1 Vulvar and Ovarian Disease Flashcards
Autoantibodies attack extracellular matrix and basement membrane —> immune dysfunction affecting all levels of the skin
Lichen Sclerosus
What are some environmental factors that can affect/exacerbate lichen sclerosus?
Incontinence
Infection
Contact dermatitis
Trauma (Kobner’s phenomenon)
What population is most likely to experience lichen sclerosus?
Postmenopausal women
Most common symptom for women with lichen sclerosus
Pruritis
Common for them to describe sleeping with ice packs to numb the vulva
Clinical presentation of lichen sclerosus
Typically postmenopausal women
Pruritis**
Dysuria
Dyspareunia
Physical exam findings for lichen sclerosus
Sharply, well-demarcated white plaques - “cellophane paper”, waxy, and/or hyperkeratotic in appearance
Fragility is hallmark - purpura, erosions, fissures
Usually begins periclitorally —> spread to perineal skin
Not usually seen in keratinized, hair-bearing labia majors or mucus membranes
“Cellophane paper” plaques
Lichen sclerosus
Sparing of keratinized, hair-bearing labia Majorca
Lichen sclerosus
_________ occurs in 5% of women with untreated lichen sclerosus
Squamous cell carcinoma
Risk factors = elderly, hyperkeratotic lesions
Patients with lichen sclerosus have a higher incidence of associated _______
Hypothyroidism
What lab do you need to diagnose lichen sclerosus?
Vulvar punch biopsy
Treatment for lichen sclerosus
Topical ultra potent steroid OINTMENT*** (b/c has to penetrate keratinized skin)
First line = Temovate 0.05% BID until texture is normal, then 1-3x/week for maintenance
Side fx = atrophy, dermatitis, rosacea (signs you’re using it too often)
Alternative = topical estrogen
What patient ed do you need to give for lichen sclerosus?
Does not go away - needs long term follow up
Encourage self exams and vulvar awareness
Side effects of topical steroid (atrophy, dermatitis, rosacea) indicate you’re using the steroid too much
Bilateral glands found at teh 4 and 8 o’clock positions within the labia minora
Bartholin glands
Open into teh vestibule adjacent to the vaginal Introitus —> secrete mucus-like material to maintain moisture of the vaginal mucosa
Bartholin cysts form as a result of _______ due to ________
Duct all obstruction
Trauma or non-specific inflammation
Bartholin abscess formation results from ….
An infected cyst or primary gland infection (polymicrobial, STI)
Clinical presentation of bartholin cysts
Abrupt onset of acute, painful unilateral labial swelling
Dyspareunia
Pain with sitting or walking
Physical exam findings for bartholin cyst/abscess
Tender, fluctuating labial mass
Surrounding erythema and edema
Cellulitis
Abscess formation
Fever
Treatment for bartholin cyst
Incision and drainage with insertion of Word catheter to prevent re-accumulation of pus)
Culture purulent material
+/- empirical abx (Keflex or Doxy)
Site baths 2-3 days after I&D
No intercourse until catheter removed
What causes vulvodynia?
We have no idea!
Maybe estrogen concentration (affecting pain sensitivity)?
Maybe pelvic flood dysfunction?
Maybe psychological factors?
Maybe neurologic sensitization (secondary to chronic inflammation)?
Clinical presentation of vulvodynia
Vulvar discomfort (“burning sensation”, stinging, irritated, sore, raw, stabbing)
Absent clinical findings and no underlying vulvar/vaginal pathology
Introital pain with intercourse
How to evaluate vulvodynia
Use a Q-tip to palpate vestibule, labia majora, perineum, interglacial folds
Pain is usually limited to vestibule
Single digit exam to feel for spasm or tenderness of the pelvic floor muscles
What is the of treatment for vulvodynia?
They’ll never get back to 100% but you want to get them back to functionality
Avoid scented products, tight clothing, vigorous exercise, pantyliners/pads
Sitz baths BID followed by thin film of petroleum jelly
Couples counseling
Pelvic floor therapy
Pharmacologic treatment for vulvodynia
Topical vaginal estrogen 0.03% w/ testosterone 0.1% (QD)
Nortriptyline 50 mg QHS (begin with 10mg and titrate up)
Gabapentin 1200 mg TID (begin with 100mg and titrate up)
Local nerve block (but it wears out)
Neoplasticism cells confined to squamous epithelium
Vulvar Intraepithelial Neoplasia (VIN)
What are the classifications of VIN
VIN 1, 2, or 3 (just like CIN)
But really, you could eliminated VIN 1 and combine 2/3 as the true precursors to vulvar cancer
VIN 2/3 are further differentiated into VIN-U and VIN-D
VIN 2/3 are subdivided into _____ and ______ based on _____.
