Bowen's Disease Research Articles

Unraveling the Complex Nexus of Human Papillomavirus (HPV) in Extragenital Keratinocyte Skin Tumors: A Comprehensive Analysis of Bowen's Disease and In Situ Squamous-Cell Carcinoma.

This comprehensive study delves into the intricate landscape surrounding the role of human papillomavirus (HPV) in extragenital keratinocyte skin tumors, specifically exploring Bowen's disease (BD) and in situ squamous-cell carcinoma (iSCC). Through a multifaceted examination, this research study elucidates the nuanced interplay of HPV, gender dynamics, anatomical site variations, and potential implications for the etiopathogenesis of these malignancies.

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

The relationship between human papillomavirus (HPV) and Bowen disease (BD) is not fully understood. 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. 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. 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. 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.

Pathophysiology, Histopathology, and Differential Diagnostics of Basal Cell Carcinoma and Cutaneous Squamous Cell Carcinoma-An Update from the Pathologist's Point of View.

Basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC) are the most frequently occurring non-melanocytic skin cancers. The objective of our study is to present the pathophysiology of BCC and cSCC and its direct relationship with the histopathological diagnostics and the differential diagnostics of these types of cancer, based on the morphological characteristics, immunohistochemical profile, and genetic alterations. The qualitative study was based on emphasizing the morphological characteristics and immunohistochemistry profiles of BCC and cSCC and the differential diagnostics based on the tissue samples from the Clinical Pathology Department of Mures Clinical County Hospital between 2020 and 2022. We analyzed the histopathological appearances and immunohistochemical profiles of BCC and cSCC in comparison with those of Bowen disease, keratoacanthoma, hyperkeratotic squamous papilloma, metatypical carcinoma, pilomatricoma, trichoblastoma, Merkel cell carcinoma, pleomorphic dermal sarcoma (PDS), and melanoma. Our study showed the importance of the correct histopathological diagnosis, which has a direct impact on the appropriate treatment and outcome for each patient. The study highlighted the histopathological and morphological characteristics of NMSCs and the precursor lesions in HE and the immunohistochemical profile for lesions that may make the differential diagnosis difficult to establish.

Tracing human papillomavirus in skin and mucosal squamous cell carcinoma: a histopathological retrospective survey.

Worldwide, squamous cell carcinoma (SCC) incidence is rising. The literature debates the human papillomavirus (HPV)'s role in cutaneous SCC development. We examined HPV histopathology in SCC samples in this study. Retrospective study at tertiary referral skin center in 2020. Histopathological features of HPV, including koilocytosis, hyperkeratosis, acanthosis, hypergranulosis, parakeratosis, solar elastosis, papillomatosis, and tumor grade, were examined in SCC specimens. Two dermatopathologists independently reevaluated all samples. We examined 331 SCC cases (male:female ratio = 3.9:1). The mean age was 68.1, with 15.1 standard deviation. Lesions were most common on the face (40.5%), scalp (22.7%), and extremities (20.8%). Koilocytes were found in 50 (15.1%) lesions. Nail (38.1%, p=0.007), oral cavity (36.8%, p=0.014), and genitalia (60.0%, p=0.026) lesions had higher koilocytosis rates. SCCs were found in 6.6% of specimens, but in situ tumors had the highest koilocytosis (64.7%), significantly higher than other grades (p<0.001). SCC pathology often shows HPV and specific koilocyte histopathology. Well-differentiated SCC has a stronger association with nail, oral, and genital lesions.

Combination of vitamin D and photodynamic therapy enhances immune responses in murine models of squamous cell skin cancer

