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Background Photodynamic therapy (PDT) has been strongly recommended as an excellent alternative treatment for Bowen disease (BD). However, reported data on 5-aminolaevulinic acid-mediated PDT (ALA-PDT) with red-light irradiation are limited and the long-term effectiveness remains to be determined, especially in dark-skinned populations. Objectives We aimed to review routine clinical practice in the field of BD treatment with ALA-PDT over an extended study period (2011–2021), calculate the overall clearance rate, and explore and evaluate factors that might affect the effectiveness of therapy in a real-world setting. Methods The medical records of patients with BD who received ALA-PDT with red-light irradiation between February 2011 and June 2021 were reviewed and summarized. Univariate and multivariate analyses of clinically relevant variables that may affect treatment outcomes were conducted to identify risk predictors. Results The overall clearance rate of 122 BD lesions was 89.3% with a median follow-up time of 36 months. The correlation between the effectiveness and fluorescence intensity of pre-PDT or PDT sessions was statistically significant after eliminating the interference of confounding factors. All recurrences occurred in the first 2 years following ALA-PDT. Conclusions ALA-PDT is an effective treatment for BD in patients with darker-coloured skin. Well-executed operations and effective pretreatment are the determinants of effectiveness. Fluorescence intensity of pre-PDT appeared to be a significant predictor of final effectiveness. In addition, 2 years of follow-up is necessary following ALA-PDT. [ABSTRACT FROM AUTHOR]

Background The relationship between human papillomavirus (HPV) and Bowen disease (BD) is not fully understood. Objectives To investigate the differences in HPV detection rates in BD samples across various body regions and analyse the expression patterns of p53, p16 and Ki-67 in relation to HPV presence. Methods Tissue samples from patients diagnosed with BD, confirmed through histopathology, were retrospectively collected. Next-generation sequencing was used for HPV DNA detection. Immunohistochemistry (IHC) for p16, p53 and Ki-67 was performed. Results Out of 109 patients with BD, 21 (19.3%) were HPV-positive. All identified types were α-HPVs, with HPV-16 being the most common. The HPV detection rate was significantly higher in the pelvic (9/13, 69%, P < 0.001) and digital (5/10, 50%, P = 0.02) areas compared with those in the other regions. HPV presence was significantly correlated with p53 negativity (P = 0.002), the p53 'non-overexpression' IHC pattern (P < 0.001) and p16–p53 immunostain pattern discordance (P < 0.001). Conversely, there was no notable association between HPV presence and p16 positivity, the p16 IHC pattern or Ki-67 expression. Conclusions Our findings suggest the oncogenic role of sexually transmitted and genito-digitally transmitted α-HPVs in the pathogenesis of BD in pelvic and digital regions. Graphical Abstract Open in new tab Download slide [ABSTRACT FROM AUTHOR]

This article discusses two cases of patients with HIV who developed cutaneous squamous cell carcinomas (cSCCs) that tested positive for alpha (α)-papillomaviruses (HPVs). The patients had a history of recurrent cervical intraepithelial neoplasia (CIN) and persistent anogenital HPV infections. The study suggests that defective immunity towards α-HPVs may also occur in the skin and lead to cSCC. The detection of high-risk (HR)-HPVs in cSCC could indicate hypersusceptibility to HPV infection and may impact therapeutic strategies for cSCC. [Extracted from the article]

We report, to the best of our knowledge, the first case of Bowen disease treated with tirbanibulin. In addition to the successful treatment of the malignant lesions, the improvement in skin texture and photodamage is remarkable. With a good safety profile, tolerability and the dosing convenience of this new drug, we believe that its use in pathologies beyond Olsen grade 1 actinic keratoses is promising, but further studies are required. [ABSTRACT FROM AUTHOR]

The overall objective of the guideline is to provide up-to-date, evidence-based recommendations for the management of squamous cell carcinoma in situ (SCC in situ). The document aims to: offer an appraisal of all relevant literature up to 13th August 2021, focusing on any key developments; address important, practical clinical questions relating to the primary guideline objective; provide guideline recommendations and if appropriate research recommendations. [ABSTRACT FROM AUTHOR]

Tumour cells are either squamous or basal-like epithelial cells and the intracytoplasmic ductal structure is not visible.[2] Given the patient's history of metastatic testicular cancer, it would be important to rule out cutaneous metastases (option c). Epithelial membrane antigen (EMA) was expressed in the tumour cells but negative in the residual normal keratinocytes. Histopathological features include multifocal nests of basaloid cells contained within an acanthotic epidermis, tumour cells that stain positively with periodic acid-Schiff and evidence of cystic or ductal differentiation within the neoplasm.[3] The "Jadassohn phenomenon" is used to describe intraepidermal nests of tumour cells situated surrounded by normal keratinocytes. [Extracted from the article]

Background Renal transplant recipients have an increased cancer risk. The mammalian target of rapamycin inhibitor sirolimus (SRL) has immunosuppressive and antitumour activities but knowledge about its use in recipients with cancer is limited. Methods We retrospectively analysed 726 renal allograft recipients converted to SRL from 10 German transplant centres. Patient and graft survival were analysed depending on malignancy status prior to conversion and tumour entity. Results Malignancy before conversion to SRL was reported in 230 patients, with 137 patients having skin cancers and 101 having solid cancers. Cancer occurred 4.6 ± 9.4 (median 3.0) years after transplantation. Basal cell carcinoma, squamous cell carcinoma and Bowen's disease were the most prevalent skin cancers, while carcinomas of the kidney, colon and breast were the most prevalent solid cancers before conversion. Patients with prior malignancy were older and had better renal function at conversion compared with patients without a history of cancer. After conversion to SRL, cancer incidence rates (IRs) of all tumours were lower compared with rates before conversion. Cancer IRs after conversion were higher in patients with malignancy before conversion compared with those without. Patient survival was worse in patients with solid cancers compared with patients with skin cancers or without malignancies. Biopsy-proven acute rejections in the first year after conversion were less frequent in patients with malignancy compared with those without. Graft survival and renal function in all cancer types were better than in patients converted to SRL without cancers. Conclusions Conversion to SRL in patients with a history of cancer is safe regarding renal function and graft survival, while patient survival is largely dependent on tumour entity. [ABSTRACT FROM AUTHOR]

