Female Genital Tract

Question 1

HSV Infection

Answer 1

• red papules 3-7 days post contact.
• progress to vesicles and painful, coalescent ulcers associated with fever, malaise, tender lymphadenopathy.
• spontaneously heal within 1-3 wks but remains latent in lumbrosacral ganglia, reactivated during stress, trauma, immunosuppression, hormonal changes.
• dx: clinical findings, viral cultures.
• tx: antiviral agents to shorten.
• can be transmitted to baby.

Question 2

Molluscum Contagiosum

Answer 2

• poxvirus infection of skin and mucous membranes.
• type I = most common.
• type II = most sexually transmitted.
• 6wk intubation ⇒ dimpled, dome-shaped lesions. contain cells with intracytoplasmic viral inclusions.

Question 3

Fungal Infections

Answer 3

• yeasts are part of vaginal flora.
• expand when ecosystem disrupted = diabetes, antibiotics, pregnancy, immunosuppression.

Question 4

Trichomonas Vaginalis

Answer 4

• flagellated protozoan transmitted via sex.
• asymptomatic or present with yellow, frothy vaginal discharge, vulvovaginal discomfort, dysuria, or dyspareunia.

Question 5

Gardnerella Vaginalis

Answer 5

• gram (-) bacillus, major cause of bacterial vaginitis.
• presentation: thin, green-gray, fishy-smelling discharge.
• can precipitate premature labor.

Question 6

Pelvic Inflammatory Disease

Answer 6

• from infections that arise in vulva or vagina and ascend to involve other genital tract structures.
• causes: Gonococcus>Chlamydia>Staph, strep, coliforms, Clostridium perfringens.
• gonococcal spread via mucosal surfaces, cause acute suppurative rxn
• non-gonococcal distributed thru lymphatics and veins.
• presentation: pelvic pain, adnexal tenderness, fever, vaginal discharge.
• complications: peritonitis and bacteremia, tubal scarring and obstruction, infertility, ↑ risk of ectopic pregnancy, pelvic pain, GI pelvic adhesions cause intestinal obstruction.

Question 7

Bartholin Cyst

Answer 7

• from occlusion of draining ducts by inflammation.
• lined by flattened epithelium, can be large (3-5cm) and painful.
• can make abcesses needing drainage.
• tx: excision, marsupialization (permanent opening).

Question 8

Leukoplakia

Answer 8

• opaque, white, plaque-like thickenings.
• accompanied by pruritus and scaling.

Question 9

Lichen Sclerosus

Answer 9

• papules or macules that coalesce into smooth, white parchment-like areas.
• epidermal thinning, superficial hyperkeratosis, dermal fibrosis with scant mononuclear perivascular infiltrate.
• labia can become atrophic, stiffened, with constricted vaginal orifice.
• usually autoimmune.

Question 10

Squamous Cell Hyperplasia

Answer 10

• aka lichen simplex chronicus.
• non-specific resopnse to recurrent rubbing or scratching to relieve pruritus.
• white plaques, thickened epithelium, hyperkeratosis, dermal inflammation.
• often present at margins of vulvar carcinoma.

Question 11

Vulvar Fibroepithelial Polyps

Answer 11

• skin tags

Question 12

Squamous Papillomas (Vulva)

Answer 12

• benign exophytic proliferations lined by non-keratinizing squamous epithelium.
• single or numerous (vulvar papillomatosis).

Question 13

Condyloma Acuminatum

Answer 13

• verrucous lesions on vulva, perineum, vagina, and cervix (rare).
• sexually transmitted via HPV types 6 and 11.
• make sessile branching epithelial proliferations of stratified squamous epithelium.
• koilocytotic atypia = perinuclear cytoplasmic clearing with nuclear atypia in mature superficial cells.

Question 14

Vulvar Intraepithelial Neoplasia and Carcinoma

Answer 14

• 3% female genital cancers. women >60yrs.
• 1/3 basaloid or warty carcinomas related to HPV infection.
• 2/3 keratinizing squamous cell carcinoma unrelated to HPV.
• verrucous carcinoma and basal cell carcinoma locally aggressive but rarely metastasize.

Question 15

Keratinizing Squamous Cell Carcinoma

Answer 15

• in setting of long-standing lichen sclerosus or squamous cell hyperplasia.
• pre-malignant lesion = differentiated VIN, has basal atypia with normal superficial epithelial maturation and differentiation.
• morphology: nodules with vulvar inflammation.
  
  • infiltrating nests and tongues of malignant squamous epithelium, prominent keratin pearls.

