uterine disorders Flashcards
what are the 2 divisions of the endometrium
Functional endometrium: hormonally responsive
Basal endometrium: remaining 1/3rd which undergoes rapid growth in proliferative phase.
what are characteristic of endometrial cells in proliferative phase
mitosis
what are characteristic of endometrial cells in early secretory phase
vacuoles
what are characteristic of endometrial cells in late secretory phase
predecidual changes
what are characteristic of endometrial cells in menstrual endometrium
stromal breakdown with blood vessle rupture
what is polymenorrhea
cycles <3wks
what is oligomennorrhea
cycles >6-7wks
what is hypermenorrhea
excessive flow
what is menorrhagia
inc amt and duration of flow
what is menometrorrhagia
prolonged flow with irregular intermittent spotting bt bleeding episodes
what is DUB
uterine bleeding not caused by any underlying organic (structural) abnormality
what are prepuberty causes of abn uterine bleeding
hypothalamic, pit, or ovarian origin
what are adolescence causes of abn uterine bleeding
anovulatory cycle, coag disorders
what are repro age causes of abn uterine bleeding
preg complications organic lesion hyperplasia, carcinoma DUB dysfunctional bleeding= inadequate luteal phase
what are prepuberty causes of abn uterine bleeding
dysfunctional uterine bleeding
organic lesions
what are prepuberty causes of abn uterine bleeding
endometrial atrophy
organic lesions
what are causes of DUB
Anovulatory cycle (80%)
Inadequate luteal phase (~20%)
how does thyroid fxn affect menses
hypothyroid= heavy and frequent menses bc dec protein in blood. steroids are protein bound= inc free estrogen/prog effect
hyperthyroid= light and infrequent
what is the likely cause of DUB from anovulatory cycle
Excessive, prolonged estrogenic stimulation
No counteractive progesterone phase
what are Less likely causes of DUB from anovulatory cycle
Endocrine disorder (thyroid disease, adrenal disease, or pituitary tumors) Primary lesion of the ovary: Metabolic disturbance:
what is the pathology of anovulatory cycle caused by excessive endometrial stimulation by estrogens
Endometrial glands undergo architectural changes with cystic dilation
Endometrium attains abnormal height with increasing hypervascularity but without intervening stromal support matrix
Unopposed estrogen induces proliferation, hyperplasia and adenomatous hyperplasia
Usually self limited by the occurrence of next ovulatory cycle.
what do you need to r/o to dx DUB? what labs would you check?
R/O Hypothalamic dysfunction Perimenopause Thyroid disorders Hyperprolactinemia
check FSH, LH, TSH, Prolactin
what are the treatment options for DUB
Progesterone High dose estrogen & high dose progesterone Prostaglandin synthetase inhibitors: Desmopressin: esp with vWF dz Ablation Hysterectomy
what causes inadequate corpus luteum to cause DUB
Corpus luteum develops improperly or regresses prematurely= Decreased progesterone
what does inadequate corpus luteum manifest with
Infertility(inadequate endometrium) with increased bleeding or amenorrhea
Early menses
what would Endometrial biopsy at estimated postovulatory date show with inadequate corpus luteum
Shows secretory endometrium which lags behind expected date
how can oral contraceptives cause endometrial changes
endometrim becomes atrophic and ulceratived bc of lack of E and Prog
spiral arteries do not develope properly if not enough E
Prog only BC can lead freq break through bleeding
what is the major diff bt acute and chronic endometritis
acute presents with fever and chronic typically does not
what is the pathology of acute endometritis
inflamm limited to interstitum
what type of cells are found within the endometrial glands for acute/ chronic endometritis
acute= neutrophils chronic= lymphocytes and macrophages
how is chronic endometritis diagnosed and treated
If abnormal vaginal bleeding: endometrial biopsy is done
Lymphocytes and plasma cells within stroma
treatment is specific to cause
what is endometriosis
presence of endometrial tissue outside of the uterus
- Consists of endometrial glands and stroma
- Rarely only endometrial stroma
what is endometriosis dependent on
Estrogen-dependent disorder
what is the metastatic theory of endometriosis
Theory(appearance of endometrial tissue in extrauterine locations)
Retrograde menstruation through fallopian tube
Local spread
Distant spread through lymphatics and hematologic
according to the metastatic theory of endometriosis what may facilitate its development
Altered immune response may facilitate the development
what is the metaplastic theory of endometriosis
Endometrium arise directly from coelomic epithelium from which the endometirum itself originate during embryonic development
Undifferentiated cells differentiate to endometrial tissue
how is the immune system related to endometriosis
Activation of Inflammatory cascade in endometriosis
High levels of PGE2, IL-1beta, TNF, IL-6
-Explains why COX inhibitors are beneficial
how do endometriotic stromal cells cause endometriosis
They upregulate estrogen production due to high levels of aromatase. Estrogen enhances survival of endometrial tissue. Aromatase is absent in normal endometrium
what is letrozole
aromatase inhibitor- can be used to tx endometriosis
how are genetic alterations involved in endometriosis
Changes in key genes encoding two nuclear receptors
-Steroidogenic factor-1
-Estrogen receptor-Beta
Decreased methylation of promoters of these genes causing overexpression
-Favors overproduction of estrogen and -prostaglandin
Resistance to progesterone action.
