Week 3 Flashcards
General principles of contraception: 7 main strategies
1) Stop/block production of sperm
2) Block sperm entry into/past cervix
3) Thicken cervical mucosa: Progestin methods
4) Ligate/occlude/remove fallopian tube
5) Prevent ovulation (Progestin alone, Progestin + Estrogen Combo)
6) Avoid intercourse when ovulating
7) Thin endometrium to prevent implantation (Progestin)
Effects of exogenous Progestin (6)
1) Inhibits ovulation by suppressing function of HPO axis
2) Modifies midcycle surges of LH and FSH
3) Diminishes ovarian hormone production
4) Reduces activity of cilia
5) Produces endometrial changes unfavorable to embryo implantation
6) Thickens cervical mucus to impede sperm transit
Effects of exogenous estrogen (4)
1) Helps stabilize uterine lining → less breakthrough bleeding
2) Added suppression of FSH - less follicle development
3) Increases SHBG → less male effects (i.e. acne)
4) Reduces ovarian cancer, endometrial, colon cancer risks
Risks of estrogen
CLOTTING
Increases clotting factors 2, 7, 10, 12, 8, and fibrinogen → shift towards thrombus formation and prevention of clot dissolution → greater risk of venous and arterial clot formation
Higher estrogen = more clotting factors
Who should avoid contraception with estrogen?
Smoker > age 35
CAD, heart disease, history of clots (DVT, PE), uncontrolled HTN, diabetes with vascular changes
Migraines with aura
Active liver/gallbladder problems
Breast cancer (Estrogen dependent cancers)
Major surgery with prolonged immobilization
Copper IUD:
Creates inflammatory reaction in uterus
Copper acts as spermicide
Non-hormonal method
Emergency contraceptive options
prevent pregnancy AFTER sex
Mechanism: NOT the same as abortion pill, is basically contraceptives at a much higher dose
1) Plan B: Levonorgestrel, progestin only (75% efficacy)
2) Copper IUD: 99% effective
3) Ella: ulipristal acetate = progesterone receptor modulator, better efficacy than Plan B
Squamocolumnar junction of cervix
between stratified squamous epithelium of ectocervix and glandular columnar epithelium of endocervix
Area where 99% of HPV-associated cervical cancer arise
2013 recommendations for cervical cancer screening:
Cervical cytology screening should begin at age 21
Cervical cytology is recommended every 3 years for women between ages of 21-29 years
Cervical cytology screening with HPV co-testing is recommended every 5 years for women between age 30-65
Cervical cytology screening should stop for women at age of 65 years if she has been adequately screened and had not had CIN2 or CIN3 lesions for previous 20 years
Goal of screening for cervical carcinoma
Catch DYSPLASIA (CIN) before it develops into carcinoma
Progression from CIN –> carcinoma takes 10-20 years
PAP SMEAR = GOLD STANDARD
What do you do if you get an abnormal Pap smear test?
-Confirmatory colposcopy (visualization of cervix with magnifying glass) and biopsy
Limitations of the Pap smear?
Inadequate sampling of transformation zone (false negative screening)
Limited efficacy in screening for adenocarcinoma
Human Sexual Response Cycle
Four phases:
Excitement
Plateau
Orgasm
Resolution
Desire phase
no measurable physiologic changes, desire is different than attraction and can be augmented or inhibited by learned responses and experiences
Arousal/Excitement Phase
physiologic changes occur
1) Increased pulse and respiration
2) Shift blood flow to pelvis and genitalia
3) Shift in blood flow to skin
4) Nipple erection
Erection in men mechanism?
