Analysis of Epidermal Growth Factor Receptor Gene in a Case of Multiple Bowen's Disease

A 45-year-old woman had a triple cancer, multiple Bowen's disease, breast cancer, and carcinoma in situ of the cervical portion of her uterus. Development of all three carcinomas was discovered within a period of three years. Southern blotting analysis of the epidermal growth factor receptor (EGFRc) gene of DNA extracted from the individual lesions of multiple Bowen's disease revealed no amplification or variant other than one extra band observed in one lesion. DNA extracted from other patients with solitary Bowen's disease showed essentially the same result. In contrast to squamous cell carcinoma DNA which sometimes has amplification of this gene, our present case suggests that there is only a small possibility that the EGFRc gene plays a role in the carcinogenesis of Bowen's disease.     

Bowenoid Papulosis of the Vulva and Subsequent Periungual Bowen's Disease Induced by the Same Mucosal HPVs

We report the case of a 23-year-old woman who developed bowenoid papulosis of the vulva and subsequent periungual Bowen''s disease. She had a history of a long standing periungual wart on her right thumb before the outbreak of periungual Bowen''s disease. By HPV DNA chip, human papillomavirus (HPV) 11, 18 and 31 were identified from the periungual lesions, and HPV 11, 18 and 33 from the vulvar lesion. This case supports the theory of anogenital-digital spread of HPV, and proposes that the periungual wart may change into Bowen''s disease by mucosal HPVs. To the best of our knowledge, this case is important as the first Korean case of periungual Bowen''s disease concurrent with bowenoid papulosis of the vulva.     

Large patches of Bowen's disease treated by topical aminolaevulinic acid photodynamic therapy

Large patches of Bowen's disease (intraepidermal carcinoma in situ) can be difficult to treat by conventional methods. Photodynamic therapy (PDT) uses the combination of a photosensitizer, which preferentially accumulates in malignant cells, and photoactivation by visible light to kill the malignant cells, 5-aminolaevulinic acid (ALA) PDT uses excess exogenous ALA, which produces, via the haem synthesis pathway, a build up of the photosensitizer protoporphyrin IX. We describe the use of topical ALA PDT to treat three patients with three especially large patches of Bowen's disease. Following two treatments all three lesions achieved a complete clinical and histological response with a good cosmetic result. ALA PDT is a simple, effective and well tolerated treatment for large patches of Bowen's disease.     

European Dermatology Forum guidelines on topical photodynamic therapy 2019 Part 1: treatment delivery and established indications – actinic keratoses,Bowen's disease and basal cell carcinomas

Topical photodynamic therapy (PDT) is a widely approved therapy for actinic keratoses, Bowen's disease (squamous cell carcinoma in situ), superficial and certain thin basal cell carcinomas. Recurrence rates when standard treatment protocols are used are typically equivalent to existing therapies, although inferior to surgery for nodular basal cell carcinoma. PDT can be used both as lesional and field therapies and has the potential to delay/reduce the development of new lesions. A protocol using daylight to treat actinic keratoses is widely practised, with conventional PDT using a red light after typically a 3‐h period of occlusion employed for other superficial skin cancer indications as well as for actinic keratoses when daylight therapy is not feasible. PDT is a well‐tolerated therapy although discomfort associated with conventional protocol may require pain‐reduction measures. PDT using daylight is associated with no or minimal pain and preferred by patient. There is an emerging literature on enhancing conventional PDT protocols or combined PDT with another treatment to increase response rates. This guideline, published over two parts, considers all current approved and emerging indications for the use of topical PDT in dermatology, prepared by the PDT subgroup of the European Dermatology Forum guidelines committee. It presents consensual expert recommendations reflecting current published evidence.     

