Uterus

Question 1

Two major components of the uterus

Answer 1

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

Question 2

Histology of the menstrual cycle - Proliferative phase

Answer 2

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

Question 3

Histology of the menstrual cycle - Early secretory phase

Answer 3

Nuclei become ROUNDER with formation of secretory vacuoles underneath

Stromal cells are small

Under the influence of progesterone

Question 4

Histology of the menstrual cycle - Late secretory phase

Answer 4

Vacuoles have extruded all contents

Nuclei at the base of the cells

Stromal cells become larger

These changes are called PSEUDODECIDUALIZATION

Still progesterone influence

Question 5

Histology of the menstrual cycle - Menstrual phase

Answer 5

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

Question 6

ATROPHIC ENDOMETRIUM

Answer 6

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

Question 7

Anovulatory cycle

Answer 7

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)

Question 8

Progestational Effect

Answer 8

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)

Question 9

HRT and Progestin

Answer 9

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.

Question 10

Tamoxifen

Answer 10

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!!!

Question 11

ENDOMETRITIS

Answer 11

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

Question 12

Endometrial Polyps

Answer 12

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!

Question 13

Endometriosis and Adenomyosis

Answer 13

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

Question 14

Endometrial HYPERPLASIA

Answer 14

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!

Question 15

Risks associated with hyperplasia

Answer 15

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)

Question 16

Gland-Stroma Ratio

Answer 16

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)

Question 17

PTEN

Answer 17

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

Question 18

Endometrial Metaplasia

Answer 18

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!

Question 19

Endometrial Adenocarcinoma/Carcinoma Type 1

Answer 19

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)

Question 20

Endometrial Adenocarcinoma/Carcinoma Type 2

Answer 20

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)

Question 21

Staging of endometrial adenocarcinomas

Answer 21

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

Question 22

Endometrial STROMAL tumors

Answer 22

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

Question 23

FIBROIDS/LEIOMYOMAS

Answer 23

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.

Question 24

CARCINOSARCOMA

Answer 24

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