Female Genital Tract Flashcards

Question 1

Q

Embryology female genital tract

Answer

A

unfused upper portions of the müllerian ducts–> fallopian tubes
fused lower portions of the müllerian ducts –> uterus, cervix, and upper vagina
endometriosis is a müllerian-derived lesion
may occur in the vagina and clinically simulate a neoplasm
urogenital sinus –> lower vagina
mesonephric ducts –> normally regress
Gartner duct cysts: when remnants of the mesonephric ducts persist into adult life as epithelial inclusions adjacent to the ovaries, tubes, and uterus; in the cervix and vagina these rests may be cystic and are termed Gartner duct cysts
coelomic epithelium (mesothelium) –> lining of the female genital tract as well as the ovarian surface
morphologically similar lesions arise in various sites within the female genital tract and the adjacent peritoneal surfaces

Question 2

Q

Chlamydia trachomatis

Answer

A

Pelvic inflammatory disease; serous discharge

Question 3

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Neisseria gonorrhea

Answer

A

pelvic inflammatory disease (most serious complication of gonorrhea in women); purulent discharge; gram negative diplococci within neutrophils (PMNs

Question 4

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Trichomonas vaginalis

Answer

A

large, flagellated ovoid protozoan; yellow, frothy vaginal discharge; “strawberry cervix

Question 5

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Gardnerella vaginalis

Answer

A

gram negative bacillus; main cause of bacterial vaginosis; thin, grey-green malodorous (fishy) vaginal discharge; premature labor

Question 6

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Ureaplasma urealyticum, mycoplasma hominis

Answer

A

Pre term deliveries

Question 7

Q

Plasma cell morphology

Answer

A

Nucleus placed off to one side

Clearing around the nucleus

Question 8

Q

HSV

Answer

A

Common and involves the cervix > vagina > vulva
By age 40, 30% of females present with antibodies to type 2
HSV-1 → oropharyngeal infection
HSV-2 → genital mucosa + skin infection

Question 9

Q

HSV presentation

Answer

A

1/3 of newly infected females show painful lesions 3-7 days post-infection with fever, malaise, and tender inguinal lymph nodes
Red papules that progress to vesicles and then to painful coalescent ulcers
Cervical or vaginal lesions present with purulent discharge and pelvic pain
Lesions around the urethra may cause painful urination and urinary retention
ALL MALES are symptomatic

Question 10

Q

Viral characteristics

Answer

A

Herpesvirus family; large linear dsDNA, enveloped, icosahedral, derives envelope from nuclear membrane, contains intranuclear inclusion bodies AKA Cowdry bodies

Question 11

Q

HSV lesion

Answer

A

Herpesvirus family; large linear dsDNA, enveloped, icosahedral, derives envelope from nuclear membrane, contains intranuclear inclusion bodies AKA Cowdry bodies
Lesions
Lesions are red papules that progress to vesicles and the coalesce to ulcers that are easily visible on the vulva, but lesions on the cervix or vagina are associated with purulent discharge and pain
Vesicles & ulcers contain viral particles causing ↑ transmission rate with active infection
Lesions heal spontaneously in 1-3 weeks
Easily visible on vulvar skin and mucosa
Near urethra = painful urination (dysuria

Question 12

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Latency HSV

Answer

A

infection remains latent in lumbosacral nervous ganglia
Reactivation due to stress, trauma, UV light, hormonal changes (skin & mucosal lesions)
Immunocompromised → meningitis, hepatitis, pneumonitis
detection of anti-HSV antibodies in the serum is indicative of recurrent/latent infection

Question 13

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Morphology HSV

Answer

A

Usually biopsy the ulcer phase
Desquamated epithelium with acute inflammation at the ulcer bed
Multinucleated squamous cells with eosinophilic to basophilic viral inclusions with a “ground glass” appearance (viral cytopathic effect

Question 14

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Transmission HSV

Answer

A

Transmitted during active infection
May occur during latent phase due to subclinical viral shedding
↓ risk with condoms and antiviral therapy
Never completely prevented!
Females have higher susceptibility
Previous infection with HSV-1 ↓ risk of infection with HSV-2
HSV-2 infection enhances HIV-1 acquisition and transmission
Vertical transmission (mom to baby) warrants C-section if infection is (1° and) active

Question 15

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Diagnosis and complications HSV

Answer

A

Diagnosed clinically
Associated with a high mortality rate (2% US women)
Aspiration of exudate shows viral cytopathic effect after 48-72 hrs, and allows serotyping
Primary, acute infections do not have established antibodies in the serum
antibody (Smith antigen) detection = recurrent/latent infection
Use the Tzanck smear

Question 16

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Treatment HSV

Answer

A

There is no treatment, but some antivirals (acyclovir) can shorten the active phase

Question 17

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Molluscum contagiosum (poxvirus)

Answer

A

Skin or mucosal poxvirus with 4 subtypes
MCV1: most prevalent
MCV2: most often sexually transmitted
6 week incubation period

Question 18

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Viral characteristics molluscum contagiosum

Answer

A

dsDNA , can make its own envelope, has complex morphology, only DNA virus that replicates in the cytoplasm and has own RNA polymerase and everything it needs to replicate outside the nucleus
Guarnieri bodies, or inclusion bodies, which are sites of viral replication in the cytoplasm and a dumbbell shaped core

Question 19

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Transmission molluscum contagiosum

Answer

A

Transmission
Children (2-12 years old): spread via direct contact or shared items (towels) and is most common on the trunk, arms & legs. Think of sexual abuse if seen in genitals in kids.
Adults: sexually transmitted and seen on genitals, lower abdomen, buttocks, inner thighs

Question 20

Q

Clincial appearance molluscum contagiosum (poxvirus)

Answer

A

Pearly, dome-shaped papules with a dimpled center
The papules measure 1 to 5 mm in diameter, dimpled umbilicated center, and their central waxy core contains cells with cytoplasmic viral inclusion bodies

Question 21

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Diagnosis molluscum contagiosum (poxvirus)

Answer

A

1-5mm papules
Pearly, dome shaped with dimpled/umbilicated center
Central waxy core with cytoplasmic viral inclusions

Question 22

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Candida (moniliasis)

Answer

A

Yeast are part of many females’ normal vaginal microflora
Opportunistic yeast infection with disturbance of the microbial ecosystem
increased incidence: DM, antibiotics, pregnancy, burn patients, indwelling catheter, immunosuppression (compromise neutrophils or Th17 cells)
Most common cause of opportunistic mycosis

Question 23

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Yeast characteristics

Answer

A

Dimorphic: mold in the heat, yeast in the cold

Forms pseudohyphae and budding yeast at 20˚C and germ tubes

Question 24

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Presentation candida

Answer

A

Intense vulvovaginal pruritis, erythema, and swelling
Thick white vulvovaginal discharge “curd-like or cottage cheese-like”
If severe → mucosal ulceration

Question 25

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Diagnosis candida

Answer

A

Pseudospores or filamentous fungal hyphae in wet KOH mounts of discharge or on Pap smear
Not considered an STI

Question 26

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Trichmonas vaginalis

Answer

A

Definition and transmission
Large, flagellated ovoid protozoan
Sexual transmission
4-14 days to develop
Most common curable STI

Question 27

Q

Presentation trichmonas vaginalis

Answer

A

Yellow, frothy vaginal discharge, vulvovaginal discomfort, dysuria, dyspareunia
Fiery red mucosa of the vagina and cervix
Marked dilation of cervical mucosal vessels → ‘strawberry cervix’ (colposcopic appearance

Question 28

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Diagnose trichmonas vaginalis

Answer

A

Motile trophozoites in methylene blue wet mount, present with corkscrew motility

Question 29

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Gardnerella vaginalis

Answer

A

Gram -ve bacillus
Main cause of vaginitis (Bacterial vaginosis)
Found normally in the reproductive tract, but lactobacillus keeps it in check

Question 30

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Presentation gardnerella vaginalis

Answer

A

Present with thin, green-gray, malodorous (fishy) discharge

Pregnant patients: may cause premature labor

Question 31

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Gardnerella vaginalis diagnosis

Answer

A

Pap smear: superficial, intermediate squamous cells covered by a shaggy coating of coccobacilli (clue cells)
Cultures: also contain anaerobic pepto-streptococci and aerobic α-hemolytic streptococci
Need to differentiate it from candida and trichomonas by examining a slide to look for clue cells
Whiff Test: there is a fishy amine odor when KOH is added to it

Question 32

Q

Ureaplasma urealyticum and mycoplasma hominis

Answer

A

May cause some cases of vaginitis and cervicitis
Implicated in chorioamnionitis and premature delivery in pregnant patients
Ureaplasma: urease positive
Mycoplasma: no cell wall
Look for the fried egg appearance

Question 33

Q

Chlamydia trachomatis

Answer

A

Most common STI in the world

One of the main causes of pelvic inflammatory disease

Question 34

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Bacterial characteristics chlamydia

Answer

A

Small gram - obligate intracellular bacteria

Question 35

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Two forms of chlamydia

Answer

A

Elementary bodyL metabolically inactive, infectious form in endosome

Reticulate body: metabolically active form

Question 36

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Presentation chlamydia

Answer

A

Usually asymptomatic or presents similar to gonorrhea: primary infection is characterized by a mucopurulent discharge containing a predominance of neutrophils
chlamydia == mucopurulent (“pus-sy”)
gonorrhea == serous, thin, watery
Most infections cause cervicitis
In some patients it may ascend to the uterus and fallopian tubes → endometritis and salpingitis
infection of non-ciliated columnar or cuboidal epithelial cells of mucosal surfaces leads to granulomatous response and damage

Question 37

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Diagnose chlamydia

Answer

A

Diagnose with Nucleic Acid Amplification Test (NAAT

Question 38

Q

PID

Answer

A

Infection that begins in the vulva or vagina and spreads upward to involve most of the structures of the female genital system
Causes pelvic pain, adnexal tenderness, fever, and vaginal discharge
Most infections travel via the lymph or venous systems rather than the mucosal route (except Neisseria gonorrhea

Question 39

Q

Causes PID

Answer

A

Neisseria gonorrhea
Chlamydia trachomatis (serotypes D-K)
puerperal infections: infections after spontaneous or induced abortions and normal or abnormal deliveries
polymicrobial: may be caused by staphylococci, streptococci, coliforms, and Clostridium perfringens
PID caused by these microbes tends to show less involvement of the mucosa and the tube lumen, and more inflammation within the deeper tissue layers
bacteremia is a more frequent complication of streptococcal or staphylococcal PID than gonococcal

Question 40

Q

Acute complications PID

Answer

A

Peritonitis & bacteremia

Endocarditis, meningitis and suppurative arthritis

Question 41

Q

Chronic sequelae PID

Answer

A

hronic sequelae
Infertility, tubal obstruction, ectopic pregnancy, pelvic pain, intestinal obstruction due to adhesion between bowel and pelvic organs
Fitz-Hugh Curtis syndrome: rare complication involving liver capsule inflammation leading to the creation of adhesions (especially from Neisseria gonorrhea

Question 42

Q

Lymphogranuloma venereum

Answer

A

From Chlamydia serotypes L1-L3
Prevalent in Africa, Asia, and South America
Presents first with a painless ulcer at the site of contact then progresses to swollen lymph nodes leading to genital elephantiasis in late stage
Tertiary stage presents with ulcers, fistulas, and genital elephantiasis

Question 43

Q

Trachoma

Answer

A

From chlamydia serotypes A, B, Ba, and C – is the leading cause of preventable infectious blindness
Follicular conjunctivitis leading to conjunctival scarring; in-turned eyelashes leading to corneal scarring and blindness

Question 44

Q

Treponema pallidus (syphilis)

Answer

A

Thin spirochete, poorly visible on gram stain but has thin gram (-) envelope
Outer membrane has endotoxin-like lipids, axial filaments = endoflagella = periplasmic flagella allows for motility, cannot culture in clinical lab so serodiagnosis
Obligate pathogen, but not intracellular

Question 45

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Transmission treponema

Answer

A

Sexually or across placenta

Question 46

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Pathogenesis treponema

Answer

A

Disease is characterized by endarteritis resulting in lesions; strong tendency to chronicity

Question 47

Q

Diagnosis treponema pallidus (syphilis)

Answer

A

Visualized by immunofluorescence or dark-field microscopy
Warthin-Starry stain or steiner silver stain
Can also use VDRL or RPR

Question 48

Q

Jarisch-herxheimer reaction

Answer

A

Starts generally during the first 24 hours of antibiotic treatment and presents with increase in temperature, decrease in blood pressure, rigors, and leukopenia

