Shelley Miksis, DNP, ARNP 01-21-10 Vulvar Conditions Shelley Miksis, DNP, ARNP 01-21-10

Plan for today’s session General considerations Basis for differential Evaluation History, PE, Dx procedures Management Focus on specific conditions VIN, vulvar CA, LS, LP, & hyperplasia

General Considerations Wide array of benign, premalignant & malignant lesions Eyes alone insufficient to tell benign from malignant Biopsy needed for diagnosis and to identify neoplasia

General Considerations Symptoms related to vulvar disorders include: Pruritus Vulvodynia Superficial dyspareunia Lesions White, red, pigmented, raised, or ulcerated Patient may be asymptomatic

General Considerations Vulvar symptoms may be caused by: Infections Dermatologic disorders Neoplastic vulvar disorders Non-neoplastic vulvar disorders

Definition of terms Neoplasia= Formation of new tissue, neoplasm Neoplasm = An abnormal new growth of tissue that grows by cellular proliferation more rapidly than normal, continues to grow after the stimuli that initiated the new growth cease, shows partial or complete lack of structural organization and functional coordination with the normal tissue, and usually forms a distinct mass of tissue which may be either benign or malignant.

Classification: Non-neoplastic Non-neoplastic epithelial disorders of skin and mucosa Lichen sclerosus Squamous hyperplasia Other dermatoses [ psoriasis, lichen simplex, lichen planus, dermatits, etc. ]

Classification: Neoplastic 1986 ISSVD Classification System for Vulvar Intraepithelial Neoplasia (VIN) VIN I mild dysplasia VIN II moderate dysplasia VIN III severe dysplasia and carcinoma in situ or CIS

Problems with Old VIN Classification Natural history of VIN 1, 2, and 3 does not progress on a continuum. VIN 1 is not a precursor to cancer VIN 1 has not shown to be a reproducible or reliable diagnosis No reliable distinction between VIN 2 and 3

2004 VIN Classification Changes Classification based on morphologic criteria VIN I designation has been eliminated Low malignant potential Not a precursor to VIN 2 or 3 Does not require treatment Term VIN is now limited to histologically high grade squamous lesions (formerly VIN 2 and 3) Significant potential for progression to invasive cancer. Requires treatment

The natural history of VIN 1, 2, and 3 does not progress as a continuum like CIN, the new system thus eliminated VIN 1 and combined VIN 2 and 3. VIN 1 has not been shown to be a reproducible or reliable diagnosis, and there is likewise no reliable diagnostic distinction between VIN 2 and 3.

Classification: Neoplastic 2004 ISSVD Classification System for VIN a. VIN, usual type (r/t high risk HPV) Warty type Basaloid type Mixed (warty, basaloid) type b. VIN, differentiated type (not r/t HPV)

Classification: Neoplastic VIN, usual type – most common Basaloid and warty subtypes based on morphologic and histologic features Basaloid – thickened epithelium with relatively flat, smooth surface Warty – undulating or spiking surface, giving condylomatous appearance

Approach to differential Based on morphology of lesion, not symptoms White lesions Red lesions Dark or pigmented lesions Ulcerative or erosive lesions Solid and cystic tumors

Differential: Key to diagnoses listed If a disease or condition  regular font If an infection  Italics If malignant or pre-malignant  bold

White lesions Condyloma acuminate / genital warts Lichen sclerosus Post-inflammatory hypopigmentation Squamous cell hyperplasia VIN Vitiligo

Lichen sclerosus

White plaques of VIN

Condyloma acuminata

Red Lesions Allergic or contact/irritant dermatitis Cutaneous candidiasis Lichen planus Paget’s Disease Psoriasis VIN

Red macular lesion of VIN

Paget’s disease

Vulvar psoriasis

Allergic contact dermatitis: Neck

Dark lesions Acanthosis negricans Basal cell carcinoma Lentigo Melanoma Nevi Post-inflammatory hyperpigmentation Seborrheic keratosis VIN

Acanthosis Nigricans

Brown macular lesion of VIN

Superficial spreading melanoma

Dysplasic nevus Note: the dysplastic nevus has irregular borders and multiple colors.

