Assessment 5 Flashcards
Boundaries of Pelvic inlet: Pelvic Brim
Pubic crest
Pectineal line
Arcuate line
Ala and promontory of sacrum
Boundaries of pelvic outlet
Inferior end of pubic symphysis Ischiopubic ramus Ischial tuberosity Sacrotuberous ligament Tip of coccyx
Pelvis Major
False pelvis, above pelvic aperture
Part of abdominal cavity, abdominal viscera
Lateral: Iliac fossa
Posterior: L5 and S1
Anterior: Abdominal wall
Pelvis Minor
True pelvis, inferior to pelvic inlet
Inferior limit: inferior pelvic aperture/Pelvic brim
Conjugate diameter
Distance between sacral promontory and thickest portion of pubic symphysis
Greater sciatic foramen
Created by greater sciatic notch and sacrospinous ligament
Lesser sciatic foramen
Lesser sciatic notch
Sacrospinous ligament
Sacrotuberous ligament
Anterolateral wall of pelvis
Pubic bones
Portion of ischia
Obturator internus muscle
Lesser sciatic foramina
Posterolateral wall of pelvis
Pelvic surface of sacrum
Grater sciatic foramina
Priformis muscle
Structures originating from posterolateral wall exit…
Greater sciatic foramen
Piriformis muscle
Nerves of lumbosacral plexus
Arteris
Structures originating from anterolateral wall exit…
Lesser sciatic foramen
Obturator internus tendon
Pelvic diaphragm components
Levator ani
Coccygeus
Levator ani components
Pubocorectalis
Pubococcygeus
Iliococcygeus
Pubocorectalis
Puborectal swing, involved with incontinence
Origin of iliococcygeus
Arises from tendinous arch which comes from fascia of obturator internus
Coccygeus origin and insertion
Ischial spine to coccyx
Pelvic diaphragm - male
Urogenital diaphragm
Ureters: 3 constrictions
Ureteropelvic junction
Pelvic brim
Ureterovesical junction (bladder)
Parts of bladder
Detrusor muscle
Internal sphincter
Ureteric orifices
Interureteric fold
Rectosigmoid junction
Level of S3
Rectal ampulla
Dilation superior to pelvic diaphragm - stores feces before expulsion
Anorectal ring - pectinate line
Termination of puborectalis muscle
Blood supply to rectum: 3
Superior rectal artery
Middle rectal artery
Inferior rectal artery
Superior rectal artery origin
IMA
Middle rectal artery origin
Internal iliac artery
Inferior rectal artery origin
Internal pudendal artery
Superior rectal vein drains into..
IMV - portal system
Middle rectal vein drains into..
Internal iliac vein - caval
Inferior rectal vein drains into..
Internal pudendal then internal iliac - caval
Internal/External hemorrhoids
Internal: Dilation of veins of internal rectal plexus
External: Dilation of external veins of rectal plexus
Superior gluteal artery
Passes between lumbosacral trunk and S1
Exits greater sciatic foramen superior to piriformis muscle
Posterior division of male pelvis
Superior gluteal artery
Iliolumbar artery
Lateral sacral artery
Anterior division of male pelvic blood supply
Umbilical artery Obturator Middle rectal Inferior gluteal Internal pudendal Inferior vesical
Endopelvic fascia and spaces (ligaments)
Transverse cervical - cardinal
Uterosacral
Uterovesical
Rectouterine pouch
Adjacent to posterior fornix of vagina
Between vagina and rectum
Corpora cavernosa
Ventral portion of erectile tissue
Deep penile artery central within each tissue mass
Corpus spongiosum
Central tissue, attaches to glans
Crura of penis
Continuation of corpora cavernosa
Covered by ischiocavernosus muscle
Bulb of penis
Expanded portion at base of spongiosum
Covered by bulbospongiosus
Parts of urethra
Spongy
Intermediate (membranous)
Prostatic urethra
Intramural urethra
Parts of vagina
Mons pubis Glans clitoris Labium majus Labium minus Vestibule - space between labia minora
Scrotum female equivalent
Labia majora
Ventral surface of penis female equivalent
Labia minora
Main innervation of perineum
Pudendal nerve and branches:
Inferior rectal
Perineal nerve
Dorsal nerve of penis/clitoris
Perineal nerve branches
Superficial perineal - posterior scrotal/labial
Deep perineal - muscles of superficial and deep pouches
Ilioinguinal nerve
Anterior scrotal/labial
Genitofemoral nerve
Genital branch - overlap anterior scrotal/labial
Inferior cluneal nerve
Inferior buttock and gluteal fold
Path of pudendal nerve
From S2-S4 –> through greater sciatic foramina and lesser sciatic foramina
Superficial perineal pouch boundaries
Superior: Perineal membrane
Inferior: Perineal fascia
Lateral: Ischiopubic rami