The study is outlined in Figure 1a. Patients (one lesion each) were randomized to APDT or CPDT (2: 1; APDT: CPDT). Dear Editor, The inconvenience and pain of hospital-based photodynamic therapy (PDT) is sometimes limiting.1 We developed very low-irradiance light-emitting diodes (LEDs) for ambulatory PDT. (b) PDT treatment-cycle pain scores for conventional PDT (n = 18) and ambulatory PDT (n = 32). [Extracted from the article]

Summary: Background: Advanced stage primary cutaneous malignant melanoma (PCMM) has a high mortality. PCMM may affect any area of the skin, including the nail apparatus (malignant melanoma or subungual melanoma). Although nail apparatus malignant melanoma (NAMM) is rare, delayed diagnosis carries a poor prognosis. Aim: The primary aim was to study the range of nail presentations and identify key patterns to aid in differential diagnosis. A secondary aim was to quantify the number of patients requiring surgery, indications for biopsy, and the incidence and characteristics of NAMM. Methods: This was a prospective study of all referrals with nail apparatus pigmentation to a weekly dedicated melanoma screening clinic over a 6‐month period. Results: In total, 2246 patients were included. Of the 38 patients referred with nail pigmentation, 1 (2.6%) was diagnosed with NAMM and involved a fungating amelanotic lesion of the right hallux. The remaining patients were diagnosed with subungual haematoma (20/38; 52.6%), viral wart (2/38; 5.4%), acral fibrokeratoma (1/38; 2.6%), myxoid cyst (3/38; 7.9%), fungal nail infection (4/38; 10.5%), Pseudomonas nail infection (1/38; 2.6%), benign linear pigmentation (2/38, 5.3%), Bowen disease (1/38, 2.6%), psoriatic nail changes (2/38; 5.3%) and matrix malalignment (1/38; 2.6%). Of the eight patients (21.1%) who required surgery, five had a biopsy taken and three underwent surgery. Only 14 cases were followed up by Dermatology. NAMM accounted for 0.7% of all melanomas diagnosed. Conclusion: We illustrate the wide range of diagnoses for pigmented nail presentations and highlight the late presentation of advanced disease in a patient presenting with NAMM. [ABSTRACT FROM AUTHOR]

Objectives: We observed keratoses with "clonal" nests present as numerous tiny collections, in which cells in "pagetoid" array are found, a configuration we termed microclonal seborrheic keratosis (MSK). To better distinguish MSK from pagetoid Bowen disease (PBD), we investigated use of immunohistochemical staining.Methods: Biopsy specimens of 26 MSKs, 17 PBDs, and 11 borderline cases were reviewed for histopathology and stained with p53, Ki-67, and p16.Results: High expression of Ki-67 and p16 was observed in 12 (80%) of 15 PBDs and in one (4%) of 23 MSKs. Low expression of p16 and high expression of Ki-67 were observed in 16 (70%) of 23 MSKs and in two (13%) of 15 PBDs. Expression of p16 was elevated in 12 (80%) of 15 PBDs and in three (13%) of 23 MSKs (P < .0001).Conclusions: We describe a "microclonal" variant of seborrheic keratosis with morphology sometimes challenging to distinguish from PBD. High expression of p16 and Ki-67 or p16 alone favors the diagnosis of PBD over MSK. [ABSTRACT FROM AUTHOR]

Clinical diagnosis of skin lesions and inflammatory dermatoses is a key skill for dermatologists. The first clinical diagnosis on the histopathology request form, requested by the clinician in question, was compared with the confirmed histopathological diagnosis in all patients undergoing skin biopsy. Biopsy was undertaken for 154 lesions (139 patients), and 15 patients with rashes also underwent skin biopsy, giving a total of 169 biopsies from 154 patients [58 male, 96 female (age range 14-94 years; Fig.)]. [Extracted from the article]

Summary: Pigmented Bowen disease (pBD) is an uncommon variant of squamous cell carcinoma in situ. Sometimes it can show clinical and dermoscopic features that are seen in other pigmented lesions of the skin and mucosa, making the diagnosis difficult. We report six cases of pBD occurring on the anogenital area, and discuss the importance of dermoscopy for improving the diagnostic accuracy in pBD. [ABSTRACT FROM AUTHOR]

OBJECTIVES: The pattern of lymph node metastasis is a predominant element in tumour biology, which is closely related to optimal therapeutic modality. Controversy remains as to which histopathology type of oesophageal cancer--adenocarcinoma or squamous cell carcinoma (SCC)--is more likely to have lymph node metastasis. Therefore, this study aimed to apply propensity score-matched analysis to draw an objective conclusion for providing initial evidence of the potential need for different therapeutic strategies for these 2 cancer types. METHODS: A retrospective analysis of patients who underwent radical oesophagectomy with lymphadenectomy, but without preoperative treatment for pathologically and immunohistochemically diagnosed oesophageal adenocarcinoma or SCC, was conducted. Data for analysis included age, gender, body mass index, pathologic findings, procedures of oesophagectomy and rate of lymph node metastasis. Propensity score-matched analysis was conducted to eliminate the bias effects of confounding factors. RESULTS: A total of 1204 patients (including 118 with adenocarcinoma and 1086 with SCC) from January 2012 to June 2016 was included for analysis. In the analysis of unmatched patients, those with adenocarcinomas had significantly larger mean numbers of positive lymph nodes (3.8 and 1.5, respectively; P < 0.001) and higher rates of lymph node metastasis (71.2% and 49.0%, respectively; P < 0.001) than those with an SCC. However, other confounding factors such as surgical procedures, tumour location, pT stage and lymphovascular invasion also differed significantly between the adenocarcinoma and SCC cases. In the analysis of 96 matched patients, those confounding factors were well matched, and cases of adenocarcinoma still had a significantly larger mean number of positive lymph node (4.5 and 1.8, respectively; P = 0.003) and higher rate of lymph node metastasis (75.0% and 45.8%, respectively; P = 0.003) than did those with SCC.CONCLUSIONS: Cases of oesophageal adenocarcinoma had a higher risk of lymph node metastasis than did those with SCC in this series, which indicates that different therapeutic modalities should be applied for these 2 different malignant entities. [ABSTRACT FROM AUTHOR]

The article focuses on a study which investigates whether sequential therapy using glucocorticosteroids and imiquimod (IMQ) could produce a higher clearance rate in Bowen disease (BD) than IMQ monotherapy. Topics discussed include the immunological staining of biopsies from BD lesions in patients with complete response and partial response to IMQ monotherapy and the kinetic differences in inflammatory infiltrate composition with IMQ monotherapy and sequential therapy in BD lesions.