Question 49

Q

Primary stage treponema pallidus

Answer

A

Non-tender chancre (wart); clean, indurated edge; contagious; heals spontaneously 3-6 weeks but progresses because painless and is typically left untreated

Question 50

Q

Secondary stage treponema pallidus

Answer

A

Secondary stage
Maculopapular (copper-colored) rash that is diffuse, and includes palms and soles, patchy alopecia; condyloma lata: flat wart like perianal and mucous membrane lesions; highly infectious

Question 51

Q

Latent stage treponema

Answer

A

No symptoms

Question 52

Q

Tertiary syphilis

Answer

A

Gummas or syphilitic granulomas that are soft growths with firm necrotic centers
Aortitis and aneurysm of ascending aorta with tree-barking appearance; destroys the vasa vasorum that supplies the aorta with blood
CNS inflammation: damage to the posterior column of the spinal cord and ocular defect of Argyll Robertson (“prostitutes”) pupils which react to accommodation but has no reaction to light

Question 53

Q

Congenital

Answer

A

Desquamating maculopapular rash and tabes dorsalis
Can have Saber-shins or anterior bowing of the tibia; saddle nose; Hutchinson’s notched teeth and Mulberry molars with enamel outgrowths; deafness

Question 54

Q

Treat symphysis

Answer

A

Penicillin G

Question 55

Q

Puerperal infection

Answer

A

Infection after spontaneous or induced abortion and normal or abnormal deliveries
Polymicrobial with Staph, Strep, coliforms, Clostridium perfringens

Question 56

Q

Neisseria gonorrhea

Answer

A

Most common cause of PID
Inflammatory changes appear 2-7 days after inoculation
Involves endocervical mucosa (or Bartholin gland, other vestibular or periurethral glands)
Spreads cephalad (ascending infection) to fallopian tubes and tuboovarian region via mucosal surfaces; endometrium is usually spared
May become disseminated

Question 57

Q

Characteristics of neisseria gonorrhea

Answer

A

Phagocytosed gram -ve diplococci within neutrophils/PMNs (intracellular)
Will have pili on electron microscopy

Question 58

Q

Presentation gonorrhea

Answer

A

Females: Often asymptomatic; scarring of tubal lumen and fimbriae can → infertility or ectopic pregnancy
Males: Urethral discharge
Can lead to Fitz-Hugh Curtis syndrome

Question 59

Q

Morphology gonorrhea

Answer

A

Marked acute inflammation of involved mucosal surfaces
Acute suppurative salpingitis
Infection of the fallopian tubes
Diffusely infiltrated → epithelial injury & sloughing of plicae
Salpingo-oophoritis: exudate leaks from fimbriae of the tubal lumen to cause infection of the ovary
Tubo-ovarian abscesses: Collections of pus in the ovary and fallopian tube or in the tubal lumen (pyosalpinx)
Chronic salpingitis: Scarring of denuded tubal plicae causing gland-like spaces and blind pouches
Hydrosalpinx: due to fusion of fimbriae and the accumulation of tubal secretions and tubal distension

Question 60

Q

Diagnosis gonorrhea

Answer

A

Definitive diagnosis
Detection of DNA or RNA
Culture or NAATS
Thayer-Martin agar

Question 61

Q

Treat gonorrhea

Answer

A

antibiotics
Penicillin resistant strains have emerged
Tubo-ovarian abscesses may require surgical removal as antibiotics may not penetrate
Post abortion/postpartum are much more difficult to control due to broad spectrum of potential pathogens

Question 62

Q

Human papillomavirus presentation

Answer

A

Presentation:

Multiple warty lesions on the perineum and around the anus in low-risk types 6 and 11

Question 63

Q

HPV VIRAL CHARCTERISTICS

Answer

A

ral characteristics
Non-enveloped, double-stranded, circular DNA virus with an icosahedral capsid.
Composed

Question 64

Q

Transmission HPV

Answer

A

HPV enters the target cells by binding to its cellular receptor. This binding is dependent only on capsid protein L1 and does not require the other capsid protein L2. HPVs are generally internalized via a clathrin-dependent endocytic mechanism.
After getting internalized, the viral coat is disassembled which allow viral genomes access to the cellular transcription and replication machinery.
The virus infects the stem cells basal keratinocytes of the mucosal (genital) epithelium and delivers the genome to the nucleus.
Infected epithelial cells are called koliocytes – have a krinkled nucleus that looks like a raisin

Answer 65

A

The complete virus cycle takes place above the basal layer and without directly triggering cell lysis, limits the interaction of viral antigens (which do not spill out) with the immune cells of the host that keep an active surveillance for pathogens of the basal membrane.
Thus the immune system remains largely unaware of the infection that has taken place in the epithelium
Together these events help attain a sort of immune anergy that explains the general lack of local inflammation, the poor immune response to the virus, and the long persistence of HPVs even in healthy immunocompetent individuals

Answer 66

A

16,18,31,45

Answer 67

A

oncogenic potential of HPV can be explained by the activities of the two viral genes encoding E6 and E7

Answer 68

A

E6 == “Cutting the breaks”
E6 protein binds to and mediates the degradation of p53
E6 stimulates the expression of TERT, the catalytic subunit of telomerase
contributes to the immortalization of cells
E6 from high-risk HPV types has a higher affinity for p53 than E6 from low-risk HPV types

Answer 69

A

E7 == “Foot on the gas pedal”
The E7 protein has effects that complement those of E6, all of which are centered on speeding cells through the G- S cell cycle checkpoint
It binds to the RB protein and displaces the E2F transcription factors that are normally sequestered by RB
promoting progression through the cell cycle.
E7 proteins from high-risk HPV types have a higher affinity for RB than E7 proteins from low-risk HPV types
E7 inactivates the CDK inhibitors p21 and p27
E7 proteins from high-risk HPVs (types 16, 18, and 31) also bind and activate cyclins E and

Answer 70

A

Listeria monocytogenes can cause stillbirth, neonatal sepsis, or abortion
In infants it can lead to widespread disease (granulomatosis infantiseptica) and exudative meningitis
Facultative intracellular bacillus
Look for gram +ve intracellular bacilli in the CSF
Can also look for the bacillus if there are abscesses with alternating greyish or yellow nodules

Answer 71

A

Acute ulcerative infection that leads to painful chancroid (soft chancre)
The chancre is tender and erythematous on the external genitalia (penis, vagina/periurethral area) that erodes over a few days to make an irregular non-indurated painful ulcer. There may be multiple ulcers.
Regional lymph nodes are enlarged 1-2 weeks later (buboes) and may lead to ulceration of the overlying skin
Especially prevalent in tropical areas in Africa and southeast Asia
Cofactor in HIV transmission
Coccobacci are sometimes found on silver stain

Answer 72

A

Can cause granuloma inguinale (donovanosis): raised papular lesion on the moist stratified squamous epithelium of the genitalia or the pharynx/oral mucosa
There is eventual ulceration and lots of granulation tissue
Active lesions have epithelial hyperplasia at the borders of the ulcer
Bacterial characteristics: minute encapsulated coccobacillus
Endemic in rural developing countries
Untreated cases lead to excessive scarring –> lymphatic obstruction and lymphedema == elephantiasis
Look for encapsulated coccobacilli in macrophages (Donovan bodies) on Giemsa stain

Answer 73

A

STIs with ulcers
HSV
Syphilis
Chancroid (haemophilus ducreyi)
LGV lymphogranuloma venereum (Chlamydia trachomatis (L1-3)
Klebsiella granulomatis

Answer 74

A

Many diseases of the skin elsewhere on the body can also affect this area including psoriasis, eczema, allergic dermatitis
Prone to superficial infections due to constant exposure to secretions
Immunosuppression: vulvitis
Contains modified apocrine sweat glands

Answer 75

A

Acute inflammation (adenitis) than can create an abscess
Occur at all ages
due to obstruction of the duct by an inflammatory process
Lined with transitional or squamous epithelium
3-5 cm in diameter
Pain + local discomfort
Treatment: excised or opened permanently (marsupialization

Answer 76

A

descriptive clinical term for opaque, white, plaque-like epithelial thickening that may produce pruritus and scaling
May be due to
Inflammatory dermatoses (psoriases, chronic dermatitis)
Lichen sclerosis and squamous cell hyperplasia
Neoplasia: vulvar intraepithelial neoplasia (VIN), Paget disease, and invasive carcinoma

Answer 77

A

Smooth, white plaques or macules seen on the vulva
May enlarge and coalesce → ‘porcelain/parchment’ surface
paper-thin plaque – very, very thin
Occurs at any age, most common in post-menopausal females
labia become atrophic and agglutinated & the vaginal orifice constricts when the entire vulva is involved
autoimmune likely
presence of activated T cells in the subepithelial inflammatory infiltrate
increased frequency of autoimmune disorders in affected women

Answer 78

A

Not a premalignant lesion
women with symptomatic lichen sclerosis have a slightly increased risk of developing squamous cell carcinoma of the vulva
patients have an ↑ incidence of autoimmune disorders

Answer 79

A

Marked thinning of the epidermis (parchment paper)
Degeneration of the basal cells
Excessive keratinization (hyperkeratosis)
Sclerotic changes of the superficial dermis
Activated T cells are seen in the subepithelial inflammatory infiltrate (band-like infiltrate

Answer 80

A

Nonspecific condition resulting from rubbing or scratching of the skin to relieve pruritus
Presents as leukoplakia; histology reveals acanthosis (thickening of the epidermis) and hyperkeratosis
Not considered premalignant
sometimes present at the margins of vulvar cancers

Answer 81

A

Thickening of the epidermis + hyperkeratosis
Hyperplastic epithelium may show mitotic activity but lacks cellular atypia
Lymphocytic infiltration of the dermis may occur

Answer 82

A

inition
Benign genital warts due to low oncogenic risk HPV (6 & 11)
Usually multifocal
Involve vulvar, perineal and perianal areas +/- cervix and vagina
Not precancerous lesions

Answer 83

A

Papillary, exophytic, tree-like cores of stroma covered by thickened squamous epithelium (no mucous inside of them)
Surface epithelium: viral cytopathic changes (koilocytic atypia)
Nuclear enlargement, hyperchromasia, and a cytoplasmic nuclear halo – nucleus looks like a raisin

Answer 84

A

Condyloma latum: benign raised lesion due to syphilis == treponema pallidum

Answer 85

A

al Polyp: skin tag of the vulva similar to other places on the body

Answer 86

A

Benign exophytic proliferations covered by nonkeratinized squamous epithelium
Develop on vulvar surfaces
Single or numerous

Answer 87

A

Most common (still uncommon)
2/3 occur in females > 60 years

Answer 88

A

Basaloid & warty carcinoma related to HPV 16 (younger age, 50’s)
Keratinizing SCC not related to HPV (older age

Answer 89

A

Exophytic or indurated and ulcerated

Small tightly caked basaloid cells

Foci of central necrosis

Answer 90

A

Exophytic, papillary architecture

Prominent koilocytic atypia

Answer 91

A

Precursor lesion to basaloid & warty carcinoma of the vulva
Most common in females of reproductive age
HPV16 related

Answer 92

A

Young age at first intercourse
Multiple sexual partners
Male partner with multiple sexual partners

Answer 93

A

Multi-centric around the vulva

10-30% also have vaginal or cervical HPV related lesions

Answer 94

A

Spontaneous regression may occur

More likely to progresses to invasive carcinoma in females > 45 years old or immunocompromised

Answer 95

A

Discrete white (hyperkeratotic) or slightly raised, pigmented lesion
Epidermal thickening, nuclear atypia, increased mitoses and lack of cellular maturation
May progress to invasive carcinoma that are exophytic or indurated with central ulceration
histology: nests and cords of small, tightly packed cells that lack maturation and resemble the basal layer of the normal epithelium

Answer 96

A

Occurs in older women with long standing lichen sclerosus or squamous cell hyperplasia
Not related to HPV infection
precursor lesion is differentiated vulvar intraepithelial neoplasia (differentiated VIN, or VIN simplex

Answer 97

A

Pathogenesis
Gradual acquisition may be due to acquisition of driver mutations in oncogenes and tumor suppressors
↑ frequency of TP53 mutations
May be associated with chronic epithelial irritation (lichen sclerosus or squamous cell hyperplasia

Answer 98

A

phology
Marked atypia of the basal layer of the squamous epithelium
Normal differentiation of the superficial layers
Invasive keratinizing squamous cell carcinomas
Nests and tongues of malignant squamous epithelium
Prominent central keratin pearls