Deep perineal pouch boundaries
Superior: Inferior fascia of pelvic diaphragm
Inferior: Perineal membrane
Lateral : Obturator fascia
Epistiotomy
Controlled incision of perineum to aid passage of infant: Median and mediolateral incision
Primordial germ cells
Arise in yolk sack, migrate through umbilical cord to GI tract
Lie in intermediate mesoderm
Epithelial cells proliferate and surround PMG’s –> sex cords
Sex cords: Male and female
Early gonad has both so it is called indifferent gonad
Male sex cords develop first = primary. Located in inner region = medullary sex cords
Female sex cords develop second = secondary. Located in outer region = cortical sex cords
Medullary sex cords + TDF
Pre Sertoli cells –> Sertoli cells
Sertoli cells
Produce Anti Mullerian hormone
Leydig cells
Produce Testosterone when stimulated by LH
Anti mullerian hormone
Produced by Sertoli cells
Degenerate Mullerian duct = no uterus, cervix, superior vagina
Testes determining factor
Encoded by SRY
Female cortical sex cords development
Develop into follicle cells
Testosterone and development
Protect Wolffian duct = vas deferens, epididymis
Female development of Mullerian/Wolffian ducts
No TDF or AMH = no degeneration of Mullerian duct
No testosterone = Degeneration of Wolffian duct
Remodeling of female anatomy: Paramesonephric ducts
Paramesonephric ducts fuse caudally at pelvic urethra and thicken = Uterus, uterine tubes, cervix, fornix, superior vagina
Remodeling of female anatomy: Pelvic urethra
Endoderm, proliferates to form sinovaginal bulb
Elongates to form hymen and inferior portion of vagina
Incomplete fusion of paramesonephric ducts
Uterus bicornis: 2 uterine horns
Uterus didelphys: Double uterus
Uterus didelphys with double vagina
Incomplete formation of urorectal septum
Rectocloacal canal: Common outlet for urethra, vagina, rectum
Rectovaginal fistula: Common outlet for rectum and vagina
Androgen insensitivity sundrome
XY male with mutation of testosterone receptor
Testosterone normal/high –> converted to estrogen
Testes but no sperm, no male accessory organs
Anti mullerian hormone present = no internal female genitalia
Estrogen = female external genitalia, blind ended vagina, breasts
Formation of broad ligament
Fusion of mullerian ducts and break away from mesenchyme
Pouches anterior and posterior to broad ligament
Gubernaculum
Connects ovaries to labia majora, passes behind uterine tubes
When paramesonephric ducts fold, pulled medially
Superior: ovarian ligament
Inferior: round ligament of uterus
Kiss1 neurons
Part of HPG axis
Positive feedbak to GnRH neurons
Sex steroids inhibit Kiss1 = inhibition of GnRH
Excess and minimal GnRH and LH/FSH
Both can cause reduced LH/FSH release
HyperPRL and HPG
Decrease activity of entire axis
HyperTSH and HPG
Can activate FSH
Leptin and HPG axis
Lack of body fat can decrease HPG axis
HPG for males
FSH - sertoli cell function and spermatogenesis
LH - Leydig cell function –> testosterone
Inhibin
Released by sertoli cell, can inhibit FSH
Testicular Androgen binding protein
Need local androgen for spermatogenesis
ABP binds androgens from leydig cell to increase concentration of androgens
Exogenous androgen thus does not help with spermatogenesis
Developmental actions of testosterone
Differentiation of Wolffian ducts (DHT)
Descent of testes
Male brain
Adolescent and testosterone
Secondary sex characteristics: Voice, hair, penis size
Aggression
HP(ovarian) Axis
Requires pulsating GnRH
Developmental actions of estrogen/progesterone
Female sexual differentiation (no need for hormones)
Adolescent and estrogen/progesterone
E: Secondary sex characteristics - ovary/vagina/uterus/breast size increase
Overall process of male gonadal development
Gonads –> penis
Gonad + SRY = Testes
Mullerian ducts + AMH = degeneration
Wolffian ducts + Testosterone = Vas deferens, epidiymis, seminal vesical
DHT androgenizes external male genitalia
Critical in utero time for sex development
7-13 weeks
3 categories of DSD
- Sex chromosome DSD
- 46, XY DSD
- 46, XX DSD
Sex chromosome DSD (3)
- Turners - 45 X
- Klinefelters - 47 XXY
- Mixed gonadal dysgenesis - 45,X/46,XY
46, XY DSD etiology
Disorders of gonadal development
Disorders of androgen synthesis/action
46, XX DSD etiology
Disorders of gonadal development
Androgen excess - maternal and fetal
Palpable gonads in child = ?
