- highly transmissible DNA virus.
- hepatic ulcer phase is active.
- latent phase is inactive.
- painful, inflamed, shallow ulcers on the vulva, vagina, cervix, groin, buttocks, and thighs.
- pain, dysuria.
- diagnosed via Tzanck smear.
- sequelae are neonatal infections, spontaneous abortions.
Neonatal herpes infection
- 50% born to asymptomatic mothers.
- up to 80% mortality.
- causes conjunctivitis, keratitis, vesicular rashes, jaundice, seizures, and GI bleeds in newborn 2-12 days after delivery.
- treatment is C-section if an active maternal infection is present.
- causes vaginitis.
- may be normal flora.
- diabetes, antibiotics, pregnancy, immunosuppression.
- leukorea (thick white vaginal discharge), pruritis.
- flagellated protozoan, sexually transmitted.
- yellow, frothy discharge, pruritis, dysuria, dyspareunia.
- "strawberry" cervix.
- gray-green malodorous (foul smelling) discharge.
- diagnosed by presence of "clue cells" on pap smear.
Pelvic inflammatory disease
- infection of pelvic organs by a variety of pathogens beyond the uterine corpus.
- usually caused by gonorrhea and chlamydia.
- symptoms include lower abdominal pain, cervical tenderness.
- complications include rupture of tuboovarian abscess, infertility from scarring of tubes, ectopic pregnancy, and intestinal obstruction from fibrous bands and adhesions.
- cyst of the glands responsible for maintaining moisture of the vaginal mucosa's vestibular surface.
- may present as painless labial swelling.
- treatment is marsupialization which involves suturing the inner edge of the incision to external mucosa.
- pruritic, papular, polygonal, and scaly eruption.
- caused by a cell-mediated immune response.
Lichen sclerosus (LS&A)
- squamous atrophy.
- presents with white plaques showing epidermal atrophy.
- usually affects elderly and post-menopausal females.
- not considered precancerous, but is associated with increased risk of cancer development (1-4%).
Lichen simplex chronicus (LSC)
- squamous hyperplasia.
- histology shows squamous hyperplasia, acanthosis, and hyperkeratosis.
- no cytologic atypia.
- HPV 6 and 11.
- frequently multiple and papillary, but occasionally flat.
- histology shows koilocytes and mitosis.
- frequently regress.
- treatment is cryo, chemical, laser, or surgical excision.
Vulvar intraepithelial neoplasm (VIN)
- 30% will have dysplasia of vagina/cervix.
- multicentric on the vulva.
- high recurrence after surgery.
- risk of progression to invasive SCC depends on age, extent, and immune status.
Invasive SCC of vulva
- not very common (3% of genital cancers).
- presents as nodules or masses with a background of leukoplakia.
- usually solitary, but 10% multifocal when associated with condyloma.
- an ulcerated mass is malignant until proven otherwise.
- 2 types: warty/basaloid and keratinizing.
- impaired immune status is associated with more progressive disease.
- Lymph spread: inguinal-pelvic-iliac-paraaortic-lungs/liver.
- treatment is vulvectomy and lymphadenectomy.
- variant is verrucous carcinoma (fungating, non-metastasizing tumors that look like condyloma).
- sharply circumscribed nodule in vulva with normal overlying skin.
- considered a benign tumor derived from apocrine glands.
Extramammary paget disease
- presents as a pruritic, red, crusted, sharply demarcated area on labia majora of elderly women.
- does not have underlying carcinoma.
- PAS +, mucin +, CEA +, EMA +.
- histology shows vacuolated cells, acanthosis, hyperkeratosis, and parakeratosis.
- treatment is wide local excison but may recur.
Gartner duct cyst
- cyst of lateral vaginal wall.
- simple cyst with monolayer of benign cuboidal epithelium.
- treatment is excisional biopsy.
- abnormal development of glandular tissue in the vagina as a result of in utero exposure to diethylsilbestrol (DES) while the affected woman was a fetus.
- develops clear cell carcinoma of the vagina.
- is curable when small.
- neoplasm of girls < 5 years of age.
- have a "grape like" appearance.
- presents as polypoid mass or vaginal bleeding.
- arises in lamina propria of vaginal wall.
- high rate of surgical cure if tumor < 3cm, which tends to be localized.
- grows by local invasion with spread to nodes and distant sites.
- loss of acidosis (bleeding, intercourse, douching, antibiotics) leads to loss of normal flora and overgrowth of other bacteria.
- may be as large as 5cm.
- may cause "spotting of blood".
- treatment is polypectomy.