VIN-U (usual type)
VIN-D (differentiated)
Based on morphologic manifestations, HPV content, and clinical characteristics
Which type of VIN:
Associated with HPV type 16 and 18
VIN-U
Which type of VIN:
Seen in younger women
VIN-U
Risk factors for VIN-U
Same as for CIN
Smoking (50-80%)
Immunosuppression
Multiple sex partners
How is VIN-U diagnosed?
Vulvar colposcopy
3-5% acetic acid applied, wait 3-5 min, maybe reapply
Avoid using acetic acid in areas of inflammation and breaks in epithelium
Colposcopy findings consistent with VIN-U
Lesions are raised or flat
Range in color from gray to white or red to black
Must biopsy all pigmented (or hypopigmented) lesions**
How do patients with VIN-U typically present?
Most are ASYMPTOMATIC
Vulvar burning and pruritis in 50%
Why are colposcopies mandatory for VIN-U?
Associated with high grade CIN
What is the cure for VIN-U?
THERE IS NONE!
Frequent failure to include all lesions when surgically treating
Re-activation of latent HPV common
What are the off-label use medical therapies for VIN-U?
5FU (Efudex) cream (lots of S/E’s so women don’t like)
Interferon (Intron-A)
Imiquimod (Aldara) 5% cream - low compliance b/c freq application
What treatment is the standard of care for VIN-U?
Surgical
• CO2 laser vaporization (destruction of entire thickness of epithelium)
• Local wide excision
• Vulvectomy
Post-treatment recurrence rate is 30-50%
Which type of VIN:
Unrelated to HPV
VIN-D
Which type of VIN:
Seen in older women (>70)
VIN-D
Which type of VIN:
Involves lower 1/3 of epithelium
VIN-D
Which type of VIN:
Associated with squamous cell hyperplasia (ie - untreated Lichen Sclerosus or Lichen Simplex Chronicus)
VIN-D
What is the treatment for VIN-D?
Surgical excision
NO CO2 laser - you want clear margins
What is the recommended follow up for VIN?
If VIN-U, vaccination with Gardasil
Women w/ a hx of VIN should be considered at risk for recurrence throughout lifetime
Post treatment f/u includes colposcopy at 6 and 12 months then annually thereafter
Is vulvar cancer common?
Hahaha, NOPE
Only accounts for 5% of gyn cancers - it’s extremely rare
But for some reason she then put it’s the fourth most common malignancy of the female genital tract 🙄
10% of women with vulvar cancer also have ______ and 30-50% are _______ or _______.
Type II DM
Obese or Hypertensive
What age is most affected by vulvar cancer?
Incidence has a bimodal peak
20-40 year olds = HPV related (VIN-U)
60-70 year olds = due to chronic irritation or squamous cell hyperplasia (VIN-D)
Vulvar cancer that develops from VIN-U typically affects ______ and is related to ______
20-40 yo
HPV
Vulvar cancer that develops from VIN-D typically affects ______ and is related to ______
60-70 yo
Untreated, long-lasting lichen sclerosus, lichen simplex chronicus, or squamous cell hyperplasia
Clinical presentation of vulvar cancer
ASYMPTOMATIC (—> delayed diagnosis)
• Always inspect the vulva!
Pruritis is most common Sx if they have any
Also, vulvar bleeding and pain
What are the three types of vulvar cancer?
Squamous cell carcinoma
Basal cell carcinoma
Malignant melanoma
You inspect a woman’s vulva during her well-woman exam and find lesions varying in appearance, from large, exophytic cauliflower-like lesions to small ulcerative lesions with surrounding hyperkeratosis.
What you think?
Squamous cell carcinoma
You inspect a woman’s vulva during her well-woman exam and find a raised lesion with an ulcerated center and rolled borders.
What you think?
Basal cell carcinoma
You inspect a woman’s vulva during her well-woman exam and find lesions on the labia minora and clitoris that are raised and darkly pigmented.
What you think?
Malignant melanoma
Good for you for finding it! Most dermatologists are idiots and don’t bother looking at the hoo-ha
What is the primary treatment for vulvar cancer?