Invited Editorial on the update of the British guidelines on SCC in situ. [ABSTRACT FROM AUTHOR]

The article discusses clinical, histological and immunohistochemical markers of resistance to methyl aminolaevulinate photodynamic therapy in Bowen disease. It mentions nonresponder tumors showed histology compatible with invasive squamous cell carcinoma after Methyl aminolaevulinate (MAL) photodynamic therapy (PDT). It also mentions lower mitotic index and reduced p53 expression and proliferative capacity compared with A-431 cells.

Background Werner protein ( WRN) has DNA helicase activity and participates in recombination, replication and repair of DNA. Loss-of-function mutations in WRN gives rise to genetic instability and diseases such as premature ageing and cancer. Upregulation of WRN promotes proliferation and survival of cancer cells. Aim To evaluate the expression pattern of WRN in closely related skin cancers and their correlation with age, sex and UV exposure. Methods Immunohistochemistry was used to investigate expression of WRN in formalin-fixed, paraffin wax-embedded tissue specimens of 9 squamous cell carcinoma ( SCC), 15 actinic keratosis ( AK), 11 Bowen disease ( BD) and 11 normal-appearing peripheral tissue samples, obtained from patients during surgical resections. Results WRN expression was significantly increased in BD, AK and SCC compared with normal controls, with the mean WRN staining score being highest in BD, followed by AK and SCC. However, age, sex and sun exposure were not associated with WRN expression. Conclusions To our knowledge, this is the first report to date investigating the expression of WRN in skin cancers. The overtly high expression of WRN in premalignant lesions and in in situ cancer, with relatively low WRN expression in SCC, may indicate that WRN contributes as a checkpoint for early DNA damage response in skin tumorigenesis. [ABSTRACT FROM AUTHOR]

Three patients developed SCCs of the tongue and one patient developed SCC of the lower lip. We discuss four patients seen in our joint oral medicine and dermatology clinic who developed oral squamous cell carcinoma (SCC) on a background of chronic GvHD. Stem cell transplant patients that develop chronic GvHD have increased risk of oral SCC, with associated morbidity and mortality. [Extracted from the article]

The article describes the case of a 76-year-old woman who developed well-circumscribed erythematous depressed annular patches on palm. Topics discussed include histopathological findings which led to the diagnosis of circumscribed palmar/plantar hypokeratosis (CPH), the difference between CPH and Bowen disease (BD), and treatment options for CPH.

Hyperpigmentation, hyperkeratoses, and Bowen's disease are hallmarks of chronic arsenic exposure. The association between arsenic-induced skin lesions and subsequent internal cancers is examined by using a community-based prospective study. The cohort was enrolled from an arseniasis-endemic area in southwestern Taiwan, where 2,447 residents participated in skin examinations during the late 1980s. The number of participants diagnosed with hyperpigmentation was 673; with hyperkeratosis, 243; and with skin cancer (Bowen's disease or non–melanoma skin cancer), 378. Newly diagnosed internal cancers were ascertained through linkage with National Cancer Registry profiles. Cox regression was performed to estimate hazard ratios with 95% confidence intervals for potential risk predictors. Compared with participants without skin lesions, patients affected with skin cancers had a significantly increased risk of lung cancer (hazard ratio = 4.64, 95% confidence interval: 2.92, 7.38) and urothelial carcinoma (hazard ratio = 2.02, 95% confidence interval: 1.23, 3.30) after adjustment for potential confounders and cumulative arsenic exposure. Hyperkeratosis is significantly associated with an increased lung cancer risk (hazard ratio = 2.76, 95% confidence interval: 1.35, 5.67). A significant interactive effect on lung cancer risk between hyperkeratosis and cigarette smoking was identified, which suggests that patients with hyperkeratosis who have been exposed to arsenic should cease smoking. [ABSTRACT FROM PUBLISHER]

We describe two patients who received haematopoietic stem cell marrow transplantation, and developed male genital lichen sclerosus ( MGLSc), one of whom also had squamous carcinoma in situ (Bowen disease). MGLSc has previously been associated with graft-versus-host disease. Various aetiological factors for LSc have been proposed, including a role for chronic occluded epithelial exposure to urine. A number of factors imply that the risk of malignant transformation in this bone marrow transplant group is likely to be higher than the overall figure of 2-9% cited for MGLSc. It is vital, therefore, that clinicians involved in the care of those with haematological malignancies are adequately prepared to examine the genitals of their patients, and to recognize and refer any suspect penile lesions. [ABSTRACT FROM AUTHOR]

Background Photodynamic therapy (PDT) with methylaminolaevulinate (MAL) is an approved noninvasive treatment option for actinic keratosis and Bowen’s disease (BD), two precursors of invasive squamous cell carcinoma (SCC). Objectives To assess efficacy, prognostic features, tolerability and cosmetic outcome of MAL-PDT for the treatment of BD and SCC. Methods In total, 112 biopsy-proven lesions of BD and SCC in 55 subjects were treated in an outpatient setting. MAL cream (160 mg g−1) was applied for 3 h prior to illumination with a light-emitting diode source (wavelength range 635 ± 18 nm; light dose 37 J cm−2). A second MAL-PDT session was given 7 days later. Complete response rate at 3 months after the last treatment, recurrence rate at the 24-month follow-up, and cosmetic outcome were recorded. Results The overall complete response rates were 73·2% at 3 months and 53·6% at 2 years. Clinical thickness, atypia and lesion depth were significant predictors of the response at 3 months when using a univariate analysis ( P < 0·001). A multivariate logistic regression model, with robust variance estimation, showed that cell atypia was the only statistically significant independent predictor of the treatment outcome at 3 months. Conclusions MAL-PDT may represent a valuable, effective and well tolerated treatment option with good cosmetic outcome for superficial, well-differentiated (Broders’ scores I and II) BD and microinvasive SCC. In contrast, its use for superficial SCCs with a microinvasive histological pattern and for nodular, invasive lesions, particularly if poorly differentiated keratinocytes are present (Broders’ scores III and IV), should be avoided. [ABSTRACT FROM AUTHOR]