Expression of proliferation-associated proteins (proliferating cell nuclear antigen and Ki-67 antigen) in Bowen's disease

Bowen's disease and invasive squamous cell carcinoma arising in Bowen's disease (Bowen's carcinoma) were investigated immunohistochemically with regard to their expression of proliferating cell nuclear antigen (PCNA) and the Ki-67 antigen. Both proliferation-associated proteins were found in all layers of the tumours, and were present in nuclei of any size and shape. The nucleoli lacked PCNA immunoreactivity, but they expressed the Ki-67 antigen. The PCNA labelling index was 36.9±12.6% in Bowen's disease (n= 16), and 40.7±11.0% in Bowen's carcinoma (n=3). The Ki-67 antigen labelling index was 43.6±16.7% in Bowen's disease (n=16), and 51.7±11.6% in Bowen's carcinoma (n=3). Dyskeratotic cells were positive for PCNA and the Ki-67 antigen, suggesting that these cells are not in a post-mitotic state. We conclude that in dyskeratotic cells of Bowen's disease the cell cycle is interrupted by nuclear disorganization.     

Photodynamic therapy in dermatology: state‐of‐the‐art

Photodynamic therapy (PDT) has become an established treatment modality for dermatooncologic conditions like actinic keratosis, Bowen's disease, in situ squamous cell carcinoma and superficial basal cell carcinoma. There is also great promise of PDT for many non‐neoplastic dermatological diseases like localized scleroderma, acne vulgaris, granuloma anulare and leishmaniasis. Aesthetic indications like photo‐aged skin or sebaceous gland hyperplasia complete the range of applications. Major advantages of PDT are the low level of invasiveness and the excellent cosmetic results. Here, we review the principal mechanism of action, the current developments in the field of photosensitizers and light sources, practical aspects of topical PDT and therapeutical applications in oncologic as well as non‐oncologic indications.     

Enfermedad de Bowen gigante,con invasión dérmica tras 65 años de evolución

.—Bowen's disease is a form of squamous cell carcinoma in situ that shows full-thickness involvement of the epidermis, and the pilosebaceous units. Although it may remain in situ for long periods, about 3% to 5% of untreated patients may develop invasive carcinoma.We report the case of a 92-year-old woman with a Bowen's disease of 65-year duration which developed an invasive carcinoma.     

Mammary and extramammary Paget's disease

Paget''s disease, described by Sir James Paget in 1874, is classified as mammary and extramammary. The mammary type is rare and often associated with intraductal cancer (93-100% of cases). It is more prevalent in postmenopausal women and it appears as an eczematoid, erythematous, moist or crusted lesion, with or without fine scaling, infiltration and inversion of the nipple. It must be distinguished from erosive adenomatosis of the nipple, cutaneous extension of breast carcinoma, psoriasis, atopic dermatitis, contact dermatitis, chronic eczema, lactiferous ducts ectasia, Bowen''s disease, basal cell carcinoma, melanoma and intraductal papilloma. Diagnosis is histological and prognosis and treatment depend on the type of underlying breast cancer. Extramammary Paget''s disease is considered an adenocarcinoma originating from the skin or skin appendages in areas with apocrine glands. The primary location is the vulvar area, followed by the perianal region, scrotum, penis and axillae. It starts as an erythematous plaque of indolent growth, with well-defined edges, fine scaling, excoriations, exulcerations and lichenification. In most cases it is not associated with cancer, although there are publications linking it to tumors of the vulva, vagina, cervix and corpus uteri, bladder, ovary, gallbladder, liver, breast, colon and rectum. Differential diagnoses are candidiasis, psoriasis and chronic lichen simplex. Histopathology confirms the diagnosis. Before treatment begins, associated malignancies should be investigated. Surgical excision and micrographic surgery are the best treatment options, although recurrences are frequent.     

Photodynamic therapy of epithelial skin tumours using delta-aminolaevulinic acid and desferrioxamine

Photodynamic therapy (PDT) uses photosensitizing drugs, such as porphyrins, and light for cancer treatment. In the present clinical study we employed topical application of the porphyrin precursor delta-aminolaevulinic acid (ALA) in combination with desferrioxamine (df) for the induction of endogenous porphyrin synthesis. Irradiation was performed with a light source consisting of a halogen lamp with a red filter and a fibreoptic device. Irradiances ranged from 50 to 300mW/cm². We treated 49 patients with this PDT regimen. In 32 patients we treated a total of 34 superficial basal cell carcinomas (BCCs) and 22 nodular BCCs, in nine patients 43 solar keratoses, and in eight patients 10 lesions of Bowen's disease. After a single treatment, 30 (88.2%) of the superficial and seven (31.8%) of the nodular BCCs, 35 of 43 (81.4%) solar keratoses. and three (30%) of the Bowen's disease lesions showed complete remission. The post-treatment observation period was up to 20 months. Repeat therapy was required in six nodular and four superficial BCCs. Biopsies were obtained before treatment, and at variable intervals after treatment. Topical PDT of skin tumours with ALA-df-induced porphyrins is effective in the management of epithelial skin tumours.     

