Uterus Flashcards
Two major components of the uterus
ENDOMETRIUM –> has a glandular component, as well as a stromal component
Two divisions –> 1) FUNCTIONALIS (part where the embryo implants/part that is shed during menstruation (no implantation))
2) BASALIS –> base of the endometrium (separates it from the myometrium)
MYOMETRIUM –> consists of smooth muscle
Histology of the menstrual cycle - Proliferative phase
Proliferative phase – under the influence of estrogen, nuclei of the glands are pseudostratified, there is mitotic activity, and very small stromal cells
After ovulation, there is an INCREASE in progesterone, which causes the endometrium to enter the SECRETORY PHASE
Histology of the menstrual cycle - Early secretory phase
Nuclei become ROUNDER with formation of secretory vacuoles underneath
Stromal cells are small
Under the influence of progesterone
Histology of the menstrual cycle - Late secretory phase
Vacuoles have extruded all contents
Nuclei at the base of the cells
Stromal cells become larger
These changes are called PSEUDODECIDUALIZATION
Still progesterone influence
Histology of the menstrual cycle - Menstrual phase
At the end of the secretory phase, endometrium sheds during menstruation
Progesterone levels decrease
Tissue breaks down and the stromal cells start to separate
May see inflammatory cells
Pink = Fibrin = breakdown product
ATROPHIC ENDOMETRIUM
After menopause, the endometrium becomes ATROPHIC
Cells transition from columnar to cuboidal and have NO MITOTIC ACTIVITY
Endometrium functionalis is no longer as prominent
Stroma becomes VERY DENSE
Glands can themselves become cystic
Anovulatory cycle
Dysfunctional uterine bleeding (outside of normal menstrual cycle)
Likely hormonal cause
Anovulatory Cycle – disordered proliferative endometrium that never goes into the secretory phase because there is no ovulation to increase progesterone
Proliferation of endometrium is maintained, estrogen causes the glands to continue proliferation –> eventually they cannot be supported, breaks down and bleeding occurs
Histologically –> irregular glands (ANGULAR SHAPE), accumulation of FIBRIN (RBC breakdown)
COMMON IN OBESE, MENOPAUSAL WOMEN
Other causes of irregular bleeding include an INADEQUATE LUTEAL PHASE (not enough progesterone to maintain secretory phase), HORMONE THERAPY (oral contraceptives, estrogen replacement), and MENOPAUSAL CHANGES (likely to be many anovulatory cycles before a woman completes menopause)
Progestational Effect
Seen with several different contraceptives (OCP, Depo-Provera, Norplant, IUDs)
Causes the stroma to become PSEUDODECIDUALIZED –> mimics pregnancy
Progesterone in these cases causes a MORE EXTENSIVE SECRETORY phase (also mimicking pregnancy)
HRT and Progestin
Added to estrogen formulations to PROTECT AGAINST HYPERPLASIA AND CARCINOMA in Hormone Replacement Therapy
Estrogen on its own would induce lots and lots of unopposed proliferation –> eventually this would cause endometrial hyperplasia and cancer!
Give for as short as possible because of risk of MI, stroke, etc.
Tamoxifen
Is common drug for BREAST CANCER – anti-estrogenic effect!
BUT in the UTERUS it has a slight PRO-ESTROGEN effect
This can lead to endometrial hyperplasia, endometrial polyps, cystic changes in the glands, and potentially endometrial cancer!!!
ENDOMETRITIS
ACUTE –> most commonly associated with PREGNANCY, both in pre-term abortion and full-term pregnancy
Usually caused by STREP, STAPH, CLOSTRIDIUM, GONOCOCCUS
Infiltration of NEUTROPHILS
CHRONIC – also can be associated with pregnancy, IUD use, CHLAMYDIA, gonococcus, E coli, strep
Infiltration of PLASMA CELLS and LYMPHOCYTES
Can lead to FIBROSIS
GRANULOMATOUS, seen with TB
Endometrial Polyps
Originate when a portion of the tissue is NOT CYCLING tHROUGH THE NORMAL PHASES as the rest of the endometrium is
If it remains like this, it can become irregular and form a POLYP
Polyps originate from the BASALIS LAYER
Can lead to ABNORMAL UTERINE BLEEDING
VERY RARELY DEVELOPS INTO CANCER!