increased penile blood flow due to relaxation of penile arteries and corpus cavernosal smooth muscle
Mediated by release of NO from nerve terminals and endothelial cells → cGMP synthesis in smooth muscle cells → muscle relaxation, increased blood flow to corpus cavernosum
Plateau Phase
heightened state of arousal, physiologic changes are stable
Orgasm Phase
series of rhythmic contractions of the perineal muscles
Male → 3-7 ejaculatory spurts of seminal fluid
Female → elevation of “orgasmic platform” (posterior vaginal wall - levator ani, pubococcygeus)
Resolution phase
Males
orgasm followed by obligatory resolution phase - return to baseline, further stimulation cannot produce excitement
Varies in length from 5 minutes to 24 hours or longer
Resolution phase
Females
resolution not always obligatory, can have repeated orgasm without resolution to a basal state
Medical Model of Sexual Dysfunction: 4 parts
Sex is a physiologic process
Sexual dysfunctions result from alterations in physiology
Alterations come from “blocks” or interruptions in the sexual response cycle
Emotional responses may alter or stop response cycle
PDE5 inhibitors
Sildenafil, Vardenafil, Tadalafil
Inhibits breakdown of cGMP
No effect on absence of sexual stimulation
Side effects: headaches, dizziness, flushing, sudden hearing loss, anterior optic neuropathy
Desire Phase Disorders: (2)
almost always due to performance anxiety or aversion
1) Low Libido - Hypoactive Sexual Desire Disorder:
2) Inhibited sexual desire - Sexual Aversion Disorder:
Hypoactive Sexual Desire Disorder
Causes: Chronic disease, depression, hypoestrogenic states
Persistently or recurrently deficient sexual/erotic thoughts or fantasies and desire for sexual activity
Sexual Aversion Disorder
Results of pain or other dysfunction
Sexual aversion and HSDD are a continuum
Dyspareunia
pain with intercourse
Vaginismus
involuntary spasm of muscles around outer third of vagina
Makes penetration impossible
Causes: pain, religious orthodoxy, negative parental attitudes
Primary ovarian tumors: list them
1) Epithelial neoplasms (60-70% of ovarian tumors)
- Serous
- Mucinous
- Endometroid
- Clear cell
2) Germ cell (15-20%)
-Teratomas
-Dysgerminoma
-Yolk Sac tumor
Choriocarcinoma
3) Sex Cord Stromal Neoplasms: 5-10%
- Granulosa cell tumors
- Fibromas and thecomas
- Sertoli-Leydig cell tumors
Major risk factors for ovarian tumors?
Infertility, unopposed estrogen > 10 years, family history, nulliparity
BRCA1 and 2
BRCA1 and BRCA2
- what chromosomes?
- results in what kind of cancer?
BRCA1: Ch17
BRCA2: Chr13
DNA repair genes
Breast and ovarian cancer risk
Typically high grade SEROUS carcinoma*
Epithelial ovarian neoplasms can be ______, _______ or _________.
4 subtypes?
benign, borderline, or malignant
- Serous
- Mucinous
- Endometroid
- Clear cell
Epithelial ovarian neoplasms are derived from __________ that lines the ovary and fallopian tubes
–> fimbriated end of fallopian tube may be origin
coelomic epithelium
Benign epithelial ovarian neoplasms = ________
main features?
in pre or post menopausal women?
Cystadenomas
Single cyst, simple, flat lining
Usually in PREmenopausal women (30-40 years)
Malignant epithelial ovarian neoplasms = ________
main features?
in pre or post menopausal women?
Cystadenocarcinomas
- Complex cysts with thick, shaggy, lining
- Hemorrhage, necrosis, rapidly increasing abdominal girth
Usually in POSTmenopausal women (60-70 yrs)
Serous epithelial ovarian neoplasm
Main features?
main buzz words (2)
what serum marker is elevated?
Full of water fluid, usually also cystic
Most frequent subtype
1) HIERARCHICAL BRANCHING* cuboidal cells (resemble tubal epithelium, but without cilia)
2) PSAMMOMA BODIES*
Increased CA-125 marker
BRCA1 –> increased risk for SEROUS carcinoma
Mucinous epithelial ovarian neoplasm
Main features?
main buzz words (1)
full of mucus-like fluid, usually also cystic
Huge tumors
1) Can have GOBLET CELLS** present
Clear cell epithelial ovarian neoplasm
2 main buzzword features
Very rare, but may be aggressive
1) Associated with ENDOMETRIOSIS**
2) “HOBNAIL CELLS” - nuclei bulging into cystic space without apparent cytoplasm**
Endometrioid epithelial ovarian neoplasm
Main buzzword/fetature?
