The Female Genital Tract

Infections Lower genital tract HSV- latent, recurrence, transmission to offspring, painful ulcers, multinucleated giant cells Molluscum contagiosum –pox virus, umblicated papules Fungal infections- Candida – DM, antibiotics, pregnancy, suppression of cell-mediated immunity Trichomonas vaginalis- frothy, strawberry cervix Gardnerella vaginalis – fishy odor, clue cells Ureaplasma – Preterm labor Chlamydia –usually cervicitis LGV in tropics Syphilis – painless chancre, condyloma lata, fetal malformations Toxic Shock – S. aureus, tampons,

PID Ascending infection GC- also pharyngitis, arthritis, proctitis, ophthalmia neonatorum, Chlamydia – more mucosal involvement Puerperal infections – polymicrobial, more reaction in the deeper layers Acute salpingitis Salpingo-oophoritis Tubo-ovarian abscesses Acute complications –peritonitis, bacteremia Chronic complications- infertility, tubal obstruction, intestinal obstruction, ectopic pregnancy

Vulva Skin diseases – similar to other areas of body – infection, inflammatory, cancers Bartholin Cyst Lichen sclerosus- thinning of epidermis, dermal fibrosis Squamous cell hyperplasia (Lichen simplex chronicus) Condyloma acuminatum-HPV 6 and 11, koilocytic (expanded epithelial cells with perinuclear clearing) atypia VIN and carcinoma – basloid and warty- HPV keratinizing squamous cell- more common, not HPV Papillary hiradenoma – sweat glands Extramammary Paget disease

Vagina Vaginal adenosis and clear cell adencarinoma – DES Vaginal intraepithelial neoplasia and squamous cell carcinoma Embryonal rhadomyosarcoma- sarcoma botryoides – “bunch of grapes”

Cervix Acute and Chronic Cervicitis Intracellular gycogen Lactobacillus – lower pH May cause an abnormal PAP test Endocervical polyps – may cause vaginal bleeding

Cervix High oncogenic risk HPVs are considered to be the single most important factor in cervical oncogenesis – 16 and 18 Other risk factors- Multiple sexual partners Young age at first intercourse High parity Immunosuppression Certain HLA types Use of oral contraceptives Use of smoking

Cervix HPV Most infections are asymptomatic 50% clear in 8 months 90% clear in 2 years Persistent infection increases the risk of cervical dysplasia and carcinoma Can infect only the immature cells but replication occurs in the maturing cells Koilocytic atypia – nuclear atypia and perinuclear halo Activate cell cycle by interference with Rb and p53

Cervix Cervical Intraepithelial Neoplasia CIN I – mild dysplasia (LSIL) CIN II – moderate dysplasia (HSIL) CIN III – severe dysplasia (HSIL) Natural history LSIL – 60% regress, 30% persist, 10% progress to HSIL HSIL – 30% regress, 60% persist,10% progress to carcinoma

Cervix Cervical cancer 80% squamous cell 15% adenocarcinoma 5% adenosquamous and neuroendocrine Staging stage 0 - carcinoma in situ (CIN III, HSIL) stage I – confined to cervix stage II – beyond the cervix but not to pelvic wall or lower 1/3 of vagina stage III – extended to the pelvic wall, lower 1/3 of vagina stage IV – beyond the true pelvis, bladder or rectum or distant metastases Screening and prevention PAP smear Removal of precancerous lesions - colposcopy surgical removal of invasive cancers HPV vaccine HPV DNA testing

Endometrium “Dating” the endometrium Proliferative phase Secretory phase Exhaustion and disintegration Hypothalmic-Pituitary-Ovarian Axis Corpus luteum

Endometrium Dysfunctional Uterine Bleeding Anovulatory Cycle Menopausal changes Atrophy Inflammation Acute endometritis Retained products of conception Chronic endometritis Chronic PID Postpartum or post-abortion IUDs TB Non-specific

Endometrium Endometriosis Presence of endometrial tissue outside the uterus Infertility Dysmenorrhea Pelvic pain Metastatic theory Metaplastic theory Activation of inflammatory cascade Upregulation of estrogen production Adenomyosis Presence of endometrial tissue within the uterine wall (myometrium) Hyperplasia Prolonged estrogen stimulation of the endometrium Relationship with endometrial carcinoma Inactivation of the PTEN tumor suppressor gene Simple hyperplasia + atypia Complex hyperplasia +atypia

Endometrium Endometrial carcinoma Most common invasive tumor of the female genital tract Post-menopausal bleeding Type I Unopposed estrogen Obesity, hypertension, diabetes Endometroid Hyperplasia PTEN Indolent Type II Atrophy Thin Serous, clear cell, mixed mullerian tumor Endometrial intraepithelial carcinoma Aggressive p53 -

Myometrium Leiomyomas – fibroids Leiomyosarcomas

Ovaries Polycystic Ovarian disease persistent anovulation obesity hirsutism rarely virilism Variety of enzymes involved in androgen synthesis are poorly regulated

Ovarian Tumors Surface Epithelial- stromal Most common Most malignant Most ovarian cancers are detected when they have spread beyond the ovary; account for a disportionate number of deaths Germ cell Sex cord-stromal Metastasis to ovary- tumors of Mullerian origin, breast, GI, Krukenberg tumor

Surface Epithelial (Mullerian) Most primary neoplasms of ovary Transformation of coelmic epithelium Lower abdominal pain, enlargement GI compliants, urinary complaints, pelvic pressure CA-125, osteopontin Types Serous Mucinous Endometrioid Clear cell Brenner – transitional cell Cystadenofibroma

SerousLined by tall, columnar ciliated and noniliated epithelial cells Filled with clear serous fluid BRCA1 and BRCA2 fimbriated end of fallopian tube Higher frequency of malignancy in women of low parity

Mucinous Endometrioid KRAS Pseudomyxoma peritonei Less frequently bilateral PTEN. KRAS, beta- catenin

Germ Cell Tumors Types Teratomas Dysgerminoma Endodermal sinus (yolk sac) Choriocarcinoma Most are benign cystic teratomas

TeratomasMature (benign)- dermoid cyst Immature (malignant) Monodermal ( highly specialized) – strumi ovarii (thyroid) and carcinoid

Dysgerminoma Yolk sac Choriocarcinoma Equivalent to seminoma Gonadal dysgenesis Alpha-fetoprotein and alpha1- antitrypsin HCG Aggressive

Sex Cord-Stromal Types Fibroma – Meigs syndrome ( ovarian tumor, hydrothorax, ascites), basal cell nevus syndrome Granulosa-theca cell – estrogen, precocious puberty, endometrial hyperplasia or carcinoma, Call-Exner bodies Sertoli-Leydig cell - masculinizing

Gestational and Placental Disorders Early Pregnancy Late pregnancy Spontaneous abortion Ectopic pregnancy Twin placentas Placental Implantation abnormalities – previa and accreta Placental abruption Placental Infections Preeclampsia Eclampsia

Preeclampsia Widespread endothelial dysfunction, vasoconstriction, increased vasopermeability Hypertension, Edema, proteinuria 3-5% women Last trimester Primiparas HELLP syndrome ( hemolysis, elevated liver enzymes, low platelets) Abnormal placental vasculature- abnormal trophoblastic implantation is the initial event – remodeling of vessels does not occur Followed by endothelial dysfunction and imbalance of angiogenic and anti-angiogenic factors Coagulation abnormalities Headache and visual changes – severe preeclampsia Seizures - eclampsia

Gestational Trophoblastic Disease Hydatidiform Mole Complete Partial Invasive mole Choriocarinoma Placental-Site Trophoblastic Tumor