GYN malignancy Flashcards
cervical cancer
general
Rates are decreasing due to surveillance and vaccines!
Bimodal distribution- 30s and 60s
Main cause: HPV
How is it found?
Asymptomatic screening
Post-coital bleeding (pre-menopausal)
Post-menopausal: dysfunctional bleeding
MAIN TYPE: SQUAMOUS CELL CARCINOMA
cervical cancer
RF
1 Cause: HPV
Smoking (2-3 x increase)
Immunosuppression
Chlamydia infection
Diet low in fruits and vegetables
Obesity
Oral Contraceptive use
Intrauterine device use
Multi-full term pregnancies
First pregnancy < 17 years
cervical cancer
HPV
Most common STD in U.S.
>6 million cases per year!!
Infects females and males
Most new infections occur between ages 15-24
80% of women will have had HPV infection by age 50
Over 100 Types!
High risk types and low risk types
Acquired through sexual and genital skin-to-skin contact
Persistent cervical infections with high grade HPV genotypes required for development of cervical cancer and the precancerous lesion, CIN3
Types 16 (55-60%), 18 (10%),31,33, 45
HPV…
a player in other cancers
Vulvar Cancers-69%
Vaginal Cancers-75%
Penile Cancers-63%
Anal Cancers-89% (M) /93% (F)
Oropharyngeal Cancers 63% (F)/ 72% (M)
Dysplasia to cancer
Dysplasia= abnormal cells that have lost the ability to self regulate
PAP Smear/Liquid based cytology
Low Grade (LGSIL) c/w mild CIN 1
High Grade (HGSIL) c/w moderate to severe CIN 2-3
Cervical Intraepithelial Neoplasia (CIN) on biopsy - HOW MUCH OF THE CERVICAL EPITHELIUM IS INVOLVED
mild= CIN 1
Moderate= CIN2
Severe= CIN3
Carcinoma in situ = “cancer in place” or cancer that has not spread beyond the epithelial layer
Invasive cancer= cancer has invaded tissue beyond the epithelial layer of cells
Can be ectocervical/endocervical
Treatment of dysplastic/precancerous lesions
Will be discussed in detail by Nicole Grange (1/22/24)
Based on a number of criteria
In general treatment involves local ablative therapy
Colposcopy with Loop Electrosurgical Excision Procedure(leep)
Colposcopy with cryotherapy
cervical cancer work-up
Biopsy (near the margin is best)
Physical exam
rectovaginal exam
parametrial or rectal involvement,
lymph node survey
Inguinal
supraclavicular
CXR
pulmonary nodules
CBC, BMP,LFT
Cystoscopy/anoscopy/IVP
CT can be used for substitution
Treatment of cervical cancer
Simple vs Radical Hysterectomy
Simple/t0tal hysterectomy: removal of uterus, cervix
Subtotal/partial hysterectomy: removal of uterus only, cervix remains
Radical hysterectomy: removal of uterus, Fallopian tubes, cervix, bilateral parametrium and upper vagina
cervical cancer
Prevention
Incidence and mortality have declined since introduction of the Papanicolaou (Pap) test in the mid-20th century and testing for high-risk types of HPV however….
50% of women with cervical cancer have never had a Pap smear
30% of cancers have occurred in women who have not been screened within the last 5 years.
25% of cases and 41% of deaths occur in women 65 years of age and older
Screening Window of Opportunity
The latency period from dysplasia to cancer of the cervix is variable, but with 3 normal paps, the odds are < 1/1,000,000
Single Pap false negative rate is 20%.
HPV
screening
90% HPV infections transient
Screening strategies aimed at identifying those cervical cancer precursors likely to progress versus those which are only transient infections
Three screening modalities
PAP SMEAR
Co-testing for high risk HPV with PAP smear
Primary HPV TEST
cervical cancer
PREVENTION - HPV Vaccines
Shown to protect against types which are responsible for 98% cervical cancers and 89 and 99% genital warts in males and females, respectively
Also shown to protect against 97% vaginal cancers and 97% vulvar cancers
CDC estimates that 30,700 cancers could be prevented in US with vaccination
Gardasil (Merck) 9-valent vaccine (9vHPV)
PROTECTS against HPV 6,11,16, 18, 31, 33, 45, 52, and 58.
2 DOSE SCHEDULE IF < 15 YEARS OF AGE (0, 6-12 MONTHS)
3 DOSE SCHEDULE IF > 15 YEARS OF AGE (0, 2, 6 MONTHS)
IN 2018 FDA APPROVED USE FOR AGES 27-45 YEARS OF AGE BUT NOT PART OF GUIDELINES YET.