*Resemble normal endometrial glands - same appearance as uterine endometrioid tumors
**→ MUST exclude metastasis from uterine tumor
Usually are malignant
Sex Cord Stromal Neoplasms
Include what 3 subtypes?
Granulosa cell tumors
Fibromas and thecomas
Sertoli-Leydig cell tumors
Granulosa cell tumors
2 buzzword histology features?
Presentation?
Neoplastic proliferation of granulosa cells
Often produce estrogen → presents with signs of estrogen excess
1) Call-Exner Bodies** (resembles primitive follicle)
2) and nuclear grooves
Fibromas
benign tumor of fibroblasts
can get Meig’s Syndrome
Appears fibrous and pink
Meig’s Syndrome
Associated with pleural effusions and ascites = Meig’s Syndrome
Resolves with removal of tumor
Sertoli-Leydig cell tumors
Recapitulates developing testis
-Composed of Sertoli cells that form tubules and Leydig cells with characteristic Reinke crystals
May produce androgen → hirsutism and virilization
Germ Cell Tumors
subtypes?
1) Mature and Immature Teratomas
2) Dysgerminoma
3) Yolk sac tumors (aka endodermal sinus tumor)
4) Choriocarcinoma
Mature cystic teratoma
Females
BENIGN in females
Composed of fetal tissue derived from two or three embryologic layers (skin, hair, bone, cartilage, gut, etc.)
Usually occurs in reproductive years
Can be bilateral
Struma ovarii
teratoma composed primarily of thyroid tissue
Immature teratoma
Females
malignancy
Microscopic identification of immature neuroepithelium
Tightly packed small dark cells with lots of mitoses
Grading based on amount of immature neural tissue (more is worse)
Dysgerminoma
histological appearance?
prognosis?
what is elevated in serum?
Composed of large cells with clear cytoplasm and central nuclei (resemble oocytes) - Female counterpart to seminoma
Can be bilateral
Good prognosis
Serum LDH elevated
Yolk Sac Tumors (aka endodermal sinus tumor)
Histology?
Buzz word for histology?
Elevated serum levels of what?
Malignant tumor that mimics yolk sac
Most common germ cell tumor in children
High AFP
Contains SCHILLER-DUVAL BODIES (glomerulus-like structures)
Choriocarcinoma
malignant tumor composed of what two cell types?
Mimics what tissue?
How does it spread?
What is elevated in the patients serum?
Response to chemo?
Malignant tumor composed of cytotrophoblasts and syncytiotrophoblasts
Mimics placental tissue but villi are ABSENT
Small, hemorrhagic with early hematogenous spread
High B-hCG
Poor response to chemo
Krukenberg Tumor
metastatic mucinous tumor, involves both ovaries
Most commonly metastatic GASTRIC CARCINOMA
SIGNET RING CELL morphology
Pseudomyxoma peritonei
“Jelly Belly”
Mucin throughout abdomen
Can be due to mucinous tumor of the appendix with metastasis to the ovary
Fallopian Tube Pathology:
Intraepithelial Carcinoma (TIC):
Precursor lesion to most ovarian high grade serous carcinomas
Derived from fimbriated end of fallopian tube
Typically p53 mutations
Ectopic pregnancy
Implantation of fertilized ovum at site other than uterine wall
Most common (90%) in fallopian tube
Key risk factor is scarring (PID)