Improved treatment outcomes for non-melanoma skin cancers can be achieved if Vitamin D (Vit D) is used as a neoadjuvant prior to photodynamic therapy (PDT). However, the mechanisms for this effect are unclear. Vit D elevates protoporphyrin (PpIX) levels within tumor cells, but also exerts immune-modulatory effects. Here, two murine models, UVB-induced actinic keratoses (AK) and human squamous cell carcinoma (A431) xenografts, were used to analyze the time course of local and systemic immune responses after PDT ± Vit D. Fluorescence immunohistochemistry of tissues and flow analysis (FACS) of blood were employed. In tissue, damage-associated molecular patterns (DAMPs) were increased, and infiltration of neutrophils (Ly6G+), macrophages (F4/80+), and dendritic cells (CD11c+) were observed. In most cases, Vit D alone or PDT alone increased cell recruitment, but Vit D + PDT showed even greater recruitment effects. Similarly for T cells, increased infiltration of total (CD3+), cytotoxic (CD8+) and regulatory (FoxP3+) T-cells was observed after Vit D or PDT, but the increase was even greater with the combination. FACS analysis revealed a variety of interesting changes in circulating immune cell levels. In particular, neutrophils decreased in the blood after Vit D, consistent with migration of neutrophils into AK lesions. Levels of cells expressing the PD-1+ checkpoint receptor were reduced in AKs following Vit D, potentially counteracting PD-1+ elevations seen after PDT alone. In summary, Vit D and ALA-PDT, two treatments with individual immunogenic effects, may be advantageous in combination to improve treatment efficacy and management of AK in the dermatology clinic.

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

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. 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. 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. 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.

Bowen's Disease of Unusual Localization

Bowen's disease is a carcinoma in situ. It occurs most often at an age of over 50 years, in light phototypes, in photo-exposed areas. Anal localization is exceptional. However, its association with condyloma is not accidental. We report a case of perianal Bowen's disease occurring in systemic scleroderma.

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.

Differentiated consideration of treatment of advanced squamous cell carcinoma of the skin

Differentiated consideration of treatment of advanced squamous cell carcinoma of the skin

Metastasis of skin squamous cell carcinoma in kidney transplant recipients.

Cutaneous squamous cell carcinoma (cSCC) is the most common skin malignancy in kidney transplant recipients (KTRs) as a result of immunosuppression. A worldwide increase in kidney transplantation justifies the determination of prognostic biomarkers by collecting detailed patient data on metastasis development. This study aims to characterize the clinical, epidemiological, and histopathological profiles of KTRs who developed metastasis of cSCC. We conducted a retrospective single-center study on 18 KTRs and 21 immunocompetent patients (ICs) with metastatic cSCC, using data from 2004 to 2021. ICs were older (median age 70.5 years) than KTRs (median age: 59.5 years). Both groups were predominantly male with Fitzpatrick skin phototype I/II. The primary tumor appeared around 83.5 months post-transplant, usually in sun-exposed areas (61.1%), though some non-exposed areas in ICs (23.8%) contradicted literature findings. KTRs took longer to develop metastasis (median: 11.0 months) compared to ICs (median: 5.5 months). The mean size of the primary tumor was smaller in KTRs (2.50 cm2) compared to ICs (4.55 cm2). The main lymph node chain affected by metastasis wasparotid lymph nodes in KTRs (27.8%) and cervical/axillar lymph nodes in ICs (both 19.0%). Both groups exhibited similar primary tumor grades and metastasis evolution, but KTRs had a higher prevalence of lymphovascular invasion. Metastasis of cSCC was more common in males with low skin phototype, in KTRs, particularly on the head and neck. The study suggests a possible link between lymphovascular invasion and metastasis development in KTRs.

Multiple Bowen Disease Lesions With the "Eyeliner Sign" in a Psoriasis Patient After Long-Term Narrow-Band Ultraviolet B Light Therapy.

Multiple Bowen Disease Lesions With the "Eyeliner Sign" in a Psoriasis Patient After Long-Term Narrow-Band Ultraviolet B Light Therapy.

Tumor size associated with upstaged cutaneous squamous cell carcinoma in patients with skin of color

Tumor size associated with upstaged cutaneous squamous cell carcinoma in patients with skin of color

The mitochondrial DNA common deletion as a potential biomarker of cancer-associated fibroblasts from skin basal and squamous cell carcinomas

