A European Consensus on the Consistent Use of the Term "Keratinocyte Cancer".

Keratinocyte-derived skin cancers comprise basal cell carcinoma, squamous cell carcinoma, its precursor actinic keratosis, and Bowen's disease. Historically, this group of neoplasms has been subsumed under the term non-melanoma skin cancer. However, the term non-melanoma skin cancer can be misleading and lacks precision. Therefore, more precise and reasonable terminology, valuing the relevance of keratinocyte-derived cancer, appears pertinent to meet its clinical and scientific significance. A group of experienced dermato-oncologists initiated a consensus approach to promote the use of the term "keratinocyte cancer" instead of "non-melanoma skin cancer" when referring to carcinomas and their precursors that are derived from keratinocytes. The vote among members of the consensus group indicated unanimous agreement on the consistent use of the term "keratinocyte cancer" instead of "non-melanoma skin cancer". International delegates also voted in favour of the revised terminology. The more precise and, by means of etiopathogenesis, correct term "keratinocyte cancer" should be consistently used for malignancies originated from keratinocytes. This is expected to have a positive impact on patient-physician communication and gives better justice to this important group of keratinocyte-derived cancers.

Merkel cell carcinoma overlapping Bowen's disease: two cases report and literature review.

PURPOSE: Merkel cell carcinoma (MCC) is a rare neuroendocrine tumor of the skin, which mainly occurs in the sun exposed sites of white patients over 65 years, with a higher recurrence and metastasis rate. Clinically, MCC overlapping Bowen's disease (BD) is a very rare subtype of MCC. Few cases in the literature have been described and the management is not well defined. We summarize and update the epidemiology, clinical and histopathological features, metastasis characteristics, local recurrence rate and management of it by presenting two cases of MCC overlapping BD and reviewing the literature over the last 11 years. DESIGN: We consulted databases from PubMed, ResearchGate and Google Scholar by MeSh "Merkel cell carcinoma" and "Bowen's disease", "Bowen disease" or "squamous cell carcinoma in situ", from January 2013 to December 2023 and reviewed the literatures. We reported two additional cases. RESULTS: Total 13 cases of MCC overlapping BD were retrospectively analyzed, in whom mainly in elderly women over 70 years, the skin lesions were primarily located on the faces, followed by the extremities and trunk. Most of them were asymptomatic, firm, dark red nodules arising on rapidly growing red or dark brown patches, or presenting as isolated nodules. Dermoscopy evaluation was rarely performed in the pre-operative diagnostic setting. All cases were confirmed by histopathology and immunohistochemistry. The most definitive treatment was extended local excision, but local recurrences were common. Of the 13 cases, 4 cases experienced local or distant metastasis. One suffered from an in-transit recurrence of MCC on the ipsilateral leg after local excision and lymph node dissection, whose metastasis completely subsided after avelumab treatment and without recurrence or metastasis during 6 months of follow-up. CONCLUSIONS: MCC overlapping BD is a very rare skin tumor mainly predisposed on the faces, with high misdiagnosis rate and recurrence rate. Advanced disease at diagnosis is a poor prognostic factor, suggesting that earlier detection may improve outcome. The acronym, AEIOUN, has been proposed to aid in clinical identification. Our reports and the literature review can provide a better awareness and management of it.

Reduced burden of Arsenic-Related cancers after water mitigation in Taiwan.