Rupture = medical emergency,
Can cause hematosalpinx (bleeding into fallopian tube)
Presentation: lower abdominal pain after missed period
Inhibin A vs. B
Inhibin A - important in luteal phase
Inhibin B - important in follicular phase of menstrual cycle
Approach to evaluating Disturbances in Menstrual Cycle:
3 things you want to check, and 2 things you do NOT want to check
1) Exclude pregnancy (B-hCG)
2) Rule out high prolactin
3) DO NOT need androgen levels or GnRH stimulation test
4) Draw LH and FSH levels in first 5 days after menses starts (normally LH=FSH)
Hypogonadotropic Hypogonadism (women)
low LH, FSH, and estradiol with amenorrhea
Hypogonadotropic Hypogonadism (women)
causes
1) Congenital GnRH deficiency (Kallmann Syndrome)
2) Acquired GnRH deficiency
- Hypothalamic amenorrhea
Hypothalamic amenorrhea
Acquired GnRH deficiency
defects in amount of frequency of GnRH pulses - usually do to stress, exercise, or poor nutrition
Hypergonadotropic hypogonadism (women)
high FSH and/or LH, low estradiol and amenorrhea
Hypergonadotropic hypogonadism (women)
two congenital causes
1 acquired cause
1) Congenital:
- Turner Syndrome
- Gonadal dysgenesis (XO, XX/XO)
2) Acquired:
- Premature ovarian insufficiency (POI)
Premature ovarian insufficiency (POI)
- definition
- pathophys
ovarian failure before age 40
Typically due to autoimmune process (associated with autoimmune thyroid disease, T1DM, celiac, pernicious anemia)
Premature ovarian insufficiency (POI)
presentation (symptoms)
labs?
Presentation: irregular menses, without moliminal symptoms (breast tenderness, bloating, and cramping)
LABS:
- FSH levels rise before LH levels due to loss of inhibin
- FSH>LH in early follicular phase, low E2
Hyperandrogenic anovulation:
3 causes
1) Polycystic ovarian syndrome (PCOS)
2) Tumors causing hirsutism
3) Obesity induced anovulation
Polycystic ovarian syndrome (PCOS)
mechanism?
-high amplitude GnRH pulses causes oversecretion of LH
high LH –> theca cell stimulation and over production of androgens
decreased FSH causes follicular degeneration with fluid filled cyst formation
PCOS
presentation
Labs?
Presentation: irregular menses, anovulation, hirsutism, acne, obesity, insulin resistance
Labs:
- High LH/FSH > 2.5/1
- Increased androgens (testosterone and DHEAS)
Patients with PCOS are at increased risk for what?
increased risk of endometrial cancer (estrogen unopposed by progesterone), insulin resistance, diabetes, HTN, cardiac disease
Tumors causing hirsutism
pathophysiology?
virilizing tumors of ovary (testosterone producing) or adrenals (DHEA-S producing)
Tumors causing hirsutism
presentation?
labs?
Presentation: rapid onset, male pattern balding, hair on upper chest and back, clitoromegaly
Labs: Testosterone > 200 or DHEAS > 800 suggest TUMOR
Obesity induced anovulation
labs and presentation?
normal puberty and cycles until high weight
Labs: LH=FSH (normal) and mild elevations in androgens
Mechanism of estrogen agonist action?
how does this differ from estrogen antagonist action?