Testicles = Y chromosome
Uterus present/absent
Absent = AMH = testicles Present = No AMH = no testes = ovaries/abnormal testes
Normal puberty - males
First and second occurrences
- Testicular enlargement - 11.5yrs
- Pubic/axillary hair
Testicular enlargement before 9 is early
Spermarche
~13.5 yrs
Tanner 3-4 gonads
Growth spurt - males
Later than females
Tanner 3-4
Normal puberty females - first and second sign
- Thelarche - 10.7yrs, can be pubarche though
- Pubarche ~12yrs
Breast development before 8yrs is early
Menarche
Usually 2-2.5yrs after thelarche
Mean age - 12.7
Central precocious puberty
Gonadotropin dependent
Sexual development before: 9 in boys, 8 in girls - testes/breasts
Pubertal levels of FSH/LH
More in females
Central precocious puberty causes
Harmatomas (GnRH)
Pineal masses
Optic glioma
Abcess, encepalitis, trauma
MOST cases idiopathic
How does puberty start?
Mean LH/FSH rise - larger LH rise
Enhanced GnRH episodic secretion
Kiss1 and leptin = positve regulation
Mini puberty
Peak at 2-3 months, gone by 1yr
Males: Elevated testosterone = genitalia, sperm for later
Females: Still not sure, follicle development?
Understand HPG axis
Peripheral puberty
Gonadotropin independent
Estrogen/testosterone elevated but LH/FHS low
Gonadal causes: ovarian tumor, leydig tumor, familial testotoxicosis
Adrenal causes: CAH, tumor
HCG tumor (boys)
Exogenous exposure
Severe hypothyroidism
Precocious puberty (increase in GnRH release)
Spillover effect of TSH on FSH receptor maybe?
McCune Albright Syndrome clinical presentation
Triad of:
- Precocious puberty
- Cafe au lait pigmentation (coast of Maine
- Polyostotic fibrous dysplasia
McCune Albright Syndrome cause
Somatic activating mutation of Galpha protein
Pituitary adenomas with excess LH, FSH, GH, PRL
Bone age
Sex steroids determine ossification within epiphyses
Bone age = True physical development age
Estrogen recetor and aromatase enzyme mutations and bones?
Growth plates don’t fuse, become very tall
Constitutional delay of puberty
Delayed growth spurt but normal pre pubertal growth
Genetic
Bone age will be delayed
Hypogonadotropin hypogonadism
Isolated or part of other pituitary deficiency
Complete pituitary workup, head MRI
Kallman syndrome
Kallman 1 codes anosmin (other genes can be involved)
Gene mutation affect migration of GnRH neurons and creation/migration of olfactory neurons
Hypogonadotropin hypogonadism examples
Functional Anorexia (leptin) Prader-Willi HyperPRL Hypothyroid Cushings
Gonadal failure (boys) - common causes
Testicular failure (high gonadotropins)
Klinefelter syndrome
Mumps orchitis
Trauma/radiation
Vanishing testes
Noonan syndrome
Klinefelter syndrome
47, XXY
Most common cause of gonadal failure
Small testes, talls tature, gynecomastia, developmental delay
Noonan syndrome
Normal karyotype
Short stature, cubitis valgus, triangular fascies, mild MR
Cardiac defects
1/2 have testosterone/sperm production dysfunctions - delayed puberty
Gonadal failure (girls)
Ovarian failure (high gonadotropins)
Turners syndrome
Trisomy 21
Physical/medical injury
Autoimmune oophoritis
PCOS
Polycystic Ovarian hyperandrogenism
Amenorrhea/chronic anovulation
Elevated LH
Numerous antral follicles - LH/FSH increases resulting in immature follicles
Insulin resistance - hyperpigmentation
Overweight/obese, metabolic syndrome
Elevated androgen levels - hirsutism
Menstrual cycle overall
Ovarian cycle: Follicular genesis, Oogenesis
Uterine (endometrial cycle)
Ovarian cycle overall
Day 0-14: Follicular phase
Day 14-28: Luteal phase
Endometrial cycle overall
Day 0-4: Menses
Day 4-14: Proliferative phase
Day 14-28: Secretory phase
Atresia
Degeneration of follicles
Can happen at any stage of development
Peak oogenia
~20 weeks fetal development
6-7 million follicles
Oogonia to primary oocyte
20 weeks fetus –> birth
Oogonia enters Meiosis I and arrests at Prophase I
Many become atretic but ~400k survive to puberty and surrounded by pregranulosa cells = primordial follicles
Folliculogenesis overall
Primary oocyte Primordial follicle Primary follicle Secondary follicle Tertiary follicle
Primordial –> Primary follicle
Granulosa cells develop and connected via gap junctions
Enlarges
