Vulvar intraepithelial neoplasia: Current concepts

Transcription

1 Vulvar intraepithelial neoplasia: Current concepts L. Stewart Massad, M.D. Dept. of Obstetrics & Gynecology Washington University School of Medicine St. Louis, MO

2 Disclosure I have no financial ties to industry I will discuss FDA-unapproved use of imiquimod for VIN

3 Objectives Participants should be able to Classify VIN using ISSVD system Use history to establish risk for VIN Triage patients to biopsy Manage VIN according to ACOG/ASCCP guidelines

4 November 2011: ACOG and ASCCP released a joint committee opinion outlining classification and management of vulvar intraepithelial neoplasia

5 What is VIN?

6 What is VIN? First defined in 1982 Distinguished condylomata from premalignant lesions based on Abnormal mitoses Nuclear enlargement Cytologic atypia Crum CP et al. AJOG 1982;144:77-83

7 What is VIN? Series updated 1985: 42 cases: all severe dysplasia/cis Bimodal distribution Koilocytosis/condyloma in younger pts 22% persistence/recurrence No spontaneous regression 5 cancers 4 within 3y of diagnosis Crum CP et al. Update

8 What is VIN? This established core concepts: Precancerous Only the high-grade disease matters There are 2 broad classes HPV associated HPV unassociated

9 VIN: Natural history Untreated, 7/8 cases of VIN progressed to invasion within 8 years But others reported 14 cases of regression after 3-30mo in women <28yo <5% of treated lesions progress to cancer 15-20% of VIN excisions show occult cancer Large natural history studies now unethical Jones RW, Rowan DM. ObGyn 1994;84:741-5 & 2000;96:470-2 and Chafe W et al. Gynecol Oncol 1988;31:154-62

10 What is VIN? ISSVD classification 1986: like CIN VIN1: dysplastic cells in lower 1/3 of epithelium VIN2: dysplastic cells in mid 1/3 of epithelium VIN3: dysplastic cells in upper 1/3 of epithelium No invasion

11 Why change? Doesn t reflect dual origin of VIN/cancer HPV-associated Non HPV-associated VIN1 poorly reproducible, not precancer Even when HPV16+

12 What is VIN? New system: ISSVD 2004 VIN: usual type (HPV associated): >90% Warty type Basaloid type Mixed VIN: differentiated type: <10% With lichen sclerosus or hyperplasia) Everything else is just HPV infection (condyloma, atypia, HPV change)

13 Usual VIN, warty type Clinical: Hypo/hyperpigmented Flat or raised Multifocal Younger women Histology: Parakeratosis / hyperkeratosis Spiky or undulating surface Cytoplasmic maturation

14 VIN, Warty type Courtesy of Dr T. Darragh, UCSF

15 Usual VIN, basaloid type Clinical: Often pigmented Multifocal Older women Histology: Immature basaloid cells Smooth or undulating surface Little cytoplasmic maturation

16 Usual VIN, Basaloid type Courtesy of Dr T Darragh, UCSF

17 Differentiated VIN Clinical: white or red; plaque/ulcer/ Lichen sclerosus, invasive cancer adjacent Histology: Atypia subtle, confined to basal / parabasal areas Prominent eosinophilic cytoplasm (keratin) Keratin pearls, some basally located Nuclear chromatin changes, atypical mitoses p16 negative, p53+ in basal cells, Ki-67+

18 Differentiated VIN

19 VIN: clinical presentation Symptoms: Itching Bleeding Discharge Pain OR NONE

20 VIN: clinical presentation Exam findings: Variable size Hyper/hypopigmented: white, gray, brown, black, flesh-colored Smooth or warty Ulcerated? Suspect cancer

21 VIN: Who s at risk? Bimodal incidence 30s-50s: HPV associated: Dominate case series 60s-70s: LS associated HIV increases risk >50% are smokers 30% have concurrent/prior CIN/VAIN Risk of invasion rises with age at initial diagnosis with longer follow-up

22 VIN: diagnosis Diagnosis requires biopsy Biopsy demands clinical suspicion Biopsy most new vulvar lesions Not warts in reproductive age women Biopsy warts that fail to regress/respond Warts in older women: suspect cancer Not varicosities Not obvious flat nevi ( freckles )

