Dunn CIS : gest trophoblastic disease and pap smear Flashcards
Gestational Trophoblastic Disease (GTD)
Abnormal proliferation of trophoblast of the placenta
Broad category
Result of an aberrant fertilization event that leads to a proliferative process
Incidence higher in Asian and Latin American American countries (1:12-5800 ns 1:1000-1500 in North America and Europe)
SX: Consistent with early pregnancy
Vaginal bleeding is common – usually thought to be threatened abortion; due to separation of tumor from underlying decidua
Risk Factors
Age >35
HX of previous GTD
Benign nonneoplastic trophoblastic lesions
Exaggerated placental site
Placental site nodule
Hydatidiform mole types
(80% of cases)
Complete mole
Partial mole
Invasive mole (chorioadenoma destruens)
Gestational Trophoblastic Neoplasia (GTN)
True neoplasia – potential for local invasion or metastases - Choriocarcinoma - Placental site trophoblastic tumor - Epithelioid trophoblastic tumor Curable in 85-100% cases
Complete mole
46, XX
Can have 46, XY if fertilized by two sperm
All paternal chromosomes
Haploid sperm fertilizes an “empty” ovum
- (w/o or inactivated maternal chromosomes)
No fetal tissue
Incomplete mole
69, XXY
Fertilization of ovum with haploid maternal chromosomes by two sperm
Fetal tissue present
Causes of hydatidiform moles
Genomic imprinting
Paternal genes = Placental growth
Maternal genes = Fetal growth
Excess paternal genes excessive placental or trophoblastic growth
Mechanism Many suggested causes: - Unstable mitochondrial DNA - Overexpression of oncogenes - Downregulation of tumor suppressor genes - Telomerase activity - Cell-cell adhesion molecules
Complete Molar Pregnancy
Fertilization of an empty ovum either by two sperm or one sperm that duplicates (46XX or46XY)
Excessive uterine size for gestational age d/t tumor or hemorrhage and retained clot
Can become choriocarcinoma
Partial Molar Pregnancy
Fertilization of a haploid ovum by either two sperm or one sperm that duplicates causing 69XXX, 69XXY, or 69Xyy
Presence of a fetus; some fetal cardiac tones may be detected
Less likely to become malignant
Complications: Most due to highly elevated HCG levels
Ovarian enlargement due to theca lutein cysts
Hyperemesis gravidarum
Early development of preeclampsia (before 20 weeks)
Hyperthyroidism
Hemorrhage (<500mL common)
Risk Factors for moles
Extremes of maternal ages (<20 or >40 yo)
Diet deficient in folate or β-carotene
typical History/PE of mole
1st Trimester painless bleeding Hyperemesis gravidarum Preeclampsia/eclampsia <24 weeks Uterine size > EGA Hyperthyroidism
Diagnosis of moles
No fetal heartbeat Increased β-hCG (>100,000 mIU/mL) Pelvic exam - Enlarged ovaries (bilateral theca-lutein cysts) - Grapelike cluster expelled into vagina
U/S
- “snowstorm” appearance, cluster of grapes
- No gestational sac/fetus
Treatment of moles
D&C
- Serial β-hCG
- Until 3 consecutive values are obtained
If persistently high
- Postmolar GTN
- Chemotherapy and/or excisional surgery
Persistent disease (after moles)
15-20% after a complete mole; 3-5% after a partial mole
Characteristics that increase the likelihood of neoplasia after molar evacuation include large theca lutein cyst (>6cm),excessively enlarged uterus for dates, age over 40, previous GTD, initial hCG >100,0000 mlU/mL, the presence of hyperplasia or atypia on histology, and heterozygosity (dispermic moles)
Follow HCG levels
- T1/2 = about 48 hours
- Steady HCG levels indicates persistent disease
— Usually invasive mole; <10% choriocarcinoma
Once HCG levels are stable at <5 for 3 weeks, ok to resume attempts at pregnancy
Bacterial vaginosis
No inflammation, thus other symptoms such as pain/itching/inflammation suggest concomitant infection with other organisms
Most common cause of vaginal discharge in reproductive age women
Overgrowth of anaerobic bacteria: Gardenerella is key
Loss of lactobacilli
Risk factors: sexual activity, douching
50-70% asymptomatic