Background As Bowen’s disease of the nail apparatus is quite rare, there have been only a few reports on the prevalence of human papillomavirus (HPV) infection in this condition. Objectives The purpose of this study was to clarify the association of HPV with this disease involving the nail apparatus. Methods Five patients with Bowen’s disease of the nail apparatus were investigated clinically, virologically and histologically. Total DNAs extracted from excised skin lesions were analysed using polymerase chain reaction (PCR) for the presence of HPV DNA and the amplified products were subjected to DNA sequence analyses. Histological localization of HPV DNA was examined by in situ hybridization. Results In three of five patients, HPV was detected by PCR amplification, and subsequent sequence analyses of the PCR products showed the sequences of HPV type 56. A common clinical feature of the three HPV-positive patients was longitudinal melanonychia. In contrast, the two HPV-negative patients presented with a convex nail deformity and a periungual ulcerative lesion. In two of three positive cases, there was a silent point mutation in the L1 gene of each HPV. In the remaining one case, the nucleotide sequence was consistent with the consensus sequence of HPV 56. Sequence analyses of the E6 gene revealed the infection of different variants of HPV 56 among the three cases. The viral genomes were located in keratinocyte nuclei upon in situ hybridization. Conclusions HPV 56 may be involved in the carcinogenesis of Bowen’s disease affecting the nail matrix with longitudinal pigmentation. [ABSTRACT FROM AUTHOR]

Progression from actinic keratosis (AK) and Bowen's disease (BD) to invasive disease involves a complex cascade of events. The preparation of diclofenac 3% gel (Solaraze™; Shire Pharmaceuticals) has been shown to be efficacious and well tolerated in AK. The inhibition of the COX enzymes results in a decrease in downstream by-products of arachidonic acid metabolism. These metabolites have been shown to play a pivotal role in promoting epithelial tumour growth. Given its mechanism of action, we hypothosize that diclofenac 3% gel may have potential to halt the progression of actinic keratoses (AKs) in the setting of field cancerisation and BD. We report a series of five patients with BD, all treated with diclofenac 3% gel with clinical and histological clearance. [ABSTRACT FROM AUTHOR]

Methyl aminolaevulinate–photodynamic therapy (MAL-PDT) has advanced the management of nonmelanoma skin cancer (NMSC), providing a treatment option for actinic keratosis (AK), basal cell carcinoma [both superficial (sBCC) and nodular (nBCC)] and Bowen's disease, with good clinical outcomes, low recurrence rates and enhanced cosmetic acceptability. Excellent results have been reported, with complete responses (CRs) in AK ranging from 69% to 93% at 3 months; CRs in Bowen's disease are 93% at 3 months and 68% at 24 months. In sBCC, CRs range from 85% to 93% at 3 months and are comparable with cryosurgery up to 60 months (75% vs. 74%). In nBCC, CRs range from 75–82% at 3 months to 77% at 60 months. MAL-PDT specifically targets diseased cells, leaving healthy tissue unharmed. This noninvasive treatment option is associated with minimal risk of scarring. Moreover, systemic uptake of MAL is negligible and the local phototoxic reactions that often occur during treatment rapidly heal to produce excellent cosmetic results. The side-effects of therapy, which are predominantly local phototoxic effects (burning, stinging and prickling sensations), are of mild-to-moderate intensity, of short duration and easily managed. Overall, the efficacy and low risk of side-effects afforded by this therapy have resulted in high patient preference in clinical trials. The current evidence base for MAL-PDT in the treatment of AK and NMSC is reviewed in this article. [ABSTRACT FROM AUTHOR]

This article represents a planned regular updating of the previous British Association of Dermatologists (BAD) guidelines for management of Bowen's disease. They have been prepared for dermatologists on behalf of the BAD. They present evidence-based guidance for treatment, with identification of the strength of evidence available at the time of preparation of the guidelines. [ABSTRACT FROM AUTHOR]

Is there an optimal irradiation dose for photodynamic therapy: 37 J cm-2 or 75 J cm-2? Dear Editor, Topical photodynamic therapy (PDT) is widely used for the treatment of Bowen disease (BD) and superficial basal cell carcinoma (BCC). It is not known whether PDT outcomes for BD and BCC are influenced by light dose, specifically by 37 J cm SP -2 sp or 75 J cm SP -2 sp . [Extracted from the article]

Is there an optimal irradiation dose for photodynamic therapy: 37 J cm-2 or 75 J cm-2? Dear Editor, Topical photodynamic therapy (PDT) is widely used for the treatment of Bowen disease (BD) and superficial basal cell carcinoma (BCC). It is not known whether PDT outcomes for BD and BCC are influenced by light dose, specifically by 37 J cm SP -2 sp or 75 J cm SP -2 sp . [Extracted from the article]

A 55-year-old right-handed man presented with a 6-year history of solitary longitudinal leuconychia and nailplate grooving, with distal onycholysis and triangular-shaped plate erosion of left thumbnail. Dermoscopy showed longitudinal leucoxanthonychia with a few splinter haemorrhages and triangular-shaped nail plate distal erosion, with localized hyperkeratosis and thinning of the nail plate on the corresponding free edge (Fig.). GLO:DF2/01apr20:ced14098-fig-0001.jpg PHOTO (COLOR): Clinical and dermoscopical appearance: longitudinal leucoxanthonychia of left thumbnail with distal onycholysis, few splinter haemorrhages and triangular-shaped nail plate distal erosion. gl The differential diagnosis included squamous cell carcinoma/Bowen disease, onychopapilloma and subungual (myxoid or not) fibrokeratoma. [Extracted from the article]

Background Photodynamic therapy (PDT) has been shown to be effective in treating Bowen's disease, superficial basal cell carcinoma and actinic keratosis. Objectives To investigate the feasibility of delivering PDT using a portable light-emitting diode device. Methods A prototype diode array, comprising 37 AlGaInP diodes cast in epoxy with a diffuser, and driven by a battery pack, was designed and constructed. A pilot study was carried out in five patients with histologically proven Bowen's disease who were referred for PDT with 5-aminolaevulinic acid. They were all treated in the hospital-based dermatology PDT suite such that each received the same level of supervision as patients receiving PDT with nonambulatory light sources. Patients recorded pain levels. In accordance with our usual practice, patients received two treatments at a 4-week interval. Results Four of five patients were clear at follow-up (range 6–13 months, median 9). Pain was classified as none or mild in 80% of treatments and moderate in the remainder. Conclusions There are many potential benefits of ambulatory PDT, including the possibility of a much higher patient throughput, and allowing effective treatment at home. This pilot study provides early promising data of the safety and efficacy of this approach. [ABSTRACT FROM AUTHOR]

