Uterus - Dobson Flashcards
2 layers of endometrium
Functional layer
Basal layer
Histology of menstrual phase
Functional layer sheds, bleeding into stroma (fibrin, RBCs, inflammatory cells), stromal breakdown
Histology of proliferative phase
- Rapid growth of glands and stroma
- Straight, tubular glands
- No mucus or vacuolization
- Pseudostratified columnar cells along glands
- Numerous mitotic figures
Endothelial histology of secretory phase
- Subnuclear –> supranuclear (week 3) vacuoles in glandular epithelium
- Dilated glands (18-24)
- Tortuous glands (week 4)
- Serrated/saw-tooth
Stromal histology of secretory phase
- Spiral arterioles
- Increased ground substance and edema
- Stromal cell hypertrophy and CYTOPLASMIC EOSINOPHILIA (predecidual change)
- Resurgence of mitoses
- High glycogen and lipid (decidualized cells)
AUB definition
Uterine bleeding that lacks an underlying organic/structural abnormality
AUB most commonly due to ____
Common times?
Anovulation (no ovulation)
Menarche, peri-menopause
Anovulation causes what hormonal imbalance?
Unopposed estrogen (no corpus luteum to make progesterone)
Metabolic disturbance causes of AUB
Obesity, malnutrition, chronic systemic disease
Endocrine causes of AUB
Thyroid, adrenal, pituitary
Ovarian lesion causes of AUB
Functioning tumors, polycystic ovary disease
In anovulation, what will not be seen on morphology?
What causes bleeding?
No secretory changes or vacuolization or predecidual changes
Glands break down and shed, causing bleeding
If anovulation is symptomatic (bleeding), what can be assumed?
Repeated cycles of no ovulation (not just 1)
Fever, vaginal bleeding, pelvic pain; recently pregnant; neutrophils in the endometrial stroma
Cause?
Acute endometritis
Retained products of conception
Group A strep, staph, others
Abnormal vaginal bleeding, pain, discharge, infertility; PLASMA CELLS in the endometrial stroma
Causes? (4)
Chronic endometritis (plasma cells = pathognomonic)
Chronic PID, retained POC, IUD, TB
Neutrophils AND plasma cells in the endometrial stroma
Chlamydia-associated chronic endometritis
Endometriosis - define
Most common locations
Ectopic endometrial tissue outside of the uterus
Ovaries, uterine ligaments, rectovaginal septum, others
4 theories of endometriosis
- Regurgitation (retrograde flow of menses)
- Metastases
- Metaplastic (change of coelomic epithelium of mullerian origin)
- Stem cell (BM cells)
Things seen in the endometriosis tissue AND the normal endometrium of women with endometriosis ONLY (2)
Treatment of endometriosis?
- High release of pro-inflammatory and growth cytokines
- High estrogen production by stromal cells (high aromatase)
Aromatase inhibitors
AUB, red/blue or yellow/brown nodules on or beneath mucosa or serosa
When extensive, can cause _____
Powder burn marks - endometriosis
—> fibrous adhesions
Distorted, cystic ovaries w/ brown fluid (dried blood)
Chocolate cyst – ovarian endometriosis
Endometriosis MUST have ____ tissue to be diagnosed as such
Can also have ___ tissue
Endometrial stroma
Endothelial
Symptoms of endometriosis (possible)
Pelvic pain, dysmenorrhea or menometrorrhagia, infertility, dyspareunia, painful defecation, dysuria
Exophytic mass(es) that project into endometrial cavity – found on routine scope
Later they ulcerate, leading to ____
Endometrial polyps
–> AUB
Endometrial polyps - what might you ask your patient?
Has she taken Tamoxifen (estrogen blocker)
Endometrial hyperplasia - definition
Cause
Glandular proliferation –> increased gland:stroma ratio
Prolonged estrogen stimulation
Causes of endometrial hyperplasia
Prolonged estrogen stimulation:
- Anovulation
- Obesity (fat aromatase = androgen –> estrogen)
- Menopause (low progesterone
- Polycystic ovarian syndrome (high estrone)
- Functioning granulosa tumors of ovary
- Cortical stromal hyperplasia (excessive ovary fxn)
- Prolonged estrogen replacement therapy
Endometrial hyperplasia - genetics (causes what?)
Familial syndrome?
PTEN inactivation –> PI3K/AKT overactivation –> enhanced signaling of estrogen receptor when activated
Cowden syndrome (PTEN loss) - high endometrial/breast cancer
2 categories of endometrial hyperplasia
Non-atypical
Atypical (EIN)
Increased gland:stroma ratio, varied gland size and shape, some intervening stroma remains
Potential consequence?
Non-atypical hyperplasia
—> cystic atrophy (when estrogen is removed)
Complex pattern of proliferating glands, nuclear atypica, back-to-back w/ branching, loss of orientation to BM, vesicular (open) chromatin
How to differentiate from cancer?
