Herpes simplex virus
Morph: red papules which progress to vesicles and painful ulcers with fever, malaise, LAD
Path: 3-7 days after contact
- latent infection in lumbosacral nerve ganglia reactivated by stress, trauma, immunosuppression
- vertical transmission possible
Molluscum contagiosum
Poxvirus infection of skin and mucous membrane
Path: Type I most common, Type II sexually transmitted
Morph: dimpled dome-shaped lesions erupt, cells with viral inclusions
Trichomonas vaginalis
Flagellated protozoan by sexual contact
- asymptomatic or present with yellow frothy vaginal discharge
- vulvovaginal discomfort, dysuria, dyspareunia
Gardnerella vaginalis
Gram negative bacillus
- causes bacterial vaginitis
Sx: green-gray, fishy-smelling discharge
Pelvic Inflammatory Disease
Cause: infections in vulva or vagina and ascend to involve other genital structures
- gonococcus, chlamydia
Sx: pelvic pain, adnexal tenderness, fever, vaginal discharge
- chronic sequelae include tubal scarring and obstruction, infertility, increased ectopic pregnancy, pelvic pain, GI pelvic adhesions
Bartholin cyst
Occlusion of draining ducts by inflammation
- lined by flattened epithelium
Sx: painful, possible abscess formation
Lichen sclerosus
Path: papules or macules that coalesce into smooth, white parchment areas
- epidermal thinning, superficial hyperkeratosis, dermal fibrosis
Sx: labia atrophic and stiffened, constriction of vaginal orifice
Squamous cell hyperplasia/ Lichen simplex chronicus
Non specific response to recurrent rubbing or scratching to relieve pruritus
- white plaques that have thickened epithelium, hyperkeratosis, dermal inflammation
- no predisposition to malignancy
Papillomas
Benign exophytic proliferation lined by non-keratinizing squamous epithelium, single or numerous
Condyloma acuminatum
Verrucous lesions on vulva, perineum, vagina, cervix
Cause: sexually transmitted by HPV 6 or 11
Morph: sessile branching epithelial proliferation of squamous epithelium
- koilocytic atypia
- not precancerous
Vulvar intraepithelial neoplasia/ vulvar carcinoma
Uncommon, ~3% of genital CA
Age: older than 60
Morph: basaloid and warty carcinomas arise from precancerous in situ lesions (VIN)
- classic VIN –> discrete hyperkeratotic flesh colored or pigmented plaques
- basaloid carcinoma –> exophytic or indurated with ulceration
- varty carcinoma –> exophytic architecture with koilocytic atypia
Keratinizing sqamous cell carcinomas
long standing lichen sclerosus or squamous cell hyperplasia
- precursor differentated VIN with basal atypic
Morph: vulvar inflammation, infiltrating nests and tongues of malignant squamous epithelium with prominent keratin pearls
Papillary hidradenoma
Benign tumor
- arises from apocrine sweat glands
- sharply circumscribed nodule or tubular ducts
Extramammary paget disease
Malignant lesion
Morph: red, crusted, sharply demarcated map-like area
- large anaplastic mucin containing tumor cells lying singly or in small clusters within epidermis
- confined to epidermis and invasion rare
Malignant melanoma
Vulvar ~5% of all malignancy
Age: 60-80
Septate vagina
Double vagina with double uterus from failure of mullerian ducts
Cause: DES exposure or abnormalities of epi stromal signaling in fetal development
Vaginal adenosis
Red, granular patches of remnant endocervical type columnar epithelium replaced by normal squamous epithelium of adult vaginal mucosa
- low frequency in normal women
- exposure to DES
VIN and Squamous cell CA
Primary CA are rare, usually associated with HPV infection
- arise from VIN which is analogous to malignant precursor lesion in cervical CA
- upper posterior vagina
Embryonal rhabdomyosarcoma
Uncommon vaginal tumor in infants
Morph: polypoid, bulky asses composed of grape like clusers (sarcoma botyroides) that can protrude from vagina
- Small tumors cells, oval nuclei and eccentric cytoplasmic protrusions
Path: invade locally cause death by penetration into peritoneal cavity or obstructing urinary tract
Cervicitis
Acute: Overgrowth of pathogenic species over lactobacilli from sex, douche, bleeding
Chronic: gonorrhea, chlamydiae, mycoplasmas, HSV –> can lead to upper GI tract disease and/or complications or pregnancy
Endocervical polyps
Benign exophytic growths
Sx: present at irregular vaginal spotting
Morph: arise in endocervical canal and soft mucoid lesions composed of loose CT stroma
Premalignant and Malignant Neoplasms
Path: HPV caused 16, 18, 31, 33
- DNA virus infect immature basal cells of squamous epithelium
HSV - E6 and E7 with p53 and Rb
Cervical intraepithelial neoplasia
Associated with high risk HPV
- low grade squamous intraepithelial lesion –> mild dysplasia, involving basal layers
- high grade squamous intraepithelial lesion –> moderate to severe dysplasia, carcinoma in situ
Morph: distribution of cellular and nuclear atypia including nuclear enlargement, hyperchromasia, chromatin granularity, size variation, koilocytosis