Question 16

Basaloid and Warty Carcinomas

Answer 16

• from precancerous in situ lesions = classic vulvular intraepithelial neoplasia (VIN), aka Bowen Disease.
  
  • positive for HPV type 16.
• morphology: VIN = discrete hyperkeratotic, flesh-colored or pigmented slightly raise plaques.
  
  • ​multicentric with marked nuclear atypia, no maturation.
  • basaloid carcinoma = exophytic or indurated, ulceration. nests and cords of small, tightly packed cells resembling immature basal cells.
  • warty carcinoma = exophytic with prominent koilocytic atypia.

Question 17

Papillary Hidradenoma

Answer 17

• benign, arises from modified apocrine sweat glands.
• presentation: sharply circumscribed nodule of tubular ducts lined by non-ciliated columnar cells atop a layer of flattened myoepithelial cells.

Question 18

Extramammary Paget Disease

Answer 18

• malignant. red, crusted, sharply demarcated, map-like area.
• large, anaplastic, mucin-containing tumor cells in single layer or small clusters in epidermis and appendages.
• confined to epidermis, invasion rare.
• high recurrence rate.

Question 19

Malignant Melanoma (Vulvar)

Answer 19

• <5% vulvar malignancies, <2% female melanomas.
• peak incidence btw ages 60-80.
• 5 yr survival = <32% from delayed detection, rapid progression.

Question 20

Septate Vagina

Answer 20

• with a double uterus and is from failure of complete fusion of mullerian ducts.
• causes: genetic syndromes, in utero exposure to diethyl-stilbestrol (DES), abnormalities of epithelial-stroma signaling in fetal development.

Question 21

Vaginal Adenosis

Answer 21

• red, granular patches of remnant endocervical-type columnar epithelium that weren’t replaced by normal squamous epithelium of vaginal mucosa.
• in 35-90% women exposed to in utero DES.
  
  • can be substrate for clear cell carcinoma.

Question 22

Benign Vaginal Tumors

Answer 22

• typically in reproductive-age women.
• stromal polyps, leiomyomas, hemangiomas.

Question 23

Vaginal Squamous Cell Carcinoma

Answer 23

• primary vaginal carcinomas rare.
• associated with high risk HPV infections.
• arise from vaginal intraepithelial neoplasia (VIN).
  
  • analogous to VIN in cervical carcinoma.
• most affects upper posterior vagina.

Question 24

Embryonal Rhabdomyosarcoma

Answer 24

• aka sarcoma botryoides.
• highly malignant, uncommon.
• infants and kids, made of embryonal rhabdomyoblasts.
• polypoid, bulky masses made of grapelike clusters, protrude from vagina.
• tumor cells small, oval nuclei, small eccentric cytoplasmic protrusions.
• invade locally, cause death by penetrating into peritoneum or obstructing urinary tract.

Question 25

Acute Cervicitis

Answer 25

• normal pH is below 4.5, higher pH, from douching, bleeding, or sex, can lead to overgrowth by pathogens (acute cervicitis/vaginitis).
• pH kept low by H₂O₂ and lactic acid.

Question 26

Chronic Cervicitis

Answer 26

• found at low level in all women.
• infections with gonococci, chlamydiae, mycoplasms, HSV ⇒ significant acute/chronic cervicitis, lead to upper genital tract disease, complications with pregnancy.
• can have abnormal cytologic smears from marked cervical inflammation causing reactive and reparative epithelial changes.

Question 27

Endocervical Polyps

Answer 27

• benign exophytic growths in 2-5% women.
• presentation: irrgeular vaginal spotting.
• come from endocervical canal, are soft mucoid lesions made of loose CT stroma with dilated glands and inflammation, covered by endocervical epithelium.

Question 28

Cervical Carcinoma

Answer 28

• pre-cancerous lesions well detected by Pap smear.
• pathogenesis: risk factors = HPV types 16, 18, multiple partners, host immune response.
  
  • most HPV asymptomatic, 50% cleared in 8 months, 90% by 2 yrs. persistent infection ↑ risk of malignancy.
  • HPV = DNA virus infecting immature basal cells of squamous epithelium or metaplastic squamous cells at cervical squamocolumnar junction.
  • have koilocytotic change in non-proliferating squamous cells where HPV replicates.
  • interferes with p53 and Rb via viral E6 and E7 proteins that cause:
    
    • ↑ cyclin E expression via E7 ⇒ ↓ RB
    • stop apoptosis via E6 ⇒ ↓ p53
    • centrosome duplication and instability via E6 and E7
    • ↑ telomerase expression via E6
  • all HPV ↑ proliferation and life span of infected cells.
  • 80% squamous cell, 15% adenocarcinoma, 5% adenosquamous or neuroendocrine.
  • peak incidence of invasive is 45 yrs.
• morphology: exophytic or infiltrative.
  