BACKGROUND: Epidemiological evidence has demonstrated an association between arsenic in drinking water and increased cancer incidence. This population-based study investigates the impact of a tap water supply system installation in Blackfoot disease-endemic regions of Taiwan on cancer incidence. METHODS: By using the Taiwan Cancer Registry dataset, we enrolled patients aged 40-84 diagnosed with arsenic-related cancers, including hepatocellular carcinoma, small and squamous cell lung cancer, Bowen's disease, basal and squamous cell skin cancer, urothelial bladder cancer, and upper tract urothelial carcinoma between 1995 and 2019. Random-effects age-period-cohort models were used to estimate the cancer incidence data, and a stabilized kriging method was employed to interpolate incidence rates to more precise spatiotemporal units. RESULTS: The results showed that the age-standardized incidence rates of all six types of studied cancers were consistently higher in Blackfoot disease-endemic areas than those in other areas from 1995 to 2019. However, the gap in incidence rates between Blackfoot disease-endemic areas and the remaining regions began to narrow approximately after the 1960 birth cohort when the tap water supply system installation commenced. For small and squamous cell lung cancer, Bowen's disease, and urothelial bladder cancer, the excess incidence rates sharply declined to null for those born after the year of arsenic mitigation. For upper tract urothelial carcinoma, the excess incidence rates decreased more gradually for those born after the year of arsenic mitigation. For hepatocellular carcinoma and basal and squamous cell skin cancer, the excess incidence rates remained constant. Spatiotemporal clusters of high incidence rates were identified in the core townships of Blackfoot disease-endemic areas. These clusters began to dissipate mainly after the 1960 birth cohort. CONCLUSION: Arsenic mitigation from drinking water in Taiwan is associated with a reduced burden of small and squamous cell lung cancers, Bowen's disease, urothelial bladder cancer, and upper tract urothelial carcinoma.

Immunoexpression of Ki67, P16 and Beta-catenin in precursor lesions of cutaneous squamous cell carcinoma.

Cutaneous squamous cell carcinoma (CSCC) is the second most common type of skin cancer, after basal cell carcinoma, representing about 10-20% of all malignant skin tumors. The mortality rates of CSCC approach those of renal and oropharyngeal carcinomas, as well as melanoma, with the increasing of the risk once metastases and perineural invasion occur. Both actinic keratosis (AK) and Bowen's disease (BD) are direct precursors with the potential for progression to CSCC. In this study, we analyzed the expression of Ki67, P16 and Beta-catenin in the precursor lesions of CSCC in relation to histological prognostic parameters, respectively between them, with the aim of identifying possible correlations with a role in prognosis. Ki67 and P16 presented higher scores in advanced precancerous lesions, such as keratinocyte intraepithelial neoplasia (KIN) III and BD and low scores in seborrheic keratosis (SK). The immunoreactivity to the investigated markers confirms the multistage skin carcinogenesis, and their involvement starting from the initiation phase of the cancer process. The importance of the studied markers in the evolution and prognosis of precancerous lesions of CSCC is also supported by the linear correlations revealed between the immunoexpressions of P16, Ki67 and the membranous immunoexpression of Beta-catenin in AK.

Successful treatment of Bowen's Disease in the nipple-areola complex with a combination of photodynamic therapy and cryotherapy-A case report.

Photodynamic therapy (PDT) is a non-invasive, effective treatment for superficial skin conditions, offering superior cosmetic outcomes compared with traditional therapies. Bowen's disease (BD) of the nipple-areola complex (NAC) is rare and thus, lacks a standardized treatment approach. This report details the case of a 48-year-old woman who was successfully treated for BD of the NAC using PDT. Over a follow-up period of 30 months, there was no evidence of disease recurrence, underscoring the potential of PDT as a viable treatment option for this rare manifestation of BD.

Incidence and survival rates of primary cutaneous malignancies in Korea, 1999-2019: A nationwide population-based study.

