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.
« Descargar documento (formato PDF) »

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

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

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.

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

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.

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

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

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)


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


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

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

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

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

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

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.

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)

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

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

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

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

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

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

INSTRUMENTS
  • Hinkel-James Anoscope
  • Fansler Operative Anoscope

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

Non- squamous Types
  • Paget's disease
  • Melanoma in situ

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

Paget's Disease Association with Adenocarcinoma
  • Genital
    • Vaginal, Cervical, Uterine
  • Urologic
    • Urethra, Bladder
  • Gastrointestinal
    • Anorectal,Rectal
  • Breast

Paget's Disease Workup
  • History and PE
    • Symptoms include itching, burning
    • Signs include velvety appearance and bleeding
  • Papanicolaou smear
  • Mammogram
  • Cystoscopy
  • Colonoscopy

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)

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%

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

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)

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

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

Human Papillomavirus Proteins

  • REPLICATION
  • E1 - DNA Helicase
    E2 - Transcriptional
  • Activator / Repressor
  • TRANSFORMATION
  • E6 - Targets p53
    E7 - Targets Rb

- - -

HPV REFERENCES

Beutner KR, Conant MA, Friedman-Kien AE. Patient-applied podofilox for treatment of genital warts. Lancet 1989; 1(8642):831-4.

Conley LJ. Ellerbrock TV. Bush TJ. Chiasson MA. Sawo D. Wright TC. HIV-1 infection and risk of vulvovaginal and perianal condylomata acuminata and intraepithelial neoplasia: a prospective cohort study. [comment]. Lancet. 2002;359(9301):108 -13.

Edwards A, Atman –Ram A, Thin RN. Podophyllotoxin 0.5% vs podophyllin 20% to treat penile warts. Genitourin Med 1988;64:263-5.

Edwards L, Ferenczy A, Eron L, et al. Self-administered topical 5% imiquimod cream for external anogenital warts.HPV Study Group. Human Papilloma Virus. Arch Dermatol 1998;134:25-30.

Smith YR, Haefner HK, Lieberman RW, Quint EH. Comparison of microscopic examination and human papillomavirus DNA subtyping in vulvar lesions of premenarchal girls. Journal of Pediatric & Adolescent Gynecology. 2001;14(2):81-4.

Strand A, Brinkeborn RM, Siboulet A. Topical treatment of genital warts in men, an open study of podophyllotoxin cream compared with solution. Genitourin Med 1995;71:387-90.

Von Krogh G, Hellberg D. Self-treatment using a 0.5% pdophyllotoxin cream of external genital condylomata acuminata in women. A placebo-controlled double-blind study. Sex Transm Dis 1992;19:170-4.

Von Krogh G. Podophyllotoxin for condylomata acuminata eradication. Acta Derm Venereol Suppl (Stockh) 1981;98:1-48.


VIN (Squamous and Nonsquamous) References

Bornstein J, Kaufman R: Combination of surgical excision and carbon dioxide laser vaporization for multifocal vulvar intraepithelial neoplasia. Am J Obstet Gynecol 1988;158:459-64.

Busceman J, Naghashfar Z, Sawada E, et al.The predominance of human papillomavirus type 16 in vulvar neoplasia. Obstet Gynecol 1988;71:601-6.

Buscema J, Woodruff JD. Progressive histobiologic alterations in the development of vulvar cancer. Am J. Obstet Gynecol 1980;138:146-50.

Cardosi RJ, Bomalaski JJ, Hoffman MS. Diagnosis and management of vulvar and vaginal intraepithelial neoplasia. Obstetrics & Gynecology Clinics of North America. 2001;28:685-702.

Diaz-Arrastia C. Arany I. Robazetti SC. Dinh TV. Gatalica Z. Tyring SK. Hanningan E. Clinical and molecular responses in high-grade intraepithelial neoplasia treated with topical imiquimod 5%. Clinical Cancer Research. 2001;7:3031-3

Fanning J, Lambert HC, Hale TM, Morris PC, Schuerch C. Paget's disease of the vulva: prevalence of associated vulvar adenocarcinoma,invasive Pagetamos