Sandbox:Penile carcinoma in situ

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Vishal Devarkonda, M.B.B.S[2]

Synonyms and keywords:Bowen's disease, Bowenoid papulosis, Erythroplasia of Queyrat

Historical Perspective

EQ (erythroplasia of Queyrat) was originally described by Tarnovsky in 1891’ and appreciated as a penile disease by Fournier and Darier in 1893.’ However, not until 1911 was erythroplasia generally accepted as a distinct entity; this resulted from the intensive studies by Queyrat3 whose name the condition bears as an eponym to this day. A further milestone in the history of EQ was its recognition as carcinoma in situ by Sulzberger and Satenstein in 1933.4

Bowen disease

It was first described by the American dermatologist John T. Bowen in 1912. The etiology of Bowen's disease of the penis (BDP)

Classification

There is no established classification for Balanitits cause by Penile carcinoma in situ

Pathophysiology

Bowenoid papulosis

The exact pathogenesis of Bowenoid papulosis is unknown.

Some studies have shown, HPV type 16, 31, and 39 to play an etiological role in Bowenoid papulosis.

Associated conditions include:

• HIV
• Lymphopenia
• Depressed cell-mediated immunity

Histopathology

• The histopathology may reveal squamous cell carcinoma in situ, with widened spinous epidermal layer with proliferation of atypical basal cells, coilocytes, enlarged polimorfic and hyperchromatic nuclei as well as abnormal mitosis and hyperparakeratosis with collection of melanin of various amount seen.

Bowenoid papulosis histopathology

Erythroplasia of Queyrat

The exact pathogenesis of erythroplasia of Queyrat is unknown.

Some studies have shown, chronic irritation, Inflammation, phimosis, smoking, smegma, poor hygiene, genital herpes simplex, HPV, heat, friction, maceration, trauma, perpuce dermatoses, such Lichen sclerosis or Lichen planus, may act as a risk factors for developing Erythroplasia of Queyrat.

Associated conditions

• Epidermodysplasia verruciformis associated HPV-8
• Genital high-risk HPV-16

Histopathology

• Slight to moderate plaque-like acanthotic epidermis with focal parakeratosis and hypogranulosis with loss of epidermal cell polarity as evidenced by vacuolated cells, atypical mitoses, atypical epithelial cells with hyperchromatic nuclei, multinucleated cells, dyskeratotic cells, and mitotic figures in the upper Malpighian layers.
• The upper dermis is often edematous and densely invaded by a band-like plasma cell rich chronic round cell infiltrate.

Bowen's Disease

The exact pathogenesis of Bowen's disease is unknown.

Some studies have shown, lack of circumcision, HPV infection, phimosis, balanitis, or any chronic inflammation of the penile skin act as a risk factor in developing Bowen's disease.

Associated conditions

• HPV types 16
• HPV type 33

Histopathology

Full-thickness epidermal atypia with disordered architecture, abnormal mitoses, dyskeratosis, and involvement of associated pilosebaceous apparatus with an intact epidermal junction.

Bowen's disease histopathology

Epidemiology and Demographics

There are no comprehensive studies reporting the incidence and prevalence of penile carcinoma in situ in general population. Some studies have reported the demographics of patients presenting with these diagnosis.

Bowenoid papulosis

Bowenoid papulosis usually occurs in sexually active men aged between 20 to 40 years, with a mean age of 31 years, it occurs slightly more common in women then men.

Erythroplasia of Queyrat

Erythroplasia of Queyrat is a rare condition usually affecting uncircumcised men in their third to sixth decades of life.

Bowen's Disease

Bowen's disease is occurs equally in both men and women, with the highest incidence inpatients older than age 60 years.

Screening

There are no established screening guidelines to screen patients for penile carcinoma in situ.

Natural History, Complications, and Prognosis

Natural history

Bowenoid papulosis

Bowen's Disease

The natural course of BP is not well defined. The papules may increase, decrease, or the lesions may disappear with time; however, coexistence of BP with and transmission into invasive carcinoma have been reported.⁴⁹ The risk for progression from BP to SCC is reported as 2.6%. BP may be associated with a lesser risk for squamous carcinoma than EQ and BDP.³ It is believed that BP represents a low-grade form of SCCIS, which rarely, if ever, progresses to invasive disease but may be a risk factor for cervical neoplasia in the partners of affected men.⁴¹

Complications

Bowenoid papulosis

Bowen's Disease

Both EQ and BD are premalignant, but transformation of EQ into invasive SCC is more common than in BD, with an incidence ranging from 10% to 33%.