Answer 99

A

Once invasive lesions develop the prognosis and risk of metastases is related to tumor size, depth of invasion and involvement of lymphatic vessels
Initially spreads to inguinal, pelvic, iliac and periaortic lymph nodes
Can spread lympho-hematogenously to lungs, liver and other organs

Answer 100

A

Prognosis
Lesions < 2cm = 90% 5 year survival after treatment with vulvectomy + ladectomy
Larger lesions with involved lymph nodes have worse prognosis

Answer 101

A

Sharply circumscribed nodule
Most common on the labia majora or inter-labial folds
Tends to ulcerate = clinically confused with carcinoma
Morphology
histology is identical to intraductal papilloma of the breast
Papillary projections covered with two layers of cells
Upper layer: columnar secretory cells
Deep layer: flattened myoepithelial cells (characteristic of sweat glands and sweat gland tumors

Answer 102

A

Pruritic, red, crusted, map-like area, usually on the labia majora
Not associated with underlying cancer (unlike the counterpart in the breast)
Paget disease of the nipple == 100% of patients have underlying ductal breast carcinoma
Extramammary Paget Disease == typically not associated with underlying cancer and is confined to the epidermis of vulvar skin

Answer 103

A

Intraepithelial proliferation of malignant cells
Cells are larger than surrounding keratinocytes
May be single or in small clusters within the epidermis
Express apocrine, eccrine and keratinocyte differentiation
Express cytokeratin 7
likely arise from multipotent cells in the mammary-like gland ducts of the vulvar skin
Have pale cytoplasm with mucopolysaccharide that stains with PAS, Alcian blue, or mucicarmine stains

Answer 104

A

Location of tumor
Intraepithelial malignancy
Confined to the epidermis of vulvar skin
Cells spread laterally within the epidermis and may be present beyond the borders of the visible lesion
treatment is wide local excision

Answer 105

A

Metastasis
May remain intraepidermal for years and not invade or metastasize
Invasion = poor prognosis

Answer 106

A

_________VAGINA
Remarkably free from primary disease
squamous cell carcinoma is the most serious primary disease
In adults, inflammation often affects the vulva and perivulvar structures and spreads to the cervix without significant involvement of the vagina

Answer 107

A

Septate (double) Vagina
due to failure of Müllerian duct fusion and is accompanied by a double uterus (uterus didelphys)
Causes
Genetic syndromes
In utero exposure to DES (diethylstilbestrol)
used to prevent threatened abortions (vaginal bleeding during the first 20 weeks)
Disturbed epistromal signaling during fetal development

Answer 108

A

Embryonal epithelium: columnar, endocervical type epithelium
Replaced with squamous epithelium ascending from the urogenital sinus
small patches of residual glandular epithelium which persists into adult life == vaginal adenosis
Red, granular areas that stand out from a normal, pale-pink vaginal mucosa
Micro: columnar mucinous epithelium indistinguishable from endocervical epithelium
Most common in females exposed to DES in utero
Rarely: clear cell carcinoma can arise from DES-related adenosis
stopped using DES in the 1980s

Answer 109

A

Common lesions found along the lateral vaginal walls
Derived from Wolffian (mesonephric) duct rests
cysts In the proximal vagina are derived from müllerian epithelium
1-2cm fluid filled cysts found in the submucosa

Answer 110

A

Occur in females of reproductive age
Stromal tumors (stromal polyps)
Leiomyomas
Hemangiomas

Answer 111

A

Virtually all primary carcinomas of the vagina are squamous cell carcinomas associated with high-risk HPVs (16, 18, 31, and 33)
↑ risk: previous carcinoma of the cervix or vulva
Arises in 1-2% of females with previous invasive cervical carcinoma
premalignant lesion == vaginal intraepithelial neoplasia (VIN)
analogous to cervical squamous intraepithelial lesions
Most invasive tumors affect the posterior wall of the upper vagina at the junction of the ectocervix
Lesions of the upper 1/3 metastasize to iliac lymph nodes
Lesions in the lower 2/3 metastasize to inguinal lymph nodes

Answer 112

A

Definition
Rare tumor of malignant embryonal rhabdomyoblasts
Infants and children < 5 years
Tumors invade locally and cause death via penetration into the peritoneal cavity or obstruction of the urinary tract

Answer 113

A

Cells are small with oval nuclei and cytoplasmic protrusions (tennis racket shape)
Striations may be seen in the cytoplasm
Tumor cells may be crowded in a cambium layer beneath vaginal epithelium
Or the tumor cells can be within an edematous, loose fibromyxomatous stroma in the deep regions with inflammatory cells (often mistaken for inflammatory polyps)
Grow as polypoid, rounded, bulky masses
Appear as grapelike clusters
tend to invade locally and cause death by penetration into the peritoneal cavity or by obstruction of the urinary tract

Answer 114

A

Conservative surgery + chemotherapy

Best if diagnosed early

Answer 115

A

External vaginal portion (ectocervix)
Visible on vaginal exam
Covered with mature squamous epithelium continuous with the vaginal wall that converges at the external os

Answer 116

A

Columnar, mucus secreting epithelium that converges at the external os
Ectocervix and endocervical come together at the squamocolumnar junction

Answer 117

A

Location where squamous and columnar epithelium meet
Variable position based on age and hormonal influence
Typically moves upward into the endocervical canal with time
squamous metaplasia == the replacement of the glandular epithelium by advancing squamous epithelium

Answer 118

A

Area of the cervix where the columnar epithelium abuts the squamous epithelium
Immature squamous metaplastic epithelial cells in this zone are the most susceptible to HPV infection
The unique epithelium of the cervix makes it highly susceptible to HPV infections
HPV == leading cause of cervical cancer so this matters
MOST susceptible area
this is where cervical precursor lesions and cancers will develop

Answer 119

A

Gram +ve non-spore forming bacillus
Dominant microbial species of the normal vagina
Produces lactic acid –> maintains pH < 4.5 that suppresses growth of other saprophytic and pathogenic organisms
At low pH they produce H2O2, which is bacteriotoxic
pH becomes alkaline (> 7) due to bleeding, sexual intercourse, antibiotics, or vaginal douching
Leads to ↓ H2O2 production by lactobacilli
Promotes overgrowth of other microorganisms that can lead to cervicitis or vaginitis
Receives nutrients from intracellular glycogen vacuoles of squamous cells which start being shed at puberty

Answer 120

A

(acute or chronic)
May be due to gonococci, chlamydia, mycoplasmas, HSV
Important to identify because of associations with upper genital tract disease, pregnancy complications, sexual transmission, and pelvic inflammatory disease (PID) –> Fitz-Hugh-Curtis Syndrome (violin string adhesions)
Marked cervical inflammation can cause reparative and reactive changes of the epithelium + shedding of atypical squamous cells → abnormal Pap smear
due to infection, not neoplasm – don’t want to do a hysterectomy because of an infection, give antibiotics

Answer 121

A

Common, benign exophytic growths within the endocervical canal
Loose, fibromyxomatous stroma covered by mucus secreting endocervical glands +/- inflammation
Vary from small, sessile ‘bumps’ to large, polypoid masses that protrude through the cervical os
may be the source of irregular vaginal “spotting” (bleeding) that arouses suspicion for ominous disease

Answer 122

A

Curettage or surgical excision=curative

Answer 123

A

3rd most common cause of cancer in women worldwide
Typically progresses slowly, allowing screening, detection and treatment
50% are fatal
Significant benefits from early diagnosis & curative treatment
Pap smears detects precursor lesions and low-stage, highly curable cancers
Strong association with HPV

Answer 124

A

15 high risk HPVs, but HPV-16 accounts for 60% of cervical cancer cases (the most high-risk/prevalent == HPV-16)
HPV18 accounts for 10%

Answer 125

A

15 high risk HPVs, but HPV-16 accounts for 60% of cervical cancer cases (the most high-risk/prevalent == HPV-16)
HPV18 accounts for 10%
High Risk HPVs on cancer
Most important factor in the development of cervical cancer
Also implicated in squamous cell carcinoma at other sites (vagina, vulva, penis, anus, tonsils, oropharynx)
HPV is a DNA virus
Viral DNA remains extrachromosomal (episomal)
Alone, it is not sufficient to cause cervical cancer
Progression to carcinoma is influenced by exposure to cocarcinogens and host immune status
Cause 80% of LSIL and 100% of HSIL

Answer 126

A

Cause of condyloma acuminata
Sexually transmitted infections of the vulvar, perineal and perianal regions
E6: Fails to bind p53, but dysregulates growth & survival via the Notch pathway
E7: Bind RB with low affinity
Viral DNA remains extrachromosomal (episomal

Answer 127

A

V Infections
genital HPV infections are extremely common; most of them are asymptomatic, do not cause any tissue changes, and therefore are not detected on Pap test

Answer 128

A

50% of HPV infections are cleared within 8 months, and 90% of infections are cleared within 2 years
high-risk type infections last longer –> more time to develop a precursor lesion –> increased risk

Answer 129

A

May infect immature basal cells of the squamous epithelium in areas of epithelial breaks or immature metaplastic squamous cells at the squamocolumnar junction
Cannot infect mature superficial squamous cells covering the ectocervix, vagina or vulva unless there is damage to the surface epithelium allowing access to immature cells in the basal layer of the epithelium
cervix = large area of immature squamous metaplastic epithelium = particularly vulnerable to HPV infection
**Infects immature squamous cells
**Replicates in mature squamous cells

Answer 130

A

↑ risk == Cervix and Anus (homosexual men

Answer 131

A

↓ risk == Vulva and Penis (barring any epithelial breaks

Answer 132

A

Cannot be infected by HPV, but are the site of HPV replication
Normally arrested in G1 phase of cell cycle – “senescent”
If infected, actively progress through the cell cycle as the virus uses the host cell DNA synthesis machinery to replicate its genome

Answer 133

A

Enhanced cell cycle progression and impaired ability to repair DNA damage due to:
viral E7 binds the hypophosphorylated (active) from of RB and promotes its degradation via proteasomes
this allows E2F to dissociate and ???
viral E7 binds & inhibiting p21 & p27 (cyclin dependent kinase inhibitors, CKIs

Answer 134

A

net effect: increased proliferation of cells that are prone to acquire additional mutations
viral E6 exacerbates the defective DNA repair via binding to p53 (tumor suppressor) and promoting proteasomal degradation of p53
viral E6 upregulates telomerase expression via TERT → cellular immortalization

Answer 135

A

↑ proliferation of cells that are prone to acquire new mutations that can lead to cancer development
Expression is increased via integration into the host genome
Oncogenes near viral insertion may be dysregulated
These oncogenic proteins inactivate tumor suppressors, activate cyclins, inhibit, apoptosis, and combat cellular senescence
E6 and E7 proteins from low-risk HPV types
E7: binds to RB with lower affinity
E6: does not bind to p53 at all
dysregulates growth and survival by interfering with the Notch signaling pathway instead

Answer 136

A

Classification

Classified into a two tier system, all are most commonly caused by HPV16

Answer 137

A

Previously CIN I (mild cervical intraepithelial neoplasia)

80% of LSILs are associated with high-risk HPV types

Answer 138

A

Previously CIN II (moderate dysplasia), CIN III (severe dysplasia) & CIS (carcinoma in situ)
100% of HSILs are associated with high risk HPV types

Answer 139

A

Associated with a productive HPV infection
High level of viral replication
only mild alteration in growth of host cells
Does NOT progress directly to invasive carcinoma
Most (60%) regress spontaneously, small portion (10%) → HSIL
Not treated as a premalignant lesion
10x more common than HSIL

Answer 140

A

progressive deregulation of the cell cycle by HPV –>
increased cellular proliferation
decreased/arrested epithelial maturation
lower rate of viral replication
derangement of the cell cycle in HSIL may become irreversible and lead to a fully transformed malignant phenotype
80% of HSILs develop from LSILs; 20% of HSILs develop de novo
all HSILs are considered to be at high risk for progression to carcinoma

Answer 141

A

Diagnosed based on identification of nuclear atypia with:
Nuclear enlargement
Hyperchromasia (dark staining)
Coarse chromatin granules
Variation in nuclear size & shape
May be accompanied with cytoplasmic ‘halos’
Halos: perinuclear vacuoles due to E5 protein localization to the endoplasmic reticulum= koilocytic atypia

Answer 142

A

Highest viral loads in upper ½ of the epithelium
Ki-67 (marker of actively dividing cells) usually restricted to basal layer
viral E6 and E7 prevent cell cycle arrest –> Ki-67 seen in upper levels (where it shouldn’t be)
Overexpression of p16 (increased CDK4) [cyclin dependent kinase inhibitor]
“Both Ki-67 and p16 staining are highly correlated with HPV infection and are useful for confirmation of the diagnosis in equivocal cases of SIL

