Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
107 Cards in this Set
- Front
- Back
Histology and hormones of days 1-5 |
progesterone drops. Functionalis layer degenerates/sheds. Bleeding into stroma (fibrin, RBC's, inflammatory cells). Stromal breakdown. |
|
Day 5-Day 14 is called the ____________. |
Proliferative phase (estrogenic) |
|
Proliferative phase--what happens |
Rapid growth of glands and stroma from deeper basalis-->new functionalis. |
|
Proliferative phase histology |
glands are straight, tubular structures regular tall, pseudostratified columnar cells w/ basal nuclei No mucus secretion or vacuolization. Numerous mitotic figures in glands and stroma |
|
When does proliferative phase end? |
Ovulation (Day 14) |
|
Secretory phase (luteal phase) marked by which hormone? |
progesterone (made by corpus luteum in the ovary) |
|
Early secretory phase: |
secretory subnuclear vacuoles (day 16-17) |
|
What happens days 18-24 |
glands dilate--maximum secretion |
|
What would you see week 4? |
Tortuous and serrated or "saw-toothed" glands (due to secretory exhaustion & gland shrinkage) |
|
What happens to the vacuoles during week 3 of the cycle? (still early secretory phase) |
subnuclear vacuoles migrate and become supranuclear |
|
What happens in the late secretory phase? |
stromal changes. Prominent spiral arterioles. Increased edema. |
|
What happens day 23-24 |
predicidual change: stromal cell hypertrophy, increased cytoplasmic eosinophilia, and resurgance of stromal mitoses |
|
Decidualized cells are high in glycogen and lipid (why?) |
early nutrient supply for the blastocyst and developing fetus |
|
Abnormal uterine bleeding definition |
Uterine bleeding that lacks an underlying organic (structural) abnormality |
|
AUB most commonly stems from what? |
hormonal disturbance (hypothalamic/pituitary/ovarian axis) |
|
What is the most common cause of AUB? |
anovulatory cycle |
|
Anovulatory cycle occurs in which ages? |
adolescence, reproductive age, perimenopausal |
|
Why does anovulatory cycle cause bleeding? |
Failure of ovulation results in excessive endometrial stimulation by estrogens that is unopposed by progesterone |
|
I which ages would anatomic lesions (carcinoma, hyperplasia, and polyps) be most common? |
perimenopausal and postmenopausal. (reproductive age possible but less likely) |
|
What are the 3 most common causes of anovulatory cycle? |
Generalized metabolic probs: obesity, malnutrition, other chronic dz Endocrine: thyroid, adrenal, pituitary Ovarian lesions: functioning tumors, PCOS |
|
Obesity causes what hormone state? |
hyperestrogenic |
|
What would not be present on endometrial biopsy of somebody with anovulatory cycle? |
No subnuclear or supranuclear vacuoles because no secretory phase (progesterone driven) ex: day 22 may look like proliferative phase |
|
Young pt w/ infertility, increased irregular bleeding & sometimes amenorrhea). You notice inadequate progesterone during post-ovulatory period. EMB shows secretory endometrium that doesnt correspond with cycle day. Diagnosis? |
Inadequate Luteal Phase |
|
When would you see acute endometritis? |
After deivery/abortion/miscarriage. (Retained products of conception (POC) is substrate for infection--nutritious!) |
|
What are the most common infectious agents of acute endometritis? |
Group A hemolytic streptococci, staphylococci, others. Give abx & curettage |
|
Which is more common, chronic or acute endometritis? |
Chronic |
|
When does chronic endometritis occur? |
Chronic PID retained gestational tissue IUD TB |
|
How can pelvic TB present? (hint: 3rd world countries have way higher rates) |
Both fallopian tubes involved Tuberculous endometritis=50% Tuberculosis of cervix= 5% Ovaries=only surface involvement |
|
Do women with genital tuberculosis have TB elsewhere? (ex: lungs) |
yes. 38% |
|
Pt presents w/ abnormal bleeding, pain, discharge. You note an infection and diagnose chronic endometritis. Which organism? |
Chlamydia (ascending infection) 15% of cases show no apparent cause |
|
How do you diagnosis chronic endometritis histologically? |
plasma cells: cells w/ perinuclear hoth or clearing
|
|
Endometriosis definition |
ectopic endometrial tissue outside of the uterus |
|
Adenomyosis definition |
endometrial tissue w/in myometrium (2-3mm below the basalis layer) |
|
What patient population shows endometriosis? |
reproductive age, 3rd & 4th decade 6-10% of women affected |
|
Most common sites of endometriosis (3) |
1. Ovaries 2. Uterine ligaments 3. Rectovaginal septum (GI sx) |
|
