Bowen's Disease Research Articles

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.

Single-cell sequencing highlights heterogeneity and malignant progression in actinic keratosis and cutaneous squamous cell carcinoma.

Cutaneous squamous cell carcinoma (cSCC) is the second most frequent of the keratinocyte-derived malignancies with actinic keratosis (AK) as a precancerous lesion. To comprehensively delineate the underlying mechanisms for the whole progression from normal skin to AK to invasive cSCC, we performed single-cell RNA sequencing (scRNA-seq) to acquire the transcriptomes of 138,982 cells from 13 samples of six patients including AK, squamous cell carcinoma in situ (SCCIS), cSCC, and their matched normal tissues, covering comprehensive clinical courses of cSCC. We identified diverse cell types, including important subtypes with different gene expression profiles and functions in major keratinocytes. In SCCIS, we discovered the malignant subtypes of basal cells with differential proliferative and migration potential. Differentially expressed genes (DEGs) analysis screened out multiple key driver genes including transcription factors along AK to cSCC progression. Immunohistochemistry (IHC)/immunofluorescence (IF) experiments and single-cell ATAC sequencing (scATAC-seq) data verified the expression changes of these genes. The functional experiments confirmed the important roles of these genes in regulating cell proliferation, apoptosis, migration, and invasion in cSCC tumor. Furthermore, we comprehensively described the tumor microenvironment (TME) landscape and potential keratinocyte-TME crosstalk in cSCC providing theoretical basis for immunotherapy. Together, our findings provide a valuable resource for deciphering the progression from AK to cSCC and identifying potential targets for anticancer treatment of cSCC.

The role of radiation therapy in the treatment of early-stage skin cancer

Introduction. Radiation therapy remains one of the main methods of radical treatment of early-stage skin cancer. Its position in combination and comprehensive treatment has changed significantly as improvements of radiotherapy techniques and introduction of modern technologies led to increased effectiveness and comfort of the method and allowed to achieve better prognostic outcomes.Aim. To evaluate the role of radiotherapy in treatment of patients with early-stage skin cancer (T1–2N0M0).Materials and methods. A retrospective and prospective analyses of data from 1049 patients with early-stage skin cancer were performed. In 527 (50.23 %) cases, the tumor was localized mainly on the head and neck: 48 % of patients had nonkeratinizing squamous cell carcinoma of the skin, 7.59 % of patients had keratinizing squamous cell carcinoma, 44.41 % of patients had basal cell carcinoma.Results. Data from 527 patients (51.04 % man and 48.96 % women) with early-stage skin cancer (T1–2N0M0) who received treatment and are registered at the Republican Oncological Scientific Center of the Ministry of Health and Social Protection of the Tajikistan Republic were analyzed. The disease was more common in patients aged between 60 and 90 years. The main factor in stage determination was tumor size in accordance with the Tumor, Nodus and Metastasis (TNM) classification. In 240 (46.54 %) patients, the size of primary tumor was less than 2 cm in the largest diameter (T1N0M0), in 287 (54.46 %) patients its maximal size was between 2 and 4 cm (T2N0M0). Selection of treatment method was mainly based on morphological characteristics and location of the tumor. In 121 (50.42 %) patients with skin cancer T1N0M0, radiation therapy was performed as monotherapy in a radical program; in 88 (36.37 %) patients in combination with cobalt therapy and surgery; in 23 (9.59%) patients in combination with cobalt therapy, polychemotherapy and surgery; in 8 (3.41%) patients in combination with cobalt therapy and polychemotherapy.The capabilities of radiation therapy both as monotherapy and in combination with other treatment methods before and after surgical treatment present ample opportunities for clinicians to achieve good outcomes. The use of radiation therapy as monotherapy in a radical program in patients with T1N0M0 stage skin cancer is effective in 96.4 % of cases, in patients with stage T2N0M0 the effectiveness can reach 91.2 %.Conclusion. Radiation therapy can be successfully used in treatment of early-stage skin cancer along with other methods. Its use both independently and as part of combination and comprehensive therapy allows to achieve reliable treatment outcomes. Adequate selection of radiation therapy option in treatment of early-stage skin cancer is the key to longterm clinical remission and improvement of patients’ quality life.

Osteoinductive squamous cell carcinoma associated with a putative novel papillomavirus on the digit of a cat

ABSTRACT Case history and clinical findings An approximately 10-year-old, castrated male domestic short-haired cat developed swelling and ulceration of the second digit of the right front paw. Radiographs revealed a spherical soft tissue swelling with irregular distal margins that contained multiple lacy mineral opacities. The digit was amputated and submitted for histology. No recurrence has been observed 7 months after amputation. Pathological and molecular findings Histology revealed a moderately well-circumscribed proliferation of well-differentiated squamous cells arranged in trabeculae and nests. Numerous thin spicules of osseous metaplasia were visible throughout the neoplasm. Around 70% of the neoplastic cells contained papillomavirus-induced cell changes including large amphophilic cytoplasmic bodies and cells with shrunken nuclei surrounded by a clear halo. Intense p16CDKN2A protein immunostaining was visible within the neoplastic cells, suggesting papillomavirus-induced changes in cell regulation. A DNA sequence from a putative novel Taupapillomavirus type was amplified from the neoplasm. Diagnosis Osteoinductive squamous cell carcinoma associated with a putative novel papillomavirus type. Clinical relevance The findings in this case increase the number of papillomavirus types known to infect cats, and the squamous cell carcinoma had histological features that have not been previously reported. The neoplasm was not as invasive as is typical for a squamous cell carcinoma and excision appeared curative. This is the first report of an osteoinductive squamous cell carcinoma of the skin of cats and the neoplasm had a unique radiographic appearance.