The characteristic milky or creamy vaginal discharge of BV associated with high vag pH and Fishy odor
Diagnosis of bacterial vaginosis
Diagnosis based on 3 or more Amsel criteria - Homogenous white to gray discharge - pH > 4.5 - (+) whiff test with KOH Clue cells on wet mount Gram stain is gold standard, rarely done PCR-based assay
what we will see in bacterial vaginosis on microscope
absence of WBC’s and stippling of epithelial cells
BV: Associated complications
PID, post-abortal PID, post-hysterectomy infections
pre-term delivery, PROM, amniotic fluid infection, chorioamnionitis, post-partum endometritis
BV Treatment
Metronidazole (avoid alcohol)
- 500mg PO BID x 7 days
- 0.75% gel 5g vaginally daily x 5 days
Clindamycin
- 2% cream 5g vaginally QHS x 7 days
- 300mg PO BID x 7 days
- 100mg vaginal suppository QHS x 3 days
- 2% Clindesse cream 5g as single vaginal dose
Tindazole
- 1g PO daily x 5 days
Treatment of asymptomatic women no recommended unless prior to procedures
Treatment of partners not recommended
Trichomonas vaginalis- discharge
Bubbly discharge of vaginal fluid
Pap smears- Normal vs. Abnormal
Cellular Level:
- Increased nuclear to cytoplasmic ratio
- Abnormal cell structure
- Koilocyte indication of HPV infection
Human papilloma virus stats
20 million infected persons
6 million new HPV infections per year in the U.S.
75% of sexually active adults will be infected sometime in their life
More than 100 types of virus
40 types sexually transmitted
HPV 3 types of infection:
Latent: Accounts for most HPV No visible lesion Only diagnosed by DNA hybrid testing DNA testing performed in the evaluation of an abnormal pap smear
Subclinical Infection:
Lesions visible only during colposcopy
Frequently have an abnormal pap
Clinical Infection:
Visible “warty” growths called Condylomata Accuminata
On vulva, vagina, cervix, urethra, perianal
HPV is associated with
Genital neoplasias
Cervical, vaginal, vulvar cancers
11,000 new cervical cancers yearly
8,000 vaginal/vulvar cancers
Genital Warts (Condyloma)
HPV: External genital warts
Condylomata Accuminata
1 million new cases in U.S. yearly
HPV infection usually clears spontaneously within 2 years
HPV risk types
High Risk: 16 – 18 30
Low Risk: 6 – 11 (causes warts)
TREATING WARTS
Relieve symptoms
- Pain and bleeding
Cosmetic concerns
Psychological concerns
Cytology of pap smear
Normal
ASCUS – Atypical Squamous Cells of Undetermined
Significance
ASC – H - Atypical Squamous Cells favor high grade lesion
AGUS – Atypical Glanular Cells of Undetermined Significance
LSIL – Low Grade Squamous Intraepithelial Lesion
HSIL – High Grade Squamous Intraepithelial Lesion
Invasive Cancer
Work-up abnormal pap
Age dependent
Degree of abnormality
Risk factors
Risk Factors (cervical cancer)
No recent pap Smoking Age of 1st intercourse Number of partners Immunocompromised (HIV)
Colposcopy
Looking at Cervix through Microscope
Normal Cervix
Abnormal Cervix – patterns
Transformation Zone
Histology of cervical cancer
Cervical Intraepithelial Neoplasia CIN I - Mild Dysplasia CIN II – Moderate Dysplasia CIN III - Severe Dysplasia, Carcinoma in Situ Invasive Cancer
Activity of disease (CIN)
CIN I – 70% - regress, 20% stay the same,
10% progress
CIN II – 30% regress, 30% stay the same,
30 – 40% progress
CIN III – all need treatment
Invasive Cancer – all need treatment
Treatment of cervical cancer
Follow up Pap Destruction (cauterization, cryotherapy) Excision (loop, cone) Hysterectomy Radical Hysterectomy (includes top third vagina parametrium and lymph nodes)
Indications for Conization
Treatment for CIN II or III Endocervical disease on colposcopy Discrepancy between PAP and colposcopy Inadequate colposcopy Depth of invasion
WHO ARE THE RARELY AND ENVER SCREENED
Minorities Low SES* Foreign born Living in the US < 10 years No usual source of health care
Natural History of Cervical Cancer
HPV infection –>
(6-12 months) disappearance or
(6-24 months) CIN 1 or
CIN 2,3 (10-13 years to invasive CA)
major contributing factor to most cervical cancer deaths today.
