1. Clinico-pathologic Findings and Correlations in Anogenital Bowen Disease Irina Tudose1, Madalina Geanta2, Sabina Zurac3, Florica Staniceanu3, Simona Roxana Georgescu2, V Benea2 1 The Pathology Department, “Prof. Scarlat Longhin” Clinical Hospital 2 The Dermatology Department, “Prof. Scarlat Longhin” Clinical Hospital 3 The Pathology Department, Colentina Universitary Clinical Hospital • 1912 – John T. Bowen described “squamous intraepithelial disorders” or “Bowen disease” (BD) • 1943 – Knight et. al reported vulvar BD • According to WHO Tumor Classification, BD is “a form of squamous cell carcinoma in situ, a distinct clinicopathologic entity of the skin and mucocutaneous junction” • The suggested association with internal malignancy was not confirmed in long-term follow-up BD: Aspect: usually asymptomatic erythematous and (slightly) scaly patch or plaque (sometimes verrucous or crusted), with a sharp, but often irregular border, of variable size (mm → cm); pigmentary forms have been described; +/- erosions and/or ulceration; can occur in both sun-exposed and sun-protected sites Evolution: slow & gradual increase; no spontaneous resolution; Development of invasive squamous cell carcinoma in 3-5% (some sources: up to 10%) of cases; development of nodules or ulceration usually signals progression towards invasion • BD: • Therapeutic options: • Complete surgical excision (classical/ Mohs) • Cryotherapy • CO2 laser therapy • Topical 5-FU • Topical imiquimod • PDT • Curettage & Electrodesiccation • Local radiotherapy • Combined therapy • The anogenital BD can be misdiagnosed as: • Psoriasis • Chronic eczema/allergic contact dermatitis • Lichen planus • Fixed drug eruption • Superficial (pigmented) basal cell carcinoma • Extramammary (genital) Paget’s disease • Malignant melanoma in the anogenital area • Invasive squamous cell carcinoma • Vulvitis/balanitis circumscripta plasmacellularis (Zoon) • Tinea • consensus regarding efficiency has not been reached, but: • complete eradication (surgical) is essential in patients where adequate follow-up cannot be done • a meticulous, regular follow-up (doctor visits + self-examination) is very important; it has been sugested that dermatoscopy could play a role in monitoring BD

2. Study: materials and methods • retrospective analysis • we selected 11 patients with histopathological confirmed ano-genital BD and 20 patients with cutaneous BD • all the biopsies were fixed in formaldehyde solution and embedded in paraffin; all the paraffin sections were stained with H-E; immunohistochemestry markers (Ki67, p16, p21, p53) were used for the ano-genital cases • mean age for ano-genital BD was 60,09 years (range 44-74) Most of the patients with ano-genital BD pertained to the age group 60-69, consistent with the literature data (“commonly affects patients in the 6-8th decade”) • The presence of ulceration was evident in 64% of the cases Ano-genital BD cases • In 27% of cases only the labia major was involved, and the rest was equally divided between the labia minor, labia minor+labia major, the frenulum, the perineal region or “the genital region”

3. The treatment of ano-genital BD cases consisted of: • Complete initial surgical excision (in 3 cases) • Biopsy and HP confirmation, followed by complete surgical excision or curettage and electrodesiccation were surgery was not an option The treatment of extragenital BD cases consisted of: Complete initial surgical excision (in 10 cases) Biopsy and HP confirmation, followed by complete surgical excision in the other 10 cases • Extra-anogenital BD Cases: • Our retrospective study included 20 cases of BD with extragenital location, during last year, with the following features: • mean age 73.8 years (range 55-91); sex ratio 1:1 • most frequent location: the face (40%) • The clinical diagnoses which accompanied the biopsy specimens were: • Bowen’s disease (in 8 cases; the concordance between the clinical and pathological dgn was of 72.72%) • Lichen sclerosus et atrophicus • Genital wart • Erosive genital lichen planus - The concordance between the clinical and pathological diagnosis was of 30%, smaller compared to the situation observed for ano-genital BD - The most frequent clinical confounder was BCC (in 55% of cases)

4. p53 p16 Ki67 p21 • Histopathological aspects for both ano-genital and cutaneous BD were similar with some particularities regarding ano-genital cases: almost all the lesions were ulcerated, the inflammation was higher consisting in lymphocytes and plasma cells, there were more dyskeratotic cells and a high mitotic rate • Immunohistochemestry analysis for the ano-genital BD cases revealed a high Ki67 value (from 25% to 50%), predominant the lower part of the epithelium, apparently related with p21 high values (from 10% to 60%); p16 presented high positivity (over 20%) in only 3 cases; p53 showed over 10% positivity in 3 cases (8 cases presented less than 5% positivity) • Apparently there is no connection between immunohistochemistry markers values, except for the Ki67 and p21, both with similar positivity in 7 cases of ano-genital BD • The concordance between the clinical and pathological diagnosis was of 30% for the extra-ano-genital cases, smaller compared to the situation observed for ano-genital BD • Having in mind the fact that the observation period was only one year and all the data were collected in a hospital dedicated almost exclusively to dermatology, 11 patients is not such a small number for ano-genital location of BD