Vagina and Cervical Cancer B&B

Question 1

how does vaginal carcinoma present?

Answer 1

very rare, almost always involves HPV, most commonly an extension of cervical carcinoma

usually squamous cell carcinoma

note that lymphatic drainage is different between upper/lower vagina, affecting metastasis - upper vagina (from müllerian duct) lymph drains to iliac nodes, lower vagina (from urogenital sinus) lymph drains to inguinal nodes

Question 2

where would you be checking for metastasis to lymph nodes if a patient had an upper versus lower vaginal carcinoma?

Answer 2

lymphatic drainage is different between upper/lower vagina, affecting metastasis

upper vagina (from müllerian duct) lymph drains to iliac nodes

lower vagina (from urogenital sinus) lymph drains to inguinal nodes

Question 3

clear cell carcinoma of the cervix or vagina is associated with exposure to what?

Answer 3

rare malignancy associated with maternal use of diethylstilbestrol (DES), a non-steroidal estrogen that was previously used to prevent miscarriage or premature birth (since removed from market)

female babies had a high risk of reproductive tract abnormalities, including vaginal clear cell carcinoma

Question 4

what causes vaginal adenosis?

Answer 4

recall upper vagina is derived from müllerian duct (columnar epithelia), while lower vagina is derived from urogenital sinus (squamous epithelia)

in normal development, the squamous epithelia takes over, but if some columnar epithelium (mullerian tissue) is left over in the outer cervix/vagina, adenoma forms

associated with in utero exposure to diethylstilbestrol (DES), a non-steroidal estrogen that was previously used to prevent miscarriage or premature birth

Question 5

what causes sarcoma botryoides?

Answer 5

aka embryonal rhabdomyosarcoma: rare vaginal tumor of young children (<5yo) derived from embryonic rhabdomyoblasts (immature muscle cells - positive for desmin)

presents with bunches of grapes looking mass, may invade peritoneum (obstruct bladder)

[can also develop in boys as paratesticular tumors]

Question 6

how does sarcoma botryroids present?

Answer 6

aka embryonal rhabdomyosarcoma: rare vaginal tumor of young children (<5yo) derived from embryonic rhabdomyoblasts (immature muscle cells - positive for desmin)

presents with bunches of grapes looking mass, may invade peritoneum (obstruct bladder)

[can also develop in boys as paratesticular tumors]

Question 7

A mother brings her 2 year old daughter to the pediatrician with concern of a mass growing from the child’s vagina that resembles a bunch of grapes. What is the diagnosis? From what tissue is this derived?

Answer 7

sarcoma botryoides: aka embryonal rhabdomyosarcoma, rare vaginal tumor of young children (<5yo) derived from embryonic rhabdomyoblasts (immature muscle cells - positive for desmin)

[can also develop in boys as paratesticular tumors]

Question 8

what muscle filament is used as a marker of rhabdomyoscaroma (tumor of immature muscle cells)?

Answer 8

desmin: muscle filament found in Z-disks in sarcomeres

Question 9

where do most cervical neoplasias arise?

Answer 9

transformation zone: squamocolumnar junction where the columnar epithelium of the endocervix meets the squamous epithelium of the ectocervix

Question 10

what are the risk factors associated with cervical cancer?

Answer 10

Human papillomavirus infection (HPV)

Immunodeficiency, sexual intercourse at a young age, multiple sexual partners (these all increase risk of HPV infection)

Cigarette smoking – affects secretions in endocervical glands

Question 11

what type of virus is human papillomavirus (HPV)? which subtypes are considered high risk for cancer?

Answer 11

non-enveloped, dsDNA (circular)

most common STI, clinical disease depends on subtype (cutaneous warts, genital warts, cervical cancer)

types 16 and 18 are highest risk for cancer

Question 12

What two oncogenes does human papillomavirus (HPV) contain that allow it to cause cancer? what are their respective functions?

Answer 12

E6 gene: inhibits p53 (which activates p21 to arrest cell cycle)

E7 gene: inhibits Rb tumor suppressor (which inactivates E2F transcription factor)

Question 13

how does cervical carcinoma typically present?

Answer 13

most commonly squamous cell carcinoma in a women with HPV infection who did not get screened (progresses slowly)

usually asymptomatic, may present as vaginal bleeding (irregular/heavy menses, post-coital)

Question 14

what type of prevention is pap smear and what is it used to detect? (specifically)

Answer 14

secondary prevention for cervical neoplasia, best at detecting squamous cell carcinoma

used to detect Koilocytes (large, darkened nuclei)

Question 15

what type of gynecological neoplasm is most common in young women?

Answer 15

cervical

youngest to oldest AND also best to worst prognosis:
1. cervical - youngest, best prognosis
2. endometrial (most common overall)
3. ovarian - oldest, worst prognosis

Question 16

what are the 2 low-risk and 2 high-risk serotypes of HPV for cervical cancer?