HPV Vaccination- ACIP recommendations
Routine vaccination for females and males ages 11-12
Can be as young as 9 years of age
If < 15 years of age, only 2 doses required, given at 0 and 6-12 months.
Vaccination recommended for all ages up to 26 who have not been vaccinated previously or who have not completed the 3-dose series
Adults aged >26 years.Catch-up HPV vaccination is not recommended for all adults aged >26 years. Instead, shared clinical decision-making regarding HPV vaccination is recommended for some adults aged 27 through 45 years who are not adequately vaccinated. HPV vaccines are not licensed for use in adults aged >45 years.
VAGINAL CANCER
general and Sx
RARE
PAIN, MASS, ABNORMAL VAGINAL BLEEDING (POST-COITAL)
TWO MAIN TYPES
SQUAMOUS CELL CARCINOMA
VIRTUALLY IDENTICAL TO CERVICAL CANCER IN ETIOLOGY, DIAGNOSIS AND TREATMENT
NO VAGINAL WALL PAP USUALLY
CLEAR CELL ADENOCARCINOMA
RESULTS USUALLY FROM EXPOSURE TO DIETHYLSTIBESTEROL (DES) EITHER BY PATIENT OR MOTHER
No longer an issue
vaginal cancer
tx
TREATMENT IS USUALLY SURGICAL WITH GOAL OF PRESERVING FUNCTION
CHEMO/RT IF NOT SURGICAL CANDIDATE OR ADVANCED DISEASE
VULVAR CANCER
general and Sx
Rare, not as rare as vaginal
PRESENTATION IS USUALLY PRUITIS/SKIN CHANGES
RULE OUT INFECTION OR INFLAMMATORY PROCESS
MANY DIFFERENTIALS FOR VULVAR LESIONS
Condylomata
Epithelial hyperplasia (hyperplastic dystrophy)
Lentigo
Contact dermatitis
Seborrheic keratosis
Acanthosis nigricans
Paget’s disease*
Lichen sclerosis and lichen planus
uterine cancer
Endometrial hyperplasia
Proliferation of endometrial glands causing Thickening of uterine lining
Categorized into two groups:
Hyperplasia without atypia
usually not neoplastic (4x more likely to develop cancer)
Changes due to prolonged estrogen exposure or anovulation
Hyperplasia with atypia
Neoplastic/ premalignant lesions on the endometrium
1/3 of women develop endometrial cancer in 1 year
Also referred to as Endometrial intraepithelial neoplasia (EIN)
Either group, especially EIN, can progress to endometrial cancer
endometrial hyperplasia
RF
Similar to endometrial carcinoma
Increasing age
Obesity- adipose releases estrogen
Unopposed estrogen therapy
Early menarche
Late menopause
Nulliparity
Polycystic ovary syndrome
Diabetes mellitus
Estrogen-secreting tumor
Lynch syndrome
Family history of endometrial, ovarian, breast or colon cancer
Endometrial hyperplasia-
presentation
Most common presentation- abnormal uterine bleeding
Vaginal discharge
Abdominal pain
Abnormal cytological findings on cervical cancer screening
Atypical glandular cells, benign endometrial cells in pts > 45 years
Postmenopausal female with thickened endometrial stripe on imaging
Differential DX: endometrial cancer
Endometrial hyperplasia-
PE labs and imaging
Pelvic exam: usually normal
Lab values: Usually normal unless significant bleeding, then possible anemia
Imaging: postmenopausal women: ultrasound: thickened endometrium with multiple cystic features.
If this is seen, should further work up required
Endometrial bx.
endometrial hyperplasia
tx
Progestin therapy
oral contraceptive pills, periodic progesterone withdrawal, high-dose progestins, Progestin IUD (Mirena, Skyla, and Liletta)
Possible need to repeat bx periodically (e.g. q 3-6 months)
D and C with hysteroscope
May need progestin therapy
May need endometrial bx periodically or if returns
Hysterectomy
If high risk, or atypia is present
Uterine Cancer
Types of endometrial cancer
Type i= endometrioid
Most common
Estrogen related
Endogenous
Exogenous
Younger, obese patients
Low grade
Precursor-endometrial hyperplasia
Type II papillary serous clear cell
Rare
Unrelated to estrogen
Older, thinner women
aggressive
Different etiology
Mutant P53 overexpression
endometrial cancer
Signs and symptoms
Vaginal bleeding!!!
