Acta Derm Venereol 92
Letters to the Editor 2012 Epub ahead of print
© 2012 The Authors. doi: 10.2340/00015555-1328
Journal Compilation © 2012 Acta Dermato-Venereologica. ISSN 0001-5555
Bowenoid Papulosis and Invasive Bowen’s Disease: A Multidisciplinary Approach
Elena Campione1, Chiara Centonze2, Laura Diluvio1, Augusto Orlandi3, Cesidio Cipriani4, Alessandro Di Stefani3, Emilio
Piccione2, Sergio Chimenti1 and Luca Bianchi1
Departments of 1Dermatology, 2Gynaecology and 3Anatomic Pathology, University of Rome, Tor Vergata, Viale Oxford, 81, IT-00133 Rome, and 4Depart-
ment of Nuclear Medicine, S. Eugenio Hospital, Rome, Italy. E-mail: email@example.com
Accepted November 7, 2011.
Bowenoid papulosis (BP), Bowen’s disease (BD) and
erythroplasia of Queyrat (EQ) are distinct clinical enti-
ties with similar histological findings of intraepithelial
neoplasia, but with different clinical behaviour and dif-
ferent risks of progression to invasive squamous cell
carcinoma (SCC). In the anogenital region, BP presents
grey-brown or skin-coloured elevated papules with a
maximum diameter of 1 cm, BD shows larger well-de-
marcated plaques, and EQ appears as a well-marginated
erythematous velvety patch or plaque, mainly on the glans
penis (1). BP is rarely invasive and may even regress
spontaneously, thus conservative treatments are often
adequate. In contrast BD and especially EQ, should be
treated relatively more aggressively. Human papilloma-
virus infection (HPV) may play a causative critical role,
with variable risk of progression to invasive SCC (2,
3). It has been suggested that the management of high-
risk HPV-associated lesions is best if tailor-made with
a multidisciplinary approach. We report here the case
of a sexually active woman affected by a dramatic and
disabling HPV16-related anogenital BP and BD, with
focal progression into invasive SCC.
A 42-year-old Caucasian woman was referred to our Dermatol-
ogy Department with a 20-year history of asymptomatic, smooth,
brownish, velvety surface macules and plaques in the anogenital
region, labia minora and majora, fourchette, perianal region and
groin. Lymphocyte count, including total CD3, CD4 and CD8,
natural killer (NK)-cell and B-cell counts, as well as serum im-
munoglobulins were all within normal ranges. Tests for HIV-1,
HIV-2, HTLV-1 and HTLV-2 were negative and she had no history
of immunodepression or immunosuppressant drugs intake. She
had smoked 40 cigarettes a day for 14 years. Her gynaecological
and obstetric history included menarche at the age of 13 years
with regular menstrual cycles and sexarche at the age of 18 years
with several sexual partners. At the age of 20 years, she was sur-
gically treated for grade 3 cervical intraepithelial neoplasia and
performed an unspecified ablative technique for vulvar condy-
lomata acuminate, followed by a 6-month period of interferon-γ
(3,000,000 IU subcutaneously, 3 times a week). The patient was
disease-free for approximately 10 years and then developed new
vulvar lesions, which were treated surgically. At the age of 30
years she had a pregnancy without difficulties. Five years ago, she
was referred to the gynaecology department for multiple vulvar
lesions, clinically featuring as BP and histologically classified as
vulvar intraepithelial lesions (VIN) III, treated by multiple surgi-
cal excisions. Imiquimod therapy was started, but the patient was
not motivated to continue the treatment because of several local
side-effects, such as severe irritation and burning. In the last year,
we were consulted as dermatologists for the first time on how to
achieve clinical remission of persisting BP papules in the groin
and buttocks and BD plaques in the labial and perianal region
(Fig. 1A). Four lesions had the appearance of clinically typical
BP lesions (Fig. 1B, white arrowhead), one, within the lesion
suspicious for BD, appeared clinically as a warty verrucous nodule
clearly suspicious for a SCC (Fig. 1B, black arrowheads). All 5
lesions were surgically removed. Cervical cytological screening,
colposcopy and pelvic ultrasound gave normal results. Histological
findings of the papules and plaques (Fig. 1C) showed a variable
extent of hyperkeratosis, irregular acanthosis, papillomatosis and
cytological atypia. The warty nodule (Fig. 1D, E), measuring 1.9
cm in diameter, was a well-differentiated invasive SCC, 1.8 cm
deep (Ib International Federation of Gynecology and Obstetrics
(FIGO) staging). For HPV DNA amplification, serial paraffin tis-
