Transcript Female Reproductive Pathology

Female Reproductive Pathology
Embryo/Anatomy:
- Paired Mullerian (paramesonephric) ducts
form and fuse to make tubes, uterus, upper
vagina (default)
- Wollfian (mesonephric) ducts regress
All have same mesothelial (coelemic origin)
field defect
Infections:
Herpes (HSV2): active vesicles (painful),
latent neonatal infections (eye, rash, GI,
probably die) (spotaneous abortions) Do
Csection
Do Tzank smear: multinucleated cells with
intra-nuclear, “ground glass” inclusions
Vaginitis:
Candida: Cottage Cheese, itchy (DM, ABX,
prego, IC)
Trichamonas: yellow frothy, strawberry
cervix
MolluscumContagiosum
Intracellular inclusion
Umbilicated
tan papule
Gardnerella: green fishy, clue cells
Clue cell:
squamous
cell
covered in
coccobacilli
Pelvic Inflammatory Disease:infection beyond
uterine corpus
- Usually N. gonorrhea/Chlamydia  low ab pain,
tender to cervical manipulation (adhesions)
- Complications: tuboovarian abscess, tube scarring
 ectopic preg., GI obstruction
Bartholin Cyst (usually
gonorrhea) Rx:
marsupulization
VULVA
VIN: Vulvar Intraepithelial Neoplasm
– Risks: old, lots o warts, IC
Non-neoplastic Epithelial Disorders
– Lichen Planus(purple, polygonal, pruritic,
patches) Reticular=Wickham’s striae
– Lichen Sclerosis (LS&A)
• Pruritic, painful intercourse, NOT
precancerous but ass. With
increased risk of SCC
• Thinned epidermis, sclerotic stroma
(homogenized
– Lichen Simplex Chronicus (LSC)
• Thickened epidermis from chronic
scratching (no atypia)
• Hyperplasia/keratosis, acanthosis
• CondylomaAcuminata(HPV 6,11)
– Koilocytes: raisinoid nuclei with
surrounding cleared area
– Frequently regresses
Invasive SCC of Vulva
– Masses on background of
leukoplakia (esp ulcerated)
– 2 types (same for VIN 3)
HPV (+)
HPV (-)
Classic VIN
Simplex/Differentiated
VIN
Reproductive age
Elderly
Warty/basaloid
keratinizing
Verrucous Variant: no
infiltration, pushing
margin. Make sure you
biopsy deep enough
Vulva
(cont.)
Glandular Lesions of Vulva
• Accessory Breast Tissue: along milkline,
expands during pregnancy
• Papillary Hidradenoma: benign from
apocrine gland
• Extramammary Paget:
– pruritic, red, crusted, sharply
demarcated.
– No underlying Carcinoma
– Histo: halo cells (PAS+, CEA+, EMA+,
Mucin +)
Malignant Melanoma: poorer prognosis
b/c late presentation (S100, keratin +)
Vagina
Developmental Abnormalities
- Congenital: imperforate hymen, double
vagina
- Gartner duct cyst: Wolffian derived remnant
Vaginal Adenosis: mothers take DES 
glandular epithelium (velvety red)
replaces squamous (pink) = adenosis
clear cell carcinoma of vagina
Vaginal Neoplasm:
- 80% metastatic SCC from cervix
- HPV 16 VaIN
- Dx: cytology Prog: size and nodes
EmbryonalRhabdomyosarcoma: <5yrs
- Grape structure from vagina/ bleeding
- Histo: see Z lines
- High rate of surgical cure
Cervix
Physiology: Squamocolumnar Junction
SCJ at osEversion (Puberty)  Transformation zone
(post adolescent)  Inversion (Menopause)
transformation zone moves back up endocx canal
Neoplasms: Low Grade (CIN I)  High Grade ( CIN II-III)
Inflammations:
Acute/Chronic Cervicitis:
-Nonspecific: loss of acidosis (bleeding,
sex, douching, ABX)
- Specific: STDs
Endocervical Polyps
- common, benign, soft/mucoid
- spotting or mass of cervical os (Rx:
polypectomy)
Nabothian Cysts: obstructed mucous gland
 Cancer (10 years)
Premalignant
- CIN (cervical Intraepithelial Neoplasia)
CIN I: 1/3 basal cells and atypia
CIN III: full thickness (CIS)
- Markers: Ki-67 (cell proliferation), p16 (unregulated
cyclin E) see full thickness
- - Culposcopy: acetowhite (dysplasia), mosaic (full
thickness dysplasia)
- Adenocarcinomain situ: hard to find (path same as CIN)
Cancer
HPV :Vaccine is 100% at 5 yrs (HPV 6/11/16/18)
- SCC: S&S: bleeding after coitus, advanced local
-Risks: young age at 1st intercourse, multiple
invasion. Prog depends on TNM
partners, IC, BCPs, smoking
- die by invasion  obstruct ureters renal failure
- Infects immature, replicates mature (therefore,
- Rx: radical hysterectomy
without transformation zone, need microtears to
access immature cells)
-Adenocarcinoma (more aggressive)