Complete surgical removal of tumor with inguinal node dissection
Radiation therapy indicated with lymph node spread
What has to be present for a woman to develop VaIN?
HPV
51-62% have been previously treated for CIN
25% have undergone hysterectomy for CIN
75% have preceding or co-existing squamous cell carcinoma of the vulva or cervix
Mean age of incidence for VaIN?
35-55
Risk factors for VaIN?
Same as CIN!
Smoking
Multiple sex partners
Early onset of sexual history
History of CIN III
What is the pathogenesis of VaIN?
HPV EXPOSURE IS A MUST!
Development of VaIN following HPV exposure requires greater period of time
Frequency of VaIN not as high as CIN since vaginal epithelium is different from cervical
Most VaIN lesions are located in the ______
Upper 1/3 of the vagina
What are the different classifications of VaIN?
VaIN 1 = benign viral proliferation
VaIN 2 = intermediate risk
VaIN 3 = true precursor to vaginal cancer
How do you diagnose VaIN?
Detection via Pap smear (cytology) —> colposcopy
What are the differences in management between the different classifications of VaIN?
VaIN 1 = observation in younger women, with cytology/HPV/Colposcopy q6 months
VaIN 2/3 = surgical intervention vs chemo
What is the treatment for VaIN?
Vaginectomy - 90% success rate but you lose your vagina
Laser Vaporization - 63-90% successful
Topical chemotherapy (5FU) - 50-85% successful • Only used if other treatment options aren’t feasible (not FDA approved for this indication)
Most common cause of invasive cancer in the vagina
Metastasis from endometrium, ovary, or cervix
FIGO states only when the primary site of growth is from the vagina can it be called vaginal cancer
Age for vaginal cancer
> 50
Only <20% are diagnosed before 50
Most common type of cancer in the vagina
Squamous cell (80-92%)
Clinical presentation of vaginal cancer
ASYMPTOMATIC
Leukorrhea
Vaginal odor
Post-coital bleeding
Abnormal Pap smear
Your patient’s Pap smear is abnormal. You do a colposcopy. What changes are indicative of vaginal cancer?
Acetowhite changes, punctation, or mosaicism
Treatment for vaginal cancer
It’s super duper rare, so no STANDARD treatment
Combo vaginectomy and radiation
5 year survival rate is 61%
Polycystic Ovarian Syndrome results from…
Abnormal androgen and estrogen metabolism —> unregulated androgen production —> high serum testosterone, androstenedione, and DHEA
What is the relationship between PCOS and insulin?
PCOS —> insulin resistance and hyper insulin emit
Increased insulin alters gonadotropin (FSH/LH) effects on ovarian function
Increased insulin decreases synthesis of sex hormone binding globulin (SHBG) and insulin-like growth factor
What happens to adiponectin in PCOS patients?
Decreased
Adiponectin regulates lipid metabolism and glucose levels, so decreased adiponectin further exacerbates PCOS symptoms
What role do gonadotropins play in PCOS?
Increased LH stimulates theca cells to produce androgens
FSH is depressed (b/c negative feedback) —> decreased aromatase in the ovary —> decrecreased conversion of androgens to estrogens
In PCOS, increased androgens released from the ovary are converted to estrogen by…
Adipose tissue
This causes negative feedback to anterior pituatary and further decrease in FSH production
In PCOS, increased circulating insulin stimulates…
The ovary to produce more androgens —> elevated circulating free testosterone
Most common symptom of PCOS
Infertility
Clinical presentation of PCOS
Infertility Oligomenorrhea/amenorrhea**** Obesity Acne**** Hirsutism**** Male pattern baldness Acanthosis nigricans
What conditions must be ruled out when diagnosing PCOS?
Hyperprolactinemia
Congenital adrenal hyperplasia
Cushing’s syndrome
What is the Rotterdam Criteria of 2003 for PCOS?
2/3 must be present after exclusion of related disorders:
• Oligomenorrhea
• Clinical or biochemical signs of hyperandrogrenism
• Polycystic ovaries
Did not replace NIH definition, just expanded it to include polycystic ovaries
Ultrasound findings in PCOS
Presence of >12 follicles in each ovary 2-9mm
“String of pearls” appearance
Ovarian volume >10ml
No evidence of dominant follicle/corpus luteum
What lab do you order first if suspecting PCOS?