Efficacy of Imiquimod 3.75% for the treatment of extensive Bowen's disease of the face in an elderly patient

Bowen's disease is a cutaneous squamous cell carcinoma (SCC) in situ with a potential risk of progression to invasive SCC. Despite the high number of approved treatments, elderly patients with extensive lesions of critical sites may represent a therapeutical challenge, especially in cases of treatment failure or recalcitrant disease. Here, we report the successfully use of topical Imiquimod 3.75% to treat an extensive Bowen's disease of the cheek in an elderly.     

Multiple Bowen's Disease Associated with Squamous Cell Carcinoma

This paper reports a 50-year-old man with multiple Bowen's disease who subsequently developed squamous cell carcinoma. He had a possible history of chronic arsenical ingestion through drinking contaminated well water at a young age. The rain drop appearance of depigmented spots on the body and the warty hyperkeratosis on the palms and soles are manifestations of chronic arsenical ingestion.     

Merkel Cell Carcinoma and Multiple Bowen's Disease: Incidental Association or Possible Relationship to Inorganic Arsenic Exposure?

An 81-year-old Japanese male was referred to our clinic in 1991 with multiple Bowen's disease. The associated hyperpigmentation of the trunk and extremities and palmo-plantar keratotic nodules indicated that he had suffered from chronic arsenic poisoning. Interestingly, he was a native of Namikata in Ehime, Japan, where many residents have suffered from multiple Bowen's disease with internal malignancy. Arsenic exposure was strongly suspected. Two years later, Merkel cell carcinoma developed on the dorsum of his right hand, where Bowen's disease lesions were absent. Metastasis of this Merkel cell carcinoma led to his eventual death one year later. To our knowledge, this is the first report of Merkel cell carcinoma associated with multiple Bowen's disease. Chronic arsenic poisoning may be responsible for the association of these two rare skin neoplasms.     

Progressive Alterations of Cytokeratin Expressions in the Process of Chronic Arsenism

Recent studies of an endemic occurrence of chronic arsenism in a limited area on the southwest coast of Taiwan are focusing on its cytokeratin analysis in hopes of tracing the disease's biochemical expression. Specimens were obtained from uninvolved skin and arsenical cancers including Bowen's disease, basal cell carcinoma, and squamous cell carcinoma. In this study, we used two-dimensional polyacrylamide gel electrophoresis to analyse cytokeratin expression. Progressive alterations in cytokeratin expression were found in various skin lesions. These include an expression of K16 in the uninvolved skin; K16 and K6 in Bowen's disease; and K16, K6 and K17 in squamous cell carcinoma and basal cell carcinoma. In addition, we found that the K1 isoelectric variants shifted to more acidic forms with the complete absence of K1 in basal cell carcinoma. K16 expression in uninvolved skin indicates that it is nevertheless in a hyperproliferative status. K17 was expressed in squamous cell carcinoma and basal cell carcinoma, but not in Bowen's disease. The progressive impairment of phosphorylation of K1 and K2 in the process of chronic arsenism provides us with a suitable model for studying the biological significance of phosphorylation in intermediate filaments during chemical carcinogenesis.     

Pigmented Bowen's disease

Pigmented Bowen''s disease is rare, though more prevalent in men. It presents as a well-delineated plaque in areas unexposed to sun. There are reports of association with seborrheic keratosis, solar lentigo or exuberant pigmentation of genital and intertriginous regions. A specific dermoscopy finding is the presence of brown or gray dots in regular arrangement and coiled or dotted vessels. Thus, we aim to raise awareness of the diagnosis of pigmented Bowen''s disease in pigmented lesions.     

