Endometrial and Vulvar Biopsy Practicum

Patty Cason MS, FNP-BC Kristin Metcalf-Wilson DNP, WHNP-BC Disclosures Patty Cason

Advisory Board Teva (ParaGard, LeCette) Merck (HPV vaccines) Actavis (Levosert IUD in development) Speakers’ Bureau Teva (ParaGard) Merck (Nexplanon, Gardasil, NuvaRing, Contraception) Bayer (Mirena, Skyla)

Family Planning National Clinical Training Center · Supported by Office of Population Affairs Disclosures Kristin Metcalf-Wilson

Nothing to disclose

Family Planning National Clinical Training Center · Supported by Office of Population Affairs Learning Objectives EMB

List three indications for endometrial biopsy Demonstrate spiral technique for endometrial sampling Identify strategies for sampling the endometrium when cervical stenosis is present

Family Planning National Clinical Training Center · Supported by Office of Population Affairs Learning Objectives Vulvar Biopsy Describe characteristics of vulvar lesions that may indicate need for biopsy Demonstrate punch biopsy technique for obtaining a vulvar biopsy

Family Planning National Clinical Training Center · Supported by Office of Population Affairs Endometrial Biopsy

Family Planning National Clinical Training Center · Supported by Office of Population Affairs Outline 1) Epidemiology 2) Indications 3) Differential Diagnosis 4) Contraindications 5) Devices 6) Technique 7) Challenging situations 8) Results 9) Follow up 10)Alternative diagnostic strategies

Family Planning National Clinical Training Center · Supported by Office of Population Affairs Epidemiology Endometrial Cancer

Family Planning National Clinical Training Center · Supported by Office of Population Affairs Endometrial Cancer

4th most common female cancer Most common female genital tract cancer - 5 year survival 86-93% - 86% white; 55% AA Bimodal age distribution - Menopausal women;mean age 61 - Pre- and peri- menopausal chronic anovulators

Family Planning National Clinical Training Center · Supported by Office of Population Affairs Risk Factors Age: peak incidence 72 years old • 3x higher than 50-54 years old Chronic unopposed estrogen exposure • E-level and duration of exposure • High body mass index (BMI) • Menopause >52 • Low parity (2-3x) • Exogenous sources: ET, tamoxifen • Chronic anovulation (PCOS)

Family Planning National Clinical Training Center · Supported by Office of Population Affairs Endometrial Cancer: Risk Factors • Diabetes (RR= 2.8) • Hypertension (RR= 1.5) • Personal or family history of breast or colon cancer

Family Planning National Clinical Training Center · Supported by Office of Population Affairs Endometrial Cancer: Protection Combined Hormonal Contraceptives • Pill, patch, ring Continuous progestin contraceptive • Implant, LNG IUC, Progestin-only pills, DMPA

Family Planning National Clinical Training Center · Supported by Office of Population Affairs Indications Whom to test Purpose

Detect endometrial hyperplasia in order to prevent cancer Detect endometrial cancer as early as possible

Family Planning National Clinical Training Center · Supported by Office of Population Affairs Routine screening not recommended for:

• Asymptomatic perimenopausal or postmenopausal women • Asymptomatic chronic anovulation • Women initiating menopausal hormone therapy • Tamoxifen Users Menopausal Woman Not on Hormone Therapy

• Any bleeding • Endometrial stripe > 5 mm (postmenopausal woman only) • Cervical cytology: ⁻ Any endometrial cells ⁻ AGC Pap

Family Planning National Clinical Training Center · Supported by Office of Population Affairs Menopausal Woman On Hormone Therapy

• Unscheduled bleeding on CS-EPT (continuous- sequential estrogen-progestin therapy) • Bleeding > 3 months after start of CC-EPT (continuous-combined estrogen-progestin therapy) • Endometrial stripe > 5 mm (postmenopausal woman only)