Primary –> Secondary follicle
Granulosa divides to form layers
Stromal cells differentiate into theca cells
Vascular supply forms
Early tertiary follicles
Granulosa cells increase
Mucopolysaccharides secreted = zona pelucida
Antrum appears
Graafian follicles
Dominant follicle
Second antral stage, much larger antrum
Antrum surrounds oocyte
Pre antral stages of folliclulogenesis
Primordial
Primary
Secondary
Antral stages of folliculogenesis
Early tertiary
Late tertiary
Follicular phase dominant hormone
FSH
Later follicular phase and luteal phase hormone
LH
Domination of dominant (Graafian follicle)
Follicle with most FSH receptors and best blood supply will supply
Low FSH means others will die out - atresia
Dominant follicle will release oocyte during ovulation
LH surge
Primary signal to rupture follicle (induce ovulation)
Proteolytic enzymes weaken follicular wall
Contraction of theca externa + prostaglandins = total rupture
Primary oocyte completes meiosis I, arrested in metaphase II
1st polar body formed
Significance of 1st polar body
Can be used for genetic screening
Disease alleles can completely segregate into first polar body
Corpus luteum
Non dominant follicle cells form corpus luteum after ovulation
Secrete mainly progesterone and some estrogen
Corpus luteum and fertilization
If corpus luteum interacts with hCG due to implantation, remains
No hCG = degeneration to corpus albicans
Endometrium layers
Functionalis - shed during menstruation
Basalis - not shed, regenerates functionalis layer
Menstrual stages and hormone dominance
Menses
Proliferative - Unopposed estrogen driven
Secretory - Progesterone + estrogen driven (opposed estrogen)
Time and location of fertilization
Usually in ampulla of uterine tube
Within 24hrs of ovulation
Initiation of menstruation?
Degeneration of corpus luteum = lack of progesterone = hemorrhage of endometrium and menses
Bartholin glands
Produce lubrication during sexual arousal
Not all lubrication
Female sexual innervation
Parasympathetic: Sexual response
Sympathetic: Muscle contraction
S2-4 innervate clitoris erectile tissue
Very sensitive
Female sexual response and sperm transport
Sperm do not travel all the way only by swimming
Oxytocin release during orgasm initates muscle contraction
Contraction drives sperm to uterine ampulla
Two cell two gonadotropin model
Model by which androstedione and estradiol are produces
Theca cell produces androstedione from cholesterol –> travels to granulosa cell
Granulosa cell converts androstedione to estradiol (aromatase) - stimulated by FSH
Total Menstrual cycle
- No fertilization = no hCG so progesterone decreases and endometrium hemorrhages
- End of luteal phase and decrease in hormones = no negative GnRH feedback –> FSH increases
- FSH rise = antral follicle growth, some estrogen produced
- Decrease FSH and increase estrogen = increase GnRH pulsation and LH rise
- Declining FSH means dominant follicle arises
- Dominant follicle increases estrogen levels over 200pg/mL for 36-48hrs –> positive feedback to GnRH and subsequent LH surge, increased sensitivity to GnRH receptors
- LH surge results in meiotic maturation, ovulation, corpus luteum formation
- Rise of progesterone and estrogen (opposed) results in negative feedback to GnRH, FSH/LH decline
- Basal LH required for corpus luteum function but becomes insensitive unless there is hCG. No hCG = luteolysis and menses
Orally active steroidal estrogens
17 beta estradiol
conjugated equine estrogens
Ethinyl estradiol
Mestranol
DES
17 B estradiol
Low bioavailability but most potent
Requires high doses but thats risky, only use low dose therapy
Conjugated equine estrogens
From horse urine
Higher bioavailability but less potent
Estrone and estrone sulfate
Ethinyl estrogen
Synthetic steroidal estrogen
Decreased first pass metabolism because of ethinyl group, higher bioavailability
Can be administered in low doses but still get good therapeutic effect
Administer with progestin as contraceptive
Mestranol
First gen used in OCP
Combined with norethynodrel
Diethylstilbestrol (DES)
Synthetic estrogen
Increased breast cancer risk for mother and cervical cancer in fetus
Uses of therapeutic estrogens