Answer 143

A

Grading
Based on expansion of immature cell layer from its normal, basal location
Confined to lower 1/3 = LSIL
Expansion into upper 2/3 = HSIL

Answer 144

A

60% regress
30% persist
10% progress to HSIL

Answer 145

A

30% regress
60% persist
10% progress to carcinoma within 2-10 years
Most develop from LSIL, though 20% develop de novo

Answer 146

A

Average Age: 45 years
due to high risk HPVs (16, 18, 31, 33, and 45)
80% of cervical carcinomas are squamous cell carcinomas
15% of cervical carcinomas are adenocarcinoma (precursor lesion == adenocarcinoma in situ)
5% of cervical carcinomas are adenosquamos or neuroendocrine carcinomas
have a shorter progression time than squamous cell carcinoma
patients often present with advanced disease and less favorable prognosis

Answer 147

A

Nests and tongues of malignant squamous epithelium
Keratinizing or nonkeratinizing
Invade the underlying cervical stroma – makes it a carcinoma (i.e. malignant

Answer 148

A

Proliferation of glandular epithelium composed of malignant endocervical cells with large, hyperchromatic nuclei and mucin depleted cytoplasm = dark appearance of glands (vs. normal endocervical epithelium

Answer 149

A

Adenosquamous Morphology

Intermixed malignant glandular and squamous epithelium

Answer 150

A

Appears similar to small cell carcinoma of the lung but is +ve for high risk HPV (16, 18, 31, 33, and 45)
Very poor prognosis

Answer 151

A

Spreads via direct extension to contiguous tissues
Paracervical soft tissue
Urinary bladder
Ureters (→ hydronephrosis)
Rectum
Vagina
Lymphovascular invasion –> local and distant lymph node metastases (liver, lungs, bone marrow

Answer 152

A

Staged as carcinoma in situ (CIS) = CIN III, HSIL

Answer 153

A

I: Carcinoma confined to the cervix
I-A: preclinical carcinoma (diagnosed only with microscopy)
I-A1: stromal invasion < 3mm deep & < 7mm wide (microinvasive carcinoma)
I-A2: 3mm < max stromal invasion < 5mm from the base of the epi; horizontal < 7mm
I-B: Confined to the cervix and > stage

Answer 154

A

Stage II: Carcinoma extends beyond the cervix but not to the pelvic wall
Involves the upper 2/3 of the vagina
No involvement of the lower 1/3

Answer 155

A

Stage III: Carcinoma is extended beyond the pelvic wall
Rectal exam: no cancer free space between the tumor and pelvic wall
Involvement of the lower 1/3 of the vagina

Answer 156

A

Stage IV: Carcinoma has extended beyond the true pelvis or involves the mucosa of the bladder or rectum
Also includes cancers with metastatic dissemination

Answer 157

A

Early invasive: cervical cone excision
Invasive cancer: hysterectomy + lymph node dissection
Advanced cancer: + radiation + chemotherapy

Answer 158

A

patients tend to die from consequences of local tumor invasion (ureteral obstruction, pyelonephritis, uremia)
100% 5 year survival for microinvasive carcinomas
< 50% 5 year survival for tumors extending beyond the pelvis
50% are detected in females without regular screenings
most patients with advanced cervical cancer die of the consequences of local tumor invasion (e.g. ureteral obstruction, pyelonephritis, and uremia) rather than distant metastases

Answer 159

A

Cytologic Cancer Screening
Pap Smear: transformation zone is scraped and smeared onto a slide, fixed and stained with Papanicolaou method
Significantly ↓ mortality of cervical cancer because most cancers arise from precursor lesions over many years
Lesions shed abnormal cells
HPV DNA testing (↑ sensitivity, ↓ specificity) can also be added for females < 30 years
> 30 not recommended due to ↑ incidence of infection and low specificity of test results

Answer 160

A

Recommended at age 21 or within 3 years of the onset of sexual activity, then every three years
After age 30
Normal cytology, (-) for HPV, every 5 years
Normal cytology, (+) for high risk HPV, every 6-12 months

Answer 161

A

Follow up should include colposcopic exam of the cervix and vagina to identify the lesion
Examine mucosa after application of acetic acid, and abnormal epithelium = white spots
Abnormal areas should be biopsied
LSIL: followed in conservative fashion
can do a local ablation if there is concern about the reliability of patient follow-up
HSIL: cervical conization

Answer 162

A

Recommended for all girls and boys 11-12 years old, up to age 26
Provide nearly complete protection vs strains 16 & 18
One also provides protection vs 6 & 11 (genital warts)
Protects up to 10 years
Cervical screenings should still continue as not all strains are protected against
Gardasil: 6, 11, 16, 18

Answer 163

A

myometrium == tightly interwoven bundles of smooth muscle that form the wall of the uterus
hormonally responsive to oxytocin during parturition

Answer 164

A

endometrium == lining of the internal cavity of the uterus; composed of glands embedded in a cellular stroma
hormonally responsive to sex steroid hormones

Answer 165

A

Beginning of the menstrual cycle
this is Day 0
Shedding of the functionalis (superficial portion of the endometrium)
Day 15: Corpus luteum involutes if no fertilized egg
Progesterone drops → functionalis layer degenerates/sheds
Normal stroma breakdown (bleeding into stroma with fibrin, RBCs, and inflammatory cells)
Stem cells in basal layer regenerate after menses

Answer 166

A

rapid growth of glands & stroma from the basalis (deeper portion of the endometrium) → new functionalis
Glands are straight, tubular structures lined with regular, tall, pseudostratified columnar cells
Numerous mitotic figures
No evidence of mucus secretion or vacuolization
Endometrial stroma: actively proliferating spindle cells with scant cytoplasm
Phase ceases at ovulation
estrogen drives the proliferation of both glands and stroma

Answer 167

A

Endometrial proliferation ceases

Differentiation occurs in response to progesterone produced by the corpus luteum in the ovary

Answer 168

A

Marked appearance of secretory vacuoles beneath the nuclei in the glandular epithelium
Week 3: prominent secretory activity
Basal vacuoles move towards apical surface
Glands are dilated between days 18-24 due to max secretion
Week 4: Tortuous glands with a serrated/sawtooth (secretory phase) appearance accentuated by secretory exhaustion and shrinkage of the glands

Answer 169

A

Tortuous and serrated or saw toothed
Stromal changes during the late secretory phase are important for dating the endometrium

Progesterone down regulates the expression of estrogen receptors in the glands and stroma
Endometrial proliferation is suppressed
promotes the differentiation of the glands and causes functional changes in the stromal cells
Early secretory: secretory subnuclear vacuoles (day 16-17)
3rd week of cycle: vacuoles become supranuclear and are most prominent
Tortuous and serrated or saw toothed
Stromal changes during the Late Secretory Phase are important

Answer 170

A

Day 21-22: Appearance of prominent spiral arterioles + ↑ in ground substance & edema between stromal cells
normal placenta: maternal blood enters the intervillous space through endometrial arteries (spiral arteries) and circulates around the villi to allow gas and nutrient exchange

Answer 171

A

Day 23-24: Stromal cell hypertrophy, ↑ cytoplasmic eosinophilia (predecidual change), resurgence of stromal mitoses

Answer 172

A

Days 24-28: Pre-decidual changes occur + a normal, sparse infiltrate of neutrophils + lymphocytes
Decidualized cells high in glycogen and lipid

Answer 173

A

Leads to ↓ progesterone
Functionalis degeneration + bleeding into the stroma occurs
Stromal breakdown → onset of the next menstrual cycle

Answer 174

A

Estrogen == drives proliferation of glands & stroma during the proliferative phase
“Crosstalk” between the cells may occur
Hormonal effects on glandular proliferation occur via stromal cells
Stromal cells → growth factors (IGF1, epidermal GF) that bind to receptors on epithelial cells

Answer 175

A

Endometrial Stem Cells
Play a central role in the regeneration of endometrium after menses
May contribute to the development of ectopic endometrial tissue and endometrial cancer

Answer 176

A

Uterine bleeding that lacks an underlying (structural) abnormality
Most commonly due to hormonal disturbances
Any alteration of the hypothalamic-pituitary-ovarian system can alter release (timing or amount) of hormones

Answer 177

A

Most commonly due to hormonal disturbances
May also be due to pathologies such as chronic endometritis, endometrial polyps, submucosal leiomyomas, endometrial neoplasms

Answer 178

A

Most frequent cause of dysfunctional bleeding is anovulation (failure to ovulate)
due to subtle hormonal imbalances
most common at menarche and perimenopausal periods
failure of ovulation –> excessive endometrial stimulation by estrogens that is unopposed by progesterone

Answer 179

A

most commonly due to subtle hormonal imbalances
Endocrine disorders: thyroid, adrenal, or pituitary tumors/etiology
Ovarian lesions: granulosa cell tumors or polycystic ovaries
Generalized metabolic disturbances: obesity, malnutrition or chronic systemic disease

Answer 180

A

repeated anovulation may result in bleeding that may prompt endometrial biopsy (sometimes)
Stromal condensation
Eosinophilic epithelial metaplasia similar to menstrual epithelium BUT lacks progesterone dependent morphologic features (glandular secretory changes, stromal predecidualization) because the source of progesterone (corpus luteum) does not develop without ovulation
Endometrium exhibits pseudostratified glands with scattered mitotic figures

Answer 181

A

manifests clinically as infertility and increased bleeding or amenorrhea
due to inadequate progesterone production during postovulatory period
Secretory endometrium with features lagging behind those expected for the estimated date

Answer 182

A

Endometrium & myometrium are relatively resistant to infection
endocervix forms a barrier to ascending infection
Chronic inflammation of the endometrium (not associated with menstrual phase) is of concern

Answer 183

A

Uncommon; limited to bacterial infections that arise after delivery or miscarriage
Predisposed by retained products of conception
due to group A hemolytic streptoocci, staphylococci, etc.
Nonspecific inflammation of the stroma
treatment: curettage of fragments and antibiotics (beta-lactams for strep and staph) == curative

Answer 184

A

Most common form of endometritis
Typically caused by an ascending infection (especially chlamydia), sometimes idiopathic
if organisms are not detected on culture, proceed with antibiotic therapy to prevent sequelae
If you see one plasma cell on biopsy then it is chronic endometritis until proven otherwise
diagnosis is made on the identification of plasma cells in the stroma
plasma cells not normally seen in the normal endometrium

Answer 185

A

PID (mostly chlamydia)
Retained gestational tissue, post-partum or post-abortion
IUD
TB (miliary or from drainage of TB salpingitis) [rare in Western countries]
Chlamydia
No identified cause (15%)

Answer 186

A

Abnormal bleeding
Pain
Discharge
Infertility

Answer 187

A

Both fallopian tubes are involved
Infects the endometrium 50% of the time
Rarely infects the cervix, vagina, or vulva
If the ovaries are infected, then there is only surface infection
Mucosa of the tube may not be involved
1/3 of patients will have had TB somewhere else in the body before

Answer 188

A

Multinucleated giant cells
Histiocytes
Can see the bugs with a Kinyoun or Ziehl-Neelsen acid fast stain

Answer 189

A

Ectopic endometrial tissue seen outside of the uterus
Tissue typically includes stroma + endometrial glands (which may be absent)
Causes infertility, dysmenorrhea, and pelvic pain
Complications can occur if invasion/spread occurs
Most common in females 3-4th decade

Answer 190

A

Ovaries
Uterine ligaments
Rectovaginal septum
Cul de sac
Pelvic peritoneum
Large &amp; small bowel, appendix,
Mucosa of cervix, vagina, fallopian tubes
Laparotomy scars

Answer 191

A

Regurgitation theory: endometrial tissue implants at ectopic sites via retrograde flow of menstrual endometrium through the fallopian tubes
this occurs regularly even in normal women
Most likely theory to explain endometriosis; though not perfect

Answer 192

A

Release of proinflammatory & other factors: VEGF (need blood supply), PGE2, IL1β, TNFα, IL6, IL8, NGF, MCP1, MMPS, TIMP
↑ estrogen production by endometriotic stromal cells (↑ aromatase, which is absent in normal stroma)
inhibitors of aromatase are beneficial in the treatment of endometriosis
These contribute to invasion and establishment of neurovascular networks + decreased immune clearance = survival of ectopic tissue
↑ responsiveness to estrogen
↓ responsiveness to progesterone