Endometriosis and Adenomyosis
Endometriosis –> a condition in which endometrial tissues grow OUTSIDE OF THE UTERUS (ovary, broad ligament, bowl, anywhere in the pelvic, abdominal, thoracic cavity)
Adenomyosis –> glandular/endometrial tissue growing WITHIN THE MYOMETRIUM
Benign appearing glands within the SMOOTH MUSCLE LAYER
Endometrial HYPERPLASIA
ESTROGEN CAUSES PROLIFERATION
Too much of it can cause hyperplasia
Simple hyperplasia –> occurs when there is an INCREASED # and SIZE of glands
COMPLEX HYPERPLASIA –> due to even further proliferation –> overcrowding of the glands, irregularly shaped glands, and possible cellular ATYPIA (weird cells with rounded nuclei, prominent nucleoli, disorganized patterns)
PRE-MALIGNANT STATE!!!! Carries a risk of progression to endometrial cancer!
Risks associated with hyperplasia
Simple – 1% increased risk to carcinoma
Simple + Atypia –> 3% risk
Complex –> 8% risk
Complex + ATYPIA –> 29%!!!!! Get a hysterectomy, or if patient wants kids, consider progesterone therapy (has an anti-mitotic effect - explains why progestin is good for HRT)
Gland-Stroma Ratio
Good measure when looking for neoplastic processes
Allows for the comparison of how many and how crowded glands are to the amount of stroma present (high ratio is worse)
PTEN
PTEN staining is also a good indicator for cancer in the endometrium
Normal endometrial tissue will stain POSITIVELY with PTEN (normal brown stain))
Glands that are NEOPLASTIC will LOSE this ability and look PALE in the satin
Endometrial Metaplasia
Endometrium (which is normally glandular mucosa) can change its growth pattern into pretty much anything
Squamous metaplasia (becomes squamous) Eosinophilic metaplasia (becomes large/pink) Tubal/ciliated metaplasia (glandular tissue starts to look like the kind we see in fallopian) Mucinous metaplasia (becomes like the cervix/mucinous in nature) Papillary metaplasia (glands appear eosinophilic and become papillary)
DONT CONFUSE WITH ATYPIA!
Endometrial Adenocarcinoma/Carcinoma Type 1
Type 1 = estrogen related
Usually seen in patients RIGHT AFTER MENOPAUSE (55-65)
Associated with OBESITY, HTN, DIABETES
Endometrium stains abnormally for PTEN (pale)
INDOLENT CANCER (painless) that spreads via LYMPHATICS
These are usually ENDOMETRIOID carcinomas - cellularly looks like endometrium tissue but shows cribiform changes, fibrosis, and invades right into the myometrium
Looks like proliferative endometrium gone bad (very little stroma, many glands - high G/S ratio)
Endometrial Adenocarcinoma/Carcinoma Type 2
This is NON-estrogen related type
Older patients (65-75)
Thin/frail women
Occurs with an atrophic endometrium
Associated with p53 abnormalities
VERY AGGRESSIVE CANCER THAT SPREADS BOTH INTRAPERITONEALLY and VIA LYMPHATICS
TYPES –> SEROUS (very similar to ovarian serous, POOR prognosis, likely to have necrosis and nuclei have high grade atypic, usually fibrous areas and papillary appearance)
CLEAR CELL (pooooor prognosis, cells are clear b/c cytoplasm is filled with GLYCOGEN – big ugly cells)
Staging of endometrial adenocarcinomas
Staging = invasion of myometrium, invasion of cervix, whether it has broken through the serosa, whether it has invaded other structures
Grading is based on microscopic analysis and is determined based on NUMBER OF GLANDS, how ATYPICAL the cells are, and whether or not they are well or poorly differentiated (worse)
Treatment – Includes HYSTERECTOMY with possible lymph node dissection, radiation, chemo and hormone therapy
Endometrial STROMAL tumors
Relatively RARE, 3 types
STROMAL NODULES – benign lesions made up of endometrial stroma, can then become malignant
Low grade stromal sarcomas – extend into the uterine vessels
High grade stromal sarcomas –> more DESTRUCTIVE INVASION of the surrounding tissues; cells are more atypical
FIBROIDS/LEIOMYOMAS
Benign lesions made up of smooth muscle
Looks white and fibrous grossly
When they become malignant, they are called LEIOMYOSARCOMAS (cellular atypia, mitotic figures)
Can occur ANYWHERE IN THE UTERUS (cervix, submucosal, intramural or subserosal layer)
Very common
Present with BLEEDING, PELVIC DISCOMFORT
Complications – difficult getting pregnant, urethral obstruction, uterine degeneration, pain
TREAT –> leave alone, remove the fibroid, remove the uterus, treat with a GnRH agonist, embolize the vessels supplying the fibroid, etc.
CARCINOSARCOMA
Also known as MALIGNANT MIXED MULLERIAN TUMOR
Has both epithelial and mesenchymal origin
Patients will present with a polyploidy mass that protrudes into the uterine cavity and causes abnormal bleeding
VERY RARE, VERY POOR PROGNOSIS
Stains positive for KERATIN (epithelial part), mesenchymal part will not