  • squamous = keratinizing or not.
  • adenocarcinomas = glandular but mucin depleted.
  • adenosquamous = made of intermixed malignant squamous and glandular elements.
  • neuroendocrine = resemble small cell malignancy of lung.
• presentation: early tx by cervical cone biopsy. then hysterectomy and lymph node dissection, irradiation.
  
  • microinvasive = 95% 5 yr survival.
  • most advanced = <50% 5 yr survival.
    
    • neuroendocrine have poor prognosis.

Question 29

Cervical Intraepithelial Neoplasia

Answer 29

• precancerous epithelial changes, 2 types:
• low grade squamous intraepithelial lesions (LSIL): 80% have high risk HPV (type 16).
  
  • mild dysplasia in basal layers of epithelium. no significant alteration of cell cycle.
  • 60% regress within 2 yrs, 30% persist, 10% ⇒ HSIL.
  • not considered precancerous lesion.
• high grade squamous intraepithelial lesions (HSIL): 100% associated with high risk HPV (type 16).
  
  • moderate to severe dysplasia, involves more of epithelium, includes carcinoma in situ.
  • HPV deregulates cell cycle (↑ proliferation, ↓ epithelial maturation, ↓ viral replication).
  • 30% regress over 2 yrs, 60% persist, 10% progress to carcinoma within 2-10 yrs.
• morphology: LSIL = atypia only in basal third of epithelium.
  
  • HSIL = atypia extends to 2/3rds or more of epithelial thickness.

Question 30

Cervical Cancer Screening and Prevention

Answer 30

• Pap test has false negative rate btw 10-20%.
• can add HPV DNA testing.
• abnormal pap followed up by colposcopic exam with biopsies.
• LSIL lesions followed, HSIL treated with cervical cone and life-long follow up.
• prophylactic vaccine against HPV types 6 and 11 (condylomas) and 16 and 18 (cervical cancer) reduce incidence of HSIL.

Question 31

Dysfunctional Uterine Bleeding (DUB)

Answer 31

• abnormal bleeding in absence of organic lesion.
• usually from hyperestrogenic states but can be from endocrine disorders, metabolic disturbances.
  
  • hyperestrogenic state ⇒ cystic glandular changes with sporadic endometrial breakdown and bleeding.
• anovulatory cycle = lack of ovulation ⇒ excesive estrogen. due to subtle hormonal imbalances.
  
  • when with menopause, DUB may be from ovarian insufficiency and anovulatory cycles.
• inadequate luteal phase = inadequate corpus luteus ⇒ low progesterone output with early menses, associated with infertility.

Question 32

Uterine Bleeding in Prepuberty

Answer 32

• from precocious puberty (hypothalamic, pituitary, or ovarian origin).

Question 33

Uterine Bleeding in Adolescence

Answer 33

• anovulatory cycle, coagulation disorders.

Question 34

Uterine Bleeding Reproductive Ages

Answer 34

• pregnancy complications (abortion, trophoblastic disease, ectopic pregnancy).
• organic lesion (leiomyoma, adenomyosis, polyps, endometrial hyperplasia, carcinoma).
• anovulatory cycles.
• ovulatory dysfunctional bleeding (inadequate luteal phase).

Question 35

Perimenopausal Uterine Bleeding

Answer 35

• dysfunctional uterine bleeding: anovulatory cycle, irregular shedding.
• organic lesions (carcinoma, hyperplasia, polyps).

Question 36

Postmenopausal Uterine Bleeding

Answer 36

• organic lesions (carcinoma, hyperplasia, polyps).
• endometrial atrophy.

Question 37

Acute Endometritis

Answer 37

• uncommon. caused by bacerial infections after delivery or miscarriage.
• related to retained products of conception.
• tx: curettage and antibiotics.

Question 38

Chronic Endometritis

Answer 38

• presents as abnormal bleeding, pain, discharge, and/or infertility.
• endometrial plasma cell and macrophage infiltration.
• in pts with: chronic PID from chlamydia, retained gestation tissue post abortion or postpartum, intrauterine contraceptive devices, disseminated TB, 15% unknown.