- LSIL atypia confined to basal third of epi
- HSIL atypia extends to two thirds or more
Cervical carcinoma
sq cell CA - 80%
adenocarcinoma - 15%
- all associated with HPV
Age: 45 years
Morph: Grossly - exophytic or infiltrative
Microscopic - squamous lesions keratinizing or non-keratinizing adenoCA tend to be glandular
Tx: hysterectomy, lymph node dissection
Causes of dysfunctional bleeding (2)
anovulatory cycle - excess estrogen with lack of ovulation
inadequate luteal phase - low progesterone with early menses and is often associated with infertility
prepuberty abnormal bleeding
precocious puberty (HPA or ovarian origin)
adolescence abnormal bleeding
anovulatory cycle, coag disorders
reproductive age abnormal bleeding
complications of pregnancy, organic lesions, anovulatory cycle, ovulatory dysfunctional bleeding
perimenopausal abnormal bleeding
dysfunctional uterine bleeding (anovulatory cycle, irregular shedding), organic lesions
postmenopausal abnormal bleeding
organic lesions, endometrial atrophy
Endometritis (acute and chronic)
acute - uncommon, bacterial infections after delivery or miscarriage from conception
chronic - abnormal bleeding, pain, discharge, infertility, endometrial plasma cell and macro infiltration
Endometriosis
Endometrial tissue outside of the uterus
- involves ovaries, uterine ligaments, rectovaginal septum, cul de sac, pelvic peritoneum, GI tract, mucosa of cx, vagina, fallopian tube, laparotomy scars
- undergo periodic bleeding but don’t slough off like endometrial lining
Morph: red-blue to yellow brown mucosal or serosal nodules
- organizing hemorrhage and fibrosis
- endometrial glands and stroma with or without hemosiderin
Sx: severe dysmenorrheal, pelvic pain, infertility
Adenomyosis
Nests of endometrial tissue in myometrium
Endometrial polyps
exophytic masses of endometrial glands and stomra project into endometrial cavity
- associated with estrogens or tamoxifen therapy
- possible to adenocarcinoma
Endometrial hyperplasia
increased proliferation of endometrial glands relative to stroma
- cause of uterine bleeding
- precursor to carcinoma
Cause: prolonged estrogen exposure
- associated with PTEN tumor suppressor gene leading to enhanced AKT phosphorylation
Morph: simple hyperplasia without atypia - benign cystically dilated glands
simple hyperplasia with atypia - uncommon, cystically dilated glands
complex hyperplasia without atypia - apposed glands of size together into clusters, epi cytologically normal
complex hyperplasia with atypia - gland crowding and cyto changes, malignancy
Carcinoma of endometrium
Genetics: 7% of all invasive cancers
Age: 55-65 years
Types: Type I and Type II
Type I endometrial CA
Most common (80%), well differentiated from endometrial hyperplasia
Path: PTEN mutations seen in 30-80%, microsatellite instabliity, KRAS, p53
Morph: Gross - localized polypoid tumors or diffuse spreading lesions
Micro - endometrioid adenoca with epi resembling normal endometrium
Type II endometrial CA
Age: occur later in life
Path: endometrial atrophy, poorly differentiated tumors, serous carcinoma
- p53 present
Morph: Gross - large and bulky, invasive
Micro - invasive lesions exhibit papillary or glandular growth pattern
Sx: ueterine bleeding or abnormal pap smear
Malignant Mixed Mullerian tumors (MMMT)
Endometrial adenocarcinomas with malignant stroma changes from neoplastic precursor
Morph: gross - tumors are bulky, fleshy, polypoid
Micro: malignant glandular and stromal elements
Adenosarcoma
Estrogen sensitive tumors exhibit stromal neoplasia with benign glands
- large polypoid growths generally low grade malignancies
Stromal tumors
Benign stromal nodules - discrete lumps of stromal neoplasia with myometrium
Endometrial stromal sarcomas - lesions composed of malignant stroma interposed between myometrial bundles
Leiomyoma (fibroids)
Benign masses of uterine smooth muscle
- most common tumor in women
Path: t(12;14) translocation
Sx: asymptomatic or present with abnormal uterine bleeding, pain, urinary bleeding, pain, urinary bladder disorders, impaired fertility
Morph: sharply circumscribed, discrete, round, firm, gray-white nodules in myometrium, beneath serosa, beneath endometrium
micro - whorled bundles of uniform smooth muscle cells with rare mitosis
Leiomyosarcoma
Uncommon malignancies that form bulky, fleshy masses, in uterine wall or project into lumen
- wide range of atypia
- metastasize and disseminate widely
Suppurative salpingitis
Component of PID; gonococcal infections, chlamydia also factor
Tuberculous salpingitis - rare in US cause of infertility
polycystic ovarian disease and stromal hyperthecosis
Incidence: 3-6%
Path: numerous cystic follicles
Sx: oligomenorrhea, persistent anovulation, obesity, hirsuitism, insulin resistance
Stromal hyperthecosis - disorder of ovarian stroma in postmenopausal women