Answer 193

A

patients have a 3x ↑ risk of ovarian cancer of the endometrioid and clear cell types
PTEN, ARID1A mutations
Mutations are also found in endometriotic cysts, atypical endometriosis & associated carcinomas

Answer 194

A

Precursor to endometriosis-related ovarian carcinoma
Cytologic atypia of epithelium lining the endometriotic cyst without major architectural changes
OR
Glandular crowding due to excess epithelial proliferation +/- cytologic atypia → appearance similar to complex atypical endometrial hyperplasia

Answer 195

A

Active reproductive/childbearing years, 3-4th decade, 6-10% of women affected
Severe dysmenorrhea, Dyspareunia, and Pelvic pain due to intrapelvic bleeding & periuterine adhesions
Menstrual irregularities
Infertility == presenting complaint in 30-40% of patients
pain with defecation if rectal wall is involved
dysuria if bladder serosa involvement

Answer 196

A

Diagnosis via presence of endometrial glands and stroma +/- hemosiderin
May be obscured by secondary fibrosis
Rarely only stroma is identified
treatment 
Aromatase inhibitors or surgical

Answer 197

A

Aromatase inhibitors or surgical

Answer 198

A

Related to endometriosis
Presence of endometrial tissue within the uterine wall (myometrium)
Down growth of endometrial tissue into & between smooth muscle fascicles of the myometrium
Occurs in 20% of females (uteri)
Irregular nests of endometrial stroma +/- glands
Separated from basalis by 2-3mm
menometrorrhagia, colicky dysmenorrhea, dyspareunia, pelvic pain (premenstrual)
May coexist with endometriosis

Answer 199

A

Exophytic masses of variable sizes that project into the endometrial cavity
Single or multiple, sessile polyps
Occasionally: large and pedunculated (attached by a stalk)
May be asymptomatic or cause abnormal bleeding
Seen in reproductive age, peri and postmenopausal females
May (rarely) give rise to adenocarcinoma

Answer 200

A

Possess chromosomal rearrangements seen in other benign mesenchymal tumors
Stroma appear neoplastic, while the glands appear reactive
Glands may be hyperplastic, atrophic or functional (demonstrate secretory changes)
May become hyperplastic with generalized endometrial hyperplasia

Answer 201

A

Responsive to estrogen
Little to no response to progesterone
Associated with tamoxifen therapy (for estrogen receptor positive breast cancer)
tamoxifen has weak pro-estrogenic effects in the endometrium (anti-estrogenic effects in breast

Answer 202

A

Remnants of previously hyperplastic polyps

Seen mostly in postmenopausal females

Answer 203

A

↑ proliferation of the endometrial glands relative to the stroma that leads to ↑ gland:stroma ratio
Associated with prolonged estrogenic stimulation of the endometrium
anovulation
increased estrogen production from endogenous sources
exogenous sources of estrogen (hormone replacement therapy)
Important cause of abnormal bleeding
Frequent precursor to the most common type of endometrial carcinoma

Answer 204

A

Obesity (peripheral conversion of androgens → estrogens)
Menopause
Poly-Cystic Ovarian Syndrome (PCOS)
Functioning granulosa cell tumors of the ovary
Excessive ovarian cortical function (cortical stromal hyperplasia)
Prolonged administration of estrogenic substances

Answer 205

A

PTEN inactivating mutation

Answer 206

A

tumor suppressor gene
seen in both endometrial hyperplasia (20%) and endometrial carcinomas (30-80%)
Causes overactive PI3K/AKT growth regulatory pathway which enhances ability of estrogen to stimulate gene expression (i.e. endometrial and mammary epithelial cells)
loss of PTEN function –> overactive estrogen dependent gene expression
not predictive of progression to carcinoma
germline mutation == Cowden syndrome
Cowden patients have an ↑ incidence of endometrial + breast cancer

Answer 207

A

Nonatypical hyperplasia
Atypical hyperplasia (endometrial intraepithelial neoplasia)
Differ in appearance and their propensity to progress to carcinoma

Answer 208

A

↑ gland:stroma ratio
Glands vary in size & shape
May be dilated
May be back-to-back, but some intervening stroma is typically retained
due to endometrial response to persistent estrogen stimulation
may evolve to cystic atrophy if estrogen is withdrawn
Rarely progresses to adenocarcinoma

Answer 209

A

Complex patterns of proliferating glands with nuclear atypia
Nuclei have open/vesicular chromatin + conspicuous nucleoli
Glands are back-to-back and branch
Cells: rounded, losing perpendicular orientation to basement membrane
Overlaps with well-differentiated endometrioid adenocarcinoma
Differentiation may require hysterectomy

Answer 210

A

Hysterectomy
Up to half of patients are found to have carcinoma after hysterectomy
In patients who wish to remain fertile, progesterone therapy and close follow up may be trialed
Lack of regression usually prompts hysterectomy (hopefully after successful pregnancy

Answer 211

A

Most common invasive cancer of the female’s genital tract
earlier detection and eradication of the precursor lesions of cervical carcinoma
7% of all invasive cancer in women, excluding skin cancer
Bleeding is an early sign
two types: Type 1 (endometrioid) and Type II (serous)
Type I (endometrioid) == low-grade, indolent, preceded by atypical hyperplasia
Type II (serous) == high-grade, aggressive, poor prognosis, preceded by serous endometrial intraepithelial carcinoma

Answer 212

A

most common type accounting for 80% of all endometrial carcinomas
Most are well differentiated & mimic proliferative endometrial glands (endometrioid morphology)
Age 55-65
Comes from hyperplasia

Answer 213

A

Arise in the setting of endometrial hyperplasia &amp; associated with:
Obesity
Diabetes
HTN
Infertility
Unopposed estrogen stimulation

Answer 214

A

most common (hallmark) == ↑ signaling via PI3K/AKT pathway via multiple mutations
increasing sensitivity to estrogen as more mutations occur
PTEN, PIK3CA, KRAS
PIK3CA mutations rarely occur in atypical hyperplasias (mutations in PIK3CA have a role in invasion)
loss-of-function mutations of ARID1A enhances PI3K/AKT signaling
seen in ovarian endometrioid and clear cell carcinomas that arise within endometriosis
Other mutations include: @MLH1, CTNNB1, FGFR2 & DNA mismatch repair defects
TP53 mutations are seen in 50% of the poorly differentiated carcinomas
thought to be a late event in tumor progression

Answer 215

A

Defects of DNA mismatch repair genes are prevalent in carcinomas in females from families with HNPCC (hereditary nonpolyposis colorectal carcinoma). This is Lynch syndrome
Often due to epigenetic silencing (hypermethylation

Answer 216

A

Localized polypoid tumor or diffuse infiltration of the endometrial lining
Spread via myometrial invasion, then direct extension
Invasion of broad ligament → palpable mass
Late metastases via lymphatics to lungs, liver, bone, etc
Chemotherapy is given to these patients if the cancer has spread beyond the uterus

Answer 217

A

Grade 1: Well differentiated, well-formed glands

distinguished from hyperplasias by lack of intervening stroma

Answer 218

A

Grade 2: Moderately differentiated, well-formed glands mixed with solid sheets of cells (50% or less or tumor mass

Answer 219

A

Grade 3: Poorly differentiated greater than 50% solid growth

Answer 220

A

Lack of intervening stroma will differentiate well differentiated tumors from hyperplasia
There can be squamous elements too, but these are ignored in the grading

Answer 221

A

Also applies to Malignant Mixed Mullerian Tumors

Answer 222

A

Stage I: carcinoma is confined to the corpus uteri (body of the uterus

Answer 223

A

Stage II: carcinoma involves the copus + cervix

Answer 224

A

Stage III: carcinoma extends outside the uterus but not out of the true pelvis

Answer 225

A

Stage IV: carcinoma extends outside the true pelvis or involves the mucosa of the bladder or rectum

Answer 226

A

Arise in the setting of endometrial atrophy in women 10 years older than type I (age 65-75)
uncommon <40 years olds
More common in African Americans
Poorly differentiated (grade 3) tumors with poor prognosis due to cell exfoliation, travel through fallopian tubes & implantation on peritoneal surfaces
Often already spread out of the uterus at presentation

Answer 227

A

Subtypes
Serous (most common), clear cell carcinoma, malignant mixed mullerian tumor

Answer 228

A

90% have TP53 missense mutations == accumulation of altered protein
Precursor lesion: serous endometrial intraepithelial carcinoma (also has altered TP53)
Identical cells, but lack stromal invasion (i.e. are not malignant; confined to epithelial surfaces)
Likely begins as a surface epithelial neoplasm that extends to adjacent glands, then invades stroma
Other mutations: PI3K, PP2A which are also seen in the precursor lesions (early events

Answer 229

A

Seen in small, atrophic uteri
Tumors are large and bulky or invasive into the myometrium
Papillary growth pattern
↑ nuclear: cytoplasmic ratio, atypical mitotic figures, hyperchromasia, prominent nucleoli
May also have a glandular growth pattern, but can differentiate by looking for the nuclear atypia

Answer 230

A

No screening test available
Asymptomatic or with irregular or post-menopausal bleeding with excessive leukorrhea
No uterine enlargement in early stages
Diagnosis requires histological exam of tissue from biopsy or curettage
Most patients are cured if there is postmenopausal bleeding as this leads to early detection

Answer 231

A

Prognosis is based on stage at presentation
Most (in USA) are stage I and well-moderately differentiated
Stage I (grade 1 or 2): 90% 5 year survival
treatment with surgery +/- irradiation
Stage I (grade 3): 75% 5 year survival
Stage II or III: < 50% 5 year survival

Answer 232

A

Propensity for extrauterine spread
More frequent in African American females
2x mortality for African Americans
18-27% 5 year survival even if confined to the uterus, 80% recurrence
Adjuvant radiation may reduce local recurrence
Chemotherapy may be given, even in the absence of detectable extrauterine spread

Answer 233

A

Endometrial adenocarcinomas with a malignant mesenchymal component
Mesenchymal component may be tumor cells resembling uterine mesenchymal elements (stromal sarcoma, leiomyosarcoma) or contain heterologous malignant cell types (rhabdomyosarcoma, chondrosarcoma).
Epithelial & stromal components are from the same founding cell
Majority are carcinomas with sarcomatous differentiation

Answer 234

A

Mutations
PTEN, TP53, PIK3CA (similar to endometrial carcinoma)
Alterations typical of those in sarcomas are absent
mechanism of sarcomatous transformation is unknown

Answer 235

A

Bulky, polypoid, and may protrude through the cervical os
Usually consist of adenocarcinoma (glandular) mixed with malignant mesenchymal elements (sarcomatous)
The metastases typically only have the epithelial components

Answer 236

A

Seen in postmenopausal women
Present with bleeding
resemble endometrial carcinoma genetically
poor outcomes with current therapies

Answer 237

A

Prognosis based on depth of invasion and stage
Also based on differentiation of the mesenchymal component
patients with tumors that have a heterologous mesenchymal component do worse than those who do not
25-30% 5 year survival for high-stage disease

Answer 238

A

stromal neoplasm admixed with benign glands
Large, broad based endometrial polypoid growths
May prolapse through the cervical os
Females in 4-5th decade
Low grade malignancy
25% recur and are confined to the pelvis

Answer 239

A

Based on malignant appearing stroma and coexistent benign but abnormally shaped endometrial glands
need to distinguish adenosarcomas from large benign polyps
adenosarcomas are estrogen-sensitive and responds to oophorectomy

Answer 240

A

stromal nodules == benign, well-circumscribed tumors
low-grade endometrial tumor sarcoma == infiltrate into the surrounding myometrium
high-grade endometrial tumor sarcoma == marked atypia
associated with chromosomal translocations that create fusion genes

Answer 241

A

JAZF1 (transcription repressor)/SUZ12 (polycomb gene family)

Answer 242

A

“other gene fusions,” function of which is currently unknown

Answer 243

A

Most common tumor in women
Benign, smooth muscle neoplasms
Multiple > single

Answer 244

A

Commonly have normal karyotypes
40% have a simple chromosome abnormality
T(12q14;6p): HMGIC, HMGIY – genes that regulate chromatin structure
^^ also implicated in a variety of other benign neoplasms
MED12 mutations seen in 70% of tumors

Answer 245

A

Found in the myometrium of the corpus

Infrequently involve uterine ligaments, lower uterine segment or cervix

Answer 246

A

Sharply circumscribed, discrete, round, firm, gray-white tumors that vary in size
Characteristic whorled pattern of smooth muscle bundles resembling the uninvolved myometrium
Individual muscle cells are uniform in size and shape
Characteristic oval nucleus & long, slender bipolar cytoplasmic processes
Scarce mitotic figures (helps to differentiate from leiomyosarcoma)
Large: develop yellow-brown-red areas of softening