Question 39

Endometriosis

Answer 39

• presence of endometrial tissue outside the uterus.
• involves: ovaries, uterine ligaments, rectovaginal septum, cul de sac, pelvic peritoneum, GI tract, mucosa of cervix/vagina/fallopian tube, laparotomy scars.
• under influence of ovarian hormones, undergo cyclic menstrual changes, periodically bleed but can’t slough off.
• retrograde menstruation through fallopian tubes ⇒ seeding of endometrial tissue.
• has marked activation of inflammatory cascades and ↑ stromal aromatase activity (↑ estrogen production).
• overproduces estrogen and prostaglandins ⇒ enhanced survival and peristence of endometriotic foci.
• morphology: red-blue to yellow-brown mucosal or serosal nodules. can have organizing hemorrhage and fibrosis.
  
  • have endometrial glands and stroma with or without hemosiderin.
• presentation: women during repdorductive age. severe dysmenorrhea, pelvic pain, infertility. rarely becomes malignant.

Question 40

Adenomyosis

Answer 40

• characterized by nests of endometrial tissues in uterine myometrium.
• continuous with endometrial lining, form by down-growth.
• affects 20% women.
• symptoms similar to endometriosis.

Question 41

Endometrial Polyps

Answer 41

• exophytic masses of endometrial glands and stroma that project into endometrial cavity.
• associated with ↑ estrogens or tamoxifen therapy.
• usually benign, manifest with abnormal bleeding.
• occasionally develop into adenocarcinoma.

Question 42

Endometrial Hyperplasia

Answer 42

• ↑ proliferation of endometrial glands relative to stroma.
• causes abnormal uterine bleeding.
• precursor lesion in continuum to endometrial carcinoma.
• associated with prolonged estrogen stimulation of endometrium.
• causes; exogenous estrogen, anovulation, obesity, polycystic ovarian disease, functioning estrogen-producing tumors.
• associated with inactivated PTEN ⇒ enhanced AKT phosphorylation with ↑ proliferation and ↓ apoptosis.
• morphology: simple hyperplasia without atypia = cystic or mild hyperplasia. benign cystically dilated glands. rarely goes to adenocarcinoma.
  
  • simple hyperplasia with atypia = uncommon. cystically dilated glands, cytologic atypia (loss of polarity, prominent nucleoli), 8% become malignant.
  • complex hyperplasia without atypia = closely apposed glands, varying size, crowded in clusters. epithelium normal cytologically. 3% progress to cancer.
  • complex hyperplasia with atypia = gland crowding and cytologic changes. substantial overlap with endometrial adenocarcinoma. 23-48% have concurrent malignancy.

Question 43

Carcinoma of Endometrium

Answer 43

• 7% of invasive cancers in women.
• peak incidence btw 55-65 yrs.
• type I Carcinomas: most common (80%). well-differentiated, arise in setting of endometrial hyperplasia. endometrioid carcinoma.
  
  • PTEN mutations in 30-80%.
  • microsatellite instability, mutations in PI3 kinase complex, KRAS, beta-catenin, p53.
• morphology: localized polypoid tumors, diffuse spreading lesions.
  
  • 85% endometrioid adenocarcinomas with normal looking endothelium.
  • mix of well-differentiated glands and poorly differentiated solid tumor.
  • foci of squamous differntiation in 20%.
• type II Carcinoma: arises 65-75 yrs in setting of endometrial atrophy.
  
  • poorly differentiated. usually serous carcinoma.
  • p53 mutations in 90%
  • endometrial intraepithelial carcinoma (EIC) without invasion is precursor to serous carcinoma.
• morphology: large, bulky, deeply invasive.
  
  • papillary or glandular growth pattern, marked cellular atypia.
• presentation: uterine bleeding or abnormal Pap.
  
  • confined to uterine corpus and well-differentiated = good prognosis (90% survival).
  • serous tumors have propensity for extrauterine spread.

Question 44

Malignant Mixed Mullerian Tumors (MMMT)

Answer 44

• endometrial adenocarcinomas associated with concurrent malignant stromal changes from common neoplastic precursor both lineages.
• stromal component becomes malignant mesodermal components.
• highly malignant. 5yr survival is 25-30%.
• morphology: bulky, fleshy, polypoid.
  
  • malignant glandular and stromal elements.
  • stromal elements may show muscle, cartilage, osteoid differentiation.

Question 45

Adenosarcomas

Answer 45

• estrogen-sensitive tumor.
• has stromal neoplasia with benign glands.
• large polypoid growths, low-grade malignancies.