Lentigo

Lentigo maligna melanoma

Seborrheic keratosis

Ulcerative lesions Basal cell carcinoma Erosive lichen planus Genital herpes Primary syphilis Squamous cell carcinoma

Solid & Cystic Tumors Small lesions (usually < 1 cm in diameter) Acrochordons (skin tags) Epidermal cysts Hidradenitis suppurativa

Solid & Cystic Tumors Large lesions Bartholin’s Cyst Bartholin’s Abscess Verrucous carcinoma

Bartholin’s gland abscess

Evaluation Consider both age and immune status Higher risk of malignancy if post- menopause Immune compromised - Increased risk of VIN & vulvar cancer - Exaggerated presentations of common infections

Evaluation: History 1. Onset - how long lesion has been present? 2. Character - initial appearance? current appearance? 3. Location - where on genitals? similar lesions elsewhere? 4. Timing - come and go? always there? 5. Course - staying the same? getting worse?

Evaluation: History 6. Self treatment and outcome - What’s been tried? ( herbal, OTC, Rx meds ) - Response to each thing tried? ( better, worse, no change ) 7. Aggravating & alleviating factors - What makes it worse? - What makes it better?

Evaluation: History Itching? 8. Associated symptoms focused on lesion Pain? Burning or Stinging? Feeling of rawness? Dampness? Bleeding?

If itching, ask… How intense is the itching? Does itching awaken you from sleep? Amount of scratching in response to itching?

Evaluation: History Additional associated symptoms re: Vaginal infections STIs Cervical cancer Derm conditions Low estrogren state Vulvar hygiene - See Outline, page 13 Dyspareunia

Evaluation: History Related PMH Vulvar conditions Cervical dysplasia HPV status Cervical, uterine, or ovarian cancer Allergies; asthma; skin problems Lowered immune status HIV status

Evaluation: History Previous occurrences Related FH: Diabetes, skin problems Patient profile -- Stress -- Tobacco use Impact on ADLs / quality of life

Evaluation: PE Not all vulvar conditions are symptomatic Careful inspection of external genitalia If find an asymptomatic lesion, then SA

Evaluation: PE Inspect skin non-genital areas, esp skin folds Inspect mucous membranes Lymphadenopathy – inguinal External genitalia and vulva Speculum exam, if indicated

PE: more detail Inspection of external genitalia and vulva  Good light essential  Spread hair/labia/folds to inspect all aspects

PE: Lesion characteristics Type of lesion Size & shape of individual lesions Solitary –or-- multiple & pattern Color Texture & if tender Secondary changes– crusts, etc.

Diagnostic procedures Macroscopic - Magnifying lens - Colposcopy Microscopic - wet prep - vulvar cytology 3. Biopsy

Biopsy if suspicious for malignancy asymmetry irregular border variable color bleeds rapidly changing does not heal slight ulceration in raised lesion

Also biopsy if… Diagnosis is not clear Lesion does not resolve w/ therapy Patient concerned & wants biopsy

Biopsies: Types Shave Punch Excisional Incisional

Management: General Good vulvar hygiene Soaks Corticosteroids Estrogen (topical) Pt education Follow-up

Now for specific conditions…

VIN Vulva, vagina, cervix, and anus share same embryonic origin Oncogenic stimulus (e.g.HPV) neoplasia Neoplasia influenced by host reaction VIN, usual type and differentiated  have malignant potential

VIN: Risk Factors intraepithelial neoplasia in other lower genital tract sites HPV infection immunocompromised smoking chronic vulvar irritation lighter skin pigmentation

Old VIN I – Now Condyloma/HPV Effect Well localized and delineated Flat or slightly elevated White and rough Less common red-brown

VIN, usual type (warty, basaloid, and mixed) Most common type of VIN (90-95%) Precursor lesion to HPV-associated invasive squamous cell carcinoma (SCC) HPV associated (HPV types 16, 18, 31) Presents in younger, premenopausal women

PE findings: VIN, usual type Multifocal lesions Well localized and delineated Lesions most often in interlabial grooves, posterior fourchette, & perineum Slightly elevated, white-gray, rough Less common – red-brown color or red-white patches