Background Actinic keratosis (AK) has been defined as a precancerous lesion or an early phase in the evolution of squamous cell carcinoma (SCC) and histological changes seen in the individual cells of an AK are indistinguishable from those seen in SCC, which invade the dermis. Cyclin A is an increasingly utilized proliferation marker that has functions in both S phase (DNA replication) and initiation of mitosis, whereas alterations of β-catenin, the molecule involved in cell–cell adhesion and in signalling transduction, could promote invasive and proliferative capacities of malignant tumours. Objectives To determine cyclin A and β-catenin expression pattern in cutaneous SCC and in in situ lesions classified as keratinocytic intraepidermal neoplasia (KIN) and, using traditional terms, as AK and Bowen's disease (BD), and to analyse it in relation to SCC differentiation, diameter and thickness. Methods Immunohistochemical staining was performed on 110 formalin-fixed paraffin-embedded tissue samples with the streptavidin–biotin technique using antibodies to cyclin A and β-catenin. On histological examination, 53 lesions were diagnosed as AK, 16 as BD and 41 as SCC—11 well differentiated (WD), 16 moderately differentiated (MD) and 14 poorly differentiated (PD). Using KIN classification, 22 lesions were KIN1, 23 were KIN2 and 24 were KIN3. For cyclin A, distribution and labelling index (LI), and for β-catenin, level of membranous staining and presence of aberrant (nuclear/cytoplasmic) localization were examined. Results Diffuse cyclin A presence was observed more frequently in BD than in AK ( P < 0·0001) or SCC ( P = 0·0002), and in SCC-PD compared with SCC-WD ( P < 0·0001) or SCC-MD ( P = 0·0003). Differences between KIN3 and KIN2, as well as KIN3 and KIN1 lesions, were statistically significant ( P < 0·0001), and the same result appeared when KIN1 and KIN2 cases were grouped and compared with those of KIN3 ( P < 0·0001). Cyclin A LI was significantly lower ( P < 0·05) in AK than in BD or SCC, but no difference between BD and SCC was found, and LI in BD was even higher than in SCC-WD or SCC-MD, while analysis regarding SCC differentiation and KIN classification revealed the same correlation as for the cyclin A distribution. Reduced or absent β-catenin membranous staining was found in 90 cases (81·8%), more often in SCC than in AK ( P = 0·03) or in AK and BD grouped together ( P = 0·02). There was no statistical difference between SCCs of various level of differentiation, or between different KIN grades. Diffuse loss of membranous β-catenin staining showed 36 lesions (32·7%), more frequently SCC than AK ( P = 0·003) or AK and BD grouped ( P = 0·006), as well as SCC-PD compared with SCC-WD ( P = 0·01) and SCC-MD ( P = 0·03), whereas all KIN comparisons remained nonsignificant. Aberrant β-catenin cellular localization demonstrated 28 lesions (25·5%), most often in the basal or peripheral parts and in the lesions with diffuse β-catenin loss ( P = 0·009), but revealed no correlation with the histological type, SCC level of differentiation or KIN grades. Diffuse loss of membranous β-catenin staining was found to be significantly more frequent in SCC thicker than 4 mm ( P = 0·03), while all other comparisons between cyclin A or β-catenin with the tumour size remained nonsignificant. Cyclin A LI was higher in cases with diffuse loss of membranous staining ( P = 0·001) or with aberrant cellular localization of β-catenin ( P = 0·002). Conclusions Cyclin A LI showed greater difference between AK and BD than between BD and SCC, suggesting that increased proliferation (measured by cyclin A LI) characterizes progression of in situ lesions from AK to BD, whereas reduced β-catenin expression separates more clearly SCC from the in situ lesions. Diffuse pattern of loss of membranous β-catenin staining correlated better with the type of lesion, SCC differentiation and tumour size than reduced expression in general or aberrant cellular localization of β-catenin. KIN classification does not seem to be supported by our findings, except when KIN1 and KIN2 lesions ( in situ, partial thickness) are grouped. [ABSTRACT FROM AUTHOR]

Background The use of 5-aminolaevulinic acid photodynamic therapy (ALA-PDT) for the treatment of Bowen's disease is well established. However, treatment with a continuous light source has the disadvantage of prolonged treatment time during which patients often experience significant discomfort requiring the use of local anaesthetic. Objectives The aim of this study was to assess the efficacy and safety of the pulsed dye laser (PDL) as the light source for photoactivation of the protoporphyrin IX to treat Bowen's disease by PDT. Methods Thirteen patients with a total of 17 patches of histologically proven Bowen's disease were treated with 20% 5-ALA in Unguentum M® (Crookes Healthcare, Nottingham, U.K.) under occlusion for 4 h. The patches were then irradiated using a Candela SPLTL-1b (Candela Corporation, Wayland, MA, U.S.A.) PDL using a wavelength of 585 nm, with a 7-mm diameter spot at a fluence of 10 J cm−2. The spots overlapped by 50% to cover the lesion and extend beyond the clinical margin of the patch of Bowen's disease by 0·5 cm. Patients were then followed up initially at 2 months, then at 3-monthly intervals for a period of 12 months to assess treatment success and recurrence rate. Results Subjects consisted of 10 females and three males, between 47 and 88 years. The mean area of the patches of Bowen's disease was 315·4 mm2 (range 36–2464 mm2) requiring a median of 32 pulses (range 3–260). Lesions sites were hands (two), foot (one) and lower leg (14). All patients experienced varying degrees of discomfort during treatment but none required the use of local anaesthetic. At 2 months eight treatment sites could not be assessed due to loose overlying crusts and removal of these revealed superficial erosions in seven patients. Of the 17 lesions treated, on follow-up at 1 year, 14 patches (82%) demonstrated a complete clinical response, although one of these had required a second treatment. Two patients with three lesions that would have required further therapy refused a second treatment. Prolonged crusting lasting 8 weeks occurred in eight patches and prolonged discomfort lasting 6 weeks occurred in four patients. Conclusions This study has shown that the PDL is an effective light source for ALA-PDT of Bowen's disease. Light source exposure times are shorter, although overall treatment time may not always be significantly reduced for larger lesions. The procedure was well tolerated. However, the post-treatment morbidity was relatively high compared with the more conventional treatment modalities. Further studies are needed to determine whether lower energy fluences can maintain similar efficacy while reducing post-treatment morbidity. [ABSTRACT FROM AUTHOR]

