The importance of caregivers for patients with advanced basal cell carcinoma treated with hedgehog-pathway inhibitors: an observational prospective study.

Oral targeted therapy with hedgehog pathway inhibitors has revolutionized the standard of care for patients with advanced basal cell carcinoma (BCC). These patients are frail and elderly, have various comorbidities, and receive pharmacological polytherapy. Moreover, adverse events may have a significant impact on therapeutic adherence, which must be managed by the clinician. We evaluated the impact of caregivers on the treatment of patients with advanced BCC in terms of continuation of therapy over time. All patients included in this observational prospective study had histologically confirmed metastatic or locally advanced BCC (LaBCC) and were treated with hedgehog pathway inhibitors from January 2016 to December 2021 at the Department of Dermatology at the University of Florence, Italy. The collected patient data included: age, sex, BCC site and area of spread; number of cycles, dose, duration and tolerability of therapy; marital status (single, divorced, married/living with a partner, widow/widower); and information such as living with someone, and the presence of any caregivers. Of the 34 patients included, 33 had LaBCC and one metastatic BCC. There were 11 females (32.4%) and 23 males (67.6%). Patients who were married or living with a caregiver -tolerated therapy better than single patients who lived alone. Indeed, patients with married/live-in caregivers and/or those with an adequate caregiver experienced greater therapeutic adherence and tolerance of adverse events. Given the greater therapeutic adherence of patients with live-in caregivers as partners, it is essential to consider patients' marital status. It is advisable to involve the caregiver early on, and there should be a training discussion on the various possible adverse events and the best way to mitigate them. Therapeutic success is linked not only to patients being informed but also to training of caregivers.

Results of Mohs' Micrographic Surgery of Periocular Basal Cell Carcinoma: The Swedish Experience.

The Department of Ophthalmology, Sahlgrenska University Hospital, has until recently been the only eye clinic in the Nordic countries to perform Mohs' micrographic surgery of basal cell carcinoma. This has led to the practice of only the most complicated basal cell carcinomas being operated on with this technique. The purpose of this study was to present the results of these surgeries in patients with at least 5 years of follow-up. A retrospective study of all patients operated upon in 2010-2015 was performed. Data were gathered from their medical charts. Primary outcome was recurrence of basal cell carcinoma. One-hundred and sixty-seven patients were operated on. Mohs' micrographic surgery was used for tumours that were judged as highly aggressive on preoperative biopsy, had ill-defined borders, had recurred after previous surgery, or a combination of these factors. Nine recurrences (5.4% of all radical Mohs' micrographic surgeries) were diagnosed after a mean postoperative time of 37 months (4-84 months). Interestingly, all of these 9 recurrences after Mohs' micrographic surgery were in patients who had such surgery because of a recurrent basal cell carcinoma to start with. Good results can be achieved when operating on the most complicated periocular basal cell carcinomas with Mohs' micrographic surgery but special care has to be taken to ensure radical borders when operating on recurring basal cell carcinomas.

Clinical determinants of clinical response to Sonidegib in advanced basal cell carcinoma: a monocenter experience.

OBJECTIVE: The purpose of this study is to evaluate the clinical determinants of complete response in locally advanced basal cell carcinoma (laBCC) patients receiving Sonidegib in a real-life, retrospective, observational study.  Hedgehog pathway inhibitors (Vismodegib and Sonidegib) are approved for the systemic treatment of locally advanced basal cell carcinoma (laBCC). The objective response rate was the primary endpoint of the trials for both drugs. PATIENTS AND METHODS: Adult patients with laBCC treated with Sonidegib at the Dermato-Oncology Unit of IFO San Gallicano between June 2020 and September 2022 were included in the study. Patient, tumor, and treatment characteristics were recorded. The complete response rate was the primary outcome. The median time to the best response and complete response were the secondary outcomes. Treatment-related adverse events (TRAEs) and dose adjustments were recorded. RESULTS: Of the 19 patients included in the study, eight (42.1%) achieved a complete response, seven (36.8%) had a partial response, and four experienced progressive disease (21%). The median time to the best response was 3 months in the group of patients with partial response (range 2.0-4.0, with three patients not evaluable) and 3.5 months in the group of patients with complete response (range 2-5). TRAEs occurred in 14 (73.6%) patients, with 8 (57.1%) reporting ≤2 TRAE categories and 6 (42.8%) >2. A total of 78.9% of patients received a modified treatment schedule; 12.5% of patients who achieved a complete response received full dosage from the beginning to the end of treatment, compared with 27.3% of those with a partial response. CONCLUSIONS: The associations between the clinical outcome of interest (objective response rate) and the clinicopathological and treatment characteristics were evaluated. No statistically significant association was observed. Our analysis confirms the observation that no statistically significant correlation exists between clinical response and Sonidegib alternate dose regimen.

