Justin D. Ellett, MD, PhD
S. Walker Nickles, MD
BASICS
DESCRIPTION
• Bowen Disease is squamous cell carcinoma in situ (CIS) of the follicle-bearing epithelium of the shaft and scrotum.
• Erythroplasia of Queyrat (EQ) is squamous cell carcinoma in situ (CIS) arising within the penile mucocutaneous (mucosal) epithelium of the glans penis or inner side of the foreskin. 80–90% of cases are seen in uncircumcised men.
– Sometimes EQ is referred to as “Bowen disease (BD) of the glans penis.”
– EQ more likely to develop into invasive squamous cell carcinoma of the penis than Bowen disease.
EPIDEMIOLOGY
Incidence
• Penile cancer occurs in <1% of all malignancies in men, and EQ and BE are a fraction of these
• Most often occurs in Caucasian males
• Mostly in uncircumcised men
• Majority in men ages 50–70, but described in adult males of all ages
Prevalence
N/A
RISK FACTORS
• Uncircumcised men
– Phimosis present in 75% of cases
– Smegma thought to be carcinogenic
• Coinfection of HPV type 8 and carcinogenic genital HPV types (16, 18, 39, 51) have been reported (1)
Relative risk factors:
– Therapeutic immunosuppression for organ transplants
– Immunosuppression from HIV/AIDS
– Arsenic exposure from well-water and other sources
– Ionizing radiation
– Thermal injury
– Chronic dermatoses
– Lichen sclerosis of the glans penis
– Smoking
– Multiple sexual partners
– Poor genital hygiene
– Penile trauma
Genetics
N/A
PATHOPHYSIOLOGY
• Carcinogenic insults from:
– Chronic injury and inflammation from poor hygiene, urine, smegma
– Radiation
– Exposure to chemical carcinogens, such as arsenic or smoking
– HPV infection
• Decreased immune surveillance due to HIV/AIDS or medical immunosuppression
ASSOCIATED CONDITIONS
• Progression to invasive SCC in 5–30% of cases; more likely with EQ
• Lichen sclerosis, balanitis xerotica obliterans (BXO)
GENERAL PREVENTION
• Circumcision
• Daily genital hygiene by retraction of foreskin and cleansing
• Elimination of risk for HPV infection
• Early detection of lesions
• Treatment of phimosis
DIAGNOSIS
HISTORY
• Age: Median age >50
• Sexual promiscuity (increases risk for HPV infection)
• History of phimosis or difficulty retracting foreskin
• History of exposure to ionizing radiation or arsenic
• History of nonhealing wounds, pruritus, bleeding, discharge
PHYSICAL EXAM
• Solitary or multiple nontender erythematous plaques
– EQ: Velvety, smooth, shiny on glans
– BD: Scaly, verrucoid plaque on shaft
• Individual lesion may be 10–15 mm in diameter
• Bleeding from lesion
• Presence of ulceration increases likelihood of invasive SCC
• Examination of inguinal nodes
• Important factors to assess:
– Diameter of lesion
– Location
– Number of lesions
– Morphology (papillary, nodular, ulcerous, or flat)
– Relationship to other structures (submucosal, corpora spongiosa and/or cavernosa, urethra)
DIAGNOSTIC TESTS & INTERPRETATION
Lab
Lab testing for carcinogenic HPV types
Imaging
Imaging only indicated in instances of clinical suspicion of invasion, and would include MRI or ultrasound
Diagnostic Procedures/Surgery
• Definitive diagnosis may only be made by biopsy
– Early invasion should be excluded via the use of multiple biopsies
Pathologic Findings
• Pathology will show full-thickness epidermis with:
– Discordant architecture
– Abnormal mitoses
– Dyskeratosis
– Involvement of associated pilosebaceous apparatus with intact epidermal junction
– Chronic inflammatory infiltrate into dermis
– Epithelial rete extension into submucosa that is elongated and bulbous; submucosa shows capillary proliferation and ectasia with plasma-cell rich infiltrate (these distinguish from localized balanitis)
DIFFERENTIAL DIAGNOSIS (2)
• Invasive SCC
– Ruled out by biopsy
• Bowenoid papulosis
– Benign course, but histologically similar except abnormal keratinocytes are spread discontinuously throughout epidermis
– Tendency for multiple lesions that may coalesce
– Typically in younger patients (ages 25–30)
– Usually spontaneously regresses
• Invasive SCC