Total testosterone
Normal = 40-60 ng/dL
Elevated if >60 ng/dL —> further lab eval
So your patient who you suspect has PCOS had a total testosterone >60 ng/dL.
What you wanna order next?
17-OH progesterone
DHEA-S
Cortisol
Prolactin
TSH
ßHCG
Why order this test when working up PCOS?
17-OH progesterone
R/o congenital adrenal hyperplasia
Why order this test when working up PCOS?
DHEA-S
R/o adrenal source for increased testosterone
Why order this test when working up PCOS?
Cortisol
R/O cushing’s
Why order this test when working up PCOS?
Prolactin
R/o hyperprolactinemia
Why order this test when working up PCOS?
TSH
Increased thyroid can cause oligo/amenorrhea
Why order this test when working up PCOS?
bHCG
Because pregnancy is the most common cause of secondary amenorrhea
Treatment for PCOS
WEIGHT LOSS!!!! Restores predictable cycling
Metformin ONLY for patients with hyperinsulinemia (500mg BID) - combine with Clomid for infertility
Combined oral contraceptives (pick one with low androgenic activity)
Fertility consult
Provers 10mg QD x 10d for endometrial protection
PCOS puts patients at risk for …
Endometrial hyperplasia/carcinoma T2DM Hypertension Hyperlipidemia CVD Stroke Infertility Metabolic syndrome Sleep apnea
What types of adnexal masses are benign?
Thin walled on U/S Endometrioma Hemorrhagic Teratoma Simple cysts (<3cm in premenopausal, <1cm in postmenopausal)
U/S shows Homogenous echos
Endometrioma (benign)
U/S shows network of linear or curvilinear pattern
Hemorrhagic cyst
U/S shows cyst <3 cm in a premenopausal woman
Simple cyst
<1cm in postmenopausal woman
U/S shows hyperechoic nodule with distal acoustic shadowing
Teratoma
U/S findings that suggest malignancy for adnexal masses
Thick septations (>2mm)
Solid component, appears nodular or papillary
(+) blood flow to solid component
What are the different types of ovarian cysts
Follicular*** (most common) Corpus luteum cyst Theca lutein cyst Mature teratoma Serous/mutinous cystadenoma
Follicular ovarian cysts range in diameter
2-8 cm
Are follicular cysts bad?
Nope - common and non-malignant
Will regress after 1-2 menstrual cycles
Follicular cysts result from …
Failure of the mature follicle to rupture (no ovum released)
Failure of the non-dominant follicles to undergo atresia in the presence of the mature follicle
Corpus luteum cysts range in size
3-11 cm
How do corpus luteum cysts form?
Following ovulation, blood accumulates within the cavity of the corpus luteum which stimulates resorption
If resorption doesn’t occur and the corpus luteum is greater than 3cm it is considered a cyst
Usually resolve after 1-2 menstrual cycles
When do you patients develop theca lutein cysts?
With elevated chorionic gonadotropin levels (those going through infertility treatment
Usually seen bilaterally
Fluid in theca lutein cysts is…
Clear, straw colored
Where do mature teratomas originate from?
Parthenogenic theory:
• Originate from primordial germ cells
• Teratomas are found along the migration pathway of germ cells from yolk sac to gonads
Which germ layer is the most common type of mature teratoma?
Ectodermal
That’s why you get hair, teeth, etc in them
What does the histology look like for mature teratomas?
Cyst is lined with keratinized squamous epithelium with abundant sebaceous and apocrine glands
How do mature teratomas present?
Asymptomatic - found via pelvic exam or incidental finding on other radiologic studies
Pelvic pain is usually secondary to torsion or rupture (rare)
Urinary frequency/urgency
Back pain
What do you need to do to diagnose mature teratomas?
PE - pelvic mass on bimanual exam
Transvaginal U/S - shows unilateral, complex cyst
CEA, CA-125, AFP, and ßHCG all should be within normal limits
Treatment for mature teratoma
Laparotomy vs laparoscopy (depends on size)
Ovarian cystectomy vs oophorectomy
Recurrence is ~10%
Who usually gets serous/mutinous cystadenomas?
Women 30-50 yo
Histology of serous/mutinous cystadenomas
Lined with columnar epithelium
Secrete thick, gelatinous mucin
Thin-walled, uni- or multilocular, and range in size from 5 to over 20 cm
How do you treat serous/mutinous cystadenomas?
