Colposcopy of VIN and Vulvar Cancer

Hope K. Haefner, M.D. Director, The University of Michigan. Center for Vulvar Diseases.

Fuente: Colposcopy of VIN and Vulvar Cancer.
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Learning Objectives

• To understand colposcopy of vulvar abnormalities
• To understant the neoplastic potential of VIN
• To recognize vulvar intraepithelial neoplasia and vulvar cancer
• To list the gross and colposcopic findings of VIN and vulvar cancer

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Other Means of Magnification

• Spalding Magnifiers Part 81-33-05 Toll free 1-888-855-8666
• Local 713-466-3113
• Houston, Texas.

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Colposcopic Techniques

• 5% acetic Acid
• Soak initially for 3-5 minutes
• Use copious amounts
• Reapply often
• A void using in presence of breaks in epithelium or inflammation.

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Other Solutions

• Lugol's
  • Not useful (little glycogen present outside Hart's line)
• Toluidine blue (1%)
  • Historic- stains normal tissue

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Clinical Pitfalls of vulvar Colposcopy

• Acetowhitenings is nonspecific
• Normal anatomic variants- like vestibular micropapillae- often confused with HPV colposcopically and histologically
• Marked acetowhite changes in up to 65% of normal women.

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Vulvar Biopsy Techniques

• Anesthesia
  • 1 % xylocaine with or without epinephrine
  • 27-30 gauge needle to inject 1-3 cc's of anesthetic agent
  • Inject subepidermally
• Punch biopsy
  • Tischler cervical biopsy
  • Keyes punch
  • 3-5 mm diameter dermatologic instruments (usually 4 mm)
• Fine suture (3.0 or 4.0 Vicryl Rapide) vs. Monsel's/ Silver nitrate

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Condyloma

• Over 100 types of VPH
  • 30 are found on the genital area
• May cause itching, bleeding and occasionally pain

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Intraepithelial Neoplastic Disorders of the Vulvar Skin and Mucosa

• Squamous
  • Vulvar intraepithelial neoplasia type 1 (VIN I)
    • - mild dysplasia 2.
  • VIN II – moderate dysplasia
  • VIN III – Severe dysplasia
• Other
  • Paget's disease (intraepithelial)
  • Melanoma in situ (level I)

*Classification system developed by the International Society for the Study of Vulvovaginal Diseases.

ISSSUD 2003 new terminology

1986 2002 -2003

VIN 1 HPV effect

VIN 2 VIN

VIN 3 VIN

VIN 3 Diferentiated VIN

Diff Type - Unclassified VIN (NOS)

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Incidence of Vulvar Intraepithelial Neoplasia (VIN)

• Incidence increasing
• Over the past 20 years, incidence has doubled, especially in women less than 40 years of age (50% of all cases)
• Progression to carcinoma appears to be uncommon in this age group, in the non-immunosuppressed patient.

Low grade VIN High grade VIN Risk of cancer

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History of VIN III

• Before 1970, VIN was found most often in women in the fifth or sixth decade of life
  • Older women with VIN more often have solitary lesions with a higher risk for progression to cancer

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Increasing Incidence of VIN

• Heightened awareness of neoplasia
• Increased tendency to perform biopsies
• Commonly associated with other lower genital tract neoplasia (anus, vagina, cervix) and/or carcinomas

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Human Papillomavirus and VIN

• HPV 16 and 33 are the most common subtypes detected in VIN (90% of VIN lesions associated with these two types)
• 1/3 of patients with HPV are at risk for recurrence of disease after treatment

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Risk Factors for VIN

• History of HPV (vulva, Vagina, cervix)
• Early age of onset of Sexual intercourse
• * HIV
• Cigarette smoking
• Immunosuppression
• * Pregnancy
• * Autoimmune connective tissue disorders
• * Transplant recipient
• -
• -
• * Diabetes
• * Chronic hepatitis
• -
• -
• -
• * Chemotherapy

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Relationship of VIN to Various Factors

• Group I
• Group II
• Age (y)
• 35-65
• 55-85
• Condyloma history
• Common
• Uncommon
• STD history
• Common
• Uncommon
• Prior vulvar lesion
• VIN
• LS, SCH
• Histology
• Basaloid
• Keratinizing
• Cervical neoplasia
• High Presence
• Low presence
• Smoking
• High Presence
• Low Presence
• HPV DNA
• Common
• Seldom

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Vulvar Intraepithelial Neoplasia Squamous Type

• VIN I
  • 1/3 mild dysplasia (formerly mild atypia) 40% of VIN (ICD9=624.8)
• VIN II
  • 1/3 to 2/3 moderate dysplasia (formerly moderate atypia) 14% of VIN (ICD9=624.8)
• VIN III
  • 2/3 severe dysplasia (formerly severe atypia), (carcinoma in situ) 46% of VIN (ICD9=233.3)
  • Es mas alta la frecuencia de VPH en vulva que no es diagnósticada por ser infección subclínica.