Primary cutaneous malignancies are among the most commonly diagnosed types of cancer worldwide. We aimed to examine the incidence and 5-year survival rates of all types of primary cutaneous malignancies in the Korean population. Data from the Korean Nationwide Cancer Registry from 1999 to 2019 were analyzed. The crude incidence rates, age-standardized incidence rates, and 5-year relative survival rates of each type of skin cancer were calculated. A total of 89 965 patients were diagnosed with primary cutaneous malignancies, which was a 7-fold increase from 1999 to 2019. The age-standardized incidence rates increased 3.4-fold in basal cell carcinoma (3.7/100 000 person-years), 2.0-fold in squamous cell carcinoma (1.6/100 000 person-years), 12.0-fold in Bowen disease (1.2/100 000 person-years), and 1.8-fold in malignant melanoma (0.7/10 000 person-years) in 2019. Average annual percentage changes in age-standardized incidence rates were statistically significant in basal cell carcinoma (15.8%), Bowen disease (5.8%), squamous cell carcinoma (5.1%), malignant melanoma (1.2%), melanoma in situ (1.1%), dermatofibrosarcoma protuberans (1.2%), mycosis fungoides (0.5%), primary cutaneous CD30+ T-cell proliferations (0.5%), adnexal and skin appendage carcinoma (0.4%), extramammary Paget's disease (0.2%), and Merkel cell carcinoma (0.2%). The 5-year relative survival rates were the highest in basal cell carcinoma (103.3%), followed by dermatofibrosarcoma protuberans (99.7%) and mycosis fungoides (96.6%), and lowest in angiosarcoma (24.7%). The 5-year relative survival rates steadily increased in extramammary Paget's disease (23.6%), cutaneous B-cell lymphoma (21.3%), mycosis fungoides (20.2%), extranodal NK/T-cell lymphoma, nasal type (18.1%), and malignant melanoma (16.1%) from 1996-2000 to 2015-2019. Most primary cutaneous malignancies have increased in incidence and survival rates in the Korean population, but to varying extents depending on the type of skin cancer.

Bowen disease is not synonymous with intraepidermal squamous cell carcinoma.

The terms 'Bowen disease' and 'intraepidermal squamous cell carcinoma' are sometimes considered synonymous. In this paper we present historical, clinical, histological and molecular evidence that this is incorrect. The term Bowen disease should be reserved for a subset of intraepidermal squamous cell carcinoma with a distinctive and reproducible morphological pattern, described in detail by Bowen in 1912. One other common subset of intraepidermal squamous cell carcinoma represents progression of actinic keratosis. In some cases the separation of these two common patterns of intraepidermal squamous cell carcinoma can be challenging and there are patterns of intraepidermal squamous cell carcinoma which appear to represent other distinct pathways. However, there is emerging biological evidence to support this distinction and reason to suspect that the types of invasive squamous cell carcinoma which arise from these different pathways may show important clinical and biological differences, particularly in the era of targeted and immunomodulatory therapy for advanced disease.

Nailbed HPV-related Bowen's disease in a man living with HIV.

Human papillomavirus (HPV) is a common sexually transmitted infection with wide-ranging clinical manifestations. High-risk anogenital HPV genotypes have also been reported to cause extragenital disease. We describe the case of a 69-year-old male patient living with HIV who was diagnosed with HPV-16 associated Bowen's Disease (BD) of the right middle finger nailbed, despite good virologic control and immune reconstitution. The lesion was managed surgically with adjunctive post-exposure HPV vaccination. This case adds to the growing body of evidence of extra-genital HPV disease attributable to anogenital genotypes in people living with HIV.

Human papillomavirus detection rates in Bowen disease: correlation with pelvic and digital region involvement and specific p53 immunostaining patterns.

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.

Expression Analysis of Retinal G Protein-coupled Receptor and its Correlation with Regulation of the Balance between Proliferation and Aberrant Differentiation in Cutaneous Squamous Cell Carcinoma.