- HPV 6/11: episome (condylomas)
Pap smear (Sensitive) + HPV DNA after 30 (Specific) =
- HPV 16/18: integrated into genome
99.5% sensitivity
-E6: p53 E7: Rb
Phase: Estrogen (simple tubules)
Uterus Proliferative
Secretory Phase: Progesterone
LH Surge: Ovulation Day 14 (subnuclear vacuoles)
Late Secretory: everything in lumen
Menstrual: stromal breakdown, hemorrhage
DUB
Unscheduled
bleeding (usually
anovulatory)
Prepuberty
Precocious puberty
Oligomenorrhea
>35 days
Adolescence
Anovulatory cycle, coagulation
Polymenorrhea
< 24 days
Menorrhagia
Regular, excessive
blood
Reproductive
age
Preg. Complications, Organic lesions,
Anovulatory cycle, inadequate luteal
Perimeno
Anovulatory, Organic lesions (BIOPSY)
Postmeno
Endometrial atrophy, Organic lesions
(BIOPSY)
Metrorrhagia
Irregular, excessive
blood
MMR
Irregular menses Anovulatory Cycle: unopposed estrogen, no progesterone
Bleeding after
- irregular, dilated glands  follicular cysts
withdrawal of
Inadequate Luteal Phase: abnormal corpus luteum = low
hormones
progesterone  corpus luteum cyst
- Infertility with meno/amenorrhagia
- Biopsy is >2 days behind clinical date
Oral contraceptives: break through bleeding
Withdrawal
bleeding
Uterus (cont)
Endometrial Polyps:sessile/pedunculated
S&S: bleeding, benign Rx: surgery
Endometritis
Acute (np): infections from delivery/miscarriage
(GAS/staph) Rx: curette
Chronic (PC): Chronic PID, IUD, Tb (3rd world), retained
products of conception
S&S: MMR, dysmeno, pain, infertility
Endometriosis:endometrial tissue outside of
uterus (us. Ovary)
Adenomyosis: endometriosis in myometrium
(watered silk)
Adenomyoma: discrete mass of adenomyosis
S&S: dysmeno, pain, infertility, scarring
2 theories:
- metastatic: implant tissue
- metaplasitc: same mullerian origin
Tissue cycles with hormones bleeding
toxic
Chocolate cyst
and powder burn
Endometrial Hyperplasia: Disordered
proliferative pattern (us. Anovulatory)
- Estrogen effect therefore diffuse
EIN (Endometrial Intraepithelial Neoplasia):
pre-neoplasia therefore focal (atypica)
Lose PTEN
Cancer
EndometrioidAdenocarcinoma (Type I)
45-55 yo fat women
-unopposed estrogen (exogenous,
endogenous, PCOD, infertility, DM, HTN)
- S&S: DUB  surgery
- direct extension, late spread to nodes/
mets
2 pathways: PTEN mutation or microsatellite
instability in KRAS (HNPCC/Lynch)
Non-endometrioidAdenocarcinoma (Type II)
old skinny sick women
- EIC  Grade 3  aggressive early spread
through lymphatics
- p53
Malignant mixed mullerian tumor (MMMT):
- bulky polypoid mass
Uterus: myometrium
Fallopian Tubes
Leiomyoma: Benign smooth mm
Symptoms by location
– Bleeding: submucosal - attenuation
of endometrium
– Pain/ sense of pelvic fullness:
infarction, large mass
– Urinary frequency: pressure against
bladder
– Infertility: may treat with
myomectomy
– Miscarriage: typically 2nd trimester
Leiomyosarcoma: 40-60yo
Mass invading uterine wall
OR
polypoid mass in lumen
Bad tumor (mitosis, atypic, necrosis)
Metastasis by blood vessel invasion
Salpingitis: part of PID
- Usually G/C
- Pyosalpinx (pus), hydrosalpinx
(fluid), tuboovarian abscess
- Complications: adhesions, infertility,
ectopic pregnancy
Paratubal cysts:Mullerianremants at
fimbriated end or in broad ligament
-translucent, thin-walled
Ectopic Pregnancy:Usually b/c of
PID/adhesions, endometriosis
DDx: torsion of ovary, appendicitis
Measure hCG take out, if not may
lead to fatal hemorrhage
Adenocarcinoma:secondary tumor (esp
serous ovarian)
Endometrial biopsy:
Aspirate : Pipelle tip
Cut: curette tip
Scrap: loop curette
Ovaries
Benign Cysts:
Follicular Cyst:
- common, simple, no LH surge
Corpus Luteum Cyst:
- opening from released egg seals off,
may hemorrhage/torsion
Endometriosis: chocolate cyst
Torsion of Ovary: (us. Cystic teratoma)
S&S: sudden unilateral pain
DDx: ectopic pregnancy Diagnose by US
Polycystic Ovary Disease (PCOD; SteinLeventhal Syndrome)commonest
endocrine of repro age women
- Oligomenorrhea(chronic
anovulatory)
-Virulization: hirsuite, muscley, bald,
large clitoris
- Polycystic ovaries: >12/ovary
- obese, acanthosisnigricans, DM
Rule out other endocrine
Surface Epithelial Tumors (65-70%)
