General
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• Bowen's disease refers to high grade dysplasia of squamous epithelium or vulvar intraepithelial neoplasia grade III, and is characterized by full thickness atypia
• Newer terminology is "usual or high grade vulvar intraepithelial neoplasia or VIN III"

Terminology
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• Previously used:
  • Intraepithelial epithelioma (AMA Arch Derm 1955;71:615)
  • Intraepidermal carcinoma (BJOG 1944; 51(5):377)
• Currently used:
  • High grade vulvar intraepithelial neoplasia
  • Vulvar intraepithelial neoplasia, grade III
  • Squamous cell carcinoma in situ
  • Basaloid variant of vulvar intraepithelial neoplasia (J Cutan Pathol 1980;7:244)
  • Usual or classic vulvar intraepithelial neoplasia

Epidemiology
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• Commonly affects relatively young women, ages 20 to 50 years (J Clin Pathol 2014;67:290)
• Incidence was increasing until 2000
• Rates may change with use of HPV vaccine (Gynecol Obstet Fertil 2007;35:1251)

Sites
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• Often involves labia majora, but can be multifocal affecting various parts of vulva
• May involve other squamous epithelia such as cervical, vaginal and anal mucosae

Pathophysiology
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• Associated with high risk HPV infection
• The HPV genetic material is integrated into the host genome (Clin Exp Dermatol 2009;34:e965)
• If untreated, 10-12% may progress to invasive carcinoma (Am J Obstet Gynecol 2010;202:e12)

Etiology
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• HPV 16 infection is more common than type 18 and other high risk HPV types (Int J Cancer 2009;124:1626)
• Risk factors include young age of first intercourse, multiple sexual partners, immunodeficiency and smoking

Clinical features
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• The lesions present as flat erythematous, pale or pigmented patches or a combination of the three, and are often asymptomatic
• May be subtle clinically; dilute acetic acid helps identify these patches (Obstet Gynecol 2014;123:181S)

Diagnosis
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• Made by clinical examination, and confirmed by histologic examination

Prognostic factors
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• Age: In younger patients (< 35 years), the risk of progression is less than in patients older than 45 years (Am J Obstet Gynecol 2010;202:e12)
• HIV status (Med Wieku Rozwoj 2003;7:487)

Case reports
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• 23 year old woman with vulvar intraepithelial neoplasia and periungual Bowen's disease (Clin Exp Dermatol 2007;32:304)
• 42 year old woman with bowenoid papulosis and invasive Bowen's disease (Acta Derm Venereol 2013;93:228)
• Human papillomavirus genome integration in multifocal vulvar Bowen's disease and squamous cell carcinoma (Clin Exp Dermatol 2009;34:e965)
• Bowen disease of the vulva successfully treated with intraarterial infusion chemotherapy (J Am Acad Dermatol 2013;69:e305)
• Two HIV positive women with multifocal Bowen's disease (Obstet Gynecol 2012;119:442)

Treatment
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• Untreated lesions only rarely undergo spontaneous resolution, and may become invasive tumors
• The objective of therapy is to prevent progression to invasive carcinoma
• Various surgical and medical therapies may be combined for better outcome (Cochrane Database Syst Rev 2014;3:CD007928, Cochrane Database Syst Rev 2011;4:CD007924)
• Surgical therapy: frequently complicated by recurrence (due to the multifocal nature of the disease) and includes:
  • Wide local surgical excision (commonly used)
  • Ablative therapies include carbon dioxide laser or cavitron ultrasonic surgical aspiration (CUSA), electrocoagulation, cryotherapy
• Medical therapy:
  • Topical Imiquimod, 5-fluorouracil creams
  • Systemic cidofivir
  • Photodynamic therapy

Clinical images
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Papules and plaques in genital and perianal area

Recurrence

VIN

Vulval disease

 

Bowen's disease

Red-brown warty plaque

Gross description
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• Pale-whitish, erythematous or pigmented patches and plaques
• The presence of nodular areas should raise the possibility of invasive carcinoma

Micro description
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• The epidermis is frequently acanthotic, but may be normal, with an overlying hyperkeratotic or parakeratotic scale or an erosion
• Background lymphoplasmacytic infiltration of submucosa is common
• Loss of epithelial maturation with full thickness atypia
• The cells are relatively small and monomorphic with high nuclear-to-cytoplasmic ratio, hyperchromatic and pleomorphic nuclei
• Koilocytic changes are not prominent, although nuclear membrane irregularity is often present
• Mitotic activity is prominent and atypical mitotic figures are not uncommon
• The dysplastic changes also involve adnexal epithelium
• Dyskeratosis and acantholysis may be present and can be prominent
• Rarely, intraepidermal nesting of clonal atypical cells may be seen, producing the so called Borst-Jadassohn phenomenon

Micro images
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Various images - courtesy of Dr. Priya Nagarajan

         

Various images - courtesy of Dr. Priya Nagarajan

Basaloid subtype, p16

p53

     

Abnormal mitotic figures and other images

Cytology description
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• Routine pap smears are not usually useful as a screening tool for vulvar pathologies

Positive stains
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• Pancytokeratin, p16
• EMA and p53 (variable)

Negative stains
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• CAM 5.2, CEA, S100, HMB45, CK7, HER2

Molecular / cytogenetics descriptions
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• HPV 16 positive
• The presence of HPV may be demonstrated by in-situ hybridization (ISH) or polymerase chain reaction (PCR)
• HPV genotyping may be useful when ISH or PCR identifies common HPV types (Clin Exp Dermatol 2007;32:304)
• Karyotyping and cytogenetic analyses are rarely performed
• A subtelomeric deletion of 11p has been identified in one case (Cancer Genet Cytogenet 1997;93:109)
• Often aneuploid

Differential diagnosis
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• Clinical:
  • Contact dermatitis
  • Extramammary Paget's disease
  • Melanoma
• Histological:
  • Bowenoid papulosis (Fujita Health University - Case 144)
  • Paget's disease

Additional references
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• Am J Surg Pathol 2013;37:53, Photochem Photobiol Sci 2011;10:802, Int J Gynaecol Obstet 2007;99:23

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