Answer 247

A

Often asymptomatic, but may have:
Abnormal bleeding
Urinary frequency (bladder compression)
Sudden pain due to infarction of a large or pedunculated tumor
Impaired fertility
Malignant transformation → leiomyosarcoma is extremely rare

Answer 248

A

↑ frequency of:
Spontaneous abortion
Fetal malpresentation
Uterine inertia (failure to contract with sufficient force)
Postpartum hemorrhage

Answer 249

A

Uterine leiomyoma that extends into vessels and spreads hematogenously to other sites
Most commonly the lung

Answer 250

A

Multiple, small peritoneal nodules

Benign

Answer 251

A

Uncommon, malignant neoplasm
Arise from myometrium or endometrial stromal precursor cells, rarely from leiomyomas (i.e. de novo)
Peak 40-60 years (before & after menopause

Answer 252

A

Complex, highly variable karyotypes, often with deletions

MED12 mutations – virtually unique to uterine smooth muscle tumors

Answer 253

A

Bulky, fleshy masses that invade the uterine wall
OR
Polypoid masses that project into the uterine lumen

Answer 254

A

50% metastasize hematogenously to lungs, bone, and brain
Local spread to abdominal cavity can also happen
40% 5 year survival
Anaplastic lesions: 10-15% 5 year survival
Often recur after surgery

Answer 255

A

Distinguished from benign counterpart via nuclear atypia, mitotic index, zonal necrosis; malignant if:
10 mitoses per high powered field
5 mitoses per high powered field with nuclear atypia or large cells

Answer 256

A

Formed from upper unfused Mullerian duct
Most commonly affected by infections and associated inflammatory conditions
Also affected by ectopic (tubal) pregnancy and endometriosis

Answer 257

A

60% of suppurative salpingitis == neisseria gonorrhea

many of the remaining cases == chlamydia trachomatis

Answer 258

A

Most common primary lesion of the fallopian tubes, excluding endometriosis
Small translucent cysts filled with clear, serous fluid
Hydatids of Morgagni: Larger cysts near the fimbriated end of the tube or in the broad ligaments that arise from remnants of the mullerian duct and are lined with benign, serous (tubal type) epithelium
Relatively insignificant

Answer 259

A

benign, uncommon
Occur sub-serosally on the tube or in the mesosalpinx
Counterpart to the same tumor of the testes or epididymis

Answer 260

A

Rare tubal mass that may be detected by pelvic exam.
Others may come to attention due to abnormal discharge, bleeding, or abnormal cells on Pap smear
~ 50% are stage 1 at diagnosis, but only have a 60% 5 year survival
Higher grade tumors are more aggressive
treatment: ovarian cancer chemotherapy protocols
at least a subset of “serous ovarian cancers” actually arise from the epithelium of the Fallopian tube

Answer 261

A

Most common lesion encountered in the ovary

Answer 262

A

müllerian epithelium
germ cells
sex cord-stromal cells

Answer 263

A

may have an autoimmune component –> autoimmune oophoritis –> may lead to infertility

Answer 264

A

very common in the ovary

Originate from unruptured graafian follicles or in follicles that ruptured and then immediately sealed

Answer 265

A

Multiple cysts < 2cm in diameter
Larger may cause pelvic pain or be palpable, if >2cm then called Follicle Cyst
Filled with a clear, serous fluid
Lined by gray, glistening membrane
Granulosa cells if not atrophied due to intraluminal pressure
Conspicuous outer theca cells due to ↑ amounts of pale cytoplasm (leutinization)

Answer 266

A

Hyperthecosis == pronounced leutinization

Often associated with ↑ estrogen production and endometrial abnormalities

Answer 267

A

Seen in the normal ovaries of reproductive age females
Lined with a rim of bright yellow tissue containing leutinizing granulosa cells
May rupture → peritoneal reaction
May be mistaken for endometriotic cysts due to old hemorrhage and fibrosis

Answer 268

A

Complex endocrine disorder characterized by hyperandrogenism (hirsutism, acne, deep voice), menstrual abnormalities (amenorrhea), polycystic ovaries, chronic anovulation, and decreased fertility
affects 6-10% of reproductive age women worldwide (common?)

Answer 269

A

underlying metabolic disorder
Obesity (altered adipose tissue metabolism)
T2DM (insulin resistance, Acanthosis Nigricans)
Premature atherosclerosis
Dysregulation of enzymes for androgen biosynthesis (excess androgen production)
Endometrial hyperplasia and carcinoma due to ↑ free estrone (E1) levels

Answer 270

A

Predominates in reproductive years

Most potent estrogen produced by aromatization of testosterone in Graafian follicle

Answer 271

A

Placental estrogen that originates in fetal adrenal gland as DHEA and converted in placenta
Least potent

Answer 272

A

Uniform enlargement of the ovary; usually bilateral
White-tan appearance
Hypercellular stroma & leutinization of stromal cells
Seen as nests of cells with vacuolated cytoplasm
Most common in post-menopausal females; overlaps with PCOS in younger females
similar presentation to PCOS
virilization may be even more striking

Answer 273

A

Theca cells proliferate and the perifollicular zone expands in response to gonadotropins released during pregnancy
Concentric theca-lutein hyperplasia
Regression of follicles → nodular appearance
Do not confuse with true luteomas of pregnancy

Answer 274

A

80% are benign; occur mostly in females 20-45 years old
Borderline tumors appear at a slightly older age
Malignant tumors are more common in older females 45-65
Most have spread beyond the ovary by the time of diagnosis –> disproportionate number of deaths from cancers of the female genital tract

Answer 275

A

Surface/fallopian tube epithelium and endometriosis
Pluripotent germ cells that migrate to the ovary from the yolk sac
Stromal cells (including sex cords) which are forerunners of the endocrine apparatus of the postnatal ovary

Answer 276

A

Abdominal pain and distention
Urinary and GI tract symptoms due to compression or invasion
Vaginal bleeding

Answer 277

A

Most primary ovarian neoplasms arise from the Müllerian epithelium

Answer 278

A

Serous
Mucinous
Endometrioid

Answer 279

A

Cystic or fibrous, and may be:
Benign (classified by tumor components)
Borderline
Malignant (cystadenocarcinomas

Answer 280

A

Type I: Low-grade with variable histology, often associated with borderline tumors or endometriosis
Type II: High-grade, most often serous, arise from serous intraepithelial carcinoma

Answer 281

A

Type I: Low-grade with variable histology, often associated with borderline tumors or endometriosis

Answer 282

A

Type II: High-grade, most often serous, arise from serous intraepithelial carcinoma

Answer 283

A

Cystic, with tubal-like epithelium
most common malignant ovarian tumor; ~40% of all cancers of the ovary
70% are benign or borderline that happen 20-45 years old
30% are malignant, occur later in life (early if familial)
All serous tumors have psammoma bodies (concentric calcifications)

Answer 284

A

Nullparity
Family history of breast/ovarian cancer
Heritable mutations in BRCA1, BRCA2
20-60% risk of cancer by age 70
↓ risk
40-59 year old that took oral contraceptive therapy or had tubal ligation

Answer 285

A

Arise in serous borderline tumors
KRAS, BRAF, ERBB2 mutations
Wildtype TP53
Responds better to chemotherapy

Answer 286

A

↑ frequency of TP53 mutations
BRCA1/2 mutations are rare (but if present always result in this class of tumor)
No KRAS, BRAF mutations
Mutations: TP53, amplification in PIK3CA, RB deletions
↑ frequency of genomic imbalances
Amplification of oncogenes
Deletion of tumor suppressors

Answer 287

A

low-grade tumors arising in serous borderline tumors have mutations in the KRAS, BRAF, or ERBB2 oncogenes, and usually have a wild-type tp53
high-grade tumors have a high frequency of tp53 mutations and lack mutations in either KRAS or BRAF

Answer 288

A

Larger areas of solid or papillary tumor mass, irregularity, and fixation/nodularity of the capsule are features associated with malignancy

Answer 289

A

Larger areas of solid or papillary tumor mass, irregularity, and fixation/nodularity of the capsule are features associated with malignancy

Answer 290

A

Smooth glistening cyst wall with no epithelial thickening or with small papillary projections
20% are bilateral
Cysts are lined with columnar epithelium with lots of cilia

Answer 291

A

↑ # of papillary projections
30% are bilateral
Often involve the surface of the ovary
Increased complexity of the stromal papillae, stratification of the epithelium, and mild nuclear atypia, but stromal invasion is not seen
Epithelial proliferation occurs in a ‘micropapillary carcinoma’ pattern that is a precursor to low grade serous carcinoma

Answer 292

A

Complex patterns of growth
Widespread infiltration of underlying stroma
Marked nuclear atypia, pleomorphism, and multinucleation
Increased mitotic activity with atypical mitosis
Cysts are lined with columnar epithelium
66% are bilateral
Often involve the surface of the ovary

Answer 293

A

Cells identical to high grade, but there is no invasion
“But there is also an invasive type? WTF is going on in this section?” - SD/OMM Fellow Marc Larsen-Hallock
Marked epithelial atypia in the fallopian tubes
Indicates a fallopian tube origin for high grade serous carcinomas
females are BRCA1/2
Germline mutations
Often seen at the time of prophylactic salpingo-oophorectomy
Associated with sporadic, high grade serous ovarian cancer

Answer 294

A

Propensity to spread to the peritoneal surfaces & omentum
Tumors are more likely to spread to the peritoneum if they are not encapsulated
Borderline tumors can arise or extend to the peritoneum and remain fixed or spread leading to intestinal obstruction after many years
Low grade may spread in this manner but survival is still good
High grade are often highly metastatic throughout the abdomen at presentation and are commonly associated with ascites
Extent of spread outside the ovaries determines the staging

Answer 295

A

Prognosis and treatment depend on pathologic classification as both low & high grade may extend to the peritoneum
Borderline & malignant, confined to the ovary: 100% & 70% 5 year survival
Borderline & malignant, spread to the peritoneum: 90%, 25% 5 year survival
Borderline tumors may recur and 5-year survival is not synonymous with cure

Answer 296

A

20-25% of all ovarian neoplasms
Most are benign or borderline tumors
Common in middle adult life, rare before puberty or after menopause

Answer 297

A

Most have KRAS mutation, more likely if the tumor is malignant

Answer 298

A

Rarely involve the surface of the ovary
Rarely bilateral, if bilateral, think non-ovarian origin (appendix)
Produce larger cystic masses

Answer 299

A

Multi-loculated tumors willed with sticky, gelatinous fluid rich in glycoproteins
May grow very large (up to 25kg)
Lined by tall, columnar epithelium with apical mucin, lacking cilia
Most show gastric or intestinal type differentiation

Answer 300

A

Epithelial stratification, tufting +/- papillary growth (vs. Cystadenomas)
Papillary growth looks very similar to tubular adenomas or villous adenomas of the intestine

Answer 301

A

Confluent glandular growth “expansile” invasion
95% 5 year survival for stage I, noninvasive.
90% 5 year survival for invasive malignant tumors.
Fatal if spread beyond the ovary
Distinguish from metastatic mucinous adenocarcinoma

Answer 302

A

Extensive mucinous ascites, cystic epithelium implants on peritoneal surfaces, adhesions, and frequent involvement of the ovaries
May result in intestinal obstruction and death
source most commonly extraovarian (appendiceal) as most ovarian tumors do not spread away from the ovary
bilateral presentation requires exclusion of nonovarian origin
most primary mucinous ovarian tumors are unilateral

Answer 303

A

Endometrioid carcinomas comprise 10-15% of all ovarian cancers
Benign endometrioid (adenofibromas) and borderline tumors may occur but are rare
Relatively good prognosis
May arise in the setting of endometriosis and borderline tumors
15-20% of cases with endometrioid carcinoma coexist with endometriosis

Answer 304

A

Can be associated with ovarian endometriosis or uterine endometrial carcinoma

Answer 305

A

Presence of tubular glands resembling benign or malignant endometrium

Answer 306

A

When associated with endometriosis, occurs in patients, on average, 10 years younger
Shared features with endometrial counterpart
mutations that increase PI3K/AKT signaling pathway (PTEN, PIK3CA, ARID1A, and KRAS)
Mutations of mismatch DNA repair and CTNNB1 (β-catenin)
TP53 mutations seen in poorly differentiated tumors

Answer 307

A

Solid + cystic areas of growth
Epithelium consists of tubular glands resembling endometrium
40% are bilateral, implies extension beyond the genital tract
Low grade tumors
75% 5 year survival (stage I)