Hormonal replacement
Contraception combined with progestin
Primary hypogonadism treatment
Estrogen adverse effects
Breast tenderness Edema Nausea/vomiting Hyperpigmentation Migration Mid cycle breakthrough bleeding
Estrogen SAE
Cancer risk: Decrease colorectal, uterine, ovarion
Increase benign hepatic adenomas, cervical, CNS
Increase gall stones
Increase cardiovascular risks: DVT, HTN, MI
Estrogen Contraindications
Estrogen dependent neoplasm
Vaginal bleeding
Thromboembolic disorder
Cerebrovascular or CAD
Heavy smoking
Congenital hyperlididemia, liver disease
PREGNANCY
Progestin physiological action
Thickened mucus
Decrease estrogen receptor, promote cell differentiation in endometrium
Decrease fallopian tube motility
Contraceptive actions
Synthetic progestin ADME
Good absorption and distribution
CYP3A4
Oral Progestin categories
C21 progestins - progesterone derivatives
C19 progestins - 19 nortestosterone derivatives
C17 progestin: Spironolactone analog
C21 progestins
Progesterone derivative
MPA
DMPA
C19 progestins
19-nortestosterone derivatives
1st gen: Northindrone acetate
2nd gen: Levonorgestrel
3rd gen: Desogestrel, Norgestimate
C17 progestin
Spironolactone analog
Drospirenone (Yaz, Yasmin)
PR activity, Anti AR activity, Anti MR activity
Increased DVT
Clinical use of progestins
Contraception: Alone or combination
Menstrual disorders
Hormone therapy
Clomiphene
1st line drug for inducing ovulation
Partial agonist of estrogen receptor
Blocks ER –> Body senses as low estrogen –> increase GnRH –> Large rise in LH/FSH –> Follicle maturation and ovulation
Ovarian enlargement and risk of multiple births
Raloxifine
2nd line for prevention of post menopausal osteoporosis
Estrogen agonist in bone - Prevents bone resorption
Estrogen antagonist in breast - Can reduce breast cancer risk
Hot flashes/DVT
Tamoxifen
Use for prevention of breast cancer
Estrogen receptor competative antagonist in breast - prevent estrogen driven genetic transcription
Estrogen agonist in endometrium so risk for uterine neoplasia
DVT
hMGs
Human Menopausal Gonadotropins
Ovulation induction when unresponsive to clomiphene
IVF
Hypothalmic/Pituitary amenorrhea
Ovarian enlargement/hyperactivity
Mifepristone
Progesterone antagonist - Morning after pill
Prevents blastocyst implantation
Induces luteolysis of early pregnancy
Vaginal bleeding, infections, ectopic pregnancy rupture
Leuprolide
GnRH analog - treatment of endometriosis, uterine fibrosis
Down regulation of GnRH receptors and reduction of hormones - LH/FSH/estrogen/Progesterone
Reversible osteoporosis
Premature ovarian failure/primary ovarian insufficiency
Amenorrhea, hypoestrogen, elevated gonadotropins
Menopause like symptoms
Issue with ovaries, do not produce necessary hormones for proper uterine function
Low inhibin = higher FSH
Can be autoimmune, chromosome issue, genetic condition, damage to ovaries
Causes of missed periods
Secondary amenorrhea Eating disorder Pregnancy Hypothyroidism Medication Exercise Stress
Functional cysts: Cystic follicle vs follicular cyst
Originate in graafian follicle
Pelvic pain
> 3cm - Follicular cyst
Luteal cyst
Form in corpus luteum
Bright yellow on gross exam
Due to preovulatory LH surge or ovulatory stimulus
May rupture and cause peritoneal reaction
Non functional cyst types and difference from functional cysts
Non functional cysts DO NOT resolve over time
- Endometriotic cyst
- Teratoma (younger)
- Cystadenoma (older)
Pathophysiology of androgen excess in PCOD
Androstedione produced in adipocytes and converted to estrone –> Estrone stimulates LH release –> LH stimulates more androstedione production –> Can travel to adipocytes OR converted to testosterone
Types of ovarian tumors
Surface epithelial tumors
Germ cell
Sex cord stroma
Metastatic (other)
Types of surface epithelial tumors
Each has benign, borderline, malignant
Serous
Mucinous
Endometroid
Clear cell
Transition cell
Types of germ cell tumors
Teratoma - Mature, immature, monodermal
Dysgerminoma - rapid growth, good prognosis
Yolk sac tumor - Elevated AFP
Sex cord tumors
Granulosa cell tumor
Sertoli-Leydig tumor
Metastatic tumors
Krukenberg
Psuedomyoxma peritonei
Atresia in aging woman
Atresia accelerates around 35-38yrs