– Ruled out by biopsy
• Nummular eczema
– Pruritic, coin-shaped plaques of small grouped papules on erythematous base
• Psoriasis
– Well-demarcated red or whitish, scaly lesion
– Usually associated with lesions at other sites
• Superficial basal cell carcinoma
– Pearly, skin-toned papule or plaque, often with overlying telangiectasias
– Treated with local excision; low malignant potential
• Balanitis circinata
– Dry and scaling lesions of the glans in circumcised or uncircumcised males
– Associated with Reiter’s syndrome
– Can be moist and erythematous in uncircumcised males
• Candidal balanitis
– Usually found in uncircumcised diabetics
– Reddened and edematous lesions
– Usually treated with antifungal therapy
• Zoon balanitis
– Usually in elderly, uncircumcised males
– Cayenne pepper-appearing red, raised lesion
– Usually distinguished from CIS on biopsy by band-like infiltrate of plasma cells
TREATMENT
GENERAL MEASURES (3)
Treatment based on multiple biopsy samples of adequate depth to rule out invasion
MEDICATION
First Line
• Topical therapy
– 5-fluorouracil cream BID for 4–5 wk or
– 5% imiquimod cream daily for 16 wk
– Proven effective for large lesions not amenable to surgery or for recurrent lesions
– Utilized with rubber condom to increase contact time
Second Line
N/A
SURGERY/OTHER PROCEDURES
• Circumcision can decrease likelihood of recurrence
• With lesions on the foreskin, circumcision, or excision with 5-mm margin is adequate for local control
– Lesions on the glans are difficult to excise with this strategy when trying to preserve penile anatomy
– Ensure adequate depth of resection to rule out invasion
• Mohs micrographic surgery has been utilized to accomplish adequate excision without disfigurement
• Nd:YAG, KTP, or carbon dioxide laser ablation has been shown to be effective
– Nd:YAG preferred due to depth of penetration
ADDITIONAL TREATMENT
Radiation Therapy
Radiation therapy can be used for patients resistant to topical treatment or who are not surgical candidates.
Additional Therapies
Additional therapies include cryotherapy, curettage, and photodynamic therapy, although their effectiveness is limited.
Complementary & Alternative Therapies
N/A
ONGOING CARE
PROGNOSIS
• 5–33% of cases have been reported to transform to SCC
– 5–10% risk in BD, 10–33% in EQ
– Carries significant risk of death
• Cure can be achieved up to 80% of the time
• All therapies have recurrence rates of 20–30%
COMPLICATIONS
Progression to invasive squamous cell carcinoma
FOLLOW-UP
Patient Monitoring
• BD and EQ surveillance parallels localized, invasive SCC of the penis with clinical exam:
– Year 1–2, every 3 mo
– Year 3–5, every 6 mo
– Year 5–10, every 12 mo
• Consider re-biopsy of recurrent lesions to rule out transformation to invasive SCC
Patient Resources
Medline Plus: Cancer Penis http://www.nlm.nih.gov/medlineplus/ency/article/001276.htm
REFERENCES
1. Wieland U, Jurk S, Weissenborn S, et al. Erythoplasia of queyrat: Coninfection with cutaneous carcinogenic HPV type 8 and genital papillomaviruses in a carcinoma in situ. J Invest Dermatol. 2000;115(3):396–401.
2. Buechner SA. Common skin disorders of the penis. BJU Int. 2002;90(5):498–506.
3. Arlette JP. Treatment of Bowen disease and erythroplasia of queyrat. Br J Dermatol. 2003;149(Suppl 66):43–49.
ADDITIONAL READING
• NCCN Guidelines Version 1.2013, Penile Cancer; from NCCN.org (Accessed April 10, 2014).
• Pettaway CA, Lance RS, Davis JW, Tumors of the penis. In: Wein, et al. Campbell-Walsh Urology. 10th ed. Philadelphia, PA: Saunders, 2012.
See Also (Topic, Algorithm, Media)
• Bowen Disease and Erythroplasia of Queyrat Image 
• Penis, Cutaneous Lesion
• Penis, Squamous Cell Carcinoma
CODES
ICD9
233.5 Carcinoma in situ of penis
ICD10
D07.4 Carcinoma in situ of penis
CLINICAL/SURGICAL PEARLS
• EQ is SCC in situ arising on the glans or inner side of the foreskin.
• BD is SCC in situ of the penile shaft or scrotum.
• 80–90% of cases seen in uncircumcised men.
• Progression to invasive SCC in 5–30%.