Background: Imiquimod, an immune response modifier that is used topically to treat different types of skin cancer, induces the production of proinflammatory cytokines that stimulate an antitumor immune response. We assessed characteristics of the imiquimod-induced immune activation in epithelial and lymphoproliferative neoplasias of human skin. We focused on plasmacytoid predendritic cells (PDCs), the primary producer of interferon alpha (IFN-alpha) after imiquimod activation in vitro.Methods: We used Affymetrix oligonucleotide arrays to compare gene expression profiles from tumors from 16 patients, 10 with superficial basal cell carcinomas (sBCCs), five with cutaneous T-cell lymphomas (CTCLs), and one with Bowen's disease, before and after topical imiquimod treatment. We used quantitative immunohistochemistry with PDC-specific antibodies against BDCA-2 and CD123 to characterize the PDC population before and after imiquimod treatment in these specimens. Activation status of PDCs from four sBCC patients was assessed by intracellular IFN-alpha staining and flow cytometry.Results: Expression of various IFN-alpha-inducible genes (e.g., CIG5, G1P2, OASL, IFIT1, STAT1, IFI35, OAS1, ISG20, MxA, and IRF7), the so-called IFN-alpha signature, was increased similarly in both sBCC and CTCL lesions after imiquimod treatment. PDCs were recruited and activated in both lesion types, and they produced IFN-alpha after imiquimod treatment in vivo (mean percentage of PDCs producing IFN-alpha = 14.5%, 95% confidence interval [CI] = 4.9% to 24%; range = 3.3%-27%, n = 4 lesions). Imiquimod induced similar immune activation patterns in all three diseases, and these patterns were associated with the number of PDCs recruited to the treatment site. Two imiquimod-treated sBCC patients who did not mount an inflammatory response to imiquimod and whose lesions lacked the IFN-alpha signature after treatment had fewer PDCs in treated lesions compared with other treated patients with such a response.Conclusions: Imiquimod induces immune activation patterns that relate to the number of the PDCs recruited to the treatment site, thus supporting the role of PDC in responsiveness to imiquimod in humans. [ABSTRACT FROM AUTHOR]

The epidermis, which is a typical stratified epithelium, has tight junctions (TJs) in the granular layer, as do simple epithelia. So far, abnormalities of TJs and involvement of claudin-1 have been reported in tumours of simple epithelia. To examine the expression of TJ-associated proteins (occludin, ZO-1, claudin-1 and claudin-4) in normal human epidermis and in malignant disorders of keratinization. Expression of the proteins in normal human epidermis, five cases of squamous cell carcinoma (SCC) of the skin and five cases of Bowen's disease (BD) was examined by immunofluorescence staining. In normal human epidermis, occludin, ZO-1 and claudin-4 were expressed at the cell–cell borders in the granular layer specifically or dominantly, whereas claudin-1 was expressed in the whole epithelium. In SCC, occludin, ZO-1, claudin-1 and claudin-4 were strongly expressed in tumour cells with keratinization such as cancer pearls. Claudin-1 was heterogeneously expressed in unkeratinized tumour cells, whereas expression of occludin, ZO-1 and claudin-4 was decreased or absent. In BD, aberrant expression of occludin, ZO-1, claudin-1 and claudin-4 was observed at the cell–cell borders in addition to their expression patterns observed in normal epidermis. Expression of occludin, ZO-1 and claudin-4 is associated with keratinization in SCC and BD. However, the heterogeneous expression of claudin-1 in SCC is not determined only by keratinization. [ABSTRACT FROM AUTHOR]

Bowen's disease of the skin may have differing clinical presentations depending on the skin surface on which it presents, but has the same histologic features of squamous cell carcinoma in situ wherever it occurs. The etiologic factors include ultraviolet light and human papillomavirus infection. The choice of therapy requires a consideration for retention of form, function and cosmosis while offering a high cure rate. The immunodualtory agent imiquimod has been shown to be an effective treatment on a variety of skin surfaces. [ABSTRACT FROM AUTHOR]

Progression of cutaneous squamous neoplasms from actinic keratosis (AK) to Bowen's disease (BD; squamous cell carcinoma in situ) has important implications for clinical management and treatment, thus requiring accurate diagnosis. p16INK4a is a cell cycle regulatory tumour suppressor protein that negatively regulates D-type cyclins in the G1 cell cycle phase via intimate interplay with the retinoblastoma gene. Expression of a paraffin-reactive p16INK4a marker has recently been shown to increase in cervical squamous neoplasms as lesions progress from low-grade dysplasia to squamous cell carcinoma in situ. p16INK4a expression in the progression of squamous cutaneous neoplasia, however, has not been evaluated. To evaluate p16INK4a expression in the progression of squamous cutaneous neoplasia. Biopsies of 203 squamous cutaneous neoplasms with unequivocal features of AK ( n = 87) and BD ( n = 116) as well as a benign squamous control group (verruca vulgaris: n = 10; seborrhoeic keratosis: n = 11; scar tissue: n = 8) obtained between January and December 2001 at Henry Ford Hospital (Detroit, MI, U.S.A.) were immunostained for p16INK4a (Dako; clone E6H4; dilution 1 : 50) using large core (1·5 mm) tissue microarray analysis. Nuclear/cytoplasmic immunoreactivity in > 10% of neoplastic cells was considered positive. Of 203 cases, 166 (81·8%) were interpretable (AK 59; BD 107). Mean patient age was 71·0 years (range 33–93); 57% were male. Sites of involvement were: head and extremities 75·9%, trunk/buttocks 21·7%, genital region 2·4%. p16INK4a immunostaining was positive in 90 of 107 (84·1%) BD cases, four of 59 (6·8%) AK cases and none of 29 benign squamous controls. The sensitivity and specificity of p16INK4a for a diagnosis of BD (vs. benign squamous controls/AK) was 84·1% and 95·5%, respectively ( P < 0·0001, Fisher's exact test, two-sided). p16INK4a is a sensitive and specific marker for distinguishing BD from AK/benign squamous cutaneous lesions and may be helpful as an adjunct to histomorphology in the diagnosis and appropriate clinical management of these lesions. [ABSTRACT FROM AUTHOR]