AGONIST:
- diffuse through membrane → enter nucleus and bind to an ER → conformational change → receptor dimerization
- ER dimers bind ERE in promoter regions of target genes → recruit co-activators → initiate transcription
ANTAGONIST
-antagonists of ERs also promote dimerization and DNA binding, but causes different conformational change and recruits co-REPRESSORS and REDUCES transcription
Effects of estrogen on development? (3)
Promote development of vagina, uterus, and breast
Secondary sex characteristics-axillary/pubic hair, fat distribution
Accelerated growth phase and closing of epiphyses of long bones at puberty
Physiologic effects of estrogen (4)
1) Breast growth
2) Endometrial growth → activates endometrium in proliferative phase
3) Decrease bone osteoclast function
4) Liver - Decreases LDL, increase HDL, increase clotting factors
Adverse effects of estrogen administration (8)
1) Clotting
2) Endometrial and breast cancer
- -> Endometrial cancer risk reduced if given with progestin
3) Postmenopausal bleeding
4) Nausea, breast tenderness
5) Anorexia, vomiting, diarrhea
6) HTN
7) Increased migraine headache frequency
8) Gallstones
Contraindications of estrogen use (4)
1) History of breast or endometrial cancer
2) Vaginal bleeding
3) Acute liver disease
4) Active thrombosis
Menopausal Hormonal Therapy: ESTROGEN (3)
want lowest effective dose and for shortest duration
1) Vasomotor symptoms → systemic treatment
2) Vulvovaginal and urogenital complaints (vaginal dryness, pruritus) → local application vaginal products preferred
3) Prevention of osteoporosis → ONLY consider if pt at SIGNIFICANT risk of osteoporosis
Physiologic vs. pharmacologic administration of estrogen
“Physiologic replacement” → hypoestrogenic menopausal symptoms
5-10 mcg ethinyl estradiol
“Pharmacologic suppression” of ovulation
20-35 mcg ethinyl estradiol in oral contraceptive
Medroxyprogesterone (megestrol)
Progesterone type
less effect on pituitary, mainly peripheral actions (endometrial tissue)
Norethindrone
Progesterone type
1st gen progesterone
Levonorgestrel
Progesterone type
2nd gen progesterone
→ increased androgenic actions**
Desogestrel-norethynodrel-norgestimate
Progesterone type
3rd gen progesterone
*LOWER ANDROGENIC ACTIONS
higher VTE risk
Drospirenone
4th gen progesterone
antimineralocorticoid and antiandrogenic activity → increased VTE risk
Effect of progesterone on endometrium?
*ANTI-ESTROGENIC action on ENDOMETRIAL proliferation
Progesterone
adverse reactions
Depression, somnolence headache
Breast enlargement/tenderness
Nausea
Elevated BP, edema, weight gain
Osteoporosis (suppress FSH and LH → estradiol levels lower)
Raloxifene
mechanism?
SERM
Agonist activity on BONE receptors (increase bone mineral density) and LIVER receptors (decrease LDL and total cholesterol)
ANTAGONIST activity (growth promoter) in UTERINE and BREAST tissue
Raloxifene
use?
what are the benefits of Raloxifene over Tamoxifen?
Prevention of osteoporosis, postmenopausal therapy
Raloxifene has NO effect on breast or endometrial tissue → no increased risk of breast cancer
Adverse effects of Raloxifene?
Still have increased clotting (via hepatic synthesis of clotting factors)
Hot flashes
Tamoxifen
how does it differ from Raloxifene in mechanism and use?
has receptor action in endometrial → increase risk of endometrial cancer (NOT present in Raloxifene), but still protects against breast cancer
Use: treatment and prevention of breast cancer
Adverse reactions of tamoxifen? (3)
Increased incidence of endometrial cancer (5 FOLD!)
Hot flashes
Thromboembolic disorders
Drug interactions with oral contraceptives?