Family Planning National Clinical Training Center · Supported by Office of Population Affairs ≥ 45

• Exclude pregnancy • Any irregular bleeding • Any suspected anovulatory uterine bleeding

Family Planning National Clinical Training Center · Supported by Office of Population Affairs Premenopausal Women

• Exclude pregnancy and infection • Prolonged abnormal uterine bleeding (AUB) intermenstrual bleeding • Unexplained post-coital or intermenstrual bleeding

Family Planning National Clinical Training Center · Supported by Office of Population Affairs Younger Than 45 Biopsy If: • No response to medical therapy • Prolonged periods of unopposed estrogen stimulation • Obesity • PCOS • Hx of oligoovulation or annovulation • Hx of oligomenorrhea or amenorrea

Note: Prior use of combined hormonal contraceptives or continuous progestins protective!

Family Planning National Clinical Training Center · Supported by Office of Population Affairs Cervical cytology: Endometrial cells

• Postmenopausal • Anovulatory (either anovulatory uterine bleeding or amenorrhea) • Amenorrhea

Family Planning National Clinical Training Center · Supported by Office of Population Affairs Cervical cytology: AGC Pap

• Favor endometrial origin • Any AGC result if patient at higher risk • Over 35 • Obesity • PCOS • Hx of oligoovulation or annovulation • Hx of oligomenorrhea or amenorrea

Family Planning National Clinical Training Center · Supported by Office of Population Affairs Cervical cytology: Atypical endometrial cells

EMB + ECC (endocervical sampling – for example with endocervical curettage)  if neg  colposcopy

Family Planning National Clinical Training Center · Supported by Office of Population Affairs If endometrial biopsy is:

• Nondiagnostic • Or shows no evidence of hyperplasia or cancer and the patients fail to respond to medical therapy

→office hysteroscopy or saline infusion sonohysterography with further sampling is indicated.

Family Planning National Clinical Training Center · Supported by Office of Population Affairs Lynch Syndrome Hereditary Non-polyposis Colorectal Cancer Syndrome (HNPCC)

• High risk • Annual screening after age 35 • Prophylactic hysterectomy and oophrectomy after childbearing complete Differential Diagnosis Other tests and other diagnostic considerations Other Testing for Abnormal Bleeding

• CT/GC • Pregnancy test (even with tubal ligation) • Sensitive β-hCG to exclude trophoblastic disease in patients who were recently pregnant • Thyroid-stimulating hormone level assessment to exclude hypothyroidism or hyperthyroidism • Prolactin level testing (If the level is elevated, the test should be repeated in the fasting state.)

Family Planning National Clinical Training Center · Supported by Office of Population Affairs Postmenopausal Bleeding: Differential Diagnosis Exogenous estrogens • HT (therapy formerly known as HRT) Endogenous estrogens • Acute stress • Estrogen-secreting ovarian tumor Atrophic vaginitis Endometrial hypoplasia (atrophy)

Family Planning National Clinical Training Center · Supported by Office of Population Affairs Contraindications Whom not to test Contraindications

 Pregnancy  Recent or active PID  Active cervical infections  Clotting disorders Technique

Family Planning National Clinical Training Center · Supported by Office of Population Affairs Caveats

Blind procedure Many areas of endometrium unsampled Endometrial polyps and other anatomic varients may be missed

Family Planning National Clinical Training Center · Supported by Office of Population Affairs Uterine Anatomy

Family Planning National Clinical Training Center · Supported by Office of Population Affairs Technique of EMB

Bimanual exam to evaluate uterine axis, size • Cleanse cervix with antiseptic • Choose correct type (rigidity) of sampler • Gently advance to fundus; expect resistance at internal os • Note depth of sounding with side markings • Pull back stylet (inner stiffening rod) to establish vacuum

Family Planning National Clinical Training Center · Supported by Office of Population Affairs

Family Planning National Clinical Training Center · Supported by Office of Population Affairs Use of the sampling device