Being rarely or never screened
Why isn’t “finding lesions” the objective of screening?
Don’t know which lesions will progress.
Need to place emphasis on:
- Persistent HPV infections
- CIN 3 (no margin for error)
CIN 2 in older women (no risk to pregnancies)
Persistent CIN 2 and CIN 2/3 in non- adolescent women
Cervical cancer screening should begin at age
21, regardless of age or sexual onset
Adolescent Needs
Care for contraception and STI screening/treatment.
No Pap test
No speculum exam for asymptomatic women
STI testing can be done using urine
Screening for ages 21-29
Cytology alone every 3 years
HPV testing “should not be used to screen”
- Not as a component of cotesting
- Not as a primary stand-alone screen
Rationale for Avoiding HPV Tests Among Women Ages 21-29
Prevalence of carcinogenic HPV approaches 20% in teens and early 20s
Most carcinogenic HPV infections resolve without intervention
Identifying carcinogenic HPV that will resolve leads to repeated call-back, anxiety, and interventions without benefit
Screening For Women Ages 30-64
Cytology + HPV testing (Cotesting) every 5 years is preferred
Cytology alone every 3 years is acceptable
Rationale for Cotesting, Ages 30-64
Increased detection of prevalent CIN3
Decreased CIN3 in subsequent screening rounds
Achieves risk of CIN3 equal to cytology alone
@ 1-3year intervals
Enhances detection of adenocarcinoma/AIS
Minimizes the increased number of colposcopies, thus it reduces harms.
Managing ASC-US/HPV negative tests
Women with ASC-US cytology and negative HPV test results should continue screening per age-specific guidelines.”
CIN3 risk of ASC-US/ HPV neg <2%, below threshold for colposcopy.
Immediate HPV genotyping
If HPV 16 or HPV16/18 positive, refer directly to colposcopy.
If HPV 16 or HPV 16/18 negative, repeat cotest in 12 months and then…
- If either repeat test is positive, refer to colposcopy
- If both tests are negative, return to routine screening.
When to Stop Screening
Stop at age 65 for women with adequate negative prior screening, no CIN2+ within the last 20y.
*** Definition of adequate negative screening:
- 3 consecutive negative Paps or
- 2 consecutive negative HPV tests
(Tests within 10 years of stopping; most recent within 5 years.)
Stop after hysterectomy with removal of cervix and no history of CIN2+
- “Evidence of adequate negative prior screening is not required”
Rationale for stopping (cervical cancer screening) after Hysterectomy
Vag cancer rate is 7/million/year
663 vag cuff Paps needed to find one VAIN
2,066 women followed after hyst. for average 89 months
– 3% had VAIN, 0 had cancer
Risk of Pap abnormality after hyst = 1%.
Compare risk of breast cancer in men for which screening is not recommended.
When NOT to stop at age 65 years
If history of CIN2, CIN3, or AIS
– Continue “routine screening” for at least 20 years, “even if this extends screening past age 65.”
Screening a Vaccinated Cohort
“ Recommended screening practices should not change on the basis of HPV vaccination.” Vaccination against HPV 16/18 - Reduces CIN3+ by 17-33% - Reduces colposcopy by 10% - Reduces treatment by 25%
But who is vaccinated?
- Recall? Completed series? HPV naïve?
“The biggest gain in reducing cervical cancer incidence and mortality would be achieved by
increasing screening rates among women rarely or never screened. . .
Clinicians, hospitals, health plans, and public health officials should seek to identify and screen these women.”
