Female GU Path - Genital Tract, Vulva, Vagina, Cervix, Body of Uterus/Endometrium, and Fallopian Tubes Flashcards
In the micro cards, we delve into details about the etiology and consequences of HPV, but we do not delve into the pathology as related to the GU system for females.
Where does HPV hit the female GU system, and what can it potentially lead to?
Infects the lower GU ract, especially the cervix transformational zone. It is usually eradicated by acute inflammation and the immune system.
It can lead to LSIL and HSIL (low/high grade squamos intraepithelial lesions = abnormal cells on pap smear)
Low vs high risk HPV subtypes and what they lead to
Low risk = 6 and 11 = condylomas
High risk = 16, 18, 31, 33 = dysplasia and carcinoma
How does the high risk HPV work?
High risk HPV produce E6 and E7 proteins which destroy tumor suppressor proteins (p53 and Rb, “6 before 7, p before rb”) leading to dysplasia
How do we stain/test for HPV?
- DNA sequencing
- ki67 and p16 staining
Discus the histology of an HPV infected cell
koilocytic change (raisin nuclei) with disordered cellular maturation and mitotic activity
As we discuss in the micro cards, HSV (not HPV) is a bigger virus. What do we see on gross inspection and on histology?
Gross - desquamated epthelium with marked inflammation in the ulcer bed.
Histo - Multinucleated squamos cells containing eosinophilic to basophilic viral inclusions with a “ground glass” appearence.
Squamos cells with 3 M’s: multinucleation, nuclear molding and margination of the chromatin.
Strawberry cervix is caused by:
Trichomonas vaginalis
If my patient presents with fishy green discharge, what does she have?
Bacterial vaginosis - Gardnerella (think a green garden) vaginalis - gram positive bacillus.
What exactly causes pelvic inflammatory disease and how does it present?
PID is an infection that begins in the vulva/vagina and spreads to involve most genital system
sx: pelvic pain, adnexal tenderness, fever, and vaginal discharge.
cause: Neisseria gonorrhoeae
We have all felt the Bartholin glands during the ICS session. What causes one of these to go cystic and who is at risk for it? What do we need to be careful of?
sx: Enlarged unilateral lesion in lower vestibule adjacent to the vaginal canal
cause: STD/STI or infection=inflammation & obstruction of ducts causing back-up
risk: women of reproductive age
can lead to: abscess
Compare lichen sclerosus to lichen simplex chronicus (also called squamos cell hyperplsia)
These are both benign non-neoplstic epithelial disorders.
Lichen sclerosus is a thinning epidermis that becomes fibrotic with disappearence of rete pegs (the epidermal extensions that dip down into the dermis at the ED junction). LSC (hyperplasia) is the opposite, we see hyperplasia of vulvar squamos epithelium.
Due to their different results, they appear different as well, with the thinning slcerosus looking like a leukoplakia thin like parchment and the hyperplasia lookling like thick leathery white vulvar skin.
Sclerosing is something that happens with age (skin gets thinner) so we see it more often in post menopausal women, putting them at a higher risk for squamos cell carcinoma (SCC). Thickening with hyperplasia, as per usual, happens due to constant irritation, and thus has no increased risk of development for SCC.
What is the fancy name for genital warts, what causes them, and how do they present?
Condyloma Acuminatum
STD that causes red/pink warty growths on anogenital skin due to HPV 6/11
What does a genital wart look like under histology?
Histology:
- branching/villous, papillary CT stroma covered by epithelium
- hyperkeratosis & acanthosis (thickening)
- koilocytosis (Cytoplasmic vacuolization of squamous cells = wrinkly raisin nucleus)
- squamous cells with enlarged, hyperchromatic nuclei with perinuclear halo
- condensed peripheral rim of plasma membrane
What is VIN and how does it present?
VIN = Vulvar intraepithelial Neoplasia
This is dysplasia in vulvar squamos epithelial lining.
Sx are a huge range, appearing very similar to condyloma acum. We see a Bowenoid papule (pigmented keratinized lesion, similar to the raised white warty papules of cond.), possibly a leukoplakia, and in general squamos hyperplasia.
DANGER - Distinguish from condyloma, because this guy is queued up to cause invasive SCC
Discuss the usual type of VIN vs the differentiated type
Normal type is a warty, basaloid mixed type that is multifocal, presenting with pruitis, pain and/or bumpy skin lesion. Unlike the differentiated type, this one is caused by high risk HPV (16, 18, 31). Oddly though, between the two, this one puts the patient at a lower risk for invasive SCC, so to treat it we can do a small excision without fear of missing material. We see this type in premenopausal women or those being immunosuppressed.
The differentiated type os unifocal mass in postmenopausal women not associated with HPV. Chronic dermatological issues, vichen sclerosis or erythroplasia of Queyrat (red nonkeratinized epithelium in the vestibule) lead to this. This guy has an increased chance of developing to SCC so to treat it we do a wide excision.
Vulvar carcinoma is a malignant neoplasm of vulvar squamous epithelium lining. What causes it and how does it present?