• Suction developed once device is at fundus by withdrawing inner stiffening rod • Sampling done by spiraling technique: fundus to internal os and returning to fundus

Family Planning National Clinical Training Center · Supported by Office of Population Affairs Family Planning National Clinical Training Center · Supported by Office of Population Affairs Use of the sampling device

Rotate in a helical direction from the fundus to the os in order to use the lateral cutting edge of the port • If the sampler has filled, remove  place tissue in fixative • If the sampler did not fill, repeat 2-3 more passes

Family Planning National Clinical Training Center · Supported by Office of Population Affairs Spiral Technique

Image courtesy of Dr. Anita Nelson

Family Planning National Clinical Training Center · Supported by Office of Population Affairs Use of the sampling device • If a “curette check” for completeness is desired, perform in-and-out motion in vertical strips to confirm a “gritty” feel • Cut tip of sampler and empty any remaining tissue

Family Planning National Clinical Training Center · Supported by Office of Population Affairs Family Planning National Clinical Training Center · Supported by Office of Population Affairs Challenging situations Clinical tips

Family Planning National Clinical Training Center · Supported by Office of Population Affairs Tips for Internal Os Stenosis Pain relief • Use para-cervical or intra-cervical block • Intrauterine instillation of lidocaine

Family Planning National Clinical Training Center · Supported by Office of Population Affairs Tips for Internal Os Stenosis Cervical dilation • Stabilize cervix with tenaculum Dilate cervix progressively • Lacrimal probes • Cervical os finders • Use small size Pratt or Hegar dilators

Family Planning National Clinical Training Center · Supported by Office of Population Affairs Internal Os Stenosis

• Freeze endometrial sampler to increase rigidity • Grasp sampler with ring forceps 3-4 cm from tip

Family Planning National Clinical Training Center · Supported by Office of Population Affairs Pain

Inject 1/2 cc local anesthetic agent Paracervical block Alternative diagnostic strategy with anesthesia

Family Planning National Clinical Training Center · Supported by Office of Population Affairs Results and management Result: Non-Neoplastic

• Proliferative: Einduced growth, but no ovulation • Secretory: ovulatory or recent progestin exposure • Menstrual: glandular breakdown, non-neoplastic • Disordered: out-of-phase glands (often anovulation) • Chronic endometritis/inflammation: plasma cells + wbc • Atrophic: hypoplastic glands and stroma

Family Planning National Clinical Training Center · Supported by Office of Population Affairs Result: Non-Neoplastic

• Cystic hyperplasia: hypoplastic glands and stroma • Insufficient: not enough tissue for interpretation – If adequate sampling, atrophic endometrium likely – If sounding <5 cm, may not have entered cavity Result: Neoplasm

Endometrial polyp Simple endometrial hyperplasia • Gland proliferation and crowding, but no atypia • Reversible with continuous progestin exposure

Family Planning National Clinical Training Center · Supported by Office of Population Affairs Result: Neoplasm

Atypical endometrial hyperplasia • Hyperplasia with nuclear atypia of gland cells • Premalignant; often not reversible with progestin Endometrial carcinoma • Stromal invasion of malignant glands

Family Planning National Clinical Training Center · Supported by Office of Population Affairs Follow up Management Postmenopausal Bleeding: Management

• Atrophic vaginitis: topical estrogen • Chronic endometritis: + antibiotics • Cystic hyperplasia or endometrial atrophy • Observe • Simple endometrial hyperplasia • Continuous high dose progestin, then re- biopsy in 3-4 months

Family Planning National Clinical Training Center · Supported by Office of Population Affairs Postmenopausal Bleeding: Management

• Atypical endometrial hyperplasia: hysterectomy • Endometrial cancer: hysterectomy + XRT