sue sections from lesions clinically suspicious for SCC and BP,
respectively, were accurately collected in sterile microtubes and
successively purified using the commercial QIAamp DNA Mini
Kit (Qiagen, Qiagen GmbbH, Hilden, Germany). DNA quality was
verified by human β-globin and HLA-DPB1 gene polymerase chain
reaction (PCR). The presence of HPV DNA was detected using the
SPF10-PCR and HPV Genotyping by using the Inno-Lipa HPV
Extra Kit (Innogenetics Immunogenetics NV, Gent, Belgium) ac-
cording to the manufacturer’s protocol. In both samples, the DNA
test revealed the presence of high-risk HPV, type 16 (Fig. 1F). Since
the distance of the nodular invasive SCC from the vulvar median
line was greater than 1 cm, the patient was firstly submitted to a
non-mutilating sectorial radical vulvectomy with total monolateral
inguino-femoral node dissection. After obtaining signed informed
consent and assuring contraceptive measures, we proposed the fol-
lowing combined protocol: selective dermatological β-irradiation
brachytherapy and oral isotretinoin (0.5 mg/kg/day). In the last 3
months the patient underwent four cycles of brachytherapy in the
absence of significant local or systemic adverse effects. She is now
disease-free and still taking oral isotretinoin.
The carcinogenetic role of high-risk HPVs, which are
often integrated in VIN/SCC, is still not fully under-
stood (4–6). Especially younger women tend to have
SCC and VIN associated with HPV infection (7). Beside
the high-risk HPV16 infection detected in our patient,
an additional risk factor which might have influenced
her clinical course is smoking. It has been shown that
women who are heavy smokers are more likely to have
multicentric disease. According to some studies, women
who continue to smoke after treatment are 30 times more
likely to have persistent vulvar disease (7).
Surgical excision, electrocoagulation, cryotherapy,
CO2 laser therapy, and photodynamic therapy, are
recommended treatment modalities, but they are not
always completely successful, because of the multifo-
cal distribution of the BP lesions (10). Alternatives are
chemotherapeutics including 5-fluorouracil, podophyl-
lin, cidofovir, imiquimod, and either systemic or local
Letters to the Editor
Fig. 1. (A) Multiple smooth, brownish, velvety-surface papules and plaques in
the genital and perianal area. (B) Close-up of the papules (white arrowheads)
and of the verrucous pinkish nodule at the level of the right labia majus (black
arrowhead). (C) Microscopic examination of one papule exhibiting typical
bowenoid papulosis (BP) features and of the nodule (D) showing a well-
differentiated squamous cell carcinoma (SCC). (E) At higher magnification
atypical squamous cell nests invading the dermis (C–E: haematoxylin-eosin
stain, original magnification: C and E: × 100; D: × 40). (F) Left: Reverse
transcriptase PCR for detection of human papillomavirus (HPV) infection
(lane 1: negative control; lane 2: positive control; lane 3: BP; lane 4: SCC).
Right: HPV genotyping positive for HPV16.
retinoids (10, 11). A randomized placebo-controlled
trial has demonstrated the role of oral isotretinoin in
the treatment of recalcitrant cervix condylomata (12).
Several pathways have been proposed to explain how
retinoids can control viral replication. They can down-
regulate the expression of HPV messenger-RNA or
indirectly induce transforming growth factor-β, which
inhibits cell proliferation and transcription of E6/E7
genes in cervical epithelial cells (13, 14).
Brachytherapy is a recently patented skin-focused
superficial and selective form of radiotherapy, demon-
strated to be effective in non-melanoma skin cancers
(15). A synthetic resin containing a radioactive β-emitting
isotope is applied to the lesion to perform a selective
β-irradiation treatment, reducing the radiation exposure
of the surrounding healthy tissues. We speculated that
brachytherapy in combination with isotretinoin could
cooperate to clear the bowenoid field and prevent recur-
rences, and in our patient this was accentually the case.
In conclusion, this case emphasizes the insidious
evolution of high-risk, HPV-related anogenital lesions,
featuring as BP, BD and invasive SCC, in a young sexu-
ally active patient, and describes a successful therapy
able to achieve healing of the lesions, chemoprevention
and improvement in quality of life.
The authors thank A. Francesconi for HPV analyses and Denis
Mariano for language checking.
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Acta Derm Venereol 92