Fanconi's anaemia associated with multicentric Bowen's disease and decreased NK cytotoxicity

We report a patient with Fanconi's anaemia and multiple lesions of vulvo-anal Bowen's disease. She was thrombocytopenic and lymphopenic. and NK-mediated cytotoxicity was undetectable. The vulvar lesions did not contain papillomavirus DNA. In vitro studies showed a possible benefit from acitretin treatment on bone marrow stem cells. However, low-dose acitretin given for 14 months did not prevent the development of an anal squamous carcinoma. Acitretin therapy was, however, associated with a sustained rise in the platelet count.     

Photodynamic therapy of non-melanoma malignant tumours of the skin using topical δ-amino levulinic acid sensitization and laser irradiation

Eighty basal cell carcinomas (BCCs) in 21 patients, 10 lesions of Bowen's disease in three patients, and four lesions of cutaneous T-cell lymphoma in two patients, were treated with photodynamic laser therapy (PDT), using topical application of the haem precursor δ-amino levulinic acid (ALA). The diagnoses were confirmed histologically prior to treatment. Fifty-five of the BCCs were superficial lesions, and 25 were nodular. Of the 80 BCCs, 39 (49%) were located on the trunk, 36 (45%) on the head and neck region, four (15%) on the leg and one on the arm. The two principal locations of the 10 Bowen's disease lesions were the leg (50%) and the trunk (40%). The T-cell lymphoma lesions were located on the shoulder and on the arm. A water-in-oil based cream containing 20% ALA was applied to the lesions, with a margin of about 10–20 mm beyond the visible tumour border, 4–6 h before the laser procedure. During this period of time the highly fluorescent and photodynamically active substance protoporphyrin IX (Pp IX) is synthesized via the haem cycle. Laser-induced fluorescence (LJF) was used for real-time monitoring of the Pp IX distribution in the tumour and in the normal surrounding skin, before and after treatment in all patients. Before laser treatment the Pp IX distribution demonstrated by LJF showed a demarcation between tumour and normal skin of about 15:1 for BCC and Bowen's disease, and 5:1 for T-cell lymphomas. Laser light from a pulsed frequency- doubled Nd: YAG laser pumping a dye laser with light emission at 630 nm was used for the therapy. The power density in the irradiation was kept below 110 mW/cm², in order to avoid hyperthermal effects. A total energy of 60 J/cm² was delivered for 10–20 min, depending on the tumour size. A complete response rate of 100% in superficial BCCs and 64% in nodular BCCs occurred after a single laser treatment, and a response rate of 100% was achieved after one additional treatment in the nodular BCCs. In the Bowen's disease lesions a complete response of 90% was obtained with a single treatment. Two of the four T-cell lymphomas resolved completely. The follow-up time was between 6 and 14 months.     

Occult Bowen's disease in keratinous cysts

Bowen's disease (intra-epidcrmal squamous cell carcinoma) was found in the walls of two cysts excised from the forehead of an 81-year-old man. The inapparent nature of the malignant change underscores the need for routine histological study of rapidly growing cysts.     

Incomplete efficacy of 5-aminolevulinic acid (5 ALA) photodynamic therapy in the treatment of widespread extramammary Paget's disease

Photodynamic therapy (PDT) using 5-aminolevulinic acid (5-ALA) is an effective treatment for several conditions such as Bowen's disease, subsets of basal cell carcinomas and actinic keratosis. Surgical resection is the first-choice therapy for extramammary Paget's disease (EMPD), but extensive resection is highly invasive and recurrences are frequent. We report two cases of genital EMPD treated by PDT with partial efficacy. The first patient, a 78-year-old male, suffered from pubic and scrotal Paget's disease for 6 years despite numerous treatments. The second patient, a 78-year-old female, had vulvar involvement for 2 years that was resistant to multiple treatments. The disease was recurrent and chronic with important pruritus and significant impact on the quality of life. Methyl 5-aminolevulinate was applied for 3 h, and irradiation was applied with red light (630 nm) using a total light dose of 37 J/cm(2) for a period of 10 min. The patients were treated every 2 to 4 weeks for a total of at least three treatments. Both patients experienced a partial transient reduction in their symptoms. One patient had a partial transient remission (< 50% reduction of the involved surface), whereas in the other patient, PDT failed to reduce the surface area of the lesions.