VIN, usual type white-gray lesion

VIN, usual type red lesion

VIN, usual type brown lesion

VIN, differentiated Less common type of VIN (6-10% of cases) Frequently associated with SCC, LS, Squamous hyperplasia Mainly postmenopausal women Not related to HPV

PE findings: VIN, differentiated Commonly encountered in background of lichen sclerosis Unifocal lesions Erosive or ulcerative areas Hyperpigmented, fixed, or indurated lesions Warty papule Hyperkeratotic plaque

White plaques of VIN

VIN

VIN: Diagnosis Early dx depends on regular vulvar exams High index of suspicion If suspect, biopsy (via colposcopy best) Refer confirmed VIN to MD

VIN: Treatment Wide local excision Laser vaporization Skinning vulvectomy (w/ or w/out graft) Immunomodulators *Agents that enhance or induce a strong cell-mediated immune response likely hold the greatest promise not only for control of HPV-related disease, but also for reduction of future recurrences

Vulvar Cancer 4th most common gyn cancer Bimodal age distribution – represents two distinct etiologies Young women – related to HPV (60% of vulvar CAs) Older women – not related to HPV (chronic inflammatory or auto-immune process) Most ( > 90%) are squamous cell CAs Risk factors same as VIN risk factors, plus if PMH of VIN Many women are asymptomatic

Vulvar Cancer: Symptoms Most common  Pruritus Less common, when more advanced -- vulvar bleeding or discharge -- dysuria -- enlarged lymph node in groin

Vulvar Cancer: PE Findings Most often  unifocal vulvar plaque, ulcer, or mass (fleshy, nodule, or warty) on labia majora

Vulvar Cancer

SCC and LS

Vulvar Cancer: Diagnosis Histological evaluation essential - diagnosis - depth of involvement  biopsy center of lesion If suspect or diagnose vulvar cancer, must refer to an MD

Lichen Sclerosus Chronic, progressive, inflammatory skin condition found most often in the anogenital region. Does not occur in the vagina Accounts for ~70% of non-neoplastic vulvar lesions Occurs most in post-menopausal women, although not exclusively

Lichen Sclerosus: Symptoms  PRURITIS is HALLMARK of LS Intensity may awaken Other symptoms: Rectal itching, fissures, bleeding, painful defecation Dyspareunia Decreased sexual sensation, anorgasmia Dysuria, difficulty voiding *May be asymptomatic – 1/3 of patients

LS: PE findings Classic LS = thin, white, wrinkled skin on labia minora and/or labia majora. “Parchment-like” “Keyhole” pattern Fissures in labial folds, around clitoris or anus Excoriations and lichenification r/t scratching Telangiectasia / hematoma / ecchymoses Changes in vulvar architecture

LS: Changes in vulvar architecture None early in course of LS Labia majora/minora become less distinct. - Adhesion of labia minora to majora Clitoris covered under fused prepuce. - Edema or agglutination of prepuce and frenulum “bury clitoris” Stenosis or constriction of introitus

Lichen sclerosus

Lichen Sclerosus

Lichen sclerosus White appearance from: hyperkeratosis loss of pigmentation relatively less vascularity

LS: Keyhole pattern Perianal LS

LS: Loss of architecture Asymptomatic in 1/3 of patients. Can progress to scarring and loss of vulvar architecture

Lichen Sclerosus

When suspect LS, differential includes: Lichen planus Squamous cell hyperplasia (usually lichen simplex chronicus) Vitiligo Psoriasis Candidiasis

When suspect LS… MUST rule out VIN and vulvar cancer before initiating treatment. Women w/ vulvar LS have increased risk for invasive squamous cell cancer.