Answer 308

A

Benign and borderline types are very rare and the carcinoma subtype is still uncommon.
Large epithelial cells with abundant clear cell cytoplasm – (resembles hypersecretory gestational endometrium)
Variant of endometrioid adenocarcinoma

Answer 309

A

PIK3CA, ARID1A, KRAS, PTEN, TP53 mutations

Answer 310

A

Solid: cells are arranged in sheets or tubules
Cystic: cells line the spaces

Answer 311

A

90% 5 year survival if confined to the ovaries

Poor outcome if advanced

Answer 312

A

Small, multilocular tumors with simple papillary processes
Epithelium is variable
more pronounced proliferation of the fibrous stroma under the columnar epithelium
Benign
Borderline tumors or carcinoma rarely occur and metastatic spread is extremely uncommon

Answer 313

A

Can be solid or cystic, typically unilateral
Normal stroma with nests of neoplastic epithelial cells resemble urothelium with mucinous glands in the center
Usually benign, even when large
Incidental detection

Answer 314

A

Lower abdominal pain + abdominal enlargement
GI complaints, urinary frequency, dysuria, pelvic pressure may occur
Benign tumors are easily resected and cured

Answer 315

A

Progressive weakness, weight loss, cachexia
Massive ascites (exfoliated tumor cells) if extending through the tumor capsule to seed the peritoneal cavity
Serosal surfaces seeded with small nodules that rarely invade the parenchyma
Regional lymph nodes involved; liver, lung, GI, etc. involvement
50% cross midline to opposite ovary and indicate downhill course with death in months-years
most women with ovarian carcinoma present with high stage disease
relatively poor 5- and 10-year survival rates when compared to cervical or endometrial carcinomas
CA-125 or HE4 are biomarkers that can be used to monitor disease recurrence & progression

Answer 316

A

15-20% of all ovarian tumors; majority are benign cystic (mature) teratomas (aka dermoid cysts)
Some may have malignant behavior
Similar to germ cell tumors in the male testis

Answer 317

A

Mature (benign): majority
Immature (malignant)
Monodermal/highly specialized

Answer 318

A

Most are cystic (referred to as dermoid cysts) and almost always lined with skin-like structures
Young women during active reproductive years
Discovered incidentally or associated with paraneoplastic syndromes (inflammatory limbic encephalitis)
almost all are 46,XX
majority arise from an ovum after first meiotic division
minority arise from an ovum before first meiotic division

Answer 319

A

10-15% are bilateral
Unilocular cysts with hair + sebaceous material
Tooth structures (Rokitansky tubercle) + calcification within the walls (& other germ layers: cartilage, thyroid, neural tissue, etc.)
Walls = stratified squamous epithelium
1% undergo malignant transformation (usually the skin component) → squamous cell carcinoma

Answer 320

A

struma ovarii and carcinoid tumors
Rare: strumal carcinoid, a combo of the previously mentioned tumors in the same ovary
always unilateral
May see a contralateral teratoma
Only 2% metastasize

Answer 321

A

Composed entirely of mature thyroid tissue that may by functional → hyperthyroidism
Always unilateral

Answer 322

A

Arises from intestinal tissue in teratomas and may be functional
>7cm = 5HT (5-HIAA) production  --> carcinoid syndrome
even in absence of hepatic metastases because ovarian veins are connected directly to systemic circulation
always unilateral (metastatic intestinal carcinoid is virtually always bilateral

Answer 323

A

Tumor tissue resembles embryonal and immature fetal tissue

Seen in prepubertal patients and young women (average age: 18 at presentation)

Answer 324

A

Solid, bulky tumors with a smooth external surface
May see hair, sebaceous material, cartilage, bone, calcification
+/- necrosis & hemorrhage

Answer 325

A

Grow rapidly, frequently penetrate the capsule, and spread locally or distantly
Risk of spread is proportional to amount of tissue containing immature neuroepithelium

Answer 326

A

Stage I, grade 1 = excellent prognosis
Prophylactic chemotherapy if higher grade yet confined to the ovary
Recurrences occur in first two years
absence of disease beyond two years == excellent chance of cure

Answer 327

A

50% of all malignant ovarian germ cell tumors
Ovarian counterpart of testicular seminoma (which is the most common male germ cell tumor).
2% of all ovarian cancers
Most have no endocrine function, but may produce hCG (if syncytiotrophoblasts are present)
75% in patients in 2nd-3rd decade, but may occur in childhood
May occur in patients with gonadal dysgenesis (Pseudohermaphroditism)
all dysgerminomas are malignant

Answer 328

A

OCT3, OCT4, NANOG (as seen in seminomas) which maintain pluripotency
33% have mutations of KIT (may target for therapy

Answer 329

A

Unilateral tumors that vary in size
Large vesicular cells with clear cytoplasm (like seminoma)
Well defined borders
Central nuclei
Grow in sheets or cords
Scant fibrous stroma infiltrated by mature lymphocytes +/- granulomas

Answer 330

A

all are malignant
only ∼ 1/3 are aggressive
unilateral, non-invasive, no metastasis == 96% cure rate (excellent prognosis) after salpingo-oophorectomy
responsive to chemotherapy
overall survival is >80%

Answer 331

A

Rare tumor derived from malignant germ cells differentiating along the extraembryonic yolk sac lineage
rare, but the second most common malignant tumor of germ cell origin
Produce α-fetoprotein (AFP) that can be stained for in hyaline droplets

Answer 332

A

Glomerulus-like structure with a central blood vessel enveloped by tumor cells in a space lined by tumor cells (Schiller-Duval body) – characteristic histologic feature

Answer 333

A

Seen in children or young females
Abdominal pain and rapidly growing pelvic mass (usually involving a single ovary)
80% survival with chemotherapy regardless of disease stage

Answer 334

A

Extraembryonic differentiation of malignant germ cells of placental origin
germ cell origin can only be confirmed in prepubertal females
after puberty, ovarian ectopic pregnancy cannot be excluded
Exist in combination with other tumors (pure choriocarcinoma is extremely rare)
ovarian tumors are aggressive and have usually metastasized by presentation (lungs, liver, bone)
Elaborate high levels of chorionic gonadotropins (β-hCG) which is used for diagnosis and detecting recurrence
When found in the ovary: unresponsive to chemotherapy and often fatal
In placental tissue: responsive

Answer 335

A

histologically similar to embryonal carcinoma in the testes

Answer 336

A

malignant germ cell tumor containing so-called ‘embryoid bodies’

Answer 337

A

germ cell tumors containing various combinations of dysgerminoma, teratoma, yolk sac tumor, and choriocarcinoma

Answer 338

A

Ovarian neoplasms are derived from ovarian stroma which came from the sex cords of embryonic gonad
Undifferentiated gonadal mesenchyme:
Males: Sertoli + Leydig cells (+ fibroblasts)
Females: granulosa + theca cells (+ fibroblasts)
Tumors of all these cell types may secrete estrogens or androgens and may be feminizing or masculinizing
granulosa/theca cell tumors secrete estrogen and are feminizing
Leydig and Sertoli cells secrete androgens and are masculinizing

Answer 339

A

Composed of cells that look like granulosa cells of a developing ovarian follicle
5% of all ovarian tumors and most are adult granulosa cell tumors
2/3 occur in post-menopausal females
May elaborate large amounts of estrogen (some produce androgens)
May behave like low grade malignancies

Answer 340

A

Typically unilateral and vary from microscopic foci to large, solid, and cystic encapsulated masses
If they are hormonally active, they are yellow from stored lipids
often are hormonally active and associated with endometrial hyperplasia/cancer
The small cuboidal/polygonal cells may grow in anastomosing cords, sheets, or strands
Call-Exner bodies: small, distinct, gland-like structures filled with acidophilic material
Occasionally there is a predominant thecoma component (clusters/sheets of cuboidal/polygonal cells

Answer 341

A

Precocious puberty if the tumor is functionally active in a juvenile patient
Adult females may have proliferative breast disease, endometrial hyperplasia, and endometrial carcinoma, and/or bleeding
Masculinization or Pseudohermaphroditism if androgens are produced (most only produce estrogen though)
Some tumors elaborating hormone can lead to endometrial carcinoma

Answer 342

A

↑ serum inhibin (produced by granulosa cells) that inhibits FSH
Allows diagnosis and monitoring treatment
Most of the adult type have FOXL2 mutations (important in granulosa cell development

Answer 343

A

All are potentially malignant
tumors composed predominantly of theca cells are unlikely to be malignant
Malignant tumors are usually indolent and local recurrences are treated with surgery
can recur in the pelvis or abdomen 2=10-20 years after resection of the primary tumor
Histology does not predict tumor behavior
85% 10 year survival

Answer 344

A

Tumor arising in the ovarian stroma composed of well differentiated fibroblasts with scant interspersed collagenous stroma
by definition, hormonally inactive
90% are unilateral
Solid, spherical or slightly lobulated, encapsulated masses covered with a glistening, intact ovarian serosa
benign
Mitotic activity + ↑ nuclear:cytoplasmic ratio = Fibrosarcoma and a malignant course

Answer 345

A

Tumor arising in the ovarian stroma composed of plump spindle cells with lipid droplets
Pure = rare
If the predominant cell in a tumor, may be hormonally active
benign

Answer 346

A

Fibrothecoma
Tumor arising in the ovarian stroma composed of both fibroblasts & plump spindle cells with lipid droplets
benign

Answer 347

A

Meigs Syndrome == ovarian tumor, hydrothorax, and ascites
(Fibroma, Thecoma, Fibrothecoma) == benign
Ovarian tumor present as a pelvic mass +/- pain
Ascites if the tumor > 6cm
Hydrothorax, usually only on the right side

Answer 348

A

Functional tumors that often lead to masculinization or defeminization
Some may have estrogenic effects
Cells are in various stages of development
Females of all ages, peak in 2nd-3rd decade

Answer 349

A

DICER1 mutation in > 50%

Endonuclease essential for micro-RNA processing

Answer 350

A

Unilateral tumors
Solid grey to golden brown
Grossly resemble granulosa cell tumors
Well-differentiated: Sertoli or Leydig cells interspersed with stroma
Poorly-differentiated: sarcomatous pattern with disorderly disposition of epithelial cell cords; Leydig cells may be absent
There may be heterologous elements in some tumors (mucinous glands, bone, cartilage

Answer 351

A

functional and commonly produce masculinization or defeminization
a few have estrogenic effects
Neoplasms can block normal female sexual development in children
In adults there may be atrophy of breasts amenorrhea, sterility, loss of hair
May progress to virilization with male distribution of hair (hirsutism), hypertrophy of the clitoris, voice changes
< 5% recur or metastasize

Answer 352

A

Rare, unilateral, (predominantly) testosterone producing tumors
Ovarian tumor of sex cord or stromal origin
Benign tumor with clusters of polygonal cells around hilar vessels

Answer 353

A

unilateral tumors with large, lipid laden Leydig cells
Distinct borders
Reinke crystalloids: characteristic cytoplasmic structures

Answer 354

A

Present with evidence of masculinization: hirsutism, voice changes, clitoral enlargement
Mild vs. Sertoli-Leydig cell tumors

Answer 355

A

Surgery

Almost always benign

Answer 356

A

Ovarian tumor of sex cord or stromal origin
Rare tumor that closely resembles the corpus luteum of pregnancy
Produce virilization in pregnant patients and their female infants/progeny

Answer 357

A

Uncommon ovarian tumor of sex cord or stromal origin
Resembles immature Sertoli & granulosa cells
Seen in patients with abnormal sexual development and in patients with indeterminate gonads
80% are phenotypic females
20% are phenotypic males with undescended testicles and female internal secondary organs
coexistent dysgerminoma occurs in 50% of the cases
Excellent prognosis if tumor is completely excised

Answer 358

A

Derived from tumors of mullerian origin (most common)
Uterus
Fallopian tube
Contralateral ovary
Pelvic peritoneum
Extra-mullerian: carcinoma of the breast or GI tract
Pseudomyxoma peritonei (appendiceal tumor

Answer 359

A

Metastatic GI tumor involving the ovaries – when gastric carcinoma metastasizes to the ovaries
bilateral metastases composed of mucin producing, signet ring cancer cells usually of gastric origin

Answer 360

A

Children – congenitally malformed or long fallopian tubes, or absent mesosalpinx
Pregnancy (20%) – enlarged corpus luteum, laxity in ligaments
Pregnancy induction – multiple enlarging follicles
Ovarian tumors – benign and malignant, dermoid most common

