unlike leiomyoma
precursor lesion to endometrial carcinoma
endometrial hyperplasia
endometrial hyperplasia histo
increased gland to stroma ratio
haphazard distribution
epithelium abnormalities
true stratification of lining
etiology of endometrial hyperplasia
increased and unopposed estrogen stimulation with decreased progesterone activity
conditions promoting endometrial hyperplasia
menopause PCOS granulosa cell tumor HRT obesity Stein-leventhal syndrome
common genetic alteration in hyperplasia and endometrial carcinomas is
inactivation of PTEN suppressor gene located on chromosome 10q23.3
simple hyperplasia without atypia
cystically dilated glands, focally crowded
pseudo stratified columnar with amphophilic cytoplasm
mitotic figures
abundant, cellular, spindles enlarged nuclei, indistinct cytoplasm, increase in mitosis
endometrial hyperplasia progression to ca
simple, -atypia 1% simple, +atypia 8% complex, -atypia 3% complex, +atypia 23-48% atypical hyperplasia VERY POOR PROGNOSIS
when estrogen stimulation is withdrawn, simple hyperplasia with atypia may evolve into
cystic atrophy
cheeselike appearance, fingerglovee, and adenomatous budding is seen in
simple hyperplasia without atypia
is simple hyperplasia with atypia common?
NOOOO
simple hyperplasia with atypia morphology
loss of polarity
vesicular nuclei with open chromatin pattern
prominent nucleoli
round cells
lost normal perpendicular orientation to BM
complex hyperplasia without atypia or adenomatous hyperplasia histo
increase in number crowded back to back complex budding dense stroma with lipid laden cells
morphologic overlap with well differentiated endometrioid adenocarcinoma and an accurate distinction may not be possible without hysterectomy
complex hyperplasia with atypia
complex hyperplasia with atypia management
hysterectomy
progestin therapy in young women
atypical hyperplasia
round nuclei nucleoli starts to appear irregular thickening of nuclear membrane chromatin clumping loss of polarity more eosinophilic cytoplasm
most common cancer of the female genital tract replacing cancer of the cervix
endometrial carcinoma
accounts for 7% of all cancer in the female
endometrial carcinoma
peak incidence of endometrial cancer
55-65
usual in post and perimenopausals
endometrial cancer risk factor
advancing age obesity HPN DM infertility nulliparity hyperestrogenism
most common clinical presentation of endometrial cancer
painless vaginal bleeding
more common histo classification of endometrial carcinoma
type 1 favorable
type 1 endometrial ca histo
low grade, better differentiated
minimal or no myometrial invasion
endometrioid adenoca
type 1 endometrial ca is common in
perimenopausal women
type 1 endometrial ca genetic factor
PTEN mutation
G1 endometrial ca
well differentiate
<5% solid growth pattern tumor
G2 endometrial ca
moderately differentiated
<50% solid tumor growth
G3 endometrial ca
poorly differentiated
>50% solid growth
endometrial cancer squamous differentitaion
toward malignancy ➡️adenosquamous
PIK3CA is RARE in complex hyperplasia with atypia and they play a role in
invasion
molecular changes in type 1 endometrial ca
PIK3CA mutation
KRAS mutation
Beta-catenin mutation
aside from type 1 endometrial ca, which has also mutation in KRAS?
complex atypical hyperplasia
sporadic endometrioid ca molecular change
promoter hypermethylation of one of the DNA mismatch repair genes
type 1 and type 2 share this mutation
p53
p53 unlike KRAS is not found in
complex atypical hyperplasia
grading of type 2 endometrial ca
3
most common type 2 subtype of endometrial ca
serous carcinoma
90% of serous endometrial ca have this mutation
p53
must know features of type 2 endometrial ca
rarely associated with hyperplasia and estrogen arise from EIN or endometrial atrophy serous fingerlike lined by cuboidal cells endometrioid tubular pattern
all of nonendometrioid carcinoma are graded
3
only endometrial ca graded with 1-3
endometrioid ca
histo type of endometrial ca with 70% frequency
adeno or endometrioid
endometrial adenoca with benign sq component
adenocanthoma
stage 1 endometrial CA
ca is confined to corpus uteri
stage2 endometrial ca
corpus
cervix
stage 3 endometrial ca
outside uterus but not outside of true pelvis
stage 4 endometrial ca
outside pelvis
extended to mucosa of bladder or rectum
diagnosis of endometrial dse
transvaginal ultrasonography
endometrial biopsy
d and C
MR imaging
preferred methods for diagnosis of endometrial dse
biopsy and D&c
also know as carcinosarcomas
malignant mixed mullerian tumor or MMMT
differentiation in MMMT
presence of muscle, cartilage, osteoid
most common tumor in women
leiomyomas or fibrinoids
genes that regulate chromatin structure that is involved in leiomyomas
HMGIC
HMGIY
molecular change in leiomyomas
12q14
6p
leiomyomas are common in
reproductive age women
hormones thataffect leiomyomas
progesterone
estrogen