Menopause
12 months without menses
Loss of follicular function
Mean age 51-52yo
Premature menopause
Loss of menses before 40 yrs old
1% POI
Usually because of medication/therapy
Perimenopause
Transitionary period between normal function and menopause
Mid/late 40s for 4-6yrs
Ovarian function in perimenopause
Decrease ovary size
Decrease in # of follicles
Inhibin decrease –> FSH increase
Poor response to LH/FSH elevation
Erratic ovulation and irregular menses
Perimenopause treatment
Oral contraceptives
Improve menstrual irregularities
Decrease ovarian cancer risk, no breast cancer risk
Menopause vasomotor symptoms
Hot flashes and night sweats
Due to altered thermoregulatory function via estrogen withdrawal
Vasodilation –> increase blood flow –> Sweating –> Shivering
Vasomotor symptom treatments
Lifestyle changes: Relaxation, cool down activity
Non hormonal: SSRI, SNRI, anti-epileptic, antiHTN
Soy isoflavanoids
Hormone therapy: Estrogen (no uterus), E+P (uterus) - Low breast cancer risk in younger women
Menopause urogenital symptoms
Vaginal atrophy
Dryness/itchiness
Pain during sex
UTI’s and incontinence
Menopause urogential pathophysiology and treatment
Lack of estrogen
Loss of glycogen rich superficial cells = No lactobacillus = alkaline vagina
More pathogen colonization
Treatment: Behavioral, moisturizers/lubrication
Local estrogen therapy
HSDD
Hypoactive sexual desire disorder
Decreased libido
Low testosterone
HSDD treatment
Filabanserin
Premenopausal women only
Dopamine and serotonin levels
Where do tumors arise from in cervix?
Transition zone between endocervix and ectocervix
Cancer associated with ectocervix
Squamous cell carcinoma
Cancer associated with endocervix
Adenocarcinoma
Lower genital tract infectious agents
HSV Candida Trichomonas vaginalis Gardnerella vaginalis HPV
Lower and upper genital tract infectious agents
Neisseria gonorrhea
Chlamydia
Herpes Simplex Virus
DNA STD virus
Can be asymptomatic
Latent phase - trigger is immunosuppression or stress
Active HSV presentation/test
TEst: TZank test
Vesicles and punched out ulcers - Require C section
Congenital herpes
Baby born to active HSV mother transvaginally
Conjunctivitis, GI bleeds, jaundice, seizures
67% mortality
Candida
Fungus
10% females are carriers
White curd like discharge
Pseudohyphae and yeast
No fetus damage/sequelae
Trichomonas vaginalis
Purulent vaginal discharge
Strawberry cervix - petechial hemorrhages
Pear shaped flagellate organisms
Gardnerella Vaginalis
Most common bacterial vaginosis
Fishy oder, low viscosity discharge
Bacteria adhere to “clue cells”
Actinomyces
Associated with intrauterine device (IUD)
HPV
Human papilloma virus
Benign and malignant lesions
Low risk HPV serotypes
6/11
Most common
Spontaneously regress
Koliocytosis - Nuclear enlargement, darker nuclear stain
High risk HPV serotypes
16, 18, 31-33, 35
Kolicytosis and dysplastic changes in epithelium starting at basal layer
High Risk HPV pathogenesis
Increase E6 activity = Decrease p53
Increase E7 = Decrease RB
Pelvic Inflammatory disease
Ab pain, fever, vaginal discharge, adnexal mass
Major cause of infertility and ectopic pregnancy
Neisseria gonorrhea
Most common cause of PID and ascending bacterial infection
Acute infections: Cervicitis, urethritis, scarring of tubes
NO dysplasia or carcinoma risk
Neutrophilic disease, organisms in neutrophils
Chlamydia trachomatis
Most common STD worldwide
Follicular cervicitis
No dysplasia/carcinoma
Vulvar disease
Vulvar intraepithelial neoplasia
Invasive squamous cell carcinoma
Extramammary paget disease
VIN
Vulvar intraepithelial neoplasia
Abnormal maturation confined to epithelium
HPV 16/18 (90%) - younger, multicentric leasions, VAIN/CIN
HPV negative (10%) - Older women, p53 mutation
VIN staging
VIN I - Mild dysplasia, bottom 1/3 squamous epithelium
VIN II - Moderate, bottom 2/3 epithelium
VIN III - Severe, Full thickness abnormality
Invasion of basal layer - Squamous cell carcinoma
Non invasive can spontanouesly regress in YOUNGER WOMEN
Vulvar squamous cell carcinoma
Association with HPV
Most common vulvar malignancy
Invasion through basement membrane
Squamous cell carcinoma prognosis