Background In the current economic climate, it is important to justify the cost of treatments used in dermatology, particularly where cheaper alternatives exist. Objectives To determine which treatment modality commonly used for Bowen's disease is associated with the lowest cost to the National Health Service. Methods A cost-minimization analysis was used to compare the following six treatments for Bowen's disease: cryotherapy, curettage and cautery, excision, laser ablation, photodynamic therapy and 5-fluorouracil. These are all known to have similar recurrence rates. Information regarding use of these treatment modalities was extracted from a literature review. Costs were determined from published data, average wholesale prices of medications, staff salary pay scales and health economics departments. Results The results show that, if treatment is indeed undertaken, a single lesion of Bowen's disease is most cheaply treated by curettage or excision biopsy under local anaesthetic, and most expensively treated by photodynamic therapy. The usefulness of this information has to be taken in the context of the study design, outcome measurements and base assumptions. Conclusions Valid costing studies such as this, in conjunction with evidence of effectiveness and safety, can provide guidance for resource allocation and treatment decisions. [ABSTRACT FROM AUTHOR]

Summary Background Bowen's disease (BD; intraepithelial squamous cell carcinoma) is therapeutically challenging because lesions, which may be multiple, are frequently located at sites that heal poorly. There is a small risk of progression to invasive carcinoma. Photodynamic therapy (PDT) is an effective treatment for certain non melanoma skin cancers, but comparison studies with other, better-established therapies are limited. Objectives To compare the efficacy and tolerability of PDT and topical 5-fluorouracil (5-FU) in BD. Methods Forty patients from two centres were randomized to either topical PDT or 5-FU. The PDT group was treated with 20% 5-aminolaevulinic acid (ALA) applied 4 h before illumination with 100 J cm-2 narrowband red light (630 ± 15 nm). 5-FU was applied to lesions for 4 weeks. A repeat treatment cycle was performed after 6 weeks if required. Results Twenty-nine of 33 (88%) lesions treated with PDT initially responded completely, compared with 22 of 33 (67%) after 5-FU. After 12 months, two recurrences in the PDT group and six in the 5-FU group reduced complete clinical clearance rates to 82% and 48%, respectively. PDT was significantly more effective (P = 0·006, odds ratio 4·78, 95% confidence interval 1·56–14·62). In the 5-FU group, severe eczematous reactions developed around seven lesions, ulceration in three and erosions in two. No such reactions occurred following PDT. There was no difference in overall pain experienced during each therapy. Conclusions Topical ALA-PDT is more effective than topical 5-FU in the treatment of BD, with fewer adverse events. ALA-PDT should be considered one of the first-line therapeutic options for BD. [ABSTRACT FROM AUTHOR]

Summary We describe a 25-year-old man with epidermodysplasia verruciformis (EV) associated with neurofibromatosis type 1 (NF1). The lesions, persisting for more than 15 years, consisted of widespread planar warts on the backs of the hands and wrists, and reddish-brown macules on the trunk, neck and face. During the last 5 years, our patient developed several epithelial tumours, namely solar keratoses, plaques of Bowen's disease and squamous cell carcinomas (SCCs). He also presented with NF1 lesions with neurofibromas, café-au-lait macules, axillary freckling and Lisch nodules. He had left tibial bowing. Polymerase chain reaction analysis of the skin lesions demonstrated the presence of human papillomavirus (HPV) 15 in a flat wart, HPV 20 in a plaque of Bowen's disease, and HPV 15 and HPV 20 in an SCC lesion. Both EV and NF1 show an inherited predisposition to malignancy but the molecular mechanism underlying tumour development is not fully understood. The appearance of both diseases in our patient may be a coincidental association but may also contribute to the identification of loci for susceptibility to NF1 and EV on chromosome 17. [ABSTRACT FROM AUTHOR]

Background Bowen's disease is a well-established in situ malignancy of the epidermis. The keratin expression in Bowen's disease has been studied in many reports. However, the patterns of keratin (K) 14 expression in each case have not been closely examined. Objectives To investigate if the pattern of expression of K14 has a relationship with tumour progression, we analysed the expression patterns of K14 in relation to the nature of tumour cells, comparing tumour cells in direct contact with the dermis, tumour cells separated from the dermis, and tumour cells invading into the dermis. Methods Twenty-seven tissue sections from 22 patients were stained with anti-K14 antibody, as well as with antilaminin and periodic acid-Schiff (PAS) staining to evaluate the conditions of the basement membrane. Staining patterns of K10 and integrin β1, and their relationships with proliferating cell nuclear antigen (PCNA) and Ki-67 staining patterns, were also examined. Results Tumour cells with no, or with obscured, basement membranes always showed positive staining for K14, while those with continuous (intact) basement membranes usually did not. Of 10 sections showing dermal involvement of Bowen's disease, five were K14 positive and five were K14 negative. All of these K14-positive sections with dermal involvement showed negative or obscured laminin and PAS staining. Most of the sections having K14-negative tumour cells with dermal involvement showed K14-positive lining cells with continuous staining with laminin and PAS-positive basement membranes. K10 was reciprocally expressed with K14 in most of the sections. Integrin β1 was expressed in the basal layers of non-tumour epidermal cells, but not in tumour cells. Ki-67 and PCNA were expressed at high frequencies in tumour cells, clearly demarcating tumour cells from non-tumour cells. Conclusions Tumour cells separated from the dermis by lining cells were K14 negative with PAS- and laminin-positive basement membranes... [ABSTRACT FROM AUTHOR]

Background Photodynamic therapy (PDT) has not yet been demonstrated to be superior to conventional treatment in the treatment of superficial skin cancers and premalignant skin conditions. A limitation for PDT is the absence to date of a light source suitable for the treatment of larger lesions or ‘field changes’ where several lesions are present on one anatomical site. Objectives To investigate the safety and efficacy of a large field light source, the Waldmann PDT 1200, in the treatment of Bowen’s disease (BD), superficial basal cell carcinomas (BCCs) and solar keratoses (SKs). Methods After application of 5-aminolaevulinic acid for 4–6 h, each lesion was irradiated with 105 J cm-2 of incoherent red light centred on 640 nm. Eighty-eight patients with 239 lesions were recruited. Results Within two treatments, 88% of BD lesions, 95% of BCCs and 99% of SKs showed complete clinical clearance. At 12 months the complete response rates were 69% for BD, 82% for BCC and 72% for SK. Conclusions This study confirms that PDT is a useful treatment and that selected superficial BCCs and SKs respond well to PDT. The PDT 1200 light source proved capable of treating multiple lesions amounting to a ‘field change’ and also lesions up to 10 cm in diameter within an acceptable treatment time. Thus far, PDT has failed to become established as a routine treatment for small premalignant and malignant skin lesions as it has not proved superior to simple cheaper conventional therapies such as cryotherapy, curettage and cautery, topical chemotherapy with 5-fluorouracil, or surgery. However, PDT has become established as a treatment for selected cases in some centres. This study suggests a role for PDT in the treatment of large premalignancies, superficial BCCs and field change where existing treatments may be problematic. [ABSTRACT FROM AUTHOR]