- mucus-filled cyst on the surface of the cervix.
- keeps secreting until rupture.
- self limited.
P16 (despite high levels, HPV infected cells proliferate because the target of the p16 (RB) is inactivated by E7)
Uterine cervix (showing vaginal cuff, cervical os, and exocervix)
- vaginal cuff.
- cervical os.
Normal cervix (black - squamo columnar junction, white - squamous metaplasia)
- squamo columnar junction.
- squamous metaplasia.
- white-appearing epithelium following the application of acetic acid.
- correlate with higher nuclear density.
Adenocarcinoma in situ (AIS)
- precursor lesion to invasive adenocarcinoma (15% of malignancies).
- very difficult to recognize.
- can be difficult to visualize as can extend up endocervical canal.
- 80% SCC, 15% adenocarcinoma.
- all associated with HPV.
- >50% present in women without pap smear screening.
- usually a small and shallow tumor.
- usually present with bleeding after coitus or advanced local invasion.
- 5 year survival.
- death is by invasion of local structures, especially obstruction of ureters (50% die in renal failure).
- treatment is radical hysterectomy.
HPV vaccine (gardasil)
- vaccine for HPV 6, 11, 16, 18.
- 100% immunity against HSIL at 5 years.
- males can be vaccinated (herd immunity).
- top left - proliferative phase.
- top right - early secretory phase.
- bottom left - late secretory phase.
- bottom right - menstrual phase.
- proliferative phase.
- early secretory phase.
- late secretory phase.
- menstrual phase.
Dysfunctional uterine bleeding
- unscheduled bleeding that is presumed to be a consequence of a hormonal/functional abnormality.
- results in increased, prolonged, and unopposed estrogen stimulation.
- resulting endometrium is unstable and breaks down with bleeding.
- no known cause.
- biopsy shows irregular, dilated glands, no progesterone effect, and stromal breakdown.
- very common around menarche and in perimenopausal period.
Inadequate luteal phase
- abnormal corpus luteum function gives low progesterone in secretory phase.
- typically presents as infertility with menorrhagia or amenorrhea.
- biopsy shows histologic date is > 2 days behind the clinical date of menstrual cycle.
- have marked effects on endometrium, depending on estrogen-progesterone ratio and sequence of ingestion (combined or sequential).
- limited to infections that arise after delivery or miscarriage, especially if there are retained products of conception, like placental fragments.
- infection is by vaginal bacteria like Strept Group A and Staph.
- treatment is by curetting the endometrial cavity to remove the fragments.
- biopsy shows plasma cells which are not normal endometrial cells.
- typically associated with chronic PID, retained products of conception, IUD, tuberculosis).
- 15% are nonspecific (present with metromenorrhagia, dysmenorrhea, pain, infertility) and respond to antibiotics.
- presence of endometrial tissue (glands and tissue) outside the uterus.
- presents with infertility, dysmenorrhea, pelvic pain, scarring of involved organs.
- presence of endometrial tissue in the myometrium.
- if forms a discrete mass, it is called an adenomyoma.
- presents with infertility, dysmenorrhea, pelvic pain, scarring of involved organs.
- may be pedunculated or sessile and up to centimeters in length.
- typically present with bleeding.
- treatment is surgical removal.
Endometroid adenocarcinoma (Type I)
- 80% of endometrial cancer.
- peak age 55-65 years.
- associated with conditions of unopposed estrogen.
- typically present with abnormal bleeding.
- involves PTEN mutations and microsatellite instability.
Non-endometrioid adenocarcinoma (Type II) (p53 stain on top/bottom right)
- serous carcinoma.
- 15% of endometrial carcinomas.
- peak age 65-75 years, occurs 10 years later than endometrioid adenocarcinoma.
- p53 mutation.
- are all high grade lesions with aggressive course.
- early spread through lymphatics.
- mass invading uterine wall or polypoid mass in lumen.
- diagnosed by high mitotic rate, cytologic atypia, and tumoral necrosis.
- peak incidence 40-60 years.
- metastasize by blood vessel invasion.
- 40% 5 year survival.
- very common.
- may reach up to 5cm in size.
- forms when there is no LH surve and the cyst doesn't rupture to release its egg.
- usually harmless, often resorb after 2-3 menstrual cycles.
- smooth-walled unicameral (one chamber) simple cyst.
Corpus luteum cyst
- opening from released egg seals off the subsequent corpus luteum.
- may spontaneously resolve or grow to as large as 4cm.
- may hemorrhage or undergo torsion.
Torsion of ovary
- presents as sudden unilateral pain.