Cancer-associated fibroblasts (CAFs) are components of the tumor microenvironment and represent appealing therapeutic targets for translational studies. Conventional protein-based biomarkers for CAFs have been reported to be limited in their specificity, rendering difficult the identification of CAFs from normal fibroblasts (NFs) in clinical samples and dampening the development of CAF-targeted therapies to treat cancer. In this study, we propose the mitochondrial RNA and the mitochondrial DNA (mtDNA) common deletion (CD) as novel indicators of CAF identity. We found that cancer-activation correlated with decreased levels of the mtDNA CD, a condition not due to altered mitochondria count or cellular redox state, but potentially linked to the generalized overexpression of mtDNA maintenance genes in CAFs. Decreased mtDNA CD content in CAFs was associated with moderate to strong overexpression of mtDNA-encoded genes and to slightly improved mitochondrial function. We identified similar patterns of upregulation of mtDNA-encoded genes in independent single-cell RNA seq data obtained from squamous cell carcinoma (SCC) patients. By using the identified nucleic acids-based indicators, identification of CAFs from NFs could be improved, leading to potential therapeutic benefits in advancing translational and clinical studies.

Efficacy and Safety of Carbon Dioxide Laser Ablation Combined with Manual Dermabrasion and Intralesional 5-Fluorouracil Injection in Bowen's Disease.

Bowen's disease (BD) is a precancerous in-situ squamous cell carcinoma and has a high recurrence rate with any single treatment modality, necessitating combination therapy for a successful outcome. This study aimed to the efficacy and safety of carbon dioxide (CO2) laser ablation followed by manual dermabrasion and intralesional 5-fluorouracil (IL 5-FU) injection as combination therapy for BD. This was a retrospective, observational study comprising 29 clinically and histopathologically diagnosed BD patients with no history of prior treatment. Demographic characteristics and clinical examination of the lesions and regional lymph nodes were retrieved. All patients were subjected to CO2 laser ablation followed by manual dermabrasion and IL 5-FU injection. Mean age was 61.93 ± 9.31 years with male preponderance (62.1%). Trunk (48.3%) was the most frequently involved site. Mean tumor size was 40.8 ± 16.4 mm (range: 15-86 mm). All lesions healed with a cure rate of 96.6%. Complications seen in patients included atrophic scarring with persistent post-inflammatory hyperpigmentation in three patients (10.3%), secondary infection in two cases (6.9%), and hypertrophic scar with early keloid in one patient (3.4%). Recurrence was reported in one patient (3.4%). The study was limited by retrospective study design, small sample size, and no comparison with standard therapy. Combination approach using carbon dioxide laser ablation followed by manual dermabrasion and IL 5-FU injection has been proved to be effective, efficient and safe with good functional, oncological and aesthetic outcomes in treating BD.

Three cases of pseudoepitheliomatous hyperplasia mimicking squamous cell carcinoma of the foot: A case series

Abstract Pseudoepitheliomatous hyperplasia (PEH) is a benign condition characterized by hyperplasia and proliferation of the epidermis and adnexal epithelium which can mimic squamous cell carcinoma (SCC). In our first case, a 55-year-old female with a prior history of split skin graft presented with dark verrucous growth over the graft site with a nonhealing ulcer of 3 cm × 2 cm seen over the ventral aspect of the left foot. Our second case, a 59-year-old male with a prior history of split skin grafting presented with dark verrucous growth and pain over the right forefoot for 3 months. The third case, a 58-year-old man with diabetic foot ulcer with verrucous growth over the toes. In all the cases, the biopsy was done and diagnosed to be PEH. We report this case series of PEH for the proper distinction from the SCC of the skin.

Porokarcinom noge - dijagnostički i terapijski izazovi i potencijalni uticaj pandemije Kovida 19 na dijagnozu i lečenje

Introduction: Cutaneous porocarcinoma is a rare malignant tumor, arising from the eccrine sweat gland. High rates of extracutaneous spread, local recurrence and high mortality are observed. Definitive diagnosis could be complex due to its histopathological similarity to squamous cell skin carcinoma and Paget's disease. Primary treatment still relies on surgical excision. Patient review: A 76-year-old male presented at our clinic in January 2020, with a bleeding skin tumor of the right thigh. Multiple wide surgical excisions were performed between January 2020 and November 2022, due to repetitive local recurrence. For a period of time, our patient was lost to follow up caused by COVID-19 pneumonia and a long recovery period. Initially, a poorly differentiated squamous cell skin carcinoma was reported. In the first post-COVID-19 follow-up, in January 2022, there was a new tumor locally, and porocarcinoma was diagnosed. In follow-ups, apart from skin tumor recurrence, inguinal nodal involvement was confirmed. CT showed no signs of disseminated disease in the lungs or in the abdomen, in any of the succeeding follow-ups. Finally, MRI of the pelvis revealed a suspicious mass in the bladder, radiologically consistent with metastatic disease and the patient was referred to an oncologist and a urologist. Conclusion: Porocarcinoma remains insufficiently explored. There are no official treatment protocols. Due to its similarity to squamous cell carcinoma, a dermatopathology expert should be consulted, while a multidisciplinary approach is necessary for managing the disease. Since early diagnosis and treatment are of paramount importance, any factors that delay them, such as COVID-19 pandemic in our case, could be detrimental to the patient and poorly affects the prognosis and final outcome.