This is a relatively rare cancer that presents as a leukoplakia.
Two general patterns of cause:
40-50yo: HPV (high risk 16,18, 31, 33) –> VIN in about 10-15 years→ VC.
70+yo: long standing lichen sclerosus= inflamm→ VC
Discuss papillary hidradenoma of the breast as far as what it is and what it looks like under histology, which is really the extent of what you need to know.
This mimics intraductal papillomas of breast
histo: papillary projections w/ top columnar secretory cells & underlying flattened myoepithelial cells
What is the deal with this extramammary paget disease? How does it present?
Malignant epithelial cells in vulvar epidermis
sx: red, pruitic ulcerated skin
carcinoma in situ (Usually no underlying carcinoma)
When diagnosing EPD, how do we do it, and what must we do?
dx: Must distinguish from melanoma:
carcinoma (Paget cells) = S100(-), PAS(+) keratin(+), (mucus secreting epithelial cells)
Melanoma = S100(+) (classic sign), PAS(-), Keratin(-), (no mucus secreting epithelial)
Discuss the developmental pathology behind adenosis. Who is at risk?
persistence of columnar epithelium in the upper 1/3 of the vagina
patho: Lower ⅓ of canal is stratified squamous, upper ⅔ columnar. Over time, squamous should move up and replace columnar. Persistence of columnar = adenosis.
risk: Females exposed to DES (estrogen drug) while in utero
What is clear cell adenocarcinoma of the vagina and what causes it?
Malignant proliferation of glands w/clear cytoplasm in cells
super rare, like if this is your diagnosis, have lupus on the differential too.
cause: DES (bad rx)–> Adenosis→ columnar/glandular cells–>Clear cell.
Compare VAIN to VIN
Very similar, although Vaginal (VAIN) is less common than VIN or CIN (cervical).
We see squamos cell dysplasia/atypia without invasion.
Wait VIN can lead to SCC, does that mean VAIN…
YUP
We see carcinoma of squamous epithelium lining the vaginal mucosa
cause: high-risk HPV→ (VAIN)–>SCC
Discuss VAIN metastasis if it develops into SCC
metastasis: lower 1/3 of vagina–>inguinal nodes;
upper 2/3 –> regional iliac nodes
What the fuck is embryonal rhabdo?
Baby is making way too many gains!
sx: Bleeding with grape-like mass protruding from vagina or penis of child
What causes cervicitis?
Gonococci, chalmydiae, mycoplasms & HSV
How bad are those endocervical polyps, Chelsea?
Benign exophyic growths
2-5% of adult women
May produce irregular spotting
Cured by simple curettage or surgical excision
We talked about VAIN and VIn and brought up CIN, the cervical form. What is different about it?
As with the others we see:
- Squamous cell dysplasia/atypia without invasion
- Low-risk subtypes HPV 6 & 11= LSIL and condyloma acuminata.
- Spontaneous regression
- histo: koilocytic (raisin nuclei), disordered cellular maturation, nuclear atypia, & mitotic activity
Not really anything different. On colonoscopy, we see flat, acetowhite area.
Discuss the grading progressiong of CIN
CIN progresses: CIN I–>CIN II–>CIN III–>CIS–> invasive SCC
CIN III no longer reversible
How does cervical carcinoma present and who is at risk?
clinical: 40- 50yo w/vaginal bleeding, esp post-coital, cervical discharge
cause: High-risk subtypes HPV 16 and 18= HSIL and invasive SCC of the cervix
risk: smoking immunodeficiency (AIDS), multiple partners, CIN
location most susceptible: “transformation zone”/ squamocolumnar junction / squamous ectocervix+ glandular endocervix
How do we diagnose cervical carcinoma? What is the histology of it?
dx: colposcopy= punctation, mosaicism, or abnormal vasculature
histo: squamous dysplasia and mitotic figures present in the bottom 2/3 of the squamous epithelium or full-thickness squamous dysplasia
Discuss the invasion potential and pathology of invasive cervical cancer. What late stage issues are we worried about?
80% SCC and 15% adenocarcinomas.
We see irregular borders, lesions invaded through the basement membrane into deeper wall
can lead to: Invade through anterior uterine wall into bladder blocking ureters causing hydronephrosis and renal failure.
Tend to stay in local area not metastasize
What causes asherman syndrome and what does it lead to?
Secondary amenorrhea due to loss of basalis (stem cell layer) and scarring= no regeneration
cause: overaggressive dilation & curettage (D&C)
We’ve learned that anovulatory cycle, as the name suggests, is menstruation with a lack of ovulation. How does this present and what is the pathogenesis behind it?
patho: estrogen driven normal proliferative phase + NO progesterone driven secretory phase→ Proliferative glands break down & shed→ uterine bleeding
Sx: Uterine bleeding during menarche and menopause
What causes an inadequate luteal phase and how does it present?
inadequate corpus luteum = dec progesterone= early menses
sx: Infertility w/ bleeding or amenorrhea
What typically causes acute endometritis and how does it present?