Depends on: Tumor size, tumor invasion depth, lymphatic invasion
Less than 2cm = good prognosis with vulvectomy and lymphadectomy
Extramammary paget disease of vulva
Occurs in late reproductive age group
White over black
Pruritis, ulcerated skin lesions in labia majora/minora
Affect epidermis layer
NOT associated with carcinoma
Rhabdomyosarcoma
Sarcoma Botryoides
Malignant tumor of skeletal muscle cells
Grape like growths and hemorrhages
Under 5yrs old
Surgery + adjuvant chemo
Cervical Intraepithelial Neoplasia
Disease of young women
Sex early and often is risk factor
Pap smear diagnosis
Koliocytes, multinucleated cells
CIN staging
Same as VIN
Mild, moderate, severe
Cervical squamous cell carcinoma
Most common cervical cancer, 8th highest mortality
Treat with partial hysterectomy, remove cervix
Uterus layers
Endometrium - Glands & Stroma
Myometrium - Smooth muscle
Menstrual phase and spiral arteries
Spiral arteries become ischemic and rupture
Functionalis shed
Secretory phase histology
Piano key like structures
Glands irregularly shaped with subnuclear vacuoles
Ch5ronic endometritis
Etiology - PID, IUD, TB, idiopathic, post partum
Symptoms - Bleeding, pain, infertility
Histology - 1 or more plasma cells
Endometrial scarring
Endometriosis
Functioning endometrial tissue growing in places that aren’t endometrium: Ovary, uterine ligaments, fallopian tubes, lungs, pelvic peritoneum
Dysmenorrhea, infertility, ab pain
Hemisodern
Ovarian endometriosis
Ovarian Chocolate cyst
Pathogenesis of endometriosis
Congenital
Endometrial tissue travels back towards ovary
Shed tissue reaches blood supply and travels to other areas
Adenomyosis
Endometrial glands within myometrium
Menorrhagia, colicky dysmenorrhea, pelvic pain, bleeding
Symmetrically enlarged, boggy uterus
FUNCTIONAL ENDOMETRIAL TISSUE
Endometrial hyperplasia
Proliferation of glands
Increase gland/stroma
Precursor to endometrial carcinoma
Risk: Nulliparous, obesity, ovarian and stromal
PTEN mutation because of excess estrogen
Simple hyperplasia
No atypia: Proliferative endometrium, increase in glands, bland morphology, less than 5% carcinoma
Atypia: Proliferative endometrium + loss of polarity/prominent nuclei, 8% carcinoma
Complex hyperplasia
No atypia - Gland crowding no morphological change, 3% carcinoma
Atypia: Above with nuclear hyperchromasia, stratification, nucleoli, mitosis
Endometrial adenocarcinoma
Most common malignancy of uterus
Most common female genital tract cancer
PM women
Risk: Nulliparity, obesity, diabetes, unopposed estrogen stimulation
Two types of endometrial carcinoma
- Excess unopposed estrogen stimulation and endometrial hyperplasia
- Older individuals, p53 mutation, poor prognosis, poorly differentiated
Grading system for adenocarcinoma
Grade I: Well differentiated, Less than 5% solid growth pattern
Grade II: Moderate differentiation, 6-50% of solid growth pattern
Grade III: Poor differentiation, >50% solid growth pattern
Atypia raises grade by 1 level
Myometrium neoplasm types
Benign
Uncertain malignant potential
Malignant
Diagnosis/behavior of smooth muscle neoplasms
Necrosis
MItotic count
Borders
Leiomyoma
Most common benign smooth muscle tumor
Usually in uterine corpus
Pelvis
GI tract
Round whorled lesions, non infiltrating borders, fascicles
Cigar shaped nuclei
Leiomyosarcoma
Rare malignant smooth muscle tumor
Peri/Post menopausal woman
Enlarged pelvic mass, vaginal bleeding
Infiltrative borders, increased mitotic activity, cellular atypia
Recurring
10-40% 5 yr survival
Hysterectomy
CHEMO DOES NOTHING
Malignant neoplasms of fallopian tubes
Usually come from metastatic source from other area: Ovary, uterus, GI
Primary tumors very rare
Serous/mucinous tumors
Most common types of surface epithelial cells tumors
Cystic
Benign, borderline, malignant
Benign vs malignant serous/mucinous tumors
Benign: Cystadenoma
Single cyst, simple/flat lining, premenopasal women
Malignant: cystadenocarcinoma, multiple, large with complex lining, post menopausal women
BRCA mutation and ovary
Risk of breast and ovarian cancer
Risk of serous malignant carcinoma or ovary and fallopian tube
Endometrioid tumor
Endometrial tissue tumor, associated with endometriosis
Usually malignant