The top 100 most cited articles in the treatment of basal cell carcinoma over the last decade: A bibliometric analysis and review.

Basal cell carcinoma (BCC) represents the most prevalent cancer globally. The past decade has witnessed significant advancements in BCC treatment, primarily through bibliometric studies. Aiming to perform a comprehensive bibliometric analysis of BCC treatments to comprehend the research landscape and identify trends within this domain, a dataset comprising 100 scientific publications from the Web of Science Core Collection was analyzed. Country co-operation, journal co-citation, theme bursts, keyword co-occurrence, author co-operation, literature co-citation, and field-specific references were examined using VOSviewer and CiteSpace visualization tools. These articles, published between 2013 and 2020, originated predominantly from 30 countries/regions and 159 institutions, with the USA and Germany at the forefront, involving a total of 1118 authors. The keyword analysis revealed significant emphasis on the hedgehog pathway, Mohs micrographic surgery, and photodynamic therapy. The research shows developed nations are at the forefront in advancing BCC therapies, with significant focus on drugs targeting the hedgehog pathway. This treatment avenue has emerged as a crucial area, meriting considerable attention in BCC therapeutic strategies.

A Tale of Two Tumors: A Collision Tumor of Atypical Fibroxanthoma and Basal Cell Carcinoma.

ABSTRACT: A collision tumor is an infrequent phenomenon characterized by the presence of 2 histologically distinct tumor types (either benign or malignant) occurring within the same specific anatomical site. We describe a rare case of co-occurrence of basal cell carcinoma and atypical fibroxanthoma presenting as a single lesion on the scalp in a 76-year-old man. The lesion was clinically suspicious for basal cell carcinoma and biopsied. Histologic examination showed 2 distinct tumors, one with basaloid cells and the other one with pleomorphic spindle cells colliding and growing together. Immunohistochemical stains were crucial in establishing the diagnosis. This presentation is exceedingly rare and requires additional evaluation for diagnosis.

Line-field confocal optical coherence tomography in dermato-oncology: A literature review towards harmonized histopathology-integrated terminology.

Non-invasive diagnostics like line-field confocal optical coherence tomography (LC-OCT) are being implemented in dermato-oncology. However, unification of terminology in LC-OCT is lacking. By reviewing the LC-OCT literature in the field of dermato-oncology, this study aimed to develop a unified terminological glossary integrated with traditional histopathology. A PRISMA-guided literature-search was conducted for English-language publications on LC-OCT of actinic keratosis (AK), keratinocyte carcinoma (KC), and malignant melanoma (MM). Study characteristics and terminology were compiled. To harmonize LC-OCT terminology and integrate with histopathology, synonymous terms for image features of AK, KC, and MM were merged by two authors, organized by skin layer and lesion-type. A subset of key LC-OCT image-markers with histopathological correlates that in combination were typical of AK, squamous cell carcinoma in situ (SCCis), invasive squamous cell carcinoma (SCC), basal cell carcinoma (BCC), and MM in traditional histopathology, were selected from the glossary by an experienced dermatopathologist. Seventeen observational studies of AK (7 studies), KC (13 studies), MM (7 studies) utilizing LC-OCT were included, with 117 terms describing either AK, KC, or MM. These were merged to produce 45 merged-terms (61.5% reduction); 5 assigned to the stratum corneum (SC), 23 to the viable epidermis, 2 to dermo-epidermal junction (DEJ) and 15 to the dermis. For each lesion, mandatory key image-markers were a well-defined DEJ and presence of mild/moderate but not severe epidermal dysplasia for AK, severe epidermal dysplasia and well-defined DEJ for SCCis, interrupted DEJ and/or dermal broad infiltrative strands for invasive SCC, dermal lobules connected and/or unconnected to the epidermis for BCC, as well as single atypical melanocytes and/or nest of atypical melanocytes in the epidermis or dermis for MM. This review compiles evidence on LC-OCT in dermato-oncology, providing a harmonized histopathology-integrated terminology and key image-markers for each lesion. Further evaluation is required to determine the clinical value of these findings.

Basal Cell Carcinoma Formation Within A Spinal Cord Stimulator Surgical Scar: A Case Report.

Implanting neuromodulation devices requires that pain medicine physicians be well-versed in proper surgical technique and postoperative wound management. To be able to identify abnormal wound healing, a basic understanding of normal wound healing is required. When postoperative wounds deviate from expected healing, it is important that pain medicine physicians entertain a broad differential diagnosis, including nonsurgical dermatologic pathology.