Retinal G protein-coupled receptor (RGR), a photosensitive protein, functions as a retinal photoisomerase under light conditions in humans. Cutaneous squamous cell carcinoma (cSCC) is linked to chronic ultraviolet exposure, which suggests that the photoreceptor RGR may be associated with tumorigenesis and progression of squamous cell carcinoma (SCC). However, the expression and function of RGR remain uncharacterized in SCC. This study analysed RGR expression in normal skin and in lesions of actinic keratosis, Bowen's disease and invasive SCC of the skin with respect to SCC initiation and development. A total of 237 samples (normal skin (n = 28), actinic keratosis (n = 42), Bowen's (n = 35) and invasive SCC (n = 132) lesions) were examined using immunohistochemistry. Invasive SCC samples had higher expression of RGR protein than the other samples. A high immunohistochemical score for RGR was associated with increased tumour size, tumour depth, Clark level, factor classification, and degree of differentiation and a more aggressive histological subtype. In addition, RGR expression was inversely correlated with involucrin expression and positively correlated with proliferating cell nuclear antigen (PCNA) and Ki67 expression. Furthermore, RGR regulates SCC cell differentiation through the PI3K-Akt signalling pathway, as determined using molecular biology approaches in vitro, suggesting that high expression of RGR is associated with aberrant proliferation and differentiation in SCC.

Multiple Bowen's disease due to long-term narrow-band ultraviolet B phototherapy: A case report and literature review.

OBJECTIVE: By presenting a case study on multiple instances of Bowen's disease and the consistent use of narrow-band ultraviolet B (NB-UVB) phototherapy over a three-year period, our aim is to enhance the comprehension of domestic clinicians regarding the disease. Additionally, we seek to review existing literature, encouraging dermatologists to consider clinical secondary primary lesion diagnoses. METHOD: Our approach involves analyzing a diagnosed case of multiple Bowen's disease, examining clinical manifestations, histopathology, imaging results, and treatment methods related to NB-UVB phototherapy. We aim to facilitate discussion and understanding through a comprehensive literature analysis. RESULTS: An elderly male with a 30-year history of psoriasis vulgaris initiated continuous NB-UVB therapy three years ago. A year later, he developed red patches and plaques with distinct borders and scaly surfaces on his face, trunk, lower extremities, and scrotum. Histopathological examination confirmed Bowen's disease. Treatment involved liquid nitrogen cryotherapy, with no recurrence observed during the one-year follow-up. CONCLUSION: This case highlights that Bowen's disease, typically solitary, can manifest as multiple instances, especially in individuals with a history of psoriasis vulgaris. While NB-UVB stands as the primary treatment for psoriasis vulgaris, caution is warranted due to the potential risk of skin tumor induction with prolonged high-dose usage. Clinicians should be vigilant in monitoring and assessing the long-term implications of such therapies.

Photodynamic therapy with BF-200 ALA gel for the treatment of actinic keratosis, Bowen´s disease and basal cell carcinoma in long term immunosuppressed patients after organ transplantation.

Continuous immunosuppression after organ transplantation is associated with an increased risk of developing keratinocyte neoplastic lesions. Topical photodynamic therapy represents a therapeutic approach for different keratinocyte neoplastic lesions. However, the specific efficacy and safety of this treatment in this immunocompromised population remains largely unknown. In this case report series, we show the efficacy and safety of photodynamic therapy with BF-200 ALA gel using red-light and daylight in immunocompromised patients. Out of 8 patients presented here, 1 was treated for 8 basal cell carcinomas, 1 for 2 Bowen´s disease lesions and 6 were treated for field cancerization including 4 to 10 actinic keratoses. Treatment response rates were above 75 %. The adverse events, including pain, did not differ from those already described for PDT. These data suggest that PDT with BF-200 ALA gel could be an effective and safe option to add to the treatment portfolio for neoplastic keratinocyte lesions in this high-risk population.

Bowen's disease of the vulva and perianal area in a SLE patient successfully treated with Photodynamic therapy: A case report.

Photodynamic therapy (PDT) has emerged as a non-invasive treatment modality for superficial skin cancers. It has the advantage of greater tolerance and providing better cosmetic outcomes than conventional treatment methods. Because of the rarity of extensive Bowen's disease located in the genital area, evidence of efficacy for therapies is mainly based on case reports and clinical experience. This report presents a case of a 32-year-old female with Bowen's disease of the vulva and perianal area with systemic lupus erythematosus successfully treated by 5-aminolaevulinic acid PDT. There was no evidence of recurrence after five-years of follow-up.