• BP may progress to true BD or SCC.

Malignant potential of BD increases when its existence is compounded by concomitant disease such as HPV infection, LS or LP, or in patients with poor genital hygiene and smokers. The potential for invasive SCC to develop from BD is approximately 3% to 5% for cutaneous and 10% for genital lesions

Prognosis

Bowenoid papulosis

Diagnosis

History and symptoms

Bowenoid papulosis

Patients may be asymptomatic or present with pruritic, or painful lesions in the genital region.

Erythroplasia of Queyrat

Patients may present with non-healing lesions in the genital region, which could also be associated with scaling, crusting, and bleeding,

Bowen's Disease

Patient may be asymptomatic or present with pruritic, or painful lesions in the genital region.

Physical examination

Physical examination findings of penile carcinoma in situ
Bowenoid papulosis	Erythroplasia of Queyrat	Bowen's Disease
Multiple, small, well-demarcated, grey-brown, red, pink, or skin-colored papillomatous papules or small patches on the penile shaft, glans, or foreskin, vulva, and perianal area .The papules are nonpruritic, range in size from 2 to 10 mm, and usually lack scale	Single or multiple red, shiny, slightly raised, sharply demarcated, velvety, non-healing plaques associated with scaling, crusting, and sometimes bleeding, affecting the mucosal surfaces of the penis.	Red, sometimes slightly pigmented, scaly, moist, velvety patches and plaques of the keratinized penis.

Bowen's Disease

Laboratory findings

Definite diagnosis is made by a biopsy showing the typical histologic picture of intraepidermal carcinoma in situ.

Treatment

Bowen disease

The choice of treatment depends on an analysis of various factors such as lesion size, number, site, degree of functional impairment, modality availability, and cost. Follow-up at 6 to 12 months is recommended to evaluate for recurrence. Treatment options are local excision, Mohs micrographic surgery, cryotherapy, curettage with cautery⁄electrocautery, laser therapy with carbon dioxide, argon, and Nd:YAG lasers. Cryotherapy regimens consist of two freeze–thaw cycles of 20 seconds with a thaw period at intervals of a few weeks. Other noninvasive treatment options are photodynamic therapy, topical 5-FU.¹⁴ 5-FU is used clinically as a 5% cream once or twice daily for a variable period, ranging from 1 week to 3 months. Topical treatment for BD in perianal region may minimize the risk for scarring, poor wound healing, and functional impairment. For perianal BD, excision with wide margin is recommended. Surgery and destructive treatment modalities have a significant risk for scarring, deformity, and impaired function. Recent case studies have reported the successful treatment of penial BD and anogenital BD with topical imiquimod, an immune response modifier, as a 5% cream. The ideal dosing regimen is still under investigation, but the most studied regimen is imiquimod 5% cream once daily for 16 weeks.^{43., 44. and 45.}

BP

Treatment options for BP usually involve locally destructive or ablative therapies such as cryosurgery, electrodessication, laser vaporization (Nd:YAG, argon, and carbon dioxide lasers), and surgical excision. Scarring can be seen with these modalities. Conservative treatment for BP so far has been based on topical use of ointments and creams containing 5-FU, podophylin, retinoic acid, and cidofovir; only moderate effects have been reported.^{47. and 48.} Recently, some authors reported successful clearance of BP using imiquimod cream 5%.^{4., 47. and 48.}

EQ

Circumcision is recommended for all patients because it eliminates the mucosal surface of the prepuce and decreases the risk for local recurrence.⁵² Treatments for EQ include surgical excision, Mohs micrographic surgery, cryotherapy, electrodesiccation and curettage, radiotherapy, laser ablation, PDT, oral isotretinoin, topical 5-FU and topical imiquimod. Mohs micrographic surgery may be useful because it precisely identifies tumor-free margins while allowing minimal tissue loss. Partial or total penectomy is usually an unnecessary mutilating procedure. If urethral involvement is noted, treatment may be more challenging, with higher recurrence rates.