symptoms of leiomyoma (uncommon)
pain infertility abnormal uterine bleeding frequent urination UTI
type of leiomyoma located at outside the surface
serosal
type of leiomyoma located within uterine cavity
submucosal
degenerative changes in leiomyoma
hyaline degeneration 60% edema cystic degeneration calcification 4% myxomatous infarcted 10%
malignant transformation of myoma to malignancy is
rare
leiomyoma gross
sharply circumscribed round firm gray white sometimes nodules to massive to fill the pelvis
leiomyoma rarely found in
myometrium of corpus
uterine ligaments
cervix
leiomyoma in the myometrium
intramural
leiomyoma just beneath the endometrium
submucosal
leiomyoma beneath the serosa
subserosal
red degeneration in leiomyoma shows
yellow-brown to red softening
leiomyoma histo
oval nucleus
long slender bipolar cytoplasmic processes
extremely rare variant of leiomyoma that extends into vessels and migrates to other sites
benign metastasizing leiomyoma
presents as multiple small nodules on the peritoneum
leiomyomatosis
leiomyomatosis and benign metastasizing leiomyoma are considered
benign
not to be considered in differentiating leiomyoma and leiomyosarcoma
increased cellularity
size
hemorrhage
malignancy histo important determinant in leiomyoma
10 or more per 10 high power fields
leiomyosarcoma gross
bulky, fleshy or polypoid masses
leiomyosarcoma histo
wide range atypia
determining factors of malignancy of the smooth muscle of the endometrium
mitosis>zona necrosis>nuclear atypia
in these groups, mitotically active leiomyosarcoma may mimic histo of leiomyosarcoma
young or pregnant
normal umbilical cord insertion
paracentral
umbilical cord features gross
straight
shiny smooth outer surface
cotyledon features
reddish brown
nodular
meaty
lining of villi in placenta
syncitiotrophoblast
chorionic villi are a little bit large enclosed by
nonproliferating trophoblast cells
stroma of placental is
loose
vascular
mature placenta at
20th week of pregnancy
syncitiotrophoblast secretes
hCG
aggregation of syncitiotrophoblast on maturation with no clinical significance
knotting
presence of intervillous fibrin is
normal or physiologic feature in mature placenta
abnormal adherence of the placenta to the uterine wall ➡️inadequate separation after delivery
placenta accreta
placenta accreta cause
partial or complete absence of the decidua with adherence of the placental villous tissue directly to the myometrium
failure of placental separation
normally the placenta is attached at the uterine plate at the
basalis or decidual plate
incomplete attachment of the placenta up to myometrium
placenta increta
placenta invaded the full thickness of myometrium
placenta percreta
abnormal implantation or location of the placental at cervical os
placenta previa
usual manifestation of placenta previa
serious 3rd trimester bleeding
systemic syndrome characterized by widespread maternal endothelial dysfunction
preeclampsia
preecclampsia prevalence
6% in women
last trimester and primiparas
eclampsia is associated with
convulsion
DIC
pathogenesis of preeclampsia
abnormality of placentations ➡️placental ischemia➡️ decresse uteroplacental perfusion➡️stimulation of vasoconstrictors and inh of vasodilators
mature placenta normally has infarctions ar
periphery
manifestation of preeclampsia
HPN
edema
proteinuria
hydatidiform moles and choriocarcinoma are both associated with
increased or persistent levels of hCG
hydatidiform moles is also known as
non invasive mole
H.mole classic manifestations
discordant size of the abdomen with the gestational age
high hCG titer
gelatinous discharge
h mole gross
delicate, friable mass of thinwalled, translucent, cystic, grapelike structures of swollen villi
h mole histo
cystic swelling of chroionic villi
variable trophoblastic proliferation
complete mole karyotype
diploid 46,XX (46 XY)
partial mole karyotype
triploid
results from fertilization of an egg that has lost its chromosomes
genetic material is paternally derived
complete mole
results from fertilization of egg with two sperm
partial mole
complete mole microscopy
enlarged, edematous villi
diffuse trophoblast hyperplasia
partial mole histo
edematous villi, some with only minor changes
focal less marked trophoblastic proliferation
atypia is present in this HMole
complete hmole
hmole with 2% risk of choriocarcinoma
complete hmole
most aggressive form of GTD with 1:40 chance following complete hmole
choriocarcinoma
choriocarcinoma preceded by
complete hmole
abortion
ectopic pregnancy
term pregnancy
choriocarcinoma morphology
dimorphic
well circumscribed dark red hemorrhagic necrotic mass
no chorionic villi
chorioca from placenta
gestational trophoblast disease
chorioca from ovary
nongestational CA
choriocarcinoma response to chemotherapy
good
syncitiotrophoblast normally has
big multinucleate cells
cytotrophoblast normally has
polygonal with round central nucleus