In those with Post-menopausal bleeding – 15% have cancer
#1 cause of vaginal bleeding in post menopausal women still atrophy
Dysmenorrhea in reproductive age women
Leukorrhea -10%
If cervical stenosis
Pyometra (pus in uterus)
Hematometra (blood in uterus)
uterine cancer
workup
For vaginal bleeding:
Physical Exam
EMB, D&C – office EMB false neg 10%
Ultrasound?
Not really that useful, need biopsy
work-up for endometrial cancer
Confirm diagnosis
CBC, BMP, Ca-125
EKG
CXR
Mammogram
CT or MRI for extrauterine disease
Colonoscopy, CEA
endometerial/uterine cancer
follow up
No standard of care
Pe/Pelvic exam
every 3mo for 1st year
Every 4 mo for 2nd, 3rd year
Every 6 mo for 4th, 5th year
CT ???
Heredity and Endometrial Cancer
10% of Endometrial Cancer can be hereditary
Lynch syndrome/HNPCC
Endometrial, Colorectal, Ovarian, Breast
Mutation in DNA mismatch repair genes: MSH2, MSH6, MLH1, PMS2 or MSI
Uterine Sarcoma
general
About 1 in 12 of all uterine cancers
Classification
carcinosarcoma
Endometrial stromal sarcoma
Undifferentiated sarcoma or pure heterologous sarcoma
Leiomyosarcoma
Generally worse prognosis/more aggressive
Treatment: surgery+/- chemotherapy/RT
Gestational trophoblastic disease
Types of moles
Benign= hydatiform mole
Complete moles
Incomplete/partial moles
Malignant
Invasive molar disease
choriocarcinoma
Ovarian cancer
Genetic Predisposition
BRCA 1 or 2
Increased risk of ovarian cancer, BRCA 1 (on 17) = 40%, BRCA 2 (on 13) = 27%
Accounts for 90% of hereditary ovarian cancers (which is only 15% of all ovarian ca)
BRCA1 is more common mutation
Usually younger age at presentation, mostly serous histology, and may have better outcomes than sporadic ovarian cancers
Lynch Syndrome
Mismatch repair (MMR) mutations (MSH1, 6, MLH1)
6-10% risk of ovarian cancer
ovarian cancer
management of high risk patients
Genetic Counseling
Oral Contraceptives
CA 125 every 6 to 12 months for ages 25 to 35 years
Elevated in only 50% of Stage I EOC and 80% in all stages
Specificity is limited (many conditions cause elevation)
Increased specificity with doubling of levels > 35 U/ml
Pelvic U/S with Dopplers
Limited use because of low specificity
Usually combination Ca125 and U/S in high risk population
Risk Reducing Oophorectomy
Recommended for women with BRCA mutation after childbearing or age 35 years
Reduces risk of EOC by 96% (still at risk for primary peritoneal = 1%)
Reduced risk of breast cancer by 50% to 80%
Potentially add hysterectomy because current treatments options for Breast Cancer(Tamoxifen) increase risk of endometrial cancer
ovarian cancer
clin man
early and advanced
early: Urinary frequency
(don’t treat a negative urine culture…)
pelvic pressure
constipation
pain (back pain)
advanced:
Bloating/fullness
early satiety
epigastric pain
urinary frequency, consitpation/diarrhea
weight loss
ovarian cancer
PE/ imaging/ labs
physical exam
palpable mass, nodularity
Imaging
Ultrasound- growths, abnormal flow
CT- ascites, metastatic disease
Labs
Ca125, other tumor markers, CBC (anemia), chemistry (renal dysfunction), coags
Ovarian cancer
tumor markers
Ca125- NON-SPECIFIC glycoprotein
CEA- GI/Mucinous
CA19-9- pancreatic/upper GI (NON SPECIFIC)
Newer tests- Ova1
If you don’t know it, don’t get it
ovarian cancer
tx
Surgery (always the first choice)
Staging Laparotomy
Cytologic washings
TAH-BSO
Omentectomy
Retroperitoneal lymph node sampling
Peritoneal and diaphragm biopsies
VS DEBULKING – surgical excision of all metastatic tumor with goal of no residual/visible disease or optimal <1cm of any individual tumor size
Epithelial Ovarian Cancer highlights
Disease-specific mortality related to advanced stage on presentation
No effective screening methods
Treatment is usually surgery then adjuvant chemotherapy
Progression from chemosensitive to chemoresistant phenotype in majority
Risk reducing BSO in high risk populations (eg. Brca1/2 +)