drugs that induce or enhance estrogen metabolism (CYP450) → reduction in contraceptive effect
Rifampin, anticonvulsants (phenytoin, carbamazepine, phenobarbital), griseofulvin
Lichen sclerosis
smooth white plaques/papules
- Thinning of epidermis and fibrous (sclerosis) of dermis**
- Presents as LEUKOPLAKIA with parchment-like vulvar skin
- Typically in postmenopausal women - possible autoimmune etiology
- Benign - can have slightly increased risk for SCC
Lichen Simplex Chronicus
hyperplasia of vulvar squamous epithelium
- LEUKOPLAKIA + leathery vulvar skin
- Associated with chronic irritation and scratching
- NO increased risk of SCC (benign)
Condyloma acuminatum:
- verrucous (cauliflower), multifocal
- Caused by HPV 6 and 11
- Hyperkeratosis (thickened stratum corneum with “ghost” nuclei) and parakeratosis (especially papillae tips)
- Hypergranulosis and elongated rete ridges
**Koilocytes (crinkly raisin)
Rarely progresses to carcinoma
Molluscum contagiosum
flesh colored, pearly skin lesions
Endophytic growth with eosinophilic inclusions
Self-limited (no tx)
Benign
Trichomonas:
flagellated protozoan infection
Frothy yellow discharge
Dysuria, dyspareunia
“Strawberry cervix” on colposcopy
Candida:
normal, but can overgrow (DM, abx, pregnancy)
Curd-like discharge and pruritis
Vulva drains to ____ lymph nodes
inguinal
Vulvar Intraepithelial Neoplasia (VIN):
Nuclear atypia (Koilocytic) and lack of maturation = DYSPLASIA
- Increased mitoses, full thickness dysmaturity (cells at surface look the same as those near the base)
- Precursor lesion for SCC
Vulvar Carcinoma:
carcinoma from squamous epithelium lining vulva
Rare
Presents as LEUKOPLAKIA
Caused by HPV (high risk 16 and 18) or non-HPV causes (e.g. long standing lichen sclerosis)
HPV-Associated SCC:
Females, less than 60 years
VIN is precursor lesion
10-20 yrs from initial infection until tumor forms
Appearance: infiltrating irregular nests of malignant squamous cells eliciting a desmoplastic stromal response
Inflammatory associated SCC:
Females > 70 years
HPV negative
Lichen sclerosus/d-VIN precursor lesions
Prominent keratin pearls in well-differentiated carcinoma + increased mitoses, and pink cytoplasm
Extramammary Paget Disease:
- Malignant epithelial cells in epidermis of vulva
- Presents as erythematous, pruritic, ulcerated vulvar skin
Represents carcinoma in situ with NO underlying carcinoma (ISOLATED TO EPIDERMIS) - Paget disease OF NIPPLE almost always associated with underlying carcinoma
Extramammary paget disease must be distinguished from ____
Melanoma
Pagets = PAS+, keratin +, S100-
Malignant Melanoma: PAS-, keratin-, S100+
Embryonal rhabdomyosarcoma:
aka sarcoma botryoides
- Malignant mesenchymal proliferation of immature skeletal muscle
- Presents as bleeding + grape-like mass protruding from vagina or penis of a child (<5yrs)
- Rhabdomyoblast
Rhabdomyoblast
characteristic cell of rhabdomyosarcoma
Cytoplasmic cross-striations
Desmin +, Myogenin +
Adenosis:
focal persistence of columnar epithelium in the upper vagina (derived from MULLERIAN DUCT)
Columnar epithelium of upper vagina typically replaced by squamous epithelium of lower ⅓ of vagina during development
Increased incidence in females we were exposed to DES in utero
Clear cell adenocarcinoma:
Malignant proliferation of glands with clear cytoplasm
Rare - Associated with DES vaginal adenosis
Vaginal carcinoma:
Carcinoma arising from squamous epithelium lining the vaginal mucosa
- Usually related to high risk HPV
- Precursor lesion = VAIN (vaginal intraepithelial neoplasia)
- Spreads to regional lymph nodes:
Lower 1/3 of vagina drains to ____ lymph nodes
inguinal
Upper 1/3 of vagina drains to ____ nodes
Iliac
Endocervical polyps:
- Can cause “spotting”
- Curettage curative
- Dilated mucus-secreting glands and inflammation
Cervical Intraepithelial Neoplasia (CIN)
Koilocytic change, disordered cellular maturation, nuclear atypia, increased mitotic activity within cervical epithelium
Precursor lesion to SCC
CIN grades:
higher grade = more likely to progress to SCC