23 VIN: Colposcopy Apply 5% acetic acid via gauze sponge x 5min View at 6-10x (not 15x as for cervix) Inspect interlabial folds, under clitoral hood Distinguish hyperplasia from VIN Hyperplasia is faint gray, diffuse, flat VIN is raised, irregular, with sharp borders

24 Usual VIN, warty type, hyperpigmented

25 Central white lesion Surrounding gray lesion Usual VIN, warty type

26 Usual VIN, warty type flat, not raised

27 Warty lesion Hyperpigmented periphery, hypopigmented center, after acetic acid

28 Raised and flat VIN in HIV+ woman, both with hyper- and hypopigmented areas

29 VIN, usual type, warty, before acetic acid

30 VIN, warty type, after acetic acid

31 Hypopigmented center, hyperpigmented rim

32 Multifocal hyperpigmented VIN in HIV

33 Usual VIN, warty type, after acetic acid

34 VIN: Biopsy technique Local cleansing: Betadine, EtOh Local anesthesia: 27 gauge needle (tuberculin syringe) Buffered 1% lidocaine + epi 3mm punch vs Kevorkian + AgNO3 4+mm punches require suture hemostasis Biopsy most suspicious area (not margin)

35 VIN: Treatment options There are 3 treatment options Wide local excision Recommended if cancer suspected Laser ablation Imiquimod 5%

36 VIN: Wide local excision Preop colposcopy to define lesions + margin doubles recurrence risk Draw >5mm margins Prophylactic antibiotic to cover GPCs Minimize cautery Avoid excision >5mm to minimize bleeds Consider flap closure

37 Large left labial, perineal body defect

38 VIN: Wide local excision: Closure Closure without tension often requires skin flaps Rhomboid V-Y Lotus petal Myocutaneous flaps (gluteal, gracilis, TRAM) rarely needed after superficial excision

39 Adjacent VIN Central cancer

40 Vagina Advancing V-Y flaps sutured in midline Anus

41 Layered primary closures Vagina Bilateral V-Y flaps Anus

42 VIN: Wide local excision Positive margin is common despite colpo 50-70% of cases Recurrence risk linked to multifocality, +margin, younger age at diagnosis Re-excision not required

43 VIN: Laser ablation: technique Preop colposcopy to define margins Include 5mm lateral margin Ablate to 3 rd surgical plane (white)/2-3mm

44 VIN: Laser ablation: Physics Power density 1000 W/cm2 With 3mm beam diam, requires 60W Continuous or superpulse mode Use colposcope with micromanipulator Handpiece limits beam diameter Handpiece increases risk of defocused beam

45 Laser input High volume smoke evacuat or Colposcope with micromanipulator Wet towels

46 Laser handpiece Wet towels Depth gauge Anal tampon Gauze with acetic acid

47 Oral narcotics VIN: Laser ablation Postoperative care: Marcaine + epi before leaving OR Ice pack x 24h; hemorrhoid cushion Cotton panties or none Sitz baths tid & prn Void into basin if urine burns defect Lidocaine gel 2% + sulfadiazine cream

48 VIN: Imiquimod protocol Exclude invasion Multiple biopsies? 5% cream self-applied 32-x/wk Colposcopy q4w Le T et al. Gynecol Oncol 2007;106: and Van Seters M et al. NEJM 2008;358;

49 VIN: Treatment selection Imiquimod for small lesions, young women motivated for close follow-up Laser for multifocal lesions, no suspicion of invasion WLE for older women, DVIN, ulcerated lesions, questionable FU compliance Encourage smoking cessation

50 VIN: Post-treatment outcomes 40% recurred after laser 48% recurred after photodynamic Rx 42% recurred after WLE 0% recurred after vulvectomy 1 cancer Recurrence risk higher if multifocal, DVIN Hillemans P et al. Gynecol Oncol 2006;100:271-5

51 VIN: Post-treatment surveillance Inspection Teach self-inspection Clinician inspection Twice in first year, then annually Vulva remains at risk Role of colposcopy unclear Consider anal cytology or anoscopy

52 VIN: Conclusions Only high grade dysplasia is VIN Biopsy nonwarty lesions, warts >50, and warts that don t get better Treat VIN with excision if cancer suspected Otherwise WLE, laser, or imiquimod Follow with VSE, pelvic/pap q6mo x2, then annual exams

53 Acknowledgements ACOG Gyn Practice Committee ASCCP Practice Committee