Check for endometrium endometrioid carcinoma
Brenner tumor
Transitional cell tumor
Usually benign
Urothelial cells
Germ cell tumors
2nd most common
Occur at reproductive age
Teratoma
Dysgerminoma
Endodermal sinus
Cystic Teratoma
Cystic, bilateral, tissue from 2+ embryological tissues
Cysts contain numerous tissue types: Teeth, hair, bone, gut, skin etc
Mature = benign
Immature = malignant
Immature cystic teratoma
Mainly contains neuroectodermal tissue
Malignant
Somatic malignancy
Teratomal tissue has squamous cell carcinoma within
Bad
Dysgerminoma
Germ cell mass
Increase LDH
Good prognosis
Yolk sac tumor
Endodermal sinus tumor
Form from yolk sac
Elevated AFP
Schiller Duval bodies
Granulosa cell tumors
Excess estrogen production
Sertoli leydig cell tumor
Androgen production
Choriosarcoma
Placental tumor
Elevated bhCG
Highly aggressive, no chemo response
Meigs syndrome
Ovarian tumor
Right sided pleural effusion
Ascites
Pseudomyoxma peritonei
Mucin deposition in peritoneum
Associated with appendix
Krukenberg tumor
Metastatic tumor usually from GI tract
Signet ring
Bilateral
Inflammatory conditions of breast
Acute mastitis
Periductal mastitis
Fat necrosis
Ductal ectasia
Acute mastitis
Infection of breast usually via S. Aureus
Associated with breast feeding
Inflammation, warm erythematous breast
Treat with drainage and doxicilin
Periductal mastitis
Associate with smoking - lack of Vit D so metaplasia of columnar epithelium to squamous
Subsequent block of subareolar duct and inflammation
Subareolar mass and nipple retraction
Fat necrosis
Associated with trauma
Necrotic fat cells and giant cells
Presents as mass or calcification on mammogram
Ductal Ectasia
Inflammation of subareolar ductal wall and dilation of duct
Inflammation
Multiparous post menopausal women
Green brown discharge
Fibocystic breast changes
Cystic growth of fibrous tissue in breast
Hormone sensitive
BENIGN
Fibrosis + cyst + Apocrine metaplasia
No increased risk for invasive carcinoma even though metaplasia
Ductal hyperplasia
Increase in cells of duct
2x risk for invasive carcinoma
Atypical hyperplasia
Atypical cells in duct or lobule
5x increase risk for invasive carcinoma
Sclerosing adenosis
Development of mass due to glandular increase and stretching of tissue - associated fibrosis
2x increase risk invasive carcinoma
Granulomatous mastitis
Rare
Sarcoidosis
Infections: Mycobacteria, fungal
Dense granulomatous infection
Scattered lymphocytes, giant cells
Intraductal papilloma
Papillary finger like ductal growth surrounded by both types of epithelium
Bloody nipple discharge
Fibroadenoma
Most common benign growth in pre menopausal women
Fibrous and glands
Estrogen sensitive
No invasive cancer risk
Ductal vs Lobular carcinoma in situ
Ductal: 70-90% incidence, E cadherin (+), calcification, less frequently bilateral
Lobular: 10-30% incidence, e cadherin (-), less common calcifications, bilateral, no paget’s disease
DCIS grading
Nuclear grading
Grade 1 - nucleus same size as normal ductal epithelial cell
Grade 2: Neither NG 1 or NG3
Grade 3: Pleomorphic nuclei, 2-3x size of normal ductal epithelial cells
Invasive ductal carcinoma NOS - Luminal A
40-55% incidence
Post menopausal
ER+
Her2/Neu - Negative
Invasive ductal carcinoma NOS - Luminal B
15-20%
Non specific pt characteristics
ER/PR +
Her2+
Invasive ductal carcinoma NOS - Basal Like
13-25%
Young women, BRCA-1
Triple negative
Very bad
Invasive ductal carcinoma NOS - Her 2 positive
7-12%
Brain metastases
ER/PR negative
Her 2 +
high proliferation and 3/3 tumor grade
Axillary node management
Positive nodes: Axillary dissection
Negative: Sentinal lymph node biopsy
- Positive = axillary dissection
- Negative = No dissection
Aromatase inhibitors
Anastrazole
Letrozole
Exemestane
Post menopausal women only
Inhibit androgen conversion to estrogen
Trastuzumab
Targeted therapy
Monoclonal antibody that binds to extracellular Her 2 domain
Pertuzumab
Monoclonal antibody that prevent Her2/3 dimerization
Lapatinib
Intracellular domain action
Inhibits tyrosine kinase of Her2
Denosumab
RANK ligand inhibitor
Prevents bone destruction
Use if metastatic at presentation
Everolimus
mTOR inhibitor
Reverses endocrine resistance