Navigating a Complex Intersection: Immunotherapy and Radiotherapy Synergy in Squamous Cell Carcinoma of the Skin—A Comprehensive Literature Review

Skin squamous cell carcinoma (SCC) represents a major public health concern due to its high incidence and potential for local invasion and metastasis. Compared to local recurrence, metastatic SCC represents an even greater therapeutic challenge. Once distant metastasis occurs, the disease becomes incurable, and treatment focuses on palliation and prolonging survival. The immune microenvironment of SCC is characterized by an infiltration of immune cells, including tumor-infiltrating lymphocytes. In addition to its direct cytotoxic effects, radiotherapy also induces immunomodulatory effects within the tumor microenvironment. Radiation can promote the release of tumor-associated antigens and induce immunogenic cell death, thereby enhancing the recognition of tumor cells by the immune system. Immunotherapy and radiotherapy have emerged as promising therapeutic modalities for metastatic SCC. This literature review aims to evaluate the potential synergy between these treatments and shed light on their combined efficacy. Within the manuscript, we present a compelling case report of a patient with advanced SCC who exhibited resistance to the combined regimen of immunotherapy and radiotherapy, leading to disease progression. Despite the increasing evidence supporting the synergy between these modalities, this case underscores the complex nature of treatment response and the importance of considering individual patient characteristics.

A cohort analysis of residential radon exposure and melanoma incidence in Switzerland

Radon is a radioactive noble gas found in Earth's crust. It accumulates in buildings, and accounts for approximately half the ionizing radiation dose received by humans. The skin is considerably exposed to ionizing radiation from radon. We aimed to evaluate the association between residential radon exposure and melanoma and squamous cell carcinoma incidence.The study included 1.3 million adults (20 years and older) from the Swiss National Cohort who were residents of the cantons of Vaud, Neuchâtel, Valais, Geneva, Fribourg, and Ticino at the study baseline (December 04, 2000). Cases of primary tumours of skin (melanoma and squamous cell carcinoma) were identified using data from cantonal cancer registries. Long-term residential radon and ambient solar ultraviolet radiation exposures were assigned to each individual's address at baseline. Cox proportional hazard models with age as time scale, adjusted for canton, socioeconomic position, demographic data available in the census, and outdoor occupation were applied. Total and age specific effects were calculated, in the full population and in non-movers, and potential effect modifiers were tested.In total 4937 incident cases of melanoma occurred during an average 8.9 years of follow-up. Across all ages, no increased risk of malignant melanoma or squamous cell carcinoma incidence in relation to residential radon was found. An association was only observed for melanoma incidence in the youngest age group of 20–29 year olds (1.68 [95% CI: 1.29, 2.19] 100 Bq/m3 radon). This association was mainly in women, and in those with low socio-economic position.Residential radon exposure might be a relevant risk factor for melanoma, especially for young adults. However, the results must be interpreted with caution as this finding is based on a relatively small number of melanoma cases. Accumulation of radon is preventable, and measures to reduce exposure and communicate the risks remain important to convey to the public.

Epidemiological and histological characteristics of cutaneous squamous cell carcinoma and its precursor lesions – A single-center study

Abstract Objective: Cutaneous squamous cell carcinoma (cSCC) is a skin malignancy that is one of the non-melanocytic skin cancers (NMSCs). The objective of our study was to highlight the epidemiological and histological characteristics of cSCC diagnosed in a clinical county hospital. Methods A retrospective cross-sectional study was performed of histopathologically diagnosed cases of cSCC from the clinical Pathology Department of the Mures Clinical County Hospital, Târgu Mureș, Romania. We included 96 cases that were diagnosed between January 1, 2017, and December 31, 2020. Results: Of the 96 cases included in the study, 82 were identified as cSCC, 5 as Bowen Disease, and 9 as keratoacanthoma. The majority of the cases were diagnosed in 2018 (n = 30; 31.25%) and 2019 (n=36; 37.50%). The median age of the patients was 63.0 years. Slightly over half of the patients were male (n=50; 52.08) and 49 patients (51.04%) grew up in urban areas. Forty-six cases (56.10%) were well differentiated; 25 (30.49%) moderately differentiated, and 11 (13.41%) poorly differentiated. Almost all of the lesions (93; 96.88%) were removed within the safety excision margins. Conclusion: Most of the patients were diagnosed with cSCC in 2018 and 2019 and were over 70 years old. The majority were males who grew up in urban areas. Even though most of the lesions were well differentiated and completely excised surgically, the differential diagnoses between cSCC and other skin malignancies were made based on the morphological aspects of the lesions, followed by an immunohistochemical profile when necessary.