PERIOCULAR HIGH RISK BCCS AFTER ADDITIONAL/PARALLEL INTAKE OF TORASEMIDE, MOXONIDINE AND MIRABEGRON: IMPORTANT LINKS TO SKIN CANCER RELATED (PHOTO-) NITROSOGENESIS IN THE CONTEXT OF PHARMACO-ONCOGENESIS.

The Nitrosogenesis of skin cancer is a modern newly introduced concept in medicine, mainly concerning melanoma, but also keratinocytic cancers such as basal cell carcinoma. The nitroso-contamination of more than 300 drugs worldwide and the permanent (relatively short-term) intake of mutagen-contaminated drugs could create serious prerequisites for the development of skin cancer. Retrospective but also prospective analyses following potentially contaminated polymedication with a heterogeneous type of nitrosamines in real patients are indicative of a causal connection rather than a sporadic association between 1) intake of a possibly nitrosamine-contaminated drug and 2) generation of keratinocytic skin cancer. The pathogenesis of high-risk periocular localized basal cell carcinomas was until recently shrouded in mystery as it was mainly and until now associated with 1) intake of phototoxic drugs and 2) intense exposure to UV radiation (without intake of drugs), 3) congenital or acquired immunodeficiencies, and 4) Goltz Gorlin syndrome or 5) Xeroderma pigmentosum. Nitrosamines/ NDSRIs within the framework of polycotaminated drug intake appear to be one reasonable additional explanation for the association between carcinogen intake and subsequent skin cancer development and progression, and a relatively short-term one at that. Recently published scientific data provide information on a new ability of some of the nitrosamines - namely that some of them are photocarcinogenic or genotoxic after activation with UVA radiation. We present 4 patients who developed high-risk periocular localized basal cell carcinomas of the skin after/within the intake of potentially nitrosamine-contaminated drugs. The presented data are confirmatory with respect to previously published scientific observations on the carcinogenic effects of valsartan, candesartan, bisoprolol, metoprolol, perindopril, lisinopril and amlodipine. The contribution of newly validated data concerning potential/actual carcinogenic/genotoxic activity in the article is also due to the following newly announced nitroso preparations: torasemide, moxonidine and mirabegron. The expansion of the ˝bases of the pyramid˝ determining the stability of drug related (Photo) Nitrosogenesis/ Carcinogenesis (in terms of skin cancer generation) is growing daily. Exogenously/drug-induced Nitrosogenesis and the subsequently triggered carcinogenesis are a completely new explanatory concepts concerning the pathogenesis of skin tumors that remained unanalyzed and hidden for decades. Until now. The official lack of 1) availability, and of 2) precise concentrations regarding nitrosamines in medicinal preparations, are some of the most unexplained acts of irresponsibility to end-users and remain for the moment without a definitive answer from either regulators and manufacturers respectively. Polycontamination of polymedication in polymorbid patients remains highly problematic, at least as a cofactor in the development and progression of keratinocytic cancers, and this in the short term. Recently published data but also data from the past are suggestive that nitrosamines in tobacco are pivotal in the development of acquired mutations in p53 and RAS oncogenes in humans and rodents. The same genes are also affected by mutations in keratinocytic cancer patients. The overlapping mutation patterns of UV radiation-induced mutations in target genes such as p53 and RAS with those caused by some nitrosamines is indicative of a synergism available in terms of gene toxicity or possibly photocarcinogenicity of the latter. What leads the scientific community to believe that the nitrosamines in drugs, similar in composition and carcinogenic potency, act differently, is unclear. The link between drug intake, nitrosamine contamination, generation of some acquired mutations and subsequent cancer development becomes more than obvious and logically conditioned. The thesis of the controlled spread of cancer sounds more than logical today because: whoever controls and regulates the spread of carcinogens/mutagens/nitrosamines is also able to control the occurrence and spread of skin cancer. The Pharmaco-oncogenesis of skin cancer is determined by exogenously mediated Nitrosogenesis or the permissive availability for certain nitrosamines in drugs worldwide.

Fragile hands: targeting nonmelanoma skin cancer on older hands using 595 nm pulsed dye laser.