Family Planning National Clinical Training Center · Supported by Office of Population Affairs Persistent Spotting After Negative Sampling • On hormone therapy • Adjust balance • If proliferative increase progesterone/progestin • If atrophic increase estrogen or decrease progesterone/progestin • If persists or if not on hormone therapy •  diagnostic hysteroscopy or sonohysteroscopy

Family Planning National Clinical Training Center · Supported by Office of Population Affairs Alternative Diagnostic Strategies

Family Planning National Clinical Training Center · Supported by Office of Population Affairs Hysteroscopy

Hysteroscopy permits full visualization of the endometrial cavity and endocervix It is extremely helpful in diagnosing focal lesions that may be missed with endometrial sampling. The likelihood of endometrial cancer diagnosis after a negative hysteroscopy result is 0.4– 0.5%

Family Planning National Clinical Training Center · Supported by Office of Population Affairs Transvaginal Ultrasonography • Transabdominal imaging is less sensitive and of limited value in the evaluation of the endometrium. • Endometrial thickness alone is not considered a clinically robust observation that can be used to determine management. • Varies 4-8 mm during the proliferative phase • 8-14mm during the secretory phase • 5mm is usual cutoff to trigger further assessment

Family Planning National Clinical Training Center · Supported by Office of Population Affairs Saline Infusion Sonohysterography

Can determine the presence or absence of intracavitary lesions and depth of myometrial involvement with leiomyomas More accurately evaluates the endometrium compared with transvaginal ultrasonography alone.

Family Planning National Clinical Training Center · Supported by Office of Population Affairs VULVAR BIOPSY

Family Planning National Clinical Training Center · Supported by Office of Population Affairs Outline

1) Indications and site selection 2) Anesthesia 3) Types of biopsies and technique

Family Planning National Clinical Training Center · Supported by Office of Population Affairs Magnification

Colposcope or any mechanism to allow magnification

Family Planning National Clinical Training Center · Supported by Office of Population Affairs Indications and Site Selection When and whom to biopsy

Family Planning National Clinical Training Center · Supported by Office of Population Affairs Papular Lesions

• Papular or exophitic lesions, except genital warts • Lesions (even warty lesions) that don’t respond or worsen with treatment

Family Planning National Clinical Training Center · Supported by Office of Population Affairs Thickened Lesions

Thickened lesions to differentiate: • Vulvar Intraepithelial Neoplasia (VIN) • Squamous Cell Cancer • Lichen Sclerosis Biopsy thickest region

Family Planning National Clinical Training Center · Supported by Office of Population Affairs Hyperpigmented Lesions

Black, brown, red, pink, purple Unless obvious nevus or lentigo Use melanoma criteria Biopsy darkest area

Family Planning National Clinical Training Center · Supported by Office of Population Affairs Ulcerative or Erosive Lesions

Unless obvious herpes, syphilis or chancroid Biopsy at edge and include normal tissue

Pipkin C. Dermatol Clin. 2010;28(4):737-51

Family Planning National Clinical Training Center · Supported by Office of Population Affairs In summary:

Biopsy whenever diagnosis is uncertain

Family Planning National Clinical Training Center · Supported by Office of Population Affairs Where to biopsy

• Homogeneous lesions : one biopsy in center of lesion • Heterogeneous lesions: biopsy each different lesion

Family Planning National Clinical Training Center · Supported by Office of Population Affairs Site Selection Considerations

Choose the most suspicious area If there is a choice, avoid: • Periclitoral, urethral or anal areas • Vascular areas • Areas under tension • Curves

Family Planning National Clinical Training Center · Supported by Office of Population Affairs Diagnostic Challenges

• If the area is eroded can pose a diagnostic dilemma if epidermis missing • If area has advance scarring may get a nonspecific result if active inflammation has subsided • Multiple biopsies from different regions may be needed to show diagnostic findings

Family Planning National Clinical Training Center · Supported by Office of Population Affairs Anesthesia

Family Planning National Clinical Training Center · Supported by Office of Population Affairs Local Anesthetic Topical