- often occurs in young women.
- mass >5cm.
- R/O ectopic pregnancy.
- diagnosed by ultrasound.
Polycystic ovary disease
- most common endocrine problem of reproductive age women.
- oligomenorrhea, hyperandrogenism, polycystic ovaries, obesity, acanthosis nigricans, diabetes.
- R/O other endocrine diseases (decreased T4, prolactinemia, cushing, acromegaly).
- diagnosed via ultrasound.
- asymptomatic until late presentation.
- disease of older women (60's).
- BRCA1/BRCA2 and MSH2 (lynch II syndrome) mutations.
- prognosis depends more on stage than on cell type.
- often bilateral.
- CA-125 and ultrasound screening.
- risk is decreased by tubal ligation and BCP.
Serous borderline carcinoma
- outgrowth on cyst wall.
- no invasion.
- often arise on and extend to peritoneum.
- 100% 5 year survival.
- 65% bilateral.
- aggressive, presents late, poor prognosis.
- confined to ovary (70% 5 year), peritoneum (25% 5 year).
Serous adenocarcinoma (showing cribiform appearance, central necrosis, and micropapillary architecture)
- least likely to be bilateral.
- if bilateral, R/O metastasis.
- most are benign (80%).
- may cause pseudomyxoma peritonei (typically appendix), which produces mucin in the abdominal cavity.
- mostly carcinoma.
- may arise in endometriosis.
- 20-30% have synchronous ovarian and endometrial endometrioid carcinomas.
- PTEN and RAS mutations.
Endometrioid tumor (showing "chocolate" blood material of endometrioma and discrete malignant nodules of endometrioid carcinoma)
Surface epithelial tumors
- lower abdominal pain, GI/GU complaints, pelvic pressure, progressive weakness, weight loss, cachexia.
- diffuse seeding of peritoneum (small, shallow implants).
- diagnosed via cytology of ascites (exudative).
- CA-125 is useful for following course of disease.
- treatment is surgery followed by chemotherapy.
- preventative use of BCP and salpingo-oophorectomy in BRCA families.
Dermoids (benign cystic teratoma)
- contains 2 or 3 germ cell lines.
- filled with hair and keratin.
- distinctive Rokitanski nodule on cyst wall contains all 3 germ cell lines.
- treatment is women desiring pregnancy is cystectomy from rest of normal ovary.
- 1% will develop a cancer (usually SCC).
Immature malignant teratoma
- girls and adolescents.
- contain immature tissues (embryonal and fetal).
- rapid growth and spread.
- single tissue predominates.
- carcinoids and struma ovarii (thyroid) are commonest.
- may cause hyperthyroidism and carcinoid syndrome.
- metastatic intestinal carcinoids are unilateral.
- primary ovarian carcinoids are bilateral.
- ovarian counterpart to the seminoma of testis.
- sensitive to radiotherapy.
- only 1/3 are aggressive.
- histology shows "fried egg" cells with prominent nucleoli and lymphoid infiltrate).
- can be treated with salpingo-oophorectomy.
Endodermal sinus (yolk sac) tumor
- like testicular counterpart, very aggressive.
- produces AFP.
- has schiller-duval bodies.
- gross appearance shows myxoid degeneration, necrosis, and fibrosis.
Granulosa-theca cell tumors
- hormonally active tumors are yellow.
- 75% produce estrogen.
- inhibin may be used for diagnosis and marking.
- has call-exner bodies (small eosinophilic fluid-filled spaces between granulosal cells).
- intermediate malignancy, unpredictable.
- very common.
- solid, white, hard fibrous tumor.
- associated with meig's syndrome (ascites, pleural effusion and ovarian fibroma that resolves with resection of fibroma).
- most commonly from other organs of mullerian degeneration (uterus, fallopian tube, opposite ovary, peritoneum).
- extra-mullarian organs (breast, GI).
- bilateral metastasis of mucin-producing, signet-ring cancer cells, espically gastric origin.
- part of the spectrum of PID.
- acute form produces pus.
- if results of tube scar shut, get pyosalpinx or hydrosalpinx.
- if inflammation continues to ovary, get tubo-ovarian abscess.
- complications include adhesions, infertility, and ectopic pregnancy.
- arise in mullarian remnants at the fimbriated end of tube or in broad ligament.
- translucent, thin-walled, unicameral, often called hydatid cysts of Morgagni.
- conception occurs in distal 1/3 of the tube.
- get abnormal implantation in tube if passage is impaired (PID, adhesions, endometriosis).
- tube ruptures by the 12th week of pregnancy and may cause life-threatening hemorrhage.