Question 46

Benign Stromal Nodules

Answer 46

• discrete lumps of stromal neoplasia within myometrium.

Question 47

Endometrial Stromal Sarcomas

Answer 47

• made of malignant stroma interposed btw myometrial bundles.
• distinguished by diffuse infiltration and/or lymphatic invasion.
• recurrent t(7;17) translocation ⇒ fusion transcript with anti-apoptotic features.
• 5yr survival is 50%.

Question 48

Leiomyomas (Myometrium)

Answer 48

• aka fibroids. most common tumor in women.
• benign masses of uterine smooth muscle cells.
• 40% have balanced t(12;14) translocation, deletions of chromosome 7q, trisomy 12, rearrangements of 6p, 3q, 10q.
• asymptomatic or have abnormal uterine bleeding, pain, urinary bladder disorders, impaired fertility.
• morphology: sharply circumscribed, discrete, round, firm, gray-white nodules in myometrium (intramural), beneath serosa (subserosal), or beneath endometrium (submucosal).
  
  • whorled bundles of uniform smooth muscle cells with rare mitoses. have ↑ cellularity or atypical, bizarre cells.

Question 49

Leiomyosarcomas (Myometrium)

Answer 49

• uncommon malignancies.
• form bulky, fleshy masses in uterine wall or project into lumen.
• wide range of atypia: ↑ mitoses (5-10 per high power field), cellular atypia, necrosis.
• disseminate through abd cavity and aggressively metastasize.
• 5yr survival 40%, anaplastic is 10-15%.

Question 50

Suppurative Salpingitis

Answer 50

• component of PID.
• gonococcal infections in 60%.
• can be chlamydia or pyogenic bacteria.

Question 51

TB Salpingitis

Answer 51

• rare in USA.
• important cause of infertility worldwide.

Question 52

Paratubal Cysts

Answer 52

• most common primary lesion of fallopian tubes.
• 1-2mm translucent cysts filled with serous fluid.

Question 53

Hydatids of Morgagni

Answer 53

• larger translucent cysts filled with serous fluid near fimbria.

Question 54

Adenomatoid Tumors

Answer 54

• benign. small modules of mesothelial cells in Fallopian tubes.

Question 55

Primary Tubal Adenocarcinoma (Fallopian Tubes)

Answer 55

• associated with germline BRCA mutations.
• 40% 5 yr mortality at early stages.

Question 56

Follicle and Luteal Cysts

Answer 56

• common. multiple, <2cm.
• lined by follicular or luteinized cells with clear, serous fluid.
• derive from unruptured Graafian follicles or follicles that have resealed after rupture.
• typically asymptomatic but can rupture causing peritoneal inflammation and pain.

Question 57

Polycystic Ovarian Disease (PCOD)

Answer 57

• aka Stein-Leventhal syndrome.
• 3-6% reproductive age women.
• from disturbances in androgen biosynthesis.
• ovaries enlarged with cortical fibrosis. ** innumerable subcortical cysts have theca interna hyperplasia**.
• presentation: numerous cystic follicles, associated oligomenorrhea, persistent anovulation, obesity, hirsuitism, insulin resistance.

Question 58

Stromal Hyperthecosis

Answer 58

• disorder of ovarian stroma in postmenopausal women.
• stromal hypercellularity and luteinization seen as discrete nests of cells with vacuolated cytoplasm.
• virilization can be profound.
• similar symptoms to PCOD.

Question 59

Ovarian Tumors

Answer 59

• arise from epithelium, germ cells, or sex cord stroma.
• 80% benign. most ages 20-45 yrs.
• malignant tend to be ages 45-65 yrs, 3% female cancers.
• most detected after spreading beyond ovary.

Question 60

Serous Tumors (Mullerian Epithelium)

Answer 60

• 30% of ovarian tumors.
• 70% benign or borderline.
• most common ovarian malignancy (40%).
• even with extensive extra-ovarian spread, low grade progress slowly.
• 5 yr survival for borderline and malignant confined to ovaries 100% and 70%.
• 5 yr survival for involving peritoneum is 90% for borderline and 25% for malignant.
• pathogenesis: risk factors = nulliparity, gonadal dysgenesis, family history.
  
  • mutated BRCA1 and BRCA2, p53 in high grade.
  • low grade have KRAS and BRAF.
  • arise from fibriated end of fallopian tube.
• morphology: large cystic masses with serous fluid. can get intracystic locations.
  
