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 laborChlamydia –usually cervicitis

LGV in tropicsSyphilis – painless chancre,

condyloma lata, fetal malformations

Toxic Shock – S. aureus, tampons,

PID

Ascending infectionGC- also pharyngitis, arthritis, proctitis, ophthalmia

neonatorum, Chlamydia – more mucosal involvement

Puerperal infections – polymicrobial, more reaction in the deeper layers

Acute salpingitisSalpingo-oophoritisTubo-ovarian abscessesAcute complications –peritonitis, bacteremiaChronic complications- infertility, tubal obstruction,

intestinal obstruction, ectopic pregnancy

Vulva

Skin diseases – similar to other areas of body – infection, inflammatory, cancers

Bartholin CystLichen sclerosus- thinning of epidermis, dermal fibrosisSquamous cell hyperplasia (Lichen simplex chronicus)Condyloma acuminatum-HPV 6 and 11, koilocytic (expanded

epithelial cells with perinuclear clearing) atypiaVIN and carcinoma – basloid and warty- HPV

keratinizing squamous cell- more common, not HPVPapillary hiradenoma – sweat glandsExtramammary 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 partnersYoung age at first intercourseHigh parityImmunosuppressionCertain HLA typesUse of oral contraceptivesUse of smoking

Cervix

HPVMost infections are asymptomatic50% clear in 8 months90% clear in 2 yearsPersistent infection increases the risk of cervical dysplasia and carcinomaCan infect only the immature cells but replication occurs in the maturing cellsKoilocytic atypia – nuclear atypia and perinuclear haloActivate cell cycle by interference with Rb and p53

Cervix

Cervical Intraepithelial NeoplasiaCIN I – mild dysplasia (LSIL)CIN II – moderate dysplasia (HSIL)CIN III – severe dysplasia (HSIL)

Natural historyLSIL – 60% regress, 30% persist, 10% progress to HSILHSIL – 30% regress, 60% persist,10%

progress to carcinoma

Cervix

Cervical cancer80% squamous cell15% adenocarcinoma 5% adenosquamous and neuroendocrine

Stagingstage 0 - carcinoma in situ (CIN III, HSIL)stage I – confined to cervixstage II – beyond the cervix but not to pelvic wall or lower 1/3 of vaginastage III – extended to the pelvic wall, lower 1/3 of vaginastage IV – beyond the true pelvis, bladder or rectum or distant metastases

Screening and preventionPAP smearRemoval of precancerous lesions - colposcopysurgical removal of invasive cancersHPV vaccineHPV DNA testing

Endometrium

“Dating” the endometrium

Proliferative phase

Secretory phase

Exhaustion and disintegration

Hypothalmic-Pituitary-Ovarian Axis

Corpus luteum

Endometrium

Dysfunctional Uterine BleedingAnovulatory Cycle

Menopausal changesAtrophy

InflammationAcute endometritis

Retained products of conceptionChronic endometritis

Chronic PIDPostpartum or post-abortionIUDsTBNon-specific

Endometrium

EndometriosisPresence of endometrial tissue outside the uterus

InfertilityDysmenorrhea Pelvic pain

Metastatic theoryMetaplastic theory

Activation of inflammatory cascadeUpregulation of estrogen production

AdenomyosisPresence of endometrial tissue within the uterine wall (myometrium)

HyperplasiaProlonged estrogen stimulation of the endometrium

Relationship with endometrial carcinoma

Inactivation of the PTEN tumor suppressor gene

Simple hyperplasia + atypiaComplex hyperplasia +atypia

Endometrium

Endometrial carcinomaMost common invasive tumor of the female genital tract

Post-menopausal bleeding

Type IUnopposed estrogenObesity, hypertension, diabetesEndometroidHyperplasiaPTENIndolent

Type IIAtrophyThinSerous, clear cell, mixed mullerian tumorEndometrial intraepithelial carcinomaAggressivep53

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Myometrium

Leiomyomas – fibroids

Leiomyosarcomas

Ovaries

Polycystic Ovarian diseasepersistent anovulationobesityhirsutismrarely virilism

Variety of enzymes involved in androgen synthesis are poorly regulated

Ovarian Tumors

Surface Epithelial-stromalMost commonMost 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

TypesSerousMucinousEndometrioidClear cellBrenner – transitional cellCystadenofibroma

Serous Lined 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

Teratomas Mature (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

HCGAggressive

Sex Cord-Stromal

TypesFibroma – Meigs syndrome ( ovarian tumor, hydrothorax, ascites), basal cell nevus syndromeGranulosa-theca cell – estrogen, precocious puberty, endometrial hyperplasia or carcinoma, Call-Exner bodiesSertoli-Leydig cell - masculinizing

Gestational and Placental Disorders

Early Pregnancy

Late pregnancy

Spontaneous abortionEctopic pregnancy

Twin placentasPlacental Implantation

abnormalities – previa and accreta

Placental abruptionPlacental InfectionsPreeclampsiaEclampsia

Preeclampsia

Widespread endothelial dysfunction, vasoconstriction, increased vasopermeability

Hypertension, Edema, proteinuria3-5% womenLast trimesterPrimiparasHELLP syndrome ( hemolysis, elevated liver enzymes, low platelets)Abnormal placental vasculature- abnormal trophoblastic implantation is

the initial event – remodeling of vessels does not occurFollowed by endothelial dysfunction and imbalance of angiogenic and

anti-angiogenic factorsCoagulation abnormalitiesHeadache and visual changes – severe preeclampsiaSeizures - eclampsia

Gestational Trophoblastic Disease

Hydatidiform Mole

Complete

Partial

Invasive mole

Choriocarinoma

Placental-Site Trophoblastic Tumor