what are the diff stages of endometriosis
Stage I (minimal): Isolated implants; no significant adhesions Stage II (mild): Superficial implants -<5cm in aggregate, scattered on peritoneum and ovaries -No significant adhesions Stage III (moderate) -Multiple implants=Superficial and invasive -Adhesions may be evident=Peritubal and periovarian Stage IV (severe) -Multiple implants=Superficial and deep -Including large ovarian -Firm dense adhesions
what are the consequences of endometriosis
Infertility
Dysmenorrhea
Pelvic pain
what are the 3 ways adenomyosis can form
Invagination of endometrium
De novo from mullerian rests
Hormonal driven
- Estrogen produced in adenomyotic tissue
- Increased aromatase
what are characteristics of endometrial polyps
usually sessile
are endometrial polyps responsive to hormones
Responsive to estrogen but little or no progesterone response
what is the malignant risk with endometrial polyps
Rarely transform to adenocarcinoma
what is the pathogenesis of endometrial polyps
Stromal cells contain chromosome (6p21) rearrangements
Involve HMGI Y gene which cause benign mesenchymal tumors. A mutation activates C-MYC which is a transcription factor for replication
what is endometrial hyperplasia? what is it related to?
Increased proliferation of the endometrial glands relative to the stroma
Increased gland to stroma ratio
Related to endometrial carcinoma
what is the pathogenesis of endometrial hyperplasia
estrogen without unopposed progesterone)
what is Endometriod hyperplasia (Type I)
- associated with unopposed estrogen= more glandular
- PTEN mutation=phosphatase and tensin homologue making PTEN a inactive “brake”= activation of AKT and uncontrolled proliferation
what is Nonendometriod hyperplasia(Type II)
more stromal tissue and less glandular
- p53 mutations
- not assoc with inc estrogen
how does the WHO classify endometrial hyperplasia
WHO classification based on 2 factors 1.Glandular/Stromal architectural pattern(simple/complex hyperplasia)
2.Presence or absence of nuclear atypia
what is simple hyperplasia without atypia
Glands: various size and irregular shape
Mild increase in gland: stroma ratio
Epithelial growth similar to proliferative endometrium
what is simple hyperplasia with atypia
Appearance of simple hyperplasia
Atypia: loss of polarity, vesicular nuclei, prominent nucleoli
8% progress to CA
what is complex hyperplasia without atypia
Increase number and size of glands, gland crowding
Abundant mitotic figures
Cytology: cells normal
3% progress to CA
what is complex hyperplasia with atypia
23 to 48% to CA)
what are type 1 and 2 carcinoma of the endometrium precursors
from type 1(PTEN, K-ras mutations) or 2(p53) endo hyperplasia
what are the majority of type 1 carcinomas
Majority are endometrioid carcinoma: well differentiated and look like proliferative endometrial glands
what are the different endometriod grading for type 1 endometrial carcinoma
Grade 1: Well differentiated adenocarcinoma-50% solid)
what are the different endometriod staging
Stage I: Carcinoma confined to corpus uteri itself
Stage II: Carcinoma has involved the corpus and the cervix
Stage III: Carcinoma has extended outside uterus but not outside the true pelvis
Stage IV: Carcinoma has extended outside true pelvis or involved mucosa of bladder or rectum
what are malignant mixed mullerian tumors
Endometrial adenocarcinomas with malignant changes in the stroma( may protrude through cervical os)
Stroma differentiate into variety of malignant mesodermal components
-muscle
-cartilage
-osteoid
what is the prognosis of malignant mixed mullerian tumors
Prognosis influenced by grade and type
Highly malignant
Same staging as Type 1 endometrial carcinoma
5 year survival rate: 25-30%
what is characteristic of adenosarcomas
Prolapse through the cervical os Malignant appearing stroma coexisting with benign but abnormally shaped endometrial glands Incidence: 4th to 5th decade of life Low-grade malignancy *Reoccurrence: 25% Usually confined to pelvic
what are the 2 categories of stromal tumors
Benign stromal nodules(aggregate of endometrial stromal cells)
-Does not penetrate the myometrium
-Little consequences
Endometrial stromal sarcomas
-Lies between muscle bundles of the myometrium
-Diffuse infiltration (not nodular)
what is the pathogenesis of endometrial stromal sarcomas
Chromosomal translocation (JJAZ1 )=anti-apoptotic properties
are leiomyomas hormonally responsive
yes,
Regress in menopause
Expand in pregnancy
what is the pathology of leiomyomas
Sharply circumscribed, discrete, round, firm, gray white tumors
Vary in size
Located within the myometrium just beneath the endometrium
Malignant transformation is rare
Low mitotic index
what are the growth patterns of leiomyosarcomas
2 growth patterns
Bulky fleshy masses invading uterine wall
Polypoid masses that project into the uterine lumen
what is the difference between leiomyomas and leiomyosarcomas
Degree of nuclear atypia
Mitotic index
Zonal necrosis