  • benign cystadenomas have smooth glistening inner lining. lined by single layer of tall, columnar, ciliated epithelial cells. can form microscopic papillae.
  • cystadenocarcinomas have small mural nodularities or papillary porjections. bilateral common. multilayered epithelium with papillary ares and large, solid epithelial masses focally invading stroma.
  • borderline = mild atypia with complex micropapillary epithelial architecture without invasion.

Question 61

Mucinous Tumors (Mullerian Epithelium)

Answer 61

• 30% of ovarian neoplasms.
• 80% benign or borderline.
• risk factor: smoking, KRAS mutation.
• can seed peritoneum that produce extensive mucinous ascites = pseudomyxoma peritonei
  
  • more commonly due to primary appendiceal tumors.
• 5 yr survival for stage 1 is 90%.
• morphology: large multiloculated cystic masses filled with sticky, gelatinous fluid. <10% bilateral.
  
  • benign = lined by tall, columnar non-ciliated eipthelium with apical mucin.
  • mullerian mucinous tumors associated with endometriosis, cells resemble cervical and endometrial epithelium.
  • cystadenocarcinomas = intestinal-type epithelium, solid tumor, necrosis, stroma invasion.
  • borderline = complex growth like serous tumors but no solid growth or stromal infiltration.

Question 62

Endometrioid Tumors (Mullerian Epithelium)

Answer 62

• 20% ovarian cancers.
• epithelium can be benign or malignant.
• 15-20% have endometriosis.
• 15-30% independent endometrial carcinomas.
• PTEN, KRAS, beta-catenin mutations, microsatellite instability.
• p53 in poorly differentiated tumors.
• 5yr survival for stage 1 is 75%.
• morphology: combo of solid and cystic masses, 40% bilateral.
  
  • glandular patterns, resemble endometrial adenocarcinoma.

Question 63

Clear Cell Adenocarcinoma (Mullerian Epithelium)

Answer 63

• uncommon.
• variant of endometrioid adenocarcinoma.
• cystic or solid. large epithelial cells contain abundant clear cytoplasm.
• cancer confined to ovary = 5yr survivals 65%
• extra-ovarian spread = low 5yr survival.

Question 64

Brenner Tumor

Answer 64

• 1-30cm tumor (adenofibroma).
• dense fibrous stroma and nests of epithelium resembling urinary transitional or columnar epithelium.
• unilateral, usually benign.

Question 65

Surface Epithelial Tumors (Mullerian)

Answer 65

• presentation: lower abd pain and enlargement, symptoms from bowel or bladder compression.
• benign resected easily.
• malignant have cachexia, dissemination causing ascites and peritoneal studding.
• diagnosed when tumors are large or disseminated, poor overall survival.
• CA-125 present in serium of 80% pts with serous or endometrioid carcinomas.
  
  • monitor disease progression.
• ↑ osteopontin levels help earlier ovarian cancer detection.
• fallopian tubal ligation and oral contraceptive ↓ risk of ovarian malignancy.

Question 66

Germ Cell Tumors

Answer 66

• 15-20% ovarian tumors.
• most are benign cystic teratomas.
• arise from neoplastic transformation of totipotential germ cells.
• includes: teratomas, dysgerminomas, endodermal sinus tumor, choriocarcinomas

Question 67

Teratomas (Females)

Answer 67

• mature/benign teratomas = dermoid cysts = in young women during reproductive years.
  
  • karyotype usually 46XX, arise from ovum after 1st mitotic division.
  • cystic masses lined by squamous epithelium with adnexal structures including hair shafts, sebaceous glands.
  • have tooth structures, other germ cell layers.
  • 10-15% bilateral.
  • most cured by excision.
  • 1% become malignant, usually squamous cell carcinoma.
• monodermal teratomas = specialized. differentiate along line of single abnormal tissue. most common is struma ovarii, composed of mature thyroid tissue. ovarian carcinoid another variant.
• immature teratomas = malignant = rare, made of embryonic elements, resemble immature fetal tissues.
  
  • in adolescents and young women.
  • grow rapidly and penetrate capsule.
  • low grade have good prognosis, high grade respond well to chemo.

Question 68

Dysgerminoma

Answer 68

• counterpart of testicular seminoma.
• 2% of all ovarian cancers, 50% malignant germ cell tumors.
• ages 20-40yrs.
• no endocrine function.
• Oct2, Oct4, Nanog transcription factor expression maintain pluripotency.
• some express c-KIT.
• malignant. 1/3 are highly aggressive.
• chemosensitive so 80% survival.
• morphology: solid, yellow-white to gray-pink, fleshy. 80-90% unilateral.
  