Answer 16

low risk: HPV6 and HPV11 - cause 90% of genital warts

high risk: HPV16 and HPV18 - cause cervical, oral, penile, vulvar, and anal cancers

Question 17

cervical intraepithelial neoplasia (CIN)

Answer 17

precancerous epithelial change associated with productive HPV infection (low grade, CIN I) or premalignant for invasive cervical cancer (high grade, CIN II/III)

Question 18

condyloma acuminatum

Answer 18

aka genital warts, caused by HPV

Question 19

what forms of vulvitis do the following pathogens cause?
a. HPV
b. HSV1/2
c. N. gonorrhoeae
d. Treponema pallidum

Answer 19

all cause sexually transmitted infections

a. HPV —> condyloma acuminatum (genital warts)
b. HSV1/2 —> genital herpes
c. N. gonorrhoeae —> suppurative infection of the vulvovaginal glands
d. Treponema pallidum —> primary chancre at site of inoculation

Question 20

an important complication of vulvitis is obstruction of the ______ glands

Answer 20

excretory ducts of Bartholin glands: deep to the posterior aspect of the labia majora, secrete lubricating fluid

blockage can cause Bartholin cyst (sterile) or Bartholin abscess (infected with E. coli or N. gonorrhoeae)

Question 21

Lichen Sclerosus

Answer 21

thinning of the vaginal epidermis, disappearance of rete pegs (epithelial extensions in mucus membranes/ skin)

zone of acellular dermal fibrosis forms with band-like mononuclear inflammatory cell infiltrate - appears as smooth, white plaques (leukoplakia)

affects post-menopausal women, benign but 1-5% develop HPV-negative squamous cell carcinoma of the vulva

Question 22

thinning of the vaginal epithelium + formation of acellular dermal fibrosis with band-like mononuclear cell infiltration

Answer 22

Lichen Sclerosus: appears as smooth, white plaques (leukoplakia)

affects post-menopausal women, benign but 1-5% develop HPV-negative squamous cell carcinoma of the vulva

Question 23

which patients most often present with Lichen Sclerosus and what are they at risk of developing?

Answer 23

affects post-menopausal women, benign but 1-5% develop HPV-negative squamous cell carcinoma of the vulva

[formation of zone of acellular dermal fibrosis with band-like mononuclear inflammatory cell infiltrate - appears as smooth, white plaques (leukoplakia)]

Question 24

what is the cause of Lichen Simplex Chronicus?

Answer 24

vaginal epithelial thickening and hyperkeratosis due to chronic inflammation caused by pruritic infection

appears as an area of leukoplakia (smooth, white plaques)

Question 25

vaginal epithelial thickening and hyperkeratosis due to *chronic inflammation* caused by pruritic infection

Answer 25

*Lichen Simplex Chronicus* - appears as an area of *leukoplakia* (smooth, white plaques)

Question 26

what are the main differences between Linchen sclerosis and Linchen simplex chronicus? what are the similarities?

Answer 26

Linchen sclerosis: vaginal epithelial thinning + acellular dermal fibrosis and band-like mononuclear infiltrate, risk of developing HPV-negative squamous cell carcinoma of the vulva Linchen simplex chronicus: vaginal epithelial thickening/ hyperkeratosis due to chronic irritation caused by pruritic infection, no predisposition to cancer both appear as *leukoplakia* (smooth, white plaques), and both lesions must be biopsied to exclude squamous cell carcinoma

Question 27

Pt is a 73yo F (post-menopause) presenting with vaginal irritation consistent with vulvitis. Upon PE, leukoplakia is noted and biopsied to exclude squamous cell carcinoma. Histology reveals thinning of the vaginal epidermis and lack of rete pegs. There is a large zone of acellular dermal fibrosis and band-like mononuclear cell infiltrate. What is the diagnosis?

Answer 27

*Linchen sclerosus* - affects post-menopausal women, benign but 1-5% develop HPV-negative squamous cell carcinoma of the vulva rete pegs = epithelial extensions in mucus membranes/ skin leukoplakia = smooth, white plaques

Question 28

condylomata lata vs condylomata acuminata

Answer 28

condyloma = genital wart condyloma lata: flat lesions, occur in secondary syphilis (not common anymore) condyloma acuminata: papillary/ elevated lesions, often multiple, red-pink/pink-brown

Question 29

koilocytosis

Answer 29

cytopathic change characterized by perinuclear cytoplasmic vacuolization and a wrinkled nuclear contour characteristic feature of condylomas (genital warts), *hallmark of HPV infection* (HPV 6 or 11)

Question 30

contrast the 2 forms/presentations of vulvar squamous cell carcinoma

Answer 30

1. related to *high-risk HPV strains* (16, 18), preceded by vulvar intraepithelial neoplasia (VIN), less common and occurs in middle-aged women (esp. smokers) 2. HPV-negative, well-differentiated keratinizing squamous cell carcinoma, occurs in older women (may follow lichen sclerosis)

Question 31

how does extramammary Paget disease present?

Answer 31

*intraepithelial adenocarcinoma* of the vulva in patients 60s-70s *pruritus* is most common symptom, lesions appears *eczematoid* histology shows *large pale/clear cells* along sweat gland lines and presence of mucin

Question 32

Pt is a 76yo F presenting with vulvar pruritus and a multiple eczematous vulvar lesions. A biopsy is taken which reveals clusters of large pale/clear cells along sweat gland lines and the presence of mucin. What is the most likely diagnosis?

Answer 32

extra-mammary Paget disease: intraepithelial adenocarcinoma

Question 33

contrast the presentation of vaginitis caused by *Candida albicans* vs *Trichomonas vaginalis*

Answer 33

Candida albicans (normal flora): curdy white discharge Trichomonas vaginalis (STI): copious watery, gray-green discharge

Question 34

patient with vaginitis presents with copious watery, grey-green discharge - what is the most likely responsible pathogen?

Answer 34

*Trichomonas vaginalis* - sexually transmitted, parasites can be identified by microscopy

Question 35

what condition precedes nearly every primary vaginal squamous cell carcinoma?

Answer 35

vaginal SCC is very rare, usually originates in the cervix primary vaginal SCC is associated with *HPV infection* that causes *vaginal intraepithelial neoplasia (VIN)*

Question 36

maternal use of *diethylstilbestrol* is associated with development of which rare vaginal cancer?

Answer 36

causes *vaginal adenosis* (benign, red/granular lesions) which is a precursor to *clear cell adenocarcinoma*