The combination of holmium laser and ALA-PDT for Bowenoid Papulosis with diffuse large B-cell lymphoma.

Bowenoid Papulosis (BP) is an anogenital pre-malignancy. BP with immunosuppression may recur, worsen, or possibly evolve into squamous cell carcinoma or Bowen's disease (BD), and it may also become resistant to conventional treatment. Here, we describe a complex case of BP together with BD and Diffuse Large B-Cell Lymphoma that was effectively treated with a holmium laser in conjunction with 5-Aminolevulinic Acid Photodynamic Therapy (ALA-PDT). The lesion totally vanished and the affected area remained intact with no recurrence at five years.

Surgical excision versus topical 5% 5-fluorouracil and photodynamic therapy in treatment of Bowen's disease: A multicenter randomized controlled trial.

BACKGROUND: Randomized controlled trials comparing the effectiveness of 5-fluorouracil cream, methylaminolevulinate photodynamic therapy (MAL-PDT) and surgical excision in patients with Bowen's disease are lacking. METHODS: In this multicenter noninferiority trial, patients with a histologically proven Bowen's disease of 4-40 mm were randomly assigned to excision with 5 mm margin, 5% 5-fluorouracil cream twice daily for 4 weeks, or 2 sessions of MAL-PDT with 1 week interval. The primary outcome was the proportion of patients with sustained clearance at 12 months after treatment. A noninferiority margin of 22% was used. RESULTS: Between May 2019 and January 2021, 250 patients were randomized. The proportion of patients with sustained clearance was 97.4% (75/77) after excision, 85.7% (66/77) after 5-fluorouracil, and 82.1% (64/78) after MAL-PDT. Absolute differences were -11.7% (95% CI -18.9 to -4.5; P = .0049) for 5-fluorouracil versus excision and -15.4% (95% CI -23.1 to -7.6; P = .00078) for MAL-PDT versus excision. Both noninvasive treatments significantly more often led to good or excellent cosmetic outcome. CONCLUSIONS: Based on our predefined noninferiority margin of 22%, 5-fluorourcail is noninferior to excision and associated with better cosmetic outcome. For MAL-PDT noninferiority to excision cannot be concluded. Therefore, 5-fluorouracil should be preferred over excision and MAL-PDT in treatment of Bowen's disease.

Cryosurgery and 5-Fluorouracil Combination Therapy for Treatment of Bowen's Disease and Superficial Basal Cell Carcinoma.

BACKGROUND: Non-melanoma skin cancer (NMSC), which includes both Bowen's disease (BD) and superficial basal cell carcinoma (sBCC), is the most commonly diagnosed cancer in Canada. BD and sBCC are amenable to minimally invasive treatments however, large-scale studies assessing long-term outcomes are lacking, particularly regarding the timing and duration of non-invasive combination treatments. OBJECTIVE: Examine the clinical cure rate of BD and sBCC using a combination treatment consisting of a single cycle of cryotherapy followed by a three to four-week course of topical 5-fluorouracil (5-FU). METHODS: Retrospective chart review at a single center. Inclusion criteria included histology-proven sBCC or BD treated with either a combination protocol, cryosurgery, or 5-FU alone. RESULTS: 310 biopsy-confirmed cases of BD and 176 biopsy-confirmed cases of sBCC were analyzed. Of these, 229 cases of BD and 61 cases of sBCC were treated with cryosurgery and immediate 5-FU application, yielding a clearance rate of 90% and 86.9% at 6 months from initial treatment. CONCLUSION: Cryosurgery followed by immediate 5-FU use may be an effective mode of treatment for BD and sBCC, negating the need for invasive procedures and allowing for increased accessibility. Further studies with longer follow-up intervals, comparisons with other non-invasive treatments, and evidence of histologic cure are required. J Drugs Dermatol. 2023;22(12):1166-1171. doi:10.36849/JDD.7378.