  • sheets and cords of large vesicular cells separated by scant fibrous stroma.

Question 69

Endodermal Sinus (Yolk Sac) Tumor

Answer 69

• from differentiation of germ cells toward yolk sac structures.
• glomerulus-like structures with central vessel enveloped by germ cells within a cystic space lined by additional germ cells (Schiller-Duvall body).
• intracellular and extracellular hyaline droplets, can contain alpha-fetoprotein (AFP).
• in kids and young women.
• grow aggressively, chemoresponsive.

Question 70

Choriocarcinoma

Answer 70

• extra-embryonic differentiation of malignant germ cells.
• exist in combo with other germ cell tumors.
• identical to placental malignancies, elaborate chorionic gonadotropins.
• ovarian choriocarcinomas highly malignant, metastasize widely.
  
  • more resistant to chemo than placental.

Question 71

Granulosa-Thecal Cell Tumors

Answer 71

• 5% of ovarian tumors.
• various combos of theca and granulosa cells.
• 2/3rds in postmenopausal women.
• inhibin made by granulosa cells useful to diagnose and monitor.
• produce a lot of estrogen ⇒ precocious sexual development and endometrial hyperplasia.
  
  • predispose to endometrial carcinoma.
  • granulosa cell tumors can produce masculinizing androgens.
• 5-25% malignant but have 85% 10 yr survival.
• pure thecomas benign.
• morphology: unilateral, solid, white-yellow.
  
  • granulosa cell has small cuboidal-to-polygonal cells in cords, sheets, or strands.
  • Call-Exner body = gland-like structures with acidophilic material.
  • thecal cell has sheets of plump spindle cells with lipid droplets.

Question 72

Fibroma, Thecoma, Fibrothecoma

Answer 72

• 4% ovarian neoplasms, usually benign.
• unilateral, solid, hard, gray-white masses.
• fibroma = well-differentiated fibroblasts and scant collagenous CT.
• thecoma = plump spindle cells with lipid droplets.
• associated with Meigs syndrome = ascites and right-sided hydrothorax.
• associated with basal cell nevus syndrome.

Question 73

Sertoli-Leydig Cell Tumors

Answer 73

• aka androblastomas.
• recapitulate the cells of testes, produce masculinization or defeminization.
• unilateral, consist of tubules made of Sertoli cells and/or Leydig cells interspersed with stroma.

Question 74

Metastatic Tumors of Ovary

Answer 74

• from tumors of mullerian origin (uterus, fallopian tube, contralateral ovary, pelvic peritoneum).
• extra-mullerian metastases = carcinomas of breast and GI tract.

Question 75

Krukenberg Tumors

Answer 75

• ovarian cancers, usually bilateral, from metastatic mucin-producing signet cells, usually from stomach.

Question 76

Spontaneous Abortion

Answer 76

• aka miscarriage = pregnancy loss before 20 wk’s gestation.
• 10-15% pregnancies spontaneously abort.
• causes: maternal (diabetes, luteal-phase defects, endocrine); fetal; uterine defects; systemic disorders of maternal vasculature; infections (toxoplasmosis, mycoplasma, listeria); idopathic.

Question 77

Ectopic Pregnancy

Answer 77

• embryo implantation at site other than uterus. usually Fallopian tubes (90%), ovary, abd cavity.
• 1 in 150 pregnancies.
• predisposing factors: PID with scarring, intrauterine devices, peritubal adhesions from endometriosis or prior surgery.
• 50% in normal tubes.
• presentation: tubal pregnancies has 4 outcomes

1. intratubal hemorrhage with formation of hematosalpinx.
2. tubal rupture with intraperitoneal hemorrhage.
3. spontaneous regression with resorption of products of conception.
4. extrusion into abd cavity (tubal abortion).

• medical emergency with acute abdomen, shock.
• diagnose by hCG levels, ultrasound, endometrial biopsy (decidual changes and absent chorionic villi).

Question 78

Twin Placentas

Answer 78

• from fertilization of two ova or division of one fertilized ovum.
• placentas can be mono or dichorionic.
  
  • 1 chorion = monozygotic twins, can be mono or diamnionic.
    
    • vascular anastomoses allow sharing fetal circulations.
    • twin-twin transfusion syndrome when imbalanced flow thru arteriovenous shunt.
  • dichorionic placenta = diamniotic, with mono or dizygotic twins.

Question 79

Placenta Previa

Answer 79

• placental implantation in lower uterine segment or cervix.
• associated with severe 3rd trimester bleeding.
• complete coverage of cervical os requires cesarean.