PURPOSE: The mainstay of treatment for nonmelanoma skin cancer (NMSC) on thin skin remains surgical, but procedures on older hands may be complicated by skin fragility and dermal atrophy. Used without cooling, 595 nm (nm) pulsed dye laser (PDL) has the capability of destroying NMSC through nonspecific thermal necrosis. The purpose of this study was to understand recurrence of NMSC on dorsal hands of older patients after one or two treatments using 595 nm PDL. METHODS: A retrospective chart review identified 147 cases of NMSC located on the dorsal hands treated with 595 nm PDL. Cases of basal cell carcinomas (BCCs) and squamous cell carcinomas (SCCs) were included. All patients received one to two treatments with PDL. The primary outcome was the recurrence of carcinoma. RESULTS: Among NMSC cases treated with PDL, recurrence occurred in 12 patients (8.2%). No cases of BCC recurred during the study period. Recurrence of SCC was 4.7% for SCC in situ and 10.4% recurrence for invasive SCC (p = 0.34). Among 71 patients treated once, recurrence occurred in 10 patients (14.1%), and among 76 cases treated twice, recurrence occurred in 2 patients (2.6%, p = 0.01). CONCLUSION: Two treatments of PDL for NMSC on the dorsal hands of older patients was well tolerated, had low recurrence, and seemed more effective than one treatment.

Using optical coherence tomography to optimize Mohs micrographic surgery.

Mohs micrographic surgery (MMS) is considered the gold standard for treating high-risk cutaneous basal cell carcinoma (BCC), but is expensive, time-consuming, and can be unpredictable as to how many stages will be required or how large the final lesion and corresponding surgical defect will be. This study is meant to investigate whether optical coherence tomography (OCT), a highly researched modality in dermatology, can be used preoperatively to map out the borders of BCC, resulting in fewer stages of MMS or a smaller final defect. In this prospective study, 22 patients with BCC undergoing surgical excision were enrolled at a single institution. All patients had previously received a diagnostic biopsy providing confirmation of BCC and had been referred to our center for excision with MMS. Immediately prior to performing MMS, OCT was used to map the borders of the lesion. MMS then proceeded according to standard protocol. OCT images were compared to histopathology for agreement. Histopathologic analysis of 7 of 22 MMS specimens (32%) revealed a total absence of BCC, indicating resolution of BCC after previous diagnostic biopsy. This outcome was correctly predicted by OCT imaging in 6 of 7 cases (86%). Nine tumors (9/22, 41%) had true BCC and required a single MMS stage, which was successfully predicted by pre-operative OCT analysis in 7 of 9 cases (78%). The final six tumors (27%) had true BCC and required two MMS stages for complete excision; preoperative OCT successfully predicted the need for a second stage in five cases (5/6, 83.3%). Overall, OCT diagnosed BCC with 95.5% accuracy (Cohen's kappa, κ = 0.89 (p-value = < 0.01) in the center of the lesion. Following a diagnostic biopsy, OCT can be used to verify the existence or absence of residual basal cell carcinoma. When residual tumor is present that requires excision with MMS, OCT can be used to predict tumor borders, optimize surgery and minimize the need for additional surgical stages.

Skin Cancer Risk of Narrow-Band UV-B (TL-01) Phototherapy: A Multi-Center Registry Study with 4,815 Patients.

Narrow-band TL-01 ultraviolet B phototherapy (TL-01) is an effective and widely used treatment for many skin diseases. The purpose of the investigation was to assess the risk of skin cancers in patients treated with TL-01 phototherapy who have not received any other phototherapy modalities. This cohort study included 4,815 TL-01 treated patients in Finland with psoriasis or atopic dermatitis. Clinical information was collected from the hospital records and linked with Finnish Cancer Registry data. The follow-up started from the first TL-01 treatment and the mean follow-up time was 8.4 years. Standardized incidence ratios were calculated for basal cell carcinoma, cutaneous melanoma, and squamous cell carcinoma. The standardized incidence ratio for basal cell carcinoma was 2.5 (95% confidence interval 1.8-3.5), for cutaneous melanoma 4.0 (95% confidence interval 2.1-6.8) and for squamous cell carcinoma 3.7 (95% confidence interval 1.7-7.0). For basal cell carcinoma and squamous cell carcinoma, the standardized incidence ratios remained similar during the whole follow-up time while the standardized incidence ratio for cutaneous melanoma was markedly higher during the first 5 years of follow-up. In conclusion, an increased incidence of skin cancers was observed among TL-01 treated patients. It should be confirmed in the future whether the skin cancer risk of TL-01 phototherapy will remain high in a longer follow-up.

Genetic predisposition to childhood obesity does not influence the risk of developing skin cancer in adulthood.

The relationship between body mass index (BMI) and melanoma and other skin cancers remains unclear. The objective of this study was to employ the Mendelian randomization (MR) approach to evaluate the effects of genetically predicted childhood adiposity on the risk of developing skin cancer later in life