- stromal hypercellularity and luteinization visible
Surface epithelium tumors - serous
Majority benign or borderline
- most common ovarian malignancy
Path: BRCA1
- low grade have KRAS and BRAF mutations
- high grade have p53 mutations
Morph: large cystic masses with serous fluid
- micro - tall, columnar, ciliated epi cells, mild atypia
Surface epithelial tumors - mucinous
Majority are benign or borderline
Risk factor: smoking, KRAS
- pseudomyxoma peritonei extensive mucinous ascites
Morph: Gross - large multiloculated cystic masses with sticky gelatinous fluid
- micro - benign lesions lined by tall columnar epithelial cells non-ciliated
Surface epithelial tumors - endometrioid
Account for 20& of all ovarian cancers
- resemble benign or malignant endometrium
Path: PTEN, KRAS, microsatellite instability, p53
Morph: Grossly - lesions are combo of solid and cystic masses
Micro - glandular patterns bear resemblane to endometrial adenocarcinoma
Surface epithelial tumor - clear cell adenocarcinoma
Uncommon, variant of endometrioid adenocarcinoma
- cystic or solid
Surface epithelial tumor - brenner
variably sized solid tumor by dense fibrous stroma and nests of epi resembling urinary transiational or columnar epithelium
- unilateral
Teratoma
Mature - arise in young women during reproductive years
- cystic masses lined by squamous with many germ cell layers
- tumors are bilateral rarely
Monodermal or specialized - differentiate along one tissue, struma ovarii is composed of mature thyroid tissue, ovarian carcinoid variant
Immature - rare tumors of embryonic elements
Dysgerminoma
Age: 20-40
Path: cKIT receptor tyrosine kinase
- malignant
Morph: grossly - solid, yellow-white to gray-pink, fleshy
- Micro - sheets and cords of large vesicular cells by scant fibrous stroma
Endodermal sinus tumor (yolk sac)
Rare malignancy from differentiation of germ cells toward yolk sac structures
Path: schiller-duvall body (glomerulus like structures with a central vessel enveloped by germ cells)
- AFP elevated
Choriocarcinoma
highly malignant, metastasize widely, resistant to chemotherapy than placentral counterparts
Granulosa-theca cell tumors
Large estrogenic increase - precocious sexual development and endometral hyperplasia
- predispose to endometrial carcinoma
- malignant, most have indolent course with 10 year survival rates
Morph: grossly - unilateral, solid, white-yellow
Micro - small cuboidal to polygonal in cords, sheets or strands - CALL-EXNER bodies
- sheets of plump spindle cells often contain lipid droplets
Fibromas, thecomas, fibrothecomas
Majority are benign
- unilateral, solid, hard, gray-white masses
- composed of well differentiated fibroblasts and scant collagenous connective tissue
- associated with ascites and right sided hydrothorax (MEIGS SYNDROME)
Sertoli- Leydig cells
Masculinization or defeminization
- unilateral and consist of tubules
Spontaneous abortion
Pregnancy before 20 weeks
Causes: maternal, fetal, uterine defects, maternal vasculature disorders, infections, idiopathic
Ectopic pregnancy
Embryo implantation at site other than uterus, usually fallopian tubes
- risk of PID with scarring, intrauterine devices, peritubal adhesions
Sx: hemorrhage with formation of hematosalpinx, rupture with hemorrhage, regression with resorption of products of contraception
- tubal ruptures
placenta previa
placental implamantation in lower uterine segment or cervix, third trimester bleeding
- C section necessary or death
Placenta accreta
absence of decidua and placenta adheres to myometrium, life threatening hemorrhage
Preeclampsia and eclampsia
HTN, proteinuria, edema in 3rd trimester
- eclamsia has association with seizure and coma
- possible hypercoagulability, renal failure, pulmonary edema
HELLP - hemolysis, elevated liver enzymes, low platelets
Morph: small, periph infarcts
Hydatidiform mole
Cystic swelling of chorionic villi with trophoblastic proliferation, can cause choriocarinoma
Morph: gross - translucent grape like structures
- micro - hydropic swelling of villi
Complete: egg fertilized by 1-2 sperm, empty ovum
- karyotype is 46XX
- all villi
- diffuse trophoblast proliferation circumferential
- atypia often present
- elevated serum beta hCG
- can go to choriocarcinoma
Partial: egg with two sperms
- karyotype triploid
- some villi edema
- focal trophoblast proliferation
- no atypia
- not as high hCG
Invasive mole
penetrates and perforates uterine wall, proliferating cytotrophoblastas and syncytiotrophoblasts
- villi can embolize to distant sites
Choriocarcinoma (not germ cell)
Malignant tumor, half from hydatidiform moles
Morph: Grossly - large, soft, yellow-white tumors with necrosis and hemorrhage
Micro - mixed cytotrophoblasts and syncytiotrophoblast
Sx: vaginal bleeding and discharge after pregnancy
Placental site trophoblastic tumor
neoplastic proliferation of extravillous trophoblasts, syncytio and cytotrophoblasts absent, lower hCG