Answer 361

A

Children
Congenitally malformed or long fallopian tubes, or absent mesosalpinx
Pregnancy (20%)
Enlarged corpus luteum, laxity in ligaments
Pregnancy induction
Multiple enlarging follicles
Ovarian tumors
Benign and malignant, dermoid most common

Answer 362

A

Pregnancy loss before 20 weeks gestation, usually before 12 weeks
Occurs in 10-15% of recognized pregnancies, occurs in another 20% which are not recognized by women
70% of pregnancies terminate within 14 days of fertilization with passage of some abnormal tissue

Answer 363

A

Aneuploid, polyploid, translocation

Answer 364

A

Luteal phase defect, poorly controlled diabetes, thyroid dysfunction

Answer 365

A

Systemic disorders affecting maternal vasculature
Antiphospholipid antibody syndrome, coagulopathy, HTN
APS gives a false positive test for syphilis

Answer 366

A

Protozoa (toxoplasma), bacterial (mycoplasma, listeria), viral (CMV, HSV2, Parvovirus, Rubella)
Ascending infection is particularly common in second trimester losses
CMV: common, intranuclear inclusions

Answer 367

A

Fetal implantation outside the normal intrauterine location
Most common: fallopian tube (90%)
2% of confirmed pregnancies and for 4-10% of pregnancy related deaths

Answer 368

A

PID → chronic salpingitis
Peritubal scarring and adhesions (due to appendicitis, endometriosis, prior surgery)
use of an IUD is associated with a twofold increase of ectopic pregnancy
if you get pregnant with an IUD, it’s most likely a tubal pregnancy
Smoking

Answer 369

A

Embryonal sac implants in the lumen and is surrounded by immature chorionic villi
Chorionic villi + trophoblastic cells invade the wall
Eventually produced distention → thinning of the wall and rupture
Rupture → massive intraperitoneal hemorrhage that can be fatal, which is a medical emergency
tubal abortion == when the conceptus is extruded through the fimbriated end of the tube into the abdominal cavity

Answer 370

A

tubal pregnancy is the most common cause of hematosalpinx (blood filled fallopian tube), should always be suspected when a tubal hematoma is present
Moderate to severe abdominal pain + bleeding
6-8 weeks after the last normal menstrual period
this is when the conceptus is large enough to rupture the fallopian tube
Hemorrhagic shock and acute abdomen (sudden severe pain of less than 24hrs) if there is rupture

Answer 371

A

hCG titers (should show that you are pregnant)
Pelvic sonography (look for donut sign) -- nothing in the uterus (uh oh moment)
Endometrial biopsy: decidua without chorionic villi or implantation site
Laparoscopy to take a look

Answer 372

A

Dizygotic: fertilization of two ova
Monozygotic: division of one fertilized ovum
three types
Diamnionic dichorionic: May be fused
Diamnionic monochorionic
Monoamnionic monochorionic
Monochorionic = monozygotic (identical)
Dichorionic = nonspecific (may be mono/di zygotic

Answer 373

A

Complication of monochorionic/monozygotic/identical twin pregnancy
Vascular anastomoses connect the circulations and may include 1 or more AV shunts
Can lead to fluid overload for one & under perfusion for the other
May lead to death of one or both fetuses

Answer 374

A

a – “get a preview of the placenta”
Placenta implants in the lower uterine segment or cervix → serious 3rd trimester bleeding
Complete: covers the internal cervical os and requires c-section to avoid placental rupture and fatal maternal hemorrhage

Answer 375

A

Placenta Accreta – “abnormal attachment of the placenta”
Partial or complete absence of the decidua, thus direct attachment to myometrium
Placental villous tissue adheres directly to the myometrium = failure of placental separation at birth
Severe, life threatening postpartum bleeding can occur
Predisposed by placenta previa or history of cesarean section
Can be placenta increta or percreta too depending on the depth of invasion

Answer 376

A

Develop via
Ascending infection through the birth canal (most common, usually bacterial)
Hematogenous (transplacental) infection

Answer 377

A

Can cause premature rupture of membranes → preterm delivery
Amniotic fluid: cloudy with purulent exudate
Chorionamnion: infiltrate of neutrophils + edema & congestion of vessels
Fetal ‘vasculitis’ of umbilical and fetal chorionic plate vessels may occur
Acute villitis due to hematogenous spread is uncommon

Answer 378

A

Affect the placenta and can cause chronic villitis
Toxoplasmosis
Others (To Light Passing hovering Zambonis: TB, listeria, parvovirus, HIV, Zika)
Rubella
CMV
Herpes simplex virus
Syphilis

Answer 379

A

Develops during pregnancy
No proteinuria
Must be distinguished from preeclampsia

Answer 380

A

Systemic syndrome with widespread maternal endothelial dysfunction
Presents during pregnancy with HTN, edema, proteinuria (nephrotic range?)
Most common in the 3rd trimester & primiparas (first pregnancies)
Can lead to eclampsia

Answer 381

A

Severe manifestation of eclampsia.
Women are very ill.
Convulsions occur (seizures)
Can progress to coma

Answer 382

A

Occurs in 10% of women with severe preeclampsia
Microangiopathic hemolytic anemia
Elevated liver enzymes
Low platelets

Answer 383

A

Placenta plays a central role in pathogenesis
symptoms rapidly disappear after delivery of the placenta
Potentially due to factors released from the placenta into maternal circulation
Diffuse endothelial dysfunction
Vasoconstriction → HTN
↑ vascular permeability = proteinura + edema

Answer 384

A

Abnormal trophoblastic implantation + lack of physiologic remodeling of maternal vessels
Failure leaves the placenta ill equipped to meet the ↑ circulatory demands of late gestation
Placental ischemia may occur

Answer 385

A

Imbalance of Angiogenic/Anti-angiogenic Factors
Ischemic placenta → factors that antagonize VEGF & TGFβ released into maternal circulation
FMS-like tyrosine kinase (sFltl) antagonizes VEGF
Endoglin antagonizes TGFβ
Factors are higher in women with this condition and cause defective placental vascular development and vasoconstriction (due to TGFβ inhibition of NO)
Maternal vessels remain small caliber high resistance vessels that leads to HTN and tissue hypoperfusion

Answer 386

A

Hypercoagulable state
Likely due to ↓ PGI2 which is normally stimulated by VEGF (which these women lack)
Normally PGI2 is a potent antithrombotic factor and the deficiency leads to formation of thrombi in arterioles and capillaries especially in the Liver, kidneys, brain, and pituitary

Answer 387

A

Placental infarcts that are larger and more numerous
Exaggerated ischemic changes of chorionic villi & trophoblasts → syncytial knots
Frequent retroplacental hematomas
Abnormal decidual vessels

Answer 388

A

Liver: irregular, focal, subcapsular + intraparenchymal hemorrhages
Variable kidney lesions

Answer 389

A

Brain: foci of hemorrhage +/- thromboses

Similar changes in heart & anterior pituitary

Answer 390

A

Usually occurs > 34 weeks of gestation

Earlier in women with hydatidiform mole, pre-existing kidney disease, HTN or coagulopathy

Answer 391

A

Risk factors
age> 40
African American
renal disease
HTN
DM
clotting disorders
first pregnancy
family history

Answer 392

A

Insidious onset of HTN, edema, and proteinuria in several days
headache + visual disturbances indicate severe manifestations that may require delivery
eclampsia == seizures –> coma

Answer 393

A

Mild: close monitoring of mom + baby. Delivery is indicated with end organ damage, eclampsia, fetal compromise or HELLP syndrome regardless of age
Term: Delivery (regardless of severity)
HTN is not amenable to antihypertensive therapy
HTN & proteinuria disappear 12 weeks after delivery (unless they were present prior to pregnancy

Answer 394

A

20% of patients develop HTN and microalbuminuria within 7 years of a pregnancy complicated by this disease
2x ↑ risk of vascular disease of the heart and brain

Answer 395

A

Cystic swelling of the chorionic villi and trophoblastic proliferation
Diagnosed at ~ 9 weeks via sonogram
increased risk of persistent trophoblastic disease (invasive mole) or choriocarcinoma

Answer 396

A

Bimodal distribution: teenagers or females > 40

2X more likely in Southeast Asia

Answer 397

A

Fertilization of an egg that has lost its females chromosomes and genetic material is completely paternal
90% are 46,XX: One sperm duplicates its genetic material (androgenesis)
10% are 46,XX or 46,XY: Empty egg is fertilized by two sperm
Embryo dies early and is not identified
NO fetal tissue – complete absence of fetal tissue
2.5% risk of choriocarcinoma
15% risk of persistent or invasive mole

Answer 398

A

due to fertilization of an egg by two sperm – polyspermy
69,XXY (usually triploid); 92,XXXY (can be tetraploid)
Fetal tissue IS present
↑ risk of persistent molar disease
Not associated with choriocarcinoma
Only some villi are enlarged and edematous
Trophoblastic hyperplasia is focal and less marked

Answer 399

A

Delicate, friable mass of thin walled, translucent, cystic, grapelike structures with swollen, edematous (hydropic) villi

Answer 400

A

All/most chorionic villi are enlarged
Scalloped in shape with central cavitation (cisterns)
Covered by extensive trophoblastic proliferation of the entire/complete villi circumference

Answer 401

A

Only a fraction/partial of the villi are enlarged and edematous
Trophoblastic hyperplasia is focal and less marked than in complete moles

Answer 402

A

Partial or early complete
Spontaneous miscarriage or curettage due to abnormal villous findings on ultrasound (will see snowstorm pattern on ultrasound

Answer 403

A

HCG rate of rise is markedly increased and rises more than in normal single or multiple pregnancies
Removed via curettage
patients are monitored for 6-12m to ensure HCG levels return to normal
persistent/invasive moles = when HCG levels remain high; happens in 15% of molar pregnancies

Answer 404

A

Mole that penetrates or perforates the uterine wall (i.e. it invades)
there is invasion of the myometrium by hydropic chorionic villi, accompanied by proliferation of both cytotrophoblasts and syncytiotrophoblasts (produce β-hCG

Answer 405

A

Hydropic chorionic villi penetrate the myometrium
May embolize to lungs or brain but do not grow at these sites (will regress without chemotherapy)
Cytotrophoblasts & syncytiotrophoblasts proliferate
Tumor is locally destructive
Invasion of parametrial tissue or blood vessels

Answer 406

A

Presents as vaginal bleeding + irregular uterine enlargement

Persistently ↑ HCG

Answer 407

A

responds well to chemotherapy

may result in uterine rupture requiring hysterectomy

Answer 408

A

Uncommon malignant neoplasm of trophoblastic cells derived from a previously normal or abnormal pregnancy (e.g. extrauterine ectopic pregnancy)
Rapidly invasive, metastasizes widely == very aggressive
Responds well to chemotherapy

Answer 409

A

Complete hydatidiform mole (50%)
Previous abortion (25%)
Normal pregnancy (22%)
Ectopic pregnancy (3%)
Germ cells of the ovaries or mediastinum (rare

Answer 410

A

Soft, fleshy, yellow-white tumor
Large, pale areas of necrosis + extensive hemorrhage
Invades underlying myometrium, often penetrating blood vessels
Abundant (possibly abnormal) mitoses
May extend to uterine serosa and adjacent structures
Does not produce chorionic villi, comprised only of proliferating syncytiotrophoblasts and cytotrophoblasts

Answer 411

A

Irregular vaginal spotting of a bloody, brown fluid
May occur months after pregnancy, abortion, etc
Larger than expected uterus
high propensity for hematogenous spread (widespread):
Lungs (50%)
vagina (30-40%)
brain
liver
bones
kidney
↑ HCG, but may be low in some tumors (especially if tumor is necrotic

Answer 412

A

Evacuation of uterine contents + chemotherapy
chemotherapy results in nearly 100% remission and a high rate of cures
Cured patients can have normal subsequent pregnancies and deliveries
Non-gestational tumors that arise outside the uterus are more resistant to therapy

Answer 413

A

Neoplastic proliferation of extra-villous trophoblasts (intermediate trophoblasts)
Normal to be found in non-villous sites like the placental parenchyma and placental membranes
Polygonal mononuclear cells with abundant cytoplasm
Produce increased human placental lactogen (hPL)
Malignant trophoblastic cells diffusely infiltrating the endomyometrium
Presentation: uterine mass and abnormal uterine bleeding/amenorrhea, moderately ↑ HCG
May follow normal pregnancy (50%), spontaneous abortion, or hydatidiform mole
Localized disease = excellent prognosis
Disseminated disease = 10-15% mortality

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Female Genital Tract Flashcards

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