CIN I = < ⅓ thickness of epithelium
CIN II = < ⅔ thickness of epithelium
CIN III = slightly less than entire thickness of epithelium
CIS = entire thickness of epithelium
Cervical Squamous Cell Carcinoma (6)
- Invasive carcinoma that arises from cervical epithelium
- Typically in middle-aged women (age 40-50 yrs)
- Presentation: vaginal bleeding, post-coital bleeding, cervical discharge
- HPV related malignancy (16/18)
- Related to immunodeficiency (cervical carcinoma = AIDS defining illness)
- *Unlike endometrial cancers, the STAGING of cervical cancers is based on clinical features
Cervical cancer: Adenocarcinoma in situ: (AIS)
15% of cervical cancer cases
HPV related
Histology: hyperchromasia, mucin depletion, luminal mitoses, high N:C
Endometrial Polyps:
hyperplastic protrusion of endometrium
Presents as abnormal uterine bleeding
Dense pink stroma, haphazardly arranged glands
Acute endometrits
bacterial infection of endometrium usually due to retained products of conception
Presents as fever, abnormal uterine bleeding, pelvic pain
Increase PMNs in stroma and glands
Curettage curative
Chronic endometritis
Chronic inflammation of endometrium
Plasma cell and lymphocyte infiltrate
Causes: retained products of conception, chronic PID (Chlamydia, Gonorrhea, etc.), IUDs, TB
Presents as abnormal uterine bleeding, pain, and INFERTILITY
Endometriosis/Adenomyosis
Endometrial glands AND stroma OUTSIDE uterine endometrial lining
*Adenomyosis: (endometrial glands and stroma WITHIN UTERINE WALL), uterine myometrium involvement
Extrauterine = endometriosis
Most common site of involvement is ovary → “Chocolate cyst”
Can increase risk for carcinoma at site of endometriosis (especially in ovary)
Presentation of endometriosis/adenomyosis
dysmenorrhea, may cause Infertility
Endometrial hyperplasia
hyperplasia of endometrial glands relative to stroma
Due to unopposed estrogen (obesity, PCOS, estrogen replacement)
Presents as postmenopausal bleeding
Can progress to carcinoma
Most important predictor for progression is presence of CELLULAR ATYPIA
Simple hyperplasia:
increased gland to stroma ratio
Rarely progresses to cancer
Treated with progestins
Complex hyperplasia:
+/- cytologic atypia
Glandular crowding and architectural complexity
5-30% progress to cancer
Leiomyoma:
BENIGN neoplastic proliferation of smooth muscle arising from myometrium
Related to estrogen exposure
Multiple, spherical, firm, “white whorled”, WELL CIRCUMSCRIBED*
Most common uterine tumor
Treatment of leiomyoma
Surgery, embolization, GnRH agonist, nothing
Leiomyosarcoma
Malignant proliferation of smooth muscle arising from myometrium
Arise de novo (NOT from leiomyoma)
Usually in postmenopausal women
SINGLE lesion with areas of NECROSIS and HEMORRHAGE
INFILTRATING polypoid mass
Most common uterine sarcoma
Rapid increase in size, metastasizes to lungs, low survival
Endometrial carcinoma
malignant proliferation of endometrial glands
Most common invasive carcinoma of female genital tract
Usually presents as postmenopausal bleeding, but many asymptomatic
Type I endometrial carcinoma:
endometrioid adenocarcinoma
Molecular pathway: PTEN → KRAS → b-catenin
HYPERPLASIA pathway - arises from endometrial hyperplasia
Minimal invasion/spread
Endometrioid histology (looks like normal endometrium)
Perimenopausal - age 60
Risk factors for endometrial carcinoma
- Genetics: HNPCC (MMR genes and microsatellite instability)
- MLH1 and MSH2 gene mutations - typically
- SOMATIC mutations (non-germline)
- Colon + endometrial cancer - Unopposed estrogen (PCOS, obesity, etc.)
Type II endometrial carcinoma:
serous adenocarcinoma
Postmenopausal* - 70 years
- Aggressive - Disseminated at presentation
- 10-20% of endometrial cancers
- Papillary structures, psammoma bodies
Molecular pathway of Type II endometrial carcinoma
53 driven**
SPORADIC pathway
Carcinoma arises in atrophic endometrium with no evident precursor lesion
Staging vs. Grading of uterine cancers:
Uterine cancers: Prognosis depends on STAGE (extent of spread)