A-457 - Complete regression of Bowen's disease after incisional biopsy: case report

A-457 - Complete regression of Bowen's disease after incisional biopsy: case report

A Review of the Dermatologic Clinical Applications of Topical Photodynamic Therapy.

Topical photodynamic therapy is a widely approved therapy for actinic keratoses and low-risk nonmelanoma skin cancers with a rapidly growing range of emerging indications for other cutaneous diseases. This review summarizes the best-available evidence to provide a clinical update for dermatologists on the approved and emerging indications of photodynamic therapy. The body of evidence suggests that photodynamic therapy is superior or noninferior to other available treatment modalities for actinic keratoses, low-risk basal cell carcinomas, Bowen's disease, skin field cancerization, chemoprevention of keratinocyte carcinomas in organ transplant recipients, photoaging, acne vulgaris, and cutaneous infections including verrucae, onychomycosis, and cutaneous leishmaniasis. There is emerging evidence that photodynamic therapy plays a role in the management of actinic cheilitis, early-stage mycosis fungoides, extramammary Paget disease, lichen sclerosis, and folliculitis decalvans but there are no comparative studies with other active treatment modalities. Common barriers to topical photodynamic therapy include procedural pain, costs, and the time required for treatment delivery. There is significant heterogeneity in the photodynamic therapy protocols reported in the literature, including different photosensitizers, light sources, number of treatments, time between treatments, and use of procedural analgesia. Topical photodynamic therapy should be considered in the management of a spectrum of inflammatory, neoplastic, and infectious dermatoses. However, more comparative research is required to determine its role in the treatment algorithm for these dermatologic conditions and more methodological research is required to optimize photodynamic therapy protocols to improve the tolerability of the procedure for patients.

Shedding new light on actinic keratoses and squamous cell carcinoma in situ.

Cutaneous squamous cell carcinoma can arise from various premalignant lesions such as actinic keratosis, Bowen disease, and premalignant genital squamous cell lesions. Identification and treatment can prevent malignant transformation and death. This article describes the causes, epidemiology, and characteristics of suspicious premalignant squamous cell lesions so that clinicians can identify these lesions and refer patients for specialist treatment as appropriate.

A Retrospective Study of Cemiplimab Effectiveness in Elderly Patients with Squamous Cell Carcinoma of the Skin: Insights from a Real-Life Scenario.

This retrospective study investigates the efficacy of cemiplimab, a monoclonal antibody targeting the PD-1 receptor, in treating squamous cell carcinoma (SCC) of the skin. The study analyzes data from 50 patients with SCC, focusing on various clinical parameters, including patient demographics, tumor characteristics, treatment history, disease status at the beginning of therapy, and survival outcomes. Of the patients who received at least one cycle of cemiplimab, 42% showed a clinical response. Adverse reactions were generally low, with the safety profile deemed excellent. During a median follow-up of 9.6months, 17 patients experienced progression or death. Among these, 15 patients had died at the time of the analysis. The median progression-free survival (PFS) for the entire cohort was approximately 20.8months, while median overall survival (OS) was not reached. Univariate Cox regression analysis for PFS showed that tumors in the arms and legs were associated with higher progression risk, while age above 65years was not statistically significant. Distant metastasis exhibited a trend towards improved PFS. In terms of OS, distant metastasis was a significant predictor of reduced survival, while age above 65years was not statistically significant. In a multivariate model, only the absence of distant metastasis remained significant, with an adjusted odds ratio (OR) of 12.3 (95% confidence interval 1.3-112.1). These findings provide valuable insights into the real-world effectiveness of cemiplimab in SCC management.