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 t**ubules 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 (**h**emolysis, **e**levated **l**iver enzymes, **l**ow **p**latelets).

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.