Surgical excision
Ensure benign pathology
2nd most common gynecologic cancer
Ovarian cancer
2nd most common but most common cause of gynecologic death in the US
Highest incidence of ovarian cancer is in women…
65-74 yo
Risk factors for ovarian cancer
NULLIPARITY**** Infertility treatment Obesity and diets high in sat fat Talcum powder Personal hx of BC Family hx of breast, ovarian, or colorectal cancer Turner’s Syndrome Early menarche**** Late menopause**** Estrogen replacement therapy Caucasian race Endometriosis
Protective factors for ovarian cancer
Multiparity*** Breastfeeding Long-term oral contraceptive use**** (at least 5 years of use reduces the relative risk of ovarian cancer by 50%) Bilateral tubal ligation Low fat diet Bilateral salpingectomy
What are the four categories of ovarian cancer?
Epithelial
Germ cell
Sex cord and stromal
Neoplasms metastatic to the ovary
What are the subtypes of epithelial ovarian cancer?
High-grade serous carcinoma
Endometriod carcinoma
Clear cell carcinoma
Mucinous carcinoma
What are the subtypes of germ cell ovarian cancer?
Dysgerminoma Endodermis sinus Immature teratoma Embryonal carcinoma Choriocarcinoma
What are the subtypes of sex cord and stromal ovarian cancer?
Granulosa cell
Sertoli-stromal cell
Most common origin for metastatic ovarian cancer
Stomach
Colon
Breast
Pathophysiology of epithelial ovarian cancer in the ovary
Incessant ovulation theory - repeated ovarian epithelial trauma by follicular rupture and subsequent remain —> malignant transformation
Associated with endometriod, mucinous, or clear cell cancer
Pathophysiology of epithelial ovarian cancer in the Fallopian tube
p53 tumor suppressor gene
Associated with high grade serous papillary cancer
Which type of epithelial ovarian cancer is most common?
High-grade serous carcinoma
Arises from the Fallopian tube
Which epithelial neoplasms arise from the Fallopian tube?
High-grade serous carcinomas
Which epithelial neoplasms arise from the ovary?
Endometriod carcinoma
Clear cell carcinoma
Mucinous carcinoma
Highest incidence of germ cell ovarian cancer is in women…
20-30 years
What are the characteristics of germ cell ovarian cancers?
Younger women
Tend to grow rapidly
Favor lymphatic spread
Contain mix of tumor types
Usually unilateral
Produce tumor markers (helpful in tx)
Most common type of germ cell neoplasm
Dysgerminoma
Unilateral in 85-90%
90% in women <30
Unilateral or bilateral:
Endodermis Sinus Tumor
Bilateral
Which germ cell neoplasm type displays the most rapid growth?
Endodermal sinus tumor
Which germ cell tumors are associated with alpha fetoprotein?
Endodermal sinus tumor
Immature teratoma
Embryonal carcinoma
2nd most common type of germ cell neoplasm
Immature teratoma
Seen most commonly in patients <20
Usually unilateral
Which germ cell neoplasm is associated with both AFP and HCG?
Embryonal carcinoma
Rapid growth with extensive spread
Which type of germ cell neoplasm is seen with precocious puberty, uterine bleeding or amenorrhea?
Choriocarcinoma
Seen most commonly in the 2nd decade of life
Most common type of sex-cord/stromal tumor
Granulosa cell (70%)
(Sex-cord stromal tumors)
_______ cause hyperestrogenism
_______ cause hyper androgens
Granulosa cell
Sertoli-stromal cell
Acute sx of ovarian cancer
Pleural effusion
Bowel obstruction
Subacute sx of ovarian cancer
Adnexal mass Bloating/abdominal distention Early satiety Pelvic/abdominal pain Abnormal vaginal bleeding Altered bowel habits Dyspepsia
PE findings for ovarian cancer
Ascites
Inguinal LAD
Pelvic mass
What labs/imaging you wanna order if suspecting ovarian cancer?
Transabdominal/vaginal U/S
Mammogram/colonoscopy
CT
MRI
CXR
CA-125 (suspected epithelial ovarian cancer)
hCG, AFP, LDH (suspected germ cell tumor)
Treatment for epithelial ovarian cancer
GYN onco consult
Surgical staging (FIGO)
Chemo
Germ cell ovarian cancer treatment
GYN onco consult
Early dx allows removal of involved adnexa with preservation of contralateral adnexa and uterus
Surgical staging (FIGO)
