GYN malignancy Flashcards by Leslie Mancini

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

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cervical cancer

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

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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

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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)

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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

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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

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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

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Treatment of cervical cancer

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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

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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%.

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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

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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.

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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

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

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

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 +)