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VIN of low Grade: A Challenging Diagnosis

• Micheletti L. Barbero M, Preti M, et al
• Eur J Gynaecol Obstet 1994 ;15 ;70-4 VIN III
• VIN III (Squamous cell CIS, Bowen's disease, Erythroplasia of Queyrat, CLS simplex)

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Symptoms and Signs

• Most – completely asymptomatic
• Itching or burning
• Irritation
• Dyspareunia
• Labial erythema
• Patient notes a lesion

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VIN

• Distribution
  • Most commonly found on the non-hairbearing areas
  • Posterior vulva and periclitorial area
  • May extend to involve the anus, vagina, clitoris, or urethra

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VIN Lesions

• Unifocal or multifocal
  • White
  • Gray-brown
  • Red

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Colposcopic Features of VIN

• Similar to but not as prominent as with CIN
  • Leukoplakia
  • Acetowhitening (70%)
  • Punctation
  • Atypical vessels

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VIN Thickness

• Depht (mm)

• No.
• Deep
• Shallow
• Mean
• Hairy skin Labia majora
• 2085
• 1.04
• 0.08
• 0.37
• Non-hairy skin Labia minora
• 945
• 0.86
• 0.11
• 0.38
• Posterior fourchette
• 70
• 0.69
• 0.15
• 0.38
• Perineum
• 195
• 0.85
• 0.11
• 0.47

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Shatz P. Bergeron C. Wilkinson EJ. Arseneau J. Ferenczy A. Vulvar intraepithelial neoplasia and skin appendage involvement.

Obstetrict & Gynecology. 74(5): 769-74,1989 Nov.

Anoscopy

• Perianal involvement is noted in 33% of patients

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INSTRUMENTS

• Hinkel-James Anoscope
• Fansler Operative Anoscope

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POSITIONS

• Exaggerated Lithotomy Position
• Left Lateral or Sim´s Position
• Knee-Shoulder Position

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Non- squamous Types

• Paget's disease
• Melanoma in situ

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Paget's Disease

• Multifocal, Eczematoid red weeping area Brick red Scales, Eczematoid plaque Sharply demarcated border
• Lesiones acetoblancas nítidas sobre mucosa eccematosa (enrojecida y humeda)
• Occurs most commonly on the nipple and areola, where its presence signifies an underlying adenocarcinoma of the breast
• Apocrine gland origin
• Red velvety area with white islands of hyperkeratosis and at times may be pinkish, and eczematoid

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Paget's Disease Association with Adenocarcinoma

• Genital
  • Vaginal, Cervical, Uterine
• Urologic
  • Urethra, Bladder
• Gastrointestinal
  • Anorectal,Rectal
• Breast

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Paget's Disease Workup

• History and PE
  • Symptoms include itching, burning
  • Signs include velvety appearance and bleeding
• Papanicolaou smear
• Mammogram
• Cystoscopy
• Colonoscopy

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Differentiating Paget's From Other
Conditions

• Positive mucin as well as immunoperoxidase CEA staining can be used to differentiate
• Paget's disease from melanoma
  • Paget's (mucin and CEA positive)
  • Melanoma (mucin and CEA negative)

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Paget's Disease

• Paget's Disease
  • Wide local excision (how far?)
  • Margins
  • Extends beyond the visibly demarcated margin
  • Adequate surgical margins difficult to obtain
  • Local recurrence
  • 31 % -radical vulvectomy
  • 43% wide local excision Adenocarcinoma association as high as 26%

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Melanoma in Situ

Melanoma in situ is a lesion of uncertain natural history, but it can be treated effectively with conservative surgery.

• LS
• VIN/ Vulvar Cancer
• HPV

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Human Cancer Viruses

• Virus Human papilloma virus (HPV)
• Hepatitis B virus (HBV)
• Epstein-Barr virus (EBV)
• Human T-cell lymphotopic virus (HTLV)
• Kaposi´s sarcoma-associated herpes virus (KSHV)

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Cancer

• Anogenital cancers
• Liver ancer
• Lymphoma
• Adult T-cell leukemia
• Kaposi´s sarcoma

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Actions of Oncogenes

• Growth factors
• Intrecellular signals
• Gene expression
• Receptors
• Transcription factors

• (cell division)
• M phase
• G2 phase
• G1 Phase
• S phase
• (DNA synthesis)

• Human cancer viruses mechanisms of action
• Virus mechanism
• HPV Inactivation of P53 and pRb
• HBV Liver damage – chronic proliferation
• EBV Immortalization- myc translocation
• HTLV Transactivation by viral tax protein
• KSHV Molecular piracy (IL-6, cyclin D, bcI-2)

• P53 Damage Checkpoint Control
• Damage to DNA- p53- Inhibitor of Cdk-Cyclin –G1 Transition Blocked- S phase

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Human Papillomavirus Proteins

• REPLICATION
• E1 - DNA Helicase
  E2 - Transcriptional

• Activator / Repressor

• TRANSFORMATION
• E6 - Targets p53
  E7 - Targets Rb

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