Background Bowen’s disease (BD) is a squamous cell carcinoma in situ that rarely invades into the underlying dermis. However, little is known about its immunohistology. Objectives To evaluate the relationship between the cytological properties of the tumour cells in BD and the host immune response. Methods We examined the expression of p53, proliferating cell nuclear antigen (PCNA) and Ki67 antigen, and the number of mitotic cells, together with the number of intratumoral and dermal infiltrating CD1a+, CD3+, CD4+, CD8+, CD68+ and cutaneous lymphocyte-associated antigen (CLA)+ cells in 18 cases of genital BD. Results When compared with normal genital skin (n = 10), there was a significantly higher number of mitotic cells as well as higher expression of p53+, PCNA+ and Ki67+ cells in BD. There was significant mutual correlation between CD3+, CD4+ and CD68+ cells in the tumoral epidermis. The number of CD1a+ Langerhans cells significantly decreased in BD epidermis; however, dermal CD1a+ cells were increased. Interestingly, numbers of dermal CD1a+ cells significantly correlated with those of intratumoral CD3+, CD4+ and CD68+ cells. In situ hybridization for human papillomavirus (HPV) demonstrated that HPV-infected BD had significantly less infiltration of intratumoral CD3+ cells and CLA+ cells. Conclusions The present data suggest that dermal CD1a+ cells may participate in the immune surveillance and that HPV infection may interfere with the intratumoral infiltration of CLA+ cells in BD. [ABSTRACT FROM AUTHOR]

Background A variety of protocols exist for the treatment of Bowen’s disease by photodynamic therapy (PDT) using topical 5-aminolaevulinic acid (5-ALA). Objective To determine the optimal wavelength (red or green light) for this treatment. Methods A randomized comparison study of ALA–PDT using red (630 ± 15 nm) or green (540 ± 15 nm) light in the treatment of Bowen’s disease. Results The initial clearance rate for lesions treated by red light was 94% (30 of 32) in comparison with 72% (21 of 29) for those lesions receiving green light (P = 0·002). Over the following 12 months, there were two recurrences in the red light group and seven in the green light group reducing the clearance rates to 88% and 48%, respectively. The frequency and severity of pain experienced were similar between the two treatment groups. No hyperthermia, nor significant difference in lesional temperatures, was observed between the wavelengths studied. Conclusion Green light is less effective than red light, at a theoretically equivalent dose, in the treatment of Bowen’s disease by topical ALA–PDT. [ABSTRACT FROM AUTHOR]

Background In our departments, curettage and cautery (C&C) and liquid nitrogen cryotherapy are the preferred methods of treatment for Bowen’s disease (BD). Objectives We aimed to compare these two treatments with regard to efficacy, time to heal, morbidity and recurrence rate. Methods Cryotherapy was performed using a liquid nitrogen spray giving two freeze–thaw cycles, each freeze cycle being maintained for 5–10 s after the formation of an ice ball to the intended margin. Curettage was performed with a conventional disposable curette under local anaesthesia, and electrocautery was then used for haemostasis. Results Eighty lesions in 67 patients (55 female) were analysed. The mean age of the patients was 74 years (range 46–89). The most frequent site was the lower leg, below the knee (n = 59, 74%). The average time taken for complete healing after the procedure was 60 days. The mean size of the lesions was 336 mm2 (range 30–1890). The patients were followed up for a mean of 22 months (range 6–24, median 2 years). In the cryotherapy group (n = 36 lesions), the median time to complete healing was 46 days (range 14–210; mean 69). Twelve lesions took more than 90 days to heal. Infection requiring antibiotics developed in four patients. Thirteen of the treated lesions had recurred by 24 months. In the C&C group (n = 44 lesions), the median time to healing was 35 days (range 14–330; mean 53). Six of the lesions took more than 90 days to heal. Infection developed in two patients. Recurrence occurred in four lesions over the follow-up period. Considering BD on the lower legs separately, lesions took on average 90 days to heal in the cryotherapy group (n = 23), whereas in the C&C group (n = 36) they took 39 days to heal (P < 0·001). During the procedure and the subsequent 24 h, patients were 10·4 times more likely to report pain of any degree for lesions treated by cryotherapy than by C&C (P <... [ABSTRACT FROM AUTHOR]

We biopsied longitudinal erythronychia in 16 subjects, and found an onychopapilloma in 14 cases and Bowen’s disease in the remaining two. Shared clinical features in addition to erythronychia (or sometimes an interrupted line made up of splinter haemorrhages) were typically a longitudinal marked ridge of the nail bed expanded at the distal nail bed as subungual keratosis, and associated localized onycholysis. The presentation of Bowen’s disease in this pattern has not been previously reported. In all cases of onychopapilloma of the nail bed, acanthosis and papillomatosis were evident, and were associated with a keratogenous zone identical to the nail matrix. In addition, we found multinucleate giant cells in two onychopapillomas. We have therefore suggested that the term ‘localized, distal, subungual keratosis with multinucleate cells’ should be replaced by ‘onychopapilloma’ (nail-producing papilloma). [ABSTRACT FROM AUTHOR]

These guidelines for management of Bowen's disease have been prepared for dermatologists on behalf of the British Association of Dermatologists. They present evidence-based guidance for treatment, with identification of the strength of evidence available at the time of preparation of the guidelines, and a brief overview of epidemiological aspects, diagnosis and investigation. [ABSTRACT FROM AUTHOR]

Spontaneous regression is sometimes seen in malignant skin tumours. We report a 68-year-old woman whose Bowen's disease showed spontaneous complete regression. Prominent infiltration of T cells and increased vascularity were found in the upper dermis of the regressed lesion. Strong expression of Fas (APO-1/CD95) antigen, an apoptosis-related tumour necrosis factor receptor family protein, in the primary lesion and faint expression following regression suggest the involvement of Fas-mediated apoptosis in the spontaneous complete regression of our patient's Bowen's disease. [ABSTRACT FROM AUTHOR]