60yo women, asymp (general symp) until late (cachexia)
Hereditary associations: BRCA1/2, Lynch (HNCC)- MSH2
Bilateral: serous>endometrial>mucinous
No screening, CA-125 to trend, seeding of peritoneum
Decreased risk by tubal ligation, BCP
Serous Tumors
Cystadenoma: benign, common, single layer
Borderline: excrescences (seaweed), no invasion
Adenocarcinoma: 65% bilateral, aggressive, poor
prognosis
- May present with ascites
- Histo: psammoma, cribiform with central
necrosis
Mucinous Tumors
Cystadenoma: least likely to be bilateral, most are benign
Pseudomyxomaperitonei(us. Appendix): mucin in
peritoneum= jelly belly
Endometrioid Tumors
Adenocarcinoma: may arise from endometriosis
Same as endometriod Type I (PTEN, kras) can be
synchronous
If young: check for colon cancer (could be RAS/Lynch)
Ovaries (cont)
Germ Cell Tumors
Dysgerminoma (seminoma):
Highly sensitive to radiotherapy
1/3 aggressive
salpingooopherectomy
fried egg appearance
Endodermal sinus (yolk sac)
AFP, Schiller-Duval (glomeruloid)
Choriocarcinoma (gestat/non)
b-HCG, aggressive, hemorrhagic
Teratomas
Dermoid (Benign Cystic Teratoma): repro age
2-3 cell lines. See hair/keratin/teeth
Rokitanski nodule on cyst wall (all 3 layers)
Immature Malignant Teratoma: girls/teens
Immature tissue (fetal)
Rapid growth and spread
Monodermal (specialized) Teratomas:
mainly 1 tissue
Carcinoid: (primary= bilateral, mets =
unilateral) serotonin  flushing, diarrhea
Struma ovarii: thyroid tissue  weight loss,
heart palpitations
Sex Cord- Stromal Tumors
Granulosa-Theca Cell Tumors
- yellow, make estrogen
- S&S: precocious puberty, endometrial hyperplasia and CA,
proliferative breast disease
- Diagnosis and monitoring: inhibin
- Unpredictable
Fibromas: common, white, hard, rubbery ball
Associated with Meig’s: ascites, pleural effusion, ovarian
fibroma
Rx: resectfibroma
Thecoma: makes estrogen, plump spindle cells with lipid droplet
(stained red)
Sertoli-Leydig Cell: makes androgens virulization
Metastatic Carcinomas:
Usually from other mullerian
organs
Extra-mullerian: breast, GI
Krukenberk tumor:bilatmets of
mucin, signet ring cancer cell,
usually from GI
Placenta
Umbilical vein: carries oxygenated blood to fetus
Causes of abortion:
Umbilical arteries: carries deoxygenated blood away st
1 tri: chromosomal
from fetus
2nd tri: mechanical
Amnion: baby side
3rd tri: fetoplacental unit
Chorion: maternal side (monochorion= identical twin)
 twin twin transfusion syndrome
3rd trimester villi: more dilated capillaries and looser
stroma
Placental infection/inflammation
Placentation Problems
Placenta previa: implantation over
cervical os
S&S: painless bleeding in 3rd trimester
C section or death
Abruptio placenta: premature separation
of placenta c lot
S&S: painful bleeding
Complication of preeclapmsia
More dangerous for the fetus
Placenta accreta: attachment of placenta
directly to myometrium therefore
does not separate easily  bleeding
Asherman’s syndrome: no basalis from
surgery, c sections, endometrial
inflammation
Chorioamnionitis, villitis, funisitis
2 routes of infection
1. Ascending from vagina/cervix
(acute)
GBS (agalactaie),
2. Hematogenous (transplacental)
(chronic)
Toxoplasmosis
Other
Rubella
CMV
HSV
Hypertensive Disorders
Preeclamsia: HTN, edema, protenuria
HELLP: hemolysis, elevated liver, low
platlets
Eclampsia: pre + seizures
Gestational Trophoblastic Disease
Too much/too big
• Uterus too big
• Hyperemesis
• HTN
Higher in teens, 50s, Asians
S&S: painless bleeding during 4th month
Complete Mole
Partial Mole
46XX all sperm
69XXY sperm+Egg
No fetal parts
FETAL PARTS!!!
Villous edema with
diffuse
trophoblastic
proliferation
Few edematous
villi, slight tropho
proliferation
ChorioCA HIGH
ChorioCA low
Invasive Hydatidiform Mole
- Villi invades uterine wall and can
embolize to distant organs (not mets)
- If uterus ruptures life threatening
- Chemo (if still want kids) or
Hysterectomy
Choriocarcinoma(us. African)
- From complete mole (50%) abortion
(25%) normal (22%) or ectopic pregnancy
- bHCG (syncytiotrophoblasts) with no
villous structures
- Radiosensitive
- Better behaved than non-gestational
ones