Question 80

Placenta Accreta

Answer 80

• absence of decidua and placenta adheres directly to myometrium.
• at delivery, placenta fails to separate, potential for life threatening hemorrhage.

Question 81

Placental Infections

Answer 81

• ascending infection = bacterial via birth canal.
  
  • acute chorioamnionitis = infection of chorionic membranes then produces premature membrane rupture and preterm delivery.
  • inflammation involves chorion-amnion and fetal umbilical and chorionic plate vessels.
• hematogenous infections = from maternal sepicemia.
  
  • listerial, streptococcal, TORCH (toxoplasma, rubella, syphilis, CMV, herpes).
  • characterized by villous chronic inflammation (villitis).

Question 82

Preeclampsia

Answer 82

• characterized by HTN, proteinuria, edema.
• 3-5% pregnancies, usually 3rd trimester.
• pathogenesis: systemic endothelial dysfunction, vasoconstriction, vascular permeability driven by placental-derived factors.
  
  • abnormal placental vasculature = underlying precursor lesion. don’t convert high resistance decidual spiral arteries into high cpacitance uteroplacental vessels ⇒ placenta can’t meet perfusion demands.
  • ischemic placenta releases copious amounts anti-angiogenic factors ⇒ ↓ placental vascular development.
  • placental sFlt-1 and endoglin ⇒ widespread maternal endothelial dysfunction, inhibit VEGF and TGF-beta depenent NO and prostacyclin.
  • consequences: systemic HTN, proteinuria, edema, hypercoagulability.
• morphology: numerous small, peripheral infarcts and retroplacental hematomas.
• presentation: after 34 wk’s gestation, insidious onset.
• tx: delivery.
  
  • mild preterm disease monitored and given bed rest.
  • severe disease = anti-HTN therapy.

Question 83

Eclampsia

Answer 83

• more severe form associated with seizures and coma.
• present with hypercoagulability, renal failure, PE.
• 10% develop HELLP syndrome (hemolysis, elevated liver enzymes, low platelets).

Question 84

Hydatidiform Mole

Answer 84

• cystic swelling of chorionic villi, accompanied by variable trophoblastic proliferation.
• precursors of choriocarcinoma.
• risk highest at extremes of reproductive yrs.
• incidence 1:1000-2000.
• complete mole = when egg that has lost chromosomes is fertilized by 1 or 2 sperm. all paternally derived genes.
  
  • 90% duplicated from one sperm = 46XX.
  • 10% from 2 sperm, 46XX or 46 XY.
  • 2.5% risk choriocarcinoma.
  • don’t have fetal parts.
  • hydropic swelling of villi, inadequate vascularization of villi, significant trophoblastic proliferation.
• partial mole = egg with normal chromosomal content fertilized by 2 sperm ⇒ triploid. 69XXX, 69 XXY.
  
  • have fetal parts.
  • focal edema, focal and slight trophoblastic proliferation.
• morphology: masses of thin-walled, translucent, cystic, grapelike structures.
• presentation: diagnose by ultrasound and serum hCG.
• tx: curettage.
• 10% become invasive, 2.5% develop choriocarcinoma.

Question 85

Invasive Mole

Answer 85

• penetrates and perforates uterine wall, associated with proliferating cytotrophoblasts and syncytiotrophoblasts.
• villi embolize at distant sites but don’t grow.
• associated with persistently ↑ hCG.
• responds to chemo, can cause uterine rupture.

Question 86

Choriocarcinoma (Moles)

Answer 86

• malignant. 50% in hydatidiform moles, 25% in previous abortions, 22% normal pregnancies, rest ectopic pregnancies.
• morphology: large, soft, yellow-white, fleshy masses with necrosis and hemorrhage.
  
  • mixed cytotrophoblast and syncytiotrophoblast proliferations.
  • invades endometrium, penetrates blood vessels and lymphatics, metastasizes widely.
• presentation: vaginal bleeding and discharge in normal pregnancy, after miscarriage, or after curettage.
  
  • hCG titers higher than hydatidiform mole.
  • widespread metastases at discovery.
  • gestational choriocarcinomas sensitive to chemo, 100% remission rates, high cure rates.

Question 87

Placental-Site Trophoblastic Tumor (PSTT)

Answer 87

• <2% gestational trophoblastic tumors.
• neoplastic proliferation of extravillous (intermediate) trophoblasts.
• NO syncytio and cytotrophoblasts.
• low levels of hCG.
• locally invasive, 10-15% have metastases and death.