LS: Biopsy Biopsy to confirm diagnosis  3-4 mm punch  Specimen from advancing margin Biopsy to identify VIN or vulvar CA  Biopsy center to ensure sample most severe pathology

LS: Management Initiate treatment asap, even if asymptomatic Wet dressings or soaks x 20-30 min w/ Burrow’s sln Corticosteroids  relief of pruritus and resolution of hyperkeratosis, fissures, and ecchymoses. -- Will not reverse atrophy, whiteness or scarring. Rx: Clobetasol or halobetasol propionate 0.05% ointment BID x 4 weeks, then qhs x 4 weeks, then 1-3 x per week for maintenance. Directions: Spread sparingly to cover affected area with thin film

LS: Management Evaluate for possible associated problems Autoimmune disorders, e.g., alopecia areata, vitiligo, thyroid disease, and pernicious anemia (21% - most commonly thyroid disorder) Premature menopause Infection

LS Management: Patient Education Chronic, progressive condition; ? cause Symptom relief and treatment options Lesions do not always disappear w/ tx Do NOT stop treatment when itching stops! Continued topical therapy can slow progression Encourage sufficient sleep, diet, and exercise Encourage stress reduction techniques Support group available, if interested Regular self and clinician evaluation essential

LS Management: Follow-up On-going evaluation is essential -- Visits every 1-3 months until stable -- Every 6 months while stable Biopsy progressive, recurrent, persistent, or suspicious lesions – risk of SCC. Refer to MD, if not responsive to therapy

Lichen Planus An inflammatory autoimmune skin disorder which may affect only the vagina, vulva or may occur elsewhere on skin; also nails and mucous membranes Vulvar LP is uncommon Peak incidence, women 30-60 yrs old

Lichen Planus: Symptoms Irritating vaginal discharge and/or vulvar soreness, thought to be yeast infection Intense pruritus Burning Dyspareunia Post-coital bleeding

Lichen Planus: 3 types Papulosquamous LP: small, violaceous, intensely pruritic papules on keratinzed skin. Papules are poorly demarcated, pink, and opaque. Associated w/ “milky striae” on inner aspects of the labia.

Lichen Planus: 3 types 2. Hypertrophic LP: hyperkeratotic, rough lesions on perineum and perianal area. May appear similar to squamous cell CA.

Hypertrophic lichen planus

Lichen Planus: 3 types 3. Erosive LP: Most common variant of LP Involves vagina 70% of the time Violaceous erosions that look like glassy, reticulated, white papules and plaques. White striae along lesion margins. Progression leads to extensive erosion and ulceration and destruction of vulvar architecture.

Erosive Lichen Planus

Erosive Lichen Planus

Lichen Planus

Lichen Planus

Lichen Planus

Lichen Planus

Lichen Planus If suspect lichen planus refer to MD Hard to diagnosis! Difficult to treat! If suspect lichen planus refer to MD

Squamous cell hyperplasia Most squamous cell hyperplasia is lichen simplex chronicus Occurs in all ages Thickened skin (lichenification) is result of scratching or rubbing  Squamous cell hyperplasia may coexist with LS

Lichen Simplex Chronicus

Lichen Simplex Chronicus

Squamous cell hyperplasia Diagnosis of exclusion. Need to rule out— Lichen sclerosis Psoriasis Lichen planus Eczema HPV Candidiasis

Squamous cell hyperplasia Consider possibility of malignancy (VIN, vulvar CA) before starting treatment. Goal of treatment is to— break “itch-scratch” cycle

Squamous cell hyperplasia: Treatment Mild symptoms – use low to medium potency corticosteroid ointments Hydrocortisone 1 –or- 2.5 % Triamcinolone 0.1 % Rx: Apply twice daily for 2-4 weeks, then x 2 /week. Continue therapy at min frequency to control pruritus. More than mild symptoms – use high potency corticosteroid ointment -- Clobetasol propionate 0.05% ointmt each night x 30 days, then re-evaluate [usually 2-3 months, then taper]

Squamous cell hyperplasia: Treatment If night time itching  scratching, Rx sedating antihistamine (e.g., hydroxizine) in pediatric dosage ( 10 mg at hs)

Consulting & Referring Vulvar biopsy Consult if uncertain if vulvar biopsy indicated Refer if not skilled in vulvar biopsy techniques VIN Consult if suspect VIN Refer if VIN diagnosed

Consulting & Referring Management Whenever unfamiliar with indicated meds Consult with NP/PA specialists in derm, pharmacist, or MD to ensure appropriate med, dose, route, and timing. Refer if lesion persists despite treatment Refer whenever surgery or laser treatment is indicated (e.g., for VIN)