Endometriosis on ovary. Theory? |
Regurgitation theory
|
|
Endometriosis in amenorrhea. Theory? |
Metaplastic theory (in pelvis or abdomen) |
|
Endometriosis in men on hormones for prostate cancer. Theory? |
Stem cell theory |
|
Endometriosis in brain, lung, bone. Theory? |
Benign metastasis theory |
|
Do ectopic endometrium and intrauterine endometrium have the same requirements? |
No. ectopic needs more estrogen & a new blood supply (VEGF) & proinflammatory components (PGE2) |
|
How does ectopic endometrium get the increased estrogen needed? |
High levels of aromatase from stroma Epigenetic alterations increase response to estrogen & decrease response to progesterone |
|
The proinflammatory portion of endometriosis is associated w/ what? |
scarring, PID, ultimately infertility Fibrous adhesions (bowel obstruction) |
|
Red/blue to yellow/brown nodules on or beneath the mucosa or serosa (powder burn marks) seen in? |
Endometriosis |
|
Ovarian endometriosis (common) presents as |
cysts filled w/ brown fluid-->chocolate cyst AKA endometrioma. ovaries can look distorted and cystic |
|
Cancer risk w/ ovarian endometriosis? |
Lining can be atypical--increased risk of cancer. 3 fold increased risk of ovarian cancer of the endometroid and clear cell types |
|
Shared mutations in genes (__________ and ___________) in endometriotic cysts, atypical ndometriosis, and associated carcinomas. |
PTEN ARID1A |
|
Common presenting complaints w/ endometriosis? |
Pelvic pain & Infertility |
|
What populations are at risk for endometrial polyps? |
Reproductive age, perimenopausal, postmenopausal |
|
Sessile or pedunculated exophytic masses of varying size presenting in a patient w/ abnormal uterine bleeding |
Endometrial polyps |
|
Endometrial polyps are associated w/ which drug? |
Tamoxifen (estrogen blocker) used in breast cancers (has a pro-estrogenic effect in the endometrium) |
|
What's the greatest risk of an endometrial polyp? |
May become malignant-->adenocarcinoma can present looking like a miscarriage when passed |
|
Perimenopausal or postmenopausal woman w/ AUB, first differential should be what? |
Endometrial hyperplasia |
|
What is of greatest concern concerning endometrial hyperplasia? |
progression to adenocarcinoma |
|
How is endometrial hyperplasia diagnoses histologically? |
Increased glands: stroma ratio compared to normal proliferative endometrium |
|
What causes endometrial hyperplasia? |
Excessive estrogenic states including: Obesity, menopause, PCOS, functioning granulosa cell tumors of ovary, excessive ovarian cortical function (cortical stromal hyperplasia), exogenous estrogen therapy |
|
Perimenopausal patient w/ AUB. Markedly increased gland: stroma ratio on biopsy w/ an ovarian mass. Most likely Dx? |
Functioning granulosa cell tumors of the ovary (increased estrogen production) |
|
What is the tumor suppressor gene found to be inactivated in both endometrial hyperplasia & endometrial cancer? |
PTEN ( Phosphate & tensin homologue) |
|
Pt w/ benign cutaneous tumors along w/ endometrial & breast cancer. Dx? What would you see on molecular study? |
Answer: Cowden syndrome Inactivation of PTEN |
|
What happens w/ loss of PTEN? |
Overactivation of the PI3K/AKT pathway. Stimulates estrogen dependent gene expression. Upregulates estrogen reception in endometrium & breast |
|
What are the classifications of endometrial hyperplasia? |
Non-atypical hyperplasia Atypical hyperplasia (endometrial intraepithelial neoplasia) |
|
What is the histologic & clinical picture of non-atypical endometrial hyperplasia? |
Increased gland-stroma ratio (>50:50) Can be back to back glands, but usually intervening stroma remains. Rarely progresses to cancer (1-3%) |
|
What happens in non-atypical hyperplasia post menopause? |
Since estrogen is withdrawn, it evolves into cystic atrophy |
|
How does atypical hyperplasia (EIN) present histologically and clinically? |
complex patterns of proliferating glands displaying nuclear atypia. glands back to back and branching. Nucleolus*** Looks like well differentiated cancer |
|
How to treat reproductive age women w/ endometrial hyperplasia? |
Give progesterone. If doesn't want kids then hysterectomy |
|
Most common invasive cancer of the female genital tract? |
Endometrial Carcinoma |
|
What is the patient picture of endometrial carcinoma? (Note: there is type 1 & 2) |
Peak age 55-65 (postmenopausal) <40 uncommon. Bleeding earliest sign. |
|
Ages for Type I and Type II endometrial carcinomas |
T1: 55-65 T2: 65-75 |
|
Which is more common T1 or T2 endometrial carcinoma? |