4% liposomal lidocaine (30 min) or EMLA (60 min

Family Planning National Clinical Training Center · Supported by Office of Population Affairs Local Anesthetic: Injected

• Most lesions will require ½ cc. lidocaine or less • Epinephrine typically is unnecessary, unless longer anesthetic duration or less bleeding is critical • Use insulin syringe (smallest, sharpest needle) • Inject anesthetic s-l-o-w-l-y to minimize pain

Family Planning National Clinical Training Center · Supported by Office of Population Affairs Types of biopsy What instruments

Family Planning National Clinical Training Center · Supported by Office of Population Affairs Type of Biopsy Punch Shave biopsy Excisional biopsy

Family Planning National Clinical Training Center · Supported by Office of Population Affairs Punch

• Obtain adequate specimen (~ 3-4mm) • No need to include healthy tissue • Good anesthetic effect • Use epinephrine in lidocaine • Arrange tissue so that you are approaching at right angle to your punch • Stretch skin as needed • Stabilize your hand against adjacent tissue • Use twisting motion

Family Planning National Clinical Training Center · Supported by Office of Population Affairs • No need to exert pressure • Twist 3 or 4 mm Keyes punch back-and-forth until it “gives” into fat layer

Family Planning National Clinical Training Center · Supported by Office of Population Affairs To Collect Specimen

. Photo courtesy of Dr. Michael Policar

Family Planning National Clinical Training Center · Supported by Office of Population Affairs After Punch

• Lift specimen . with forceps or needle . Snip base . With scissors or scalpel

Family Planning National Clinical Training Center · Supported by Office of Population Affairs Shave

• Helpful with exophytic lesions and warts • Hold specimen with forceps • Shave base evenly; flat against skin • With curved scalpel

Family Planning National Clinical Training Center · Supported by Office of Population Affairs Control of Bleeding

Pressure and patience Monsel’s Solution

AgNO3 stick (Silver nitrate will not cause a tattoo) Gel Foam pieces Suturing after punch or excisional biopsy almost never necessary

Family Planning National Clinical Training Center · Supported by Office of Population Affairs Excisional

Tailor to size of lesion Use matching elliptical incisions, so defect will close most securely

Family Planning National Clinical Training Center · Supported by Office of Population Affairs Excisional

• Good anesthetic effect • Excise an ellipse; A canoe • V the incision from top to base • Avoid cutting rectangles, squares

Family Planning National Clinical Training Center · Supported by Office of Population Affairs Suture

Start with one stitch at the mid-point Then split the difference

Family Planning National Clinical Training Center · Supported by Office of Population Affairs Use a separate pathology container for each morphologically distinct area biopsied

86 Family Planning National Clinical Training Center · Supported by Office of Population Affairs References

ACOG. Practice Bulletin No. 136 Management of Abnormal Uterine Bleeding Associated With Ovulatory Dysfunction. Obstet Gynecol. 2013;122:176-85. Linda D. Bradley LD, Diagnosis of abnormal uterine bleeding with biopsy or hysteroscopy. Menopause 2011;18 (4):425-33. Gordon P, Endometrial Biopsy n engl j med 2009;361(26)e61. ACOG. Practice Bulletin No. 128 Diagnosis of Abnormal Uterine Bleeding in Reproductive –Aged women. Obstet Gynecol. 2012;120:197-206.

Family Planning National Clinical Training Center · Supported by Office of Population Affairs References

Goldstein RB, 1. Bree RL, Benson CB, et al. Evaluation of the woman with postmenopausal bleeding: Society of Radiologists in Ultrasound-Sponsored Consensus Conference statement. J Ultrasound Med 2001;20:1025-36. Trimble CL et al, Management of Endometrial Precancers. .Obstet Gynecol. 2012; 120(5):1160-75.

Family Planning National Clinical Training Center · Supported by Office of Population Affairs