Bacterial infection of the endometrium
cause: retained products of conception (2* delivery or miscarriage)
Sx: Fever, abnormal uterine bleeding, pelvic pain
What cells do we see with chronic endometritis but not acute? What symptoms do we see and what is the cause of this over acute?
Chronic inflammation with lymphocytes/plasma cell
Cause: retained products of conception, chronic PID, IUD, TB (granulomas with plasma cells)
Sx: abnormal uterine bleed, pelvic pain, infertility
What is endometriosis and what causes it?
ectopic endometrial glands/stroma outside of the uterine endometrial lining
patho: Metastatic theory - retrograde menstruation w/implantation at an ectopic site
active inflammatory cascade
Sx of endometriosis
sx:
- dysmenorrhea (painful menstruation)
- dyspareunia (painful sexual intercourse)
- infertility
- Uterine ligaments (pelvic pain)
- Pouch of Douglas (pain with defecation)
- Bladder wall (pain with urination)
- Bowel serosa (abd. pain with adhesions)
- Fallopian tube mucosa (scarring)
- soft fatty tissue (gunpowder lesions)
complications: mass effect, adhesions, torsion/rupture of an ovarian cyst and development of endometrioid carcinoma from the endometriotic tissue (particularly in the ovary)
Discuss the histology of endometriosis and the requirements for positive diagnosis
histo: flat, raised or cystic, red/brown/blue, clotted blood-containing cysts (ovarian chocolate cysts)
must have (2/3):
- endometrial glands
- endometrial stroma
- hemosiderin
inc risk of carcinoma at site of endometriosis, esp in the ovary.
What causes endometrial polyps? How does it present?
Protrusion of endometrium due to hyperplasia.
Sx: Abnormal uterine bleeding
mutation: 6p21 rearrangement of HMGIY gene
Causes: Tamoxifen (pro-estrogen effects on the uterus, anti-estrogen for breast tissue)
What causes endometrial hyperplasia? Who is at risk, and with that, how does this usually present?
Gland hyperplasia overwhelms
cause: unopposed estrogen (not followed by progesterone) 2* to obesity, PCOS,& estrogen tx
risk: postmenopausal women who no longer go through their progesterone phase
Sx- Postmenopausal uterine bleeding
What gnetics and histology should you automatically link to enddometrial hyperplasia?
mutation: inactivation (phosphorylated AKT) of PTEN tumor suppressor gene (chr 10q23.3) = loss of apoptosis= proliferation
Histo- could have cellular atypia (most important predictor for carcinoma)
What is the most common invasive cancer of the female genital tract and how does it present clinically?
Carcinoma of the endometrium
Malignant proliferation of endometrial glands
clinical: 55-65 yo postmenopausal patient with vaginal bleeding , or 40-50yo with menometrorrhagia (prolonged or excessive uterine bleeding occurs irregularly and more frequently than normal. It is thus a combination of metrorrhagia and menorrhagia)
There are two types of endometrial cancer. What is the most common and who is at risk for it?
Type I Endometrioid carcinoma (80% of them)
- Age 50s
Gross: endometrial hyperplasia, indolent tumors
Risk factors: estrogen exposure - early menarche/late menopause, nulliparity, infertility w/anovulatory cycles, & obesity.
Compare the histology of Type I vs. Type II endometrial cancers
Type I - histo: well-differentiated tumors (FIGO Grade I) endometrioid (resembling proliferative endometrial glands, without intervening stroma)
late metastasis
Type II - histo: papillary pattern= Psammoma bodies
What are fibroids and what causes them?
Benign neoplastic proliferation of smooth muscle (myometrium)
most common pelvic tumor in women
patho: hormonally- responsive to estrogens= arise during a reproductive period and undergo changes in size throughout the menstrual cycle/pregnancy
How does leiomyoma present clinically, histologically, grossly, and spiritually
sx: asymptomatic, heavy or prolonged menstrual bleeding, pelvic pain or pressure complications: mass effect= urinary frequency or constipation, infertility, fetal malpresentation, or uterine inertia during parturition
gross: well-circumscribed, firm, white/tan, round/oval, bulge into uterus, whorled-appearance on cut surface
histo: interlacing fascicles of smooth muscle bundles
Spiritually: You are almost done, good spirits
What is a leiomyosarcoma and who is at risk for it? What does it look like on histo?
Malignant proliferation of smooth muscle (myometrium)
risk: postmenopausal women
histo: a single lesion w/areas of necrosis & hemorrhage; cells with nuclear pleomorphism, atypia and abundant mitotic figures
What is chronic salpingitis and what are we worried about?
occluded tubes and fibrous adhesions
can lead to: ectopic pregnancy, Scarring and fusion of the plicae, infertility
Discuss serous carcinoma of the endometrium, the second type.
Type II is serous. 20% of the time it is this, and it presents with endometrial atrophy in older women >70 y.o.
This form is p53 driven, and results in a poorly-differentiated, large bulky/invasive tumors, papillary architecture, cytologic atypia
This type, when compared to the Type I endometrioid form, is more aggressive, much poorer prognosis ( “seed” the peritoneum)