Type 1 (80%) |
|
Which type of endometrial cancer is well differentiated and can mimic proliferative endometrial glands? |
Endometroid carcinoma (assoc w/ T1) |
|
Which type of endometrial carcinoma arises in the setting of hyperplasia? |
Type 1 |
|
Which type of endometrial carcinoma arises w/ obesity, hypertension, & diabetes? |
Type 1 |
|
What are the mutations seen in type 1 endometrial carcinoma? |
PTEN DNA MMR defects in 20% (MLH1) KRAS LOF in ARID1A TP53 only in poorly differentiated |
|
What molecular finding could you expect in a pt w/ T1 endometrial carcinoma and HNPCC? |
DNA MMR defects Also called lynch syndrome |
|
ARID1A, PIK3CA, CTNNB1, and FGFR2 may effect which quality of the neoplasm? |
They may be responsible for invasion |
|
3 histologic grades for endometroid carcinoma. |
1: well differentiated. Almost entirely well formed glands 2. Moderately diff: features of both 3. Poorly diff: 50% solid pattern |
|
Type 2 (serous) endometrial carcinoma is seen in which patients mainly? |
African Americans aged 65-75 years old |
|
Which type of endometrial carcinoma arises in the setting of endometrial atrophy and is poorly differentiated? |
Type 2 |
|
Other than serous, what are the additional types of Type 2 endometrial carcinoma? |
Clear cell, Mixed Mullerian tumor (aka carcinosarcoma) |
|
What are the mutations associated w/ T2 endometrial carcinoma? |
TP53 (90% of serous carcinomas) PI3K PP2A |
|
Which type of endometrial carcinoma is usualy associated w/ no glands, but rather papillary structures w/ marked cytologic atypia. |
Type 2 |
|
What is the precursor lesion for type 2 endometrial carcinoma? |
Serous EIN (endometrial intraepithelial neoplasm) stains w/ p53 |
|
Which type of endometrial carcinoma has a propensity for extrauterine spread (via lymphatics or tubes) |
Type 2 |
|
Which population has 2x mortality w/ T2 endometrial carcinoma? |
African American women |
|
Stage 1-Stage 4 |
1. in corpus uteri 2. corpus + cervix 3. outside uterus 4. outside pelvis or + rectum/bladder |
|
What is carcinosarcoma? |
Malignant mixed mullerian tumor (MMMT) made of malignant glandular and mesenchymal elements |
|
Mutations seen in MMMT? |
Same as others. TP53, PTEN, PIK3CA. NOTHING SPECIFIC |
|
What is a tumor showing stromal sarcoma or leiomyosarcoma(mesenchymal) + bone, fat, muscle, cartilage(sarcomatous)? |
MMMT (malignant glands AND stroma) |
|
Older Woman w/ postmenopausal bleeding. bulky polypoid mass w/ EMB showing adenocarcinoma mixed w/ malignant mesenchymal elements. Metastasis is noted but contains only the epithelial components. Dx & signs of worse prog? |
MMMT. Invasion & heterologous components=worse outcome. |
|
Endometrial stroma tumors are common/rare? |
Rare (5% of endometrial cancers) |
|
Adenosarcoma |
benign glands & malignant stroma |
|
Pure stromal tumors |
Just malignant stroma. stromal nodule vs stromal sarcoma |
|
Malignant glands benign stroma |
Endometrial cancer |
|
FYI. Younger pt (30-50), polypoid mass can protrude through os. Low grade. HIgh recurrence |
Adenosarcoma |
|
Which fusion genes seen in low grade stromal sarcoma? |
JAZF1 and SUZ12 |
|
What is the risk w/ stromal sarcomas? |
50% recur Distant mets decades later |
|
What is the main tumor of the myometrium? |
Leiomyoma (fibroids) 70% of women. Single or multiple |
|
Both benign (leiomyomas) and malignant (leimyosarcomas) present w/ which gene mutations? |
HMGIC & HMGIY MED12 (uncontrolled division) |
|
Gross features of leiomyoma |
Well circumscribed. Firm white-gray mass. |
|
Where would a leiomyoma cause abnormal intrauterine bleeding? |
Leiomyoma located below the endometrium |
|
Microscopic features of leiomyoma |
bundles of smooth muscle cells (whorled) uniform size/shape of cells ***RARE MITOSIS can degenerate |
|
Most common presentation of leiomyoma |
uterine bleeding, infertility, spontaneous abortion, breech delivery, uterine inertia |
|
Disseminated peritoneal leiomyomatosis |
multiple small peritoneal nodules from pedunculated leiomyoma that broke free |
|
Lymphangioleiomyomatosis |
Associated w/ lung disease & tuberous sclerosis (TSC2)-->pulmonary dz. Don't confuse w/ repro |
|
Where can leiomyomas be mitotically active? |
young or pregnant patients |
|
Leiomyosarcoma presentation & risk |
uncommon. (peak 40-60) more than half metastasize if >10cm then assume leiomyosarcoma |
|
Key histological features of leiomyosarcoma? |
Nuclear atypia ***Mitotic index (10 or >/10hpf=malignant) **Zonal necrosis |
|
Most common place of metastasis? |
lung-->d/t venous drainage |