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Female Reproductive Pathology

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Presentation on theme: "Female Reproductive Pathology"— Presentation transcript:

1 Female Reproductive Pathology

2 Umbilicated tan papule Intracellular inclusion
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 MolluscumContagiosum Vaginitis: Candida: Cottage Cheese, itchy (DM, ABX, prego, IC) Trichamonas: yellow frothy, strawberry cervix Gardnerella: green fishy, clue cells Umbilicated tan papule Intracellular inclusion 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 Clue cell: squamous cell covered in coccobacilli

3 VULVA Bartholin Cyst (usually gonorrhea) Rx: marsupulization
VIN: Vulvar Intraepithelial Neoplasm Risks: old, lots o warts, IC Invasive SCC of Vulva Masses on background of leukoplakia (esp ulcerated) 2 types (same for VIN 3) 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 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

4 Vulva (cont.) 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 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 +)

5 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)  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 - SCC: S&S: bleeding after coitus, advanced local invasion. Prog depends on TNM - die by invasion  obstruct ureters renal failure - Rx: radical hysterectomy -Adenocarcinoma (more aggressive) Pap smear (Sensitive) + HPV DNA after 30 (Specific) = 99.5% sensitivity 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 HPV :Vaccine is 100% at 5 yrs (HPV 6/11/16/18) Risks: young age at 1st intercourse, multiple partners, IC, BCPs, smoking Infects immature, replicates mature (therefore, without transformation zone, need microtears to access immature cells) HPV 6/11: episome (condylomas) HPV 16/18: integrated into genome E6: p E7: Rb

6 Uterus Proliferative Phase: Estrogen (simple tubules)
Secretory Phase: Progesterone LH Surge: Ovulation Day 14 (subnuclear vacuoles) Late Secretory: everything in lumen Menstrual: stromal breakdown, hemorrhage DUB Unscheduled bleeding (usually anovulatory) Oligomenorrhea >35 days Polymenorrhea < 24 days Menorrhagia Regular, excessive blood Metrorrhagia Irregular, excessive blood MMR Irregular menses Withdrawal bleeding Bleeding after withdrawal of hormones Prepuberty Precocious puberty Adolescence Anovulatory cycle, coagulation Reproductive age Preg. Complications, Organic lesions, Anovulatory cycle, inadequate luteal Perimeno Anovulatory, Organic lesions (BIOPSY) Postmeno Endometrial atrophy, Organic lesions (BIOPSY) Anovulatory Cycle: unopposed estrogen, no progesterone - irregular, dilated glands  follicular cysts Inadequate Luteal Phase: abnormal corpus luteum = low progesterone  corpus luteum cyst - Infertility with meno/amenorrhagia - Biopsy is >2 days behind clinical date Oral contraceptives: break through bleeding

7 Uterus (cont) Endometrial Polyps:sessile/pedunculated
S&S: bleeding, benign Rx: surgery Endometrial Hyperplasia: Disordered proliferative pattern (us. Anovulatory) - Estrogen effect therefore diffuse EIN (Endometrial Intraepithelial Neoplasia): pre-neoplasia therefore focal (atypica) Lose PTEN 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 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) 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 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 Chocolate cyst and powder burn

8 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 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) Leiomyosarcoma: 40-60yo Mass invading uterine wall OR polypoid mass in lumen Bad tumor (mitosis, atypic, necrosis) Metastasis by blood vessel invasion Endometrial biopsy: Aspirate : Pipelle tip Cut: curette tip Scrap: loop curette

9 Ovaries 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) 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; Stein-Leventhal 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

10 Ovaries (cont) Teratomas Germ Cell Tumors Sex Cord- Stromal Tumors
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 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 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

11 Placenta Causes of abortion: 1st tri: chromosomal 2nd tri: mechanical
Umbilical vein: carries oxygenated blood to fetus Umbilical arteries: carries deoxygenated blood away from fetus Amnion: baby side Chorion: maternal side (monochorion= identical twin)  twin twin transfusion syndrome 3rd trimester villi: more dilated capillaries and looser stroma Causes of abortion: 1st tri: chromosomal 2nd tri: mechanical 3rd tri: fetoplacental unit Placental infection/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 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 Hypertensive Disorders Preeclamsia: HTN, edema, protenuria HELLP: hemolysis, elevated liver, low platlets Eclampsia: pre + seizures

12 Gestational Trophoblastic Disease
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 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 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


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