Clinico-pathologic Findings and Correlations in Anogenital Bowen Disease

Irina Tudose1, Madalina Geanta2, Sabina Zurac3, Florica Staniceanu3, Simona Roxana Georgescu2, V Benea21 The Pathology Department, “Prof. Scarlat Longhin” Clinical Hospital2 The Dermatology Department, “Prof. Scarlat Longhin” Clinical Hospital3 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 sitesEvolution: 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

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

BD:Therapeutic options:• Complete surgical excision (classical/

Mohs)• Cryotherapy• CO2 laser therapy• Topical 5-FU• Topical imiquimod• PDT• Curettage & Electrodesiccation• Local radiotherapy• Combined therapy

- 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

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)Sex ratio

90,90%

9,10%

f

m

Age groups distribution

0

1

2

3

4

5

40-49 50-59 60-69 70-79

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”)

Yes64%

No36%

• The presence of ulceration was evident in 64% of the cases

genital region (nonspecified)

9%

perineal region9%

frenulum9%

labia major27%

labia minor9%

labia major+minor37%

• 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”

Ano-genital BD cases

0

1

2

3

4

5

6

7

8

Clinical Diagnosis

Serie1 8 1 1 1

Bowen LSA Genital wartErosive genital

LP

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

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 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)

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

Ki67

p16

p21

p53

• 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