Atypical hyperplasia (endometrial intraepithelial neoplasia)
Cancer = NO INTERVENING STROMA
Treatments for endometrial hyperplasia
Reproductive age = progesterone
Older or unresponsive = hysterectomy
Most common age group of endometrial cancer
Most common early sign of endometrial cancer
Postmenopausal women (55-65) Irregular or postmenopausal bleeding
2 types of endometrial cancer
Type 1 = endometrial carcinoma
Type 2 = serous carcinoma
60 y/o women w/ obesity and abnormal GTT. Presents w/ abnormal bleeding from her vagina. Tests show abnormal endometrial growth. Pathology shows crowded but normal-looking glands, vesicular chromatin, and no intervening stroma.
What are her 5 most common gene mutations?
What was her precursor?
Type 1 (endometrial) carcinoma
PTEN, MLH1 (DNA MMR), KRAS, PIK3CA, ARID1A
Via endometrial hyperplasia
3 forms of endometrioid (type 1) carcinoma
What morphologic characteristic do they all share (apart from hyperplasia)?
Well differentiated – all well-formed glands
Moderately differentiated - less than 50% solid sheets of cells
Poorly differentiated - > 50% solid growth pattern
NO INTERVENING STROMA
***3 classic associations w/ endometrioid carcinoma
Obesity, DM, Hypertension
Type 2 (serous) carcinoma…
- Frequently in _____
- By definition, _____
- Arises in setting of _____
- Overlaps with _____
- African americans
- Poorly differentiated (grade 3)
- Endometrial atrophy (sporadic)
- Ovarian serous carcinoma
Type 2 (serous) carcinoma – difference in genetics compared to Type 1
Type 2 = TP53 EARLY (90%)
Type 1 = TP53 LATE & only in poorly-differentiated (50%)
Type 2 (serous) carcinoma – precursor
How does it differ from the cancer?
Serous endometrial intraepithelial carcinoma
NO STROMAL INVASION
70 y/o women presents w/ abnormal bleeding from her vagina. Tests show an endometrial mass. Pathology shows a small atrophic uterus with a large bulky tumor that deeply infiltrates the myometrium.
Most likely methods of spread?
Type 2 (serous) carcinoma
–> lymphatics or tubes –> extrauterine spread
Some type 2 carcinomas can have a glandular growth pattern. How to differentiate from type 1?
Type 2 = marked cytologic atypia (NOT normal-looking)
Endometrial tumor w/ glandular and mesenchymal (stromal, muscle, cartilage, etc.) elements
Typical genetics?
Typical metastasis characteristic?
Carcinosarcoma (malignant mixed mullerian tumors)
CARCINOMA genetics (TP53, PTEN, PIK3CA), NOT stromal
Epithelial components ONLY
MMMTs - typical presentation
Extrauterine mesenchymal elements mean _______
Postmenopausal woman w/ bleeding
Worse prognosis
JAZF1-SUZ12 translocation
Pure endometrial STROMAL neoplasms (nodules, sarcomas)
Potential finding later on w/ stromal sarcoma
Distant mets DECADES LATER
Sharply circumscribed, round, firm, gray-white tumors within the uterine wall. Whorled pattern w/ oval nuclei w/ slender bipolar cytoplasmic processes
3 location possibilities
Leiomyoma (fibroids)
- Intramural (w/in the heart of the myometrium)
- Submucosal (just beneath endometrium)
- Subserosal (just beneath outer serosa)
Leiomyoma - genetics
MED12 mutations (70%), HMGIC translocations (40%)
Potential symptoms of leiomyoma (normal woman)
- Abnormal bleeding
- Urinary frequency
- Impaired fertility
- Sudden pain (infarction)
Potential symptoms of leiomyoma (pregnancy)
- Abortion
- Fetal malpresentation
- Uterine inertia (doesn’t contract well)
- Post-partum hemorrhage
2 rare subtypes of leiomyoma
- Benign metastasizing (extends into vessels and spreads)
- Disseminated peritoneal leiomyomatosis (multiple small peritoneal nodules)
Lung disease, TSC2 mutation, leiomyoma
Lymphangioleiomyomatosis
Mass in uterine wall, whorled pattern of SM bundles
Nuclear atypia, mitotic index, zonal necrosis
What classically indicates malignancy? (w/o anything else)
Leiomyosarcoma
10+ mitoses per 10 high power fields
Leiomyosarcoma…
5+ mitoses per 10 HPFs is sufficient if ______
Nuclear atypia or large epithelioid cells are present too
Leiomyosarcoma - what to know about progression
How does it get there? (vessel)
> 50% metastasize hemoatogenously (lungs esp.)
Inferior vena cava