- biopsy of endometrium will show decidual change, but no chorionic villi.
Fallopian tube adenocarcinoma
- primary carcinomas are rare.
- secondary tumors are common.
- serous carcinomas of ovary and peritoneum may arise in distal tube.
- <20 weeks gestational age.
- occurs in 10-15% of clinically recognized pregnancies.
- another 22% terminate before clinical recognition.
- 1st trimester - chromosomal causes.
- 2nd trimester - mechanical causes.
- 3rd trimester - fetoplacental unit causes.
- implantation in any site other than the normal intrauterine location.
- 1/150 pregnancies.
- 90% occur in fallopian tubes.
- predisposing condition is PID.
- risk factor is smoking.
- presents with severe abdominal pain which may lead to tubal rupture and death.
- diagnoses via b-HCG, ultrasound, laparoscopy.
Twin-Twin transfusion syndrome
- disproportionate sharing of fetal circulations (AV shunt).
- can cause death of one or both fetuses.
- implantation over or close to the cervical os (lower 1/3).
- painless bleeding occurring in the 3rd trimester.
- most common cause of antepartum hemorrhage (can result in death).
- due to a premature separation of the placenta with a resultant retroplacental clot.
- painful vaginal bleeding.
- hematomas involving 1/3 or more of the maternal surface can result in fetal death.
- significant complication of preeclampsia.
- attachment of the placenta directly to the myometrium (loss of decidua basalis).
- placenta does not separate easily after delivery causing postpartum bleeding.
- 15% have uterine rupture.
- placenta percreta is worst form (placenta penetrates the entire myometrium).
- can occur due to surgical scars (Asherman's syndrome), previous C-sections, or endometrial inflammation.
Placental infection and inflammation
- ascending infection from the vagina and cervix (group B, strepchorioamnionitis, villitis, funisitis, premature rupture of the membrane, neonatal pneumonia, sepsis, meningitis).
- hematogenous (transplacental) (TORCH - toxoplasmosis, rubella, CMV, HSV, chronic villitis).
- hypertension present in 10% of pregnancies.
- 5% of pregnant women have pregnancy induced hypertension (PIH).
- common in primiparas (first pregnancy) and women >35 years.
- preeclampsia usually starts after the 20th week of pregnancy (third trimester usually).
- begins earlier in patients with hydatidiform mole or preexisting kidney disease or hypertension.
- toxemia of pregnancy.
- systemic syndrome characterized by widespread maternal endothelial dysfunction.
- hypertension, edema, proteinuria, coagulopathies, and DIC.
- 3-5% of pregnant women.
- usually occurs in the 3rd trimester.
- HELLP syndrome (10%) (hemolysis, elevated liver enzymes, low platelets).
- new onset of grand mal seizure activity and/or unexplained coma during pregnancy or postpartum in a woman with signs or symptoms of preeclampsia.
Complete hydatidiform mole
- grossly shows friable mass of translucent cystic grape like clusters.
- no fetal parts are seen.
- histology shows villus edema with diffuse trophoblastic proliferation.
- high risk of choriocarcinoma.
Partial hydatidiform mole
- triploid or tetraploid.
- grossly shows few grape like clusters with identifiable fetal parts.
- histology shows few edematous villi and slight trophoblastic proliferation without atypia.
- low risk of choriocarcinoma.
Gestational trophoblastic disease
- gestational neoplasm suspected when uterus is too large for date and no fetal heart sounds or movements are detected.
- increased incidence of theca lutein cells.
- spontaneous abortions.
- pregnancy induced hypertension.
- incidence higher in Asian countries (causing spontaneous abortions).
- higher in teens and 5th decade.
- present with painless vaginal bleeding, usually during 4th month.
Invasive hydatidiform mole
- hydropic villi which penetrate the uterine wall.
- can cause uterine rupture and can be life threatening.
- hydropic villi may embolize to distant organs, but no metastatic potential (does not grow in those organs).
- treatment is hysterectomy or chemotherapy.
- arise from complete hydatidiform moles (50%), previous abortions (25%), and normal (22%) or ectopic pregnancies.
- higher incidence in African countries.
- b-HCG is markedly elevated.
- only composed of trophoblastic tissue and lack villous structures (central core of cytotrophoblasts surrounded by syncytiotrophoblasts).
- metastasize to lungs (cannon-ball metastases), vagina, brain, liver, etc.
- complicates 2.5% of moles, rare in normal pregnancies.
- presents with bloody brown vaginal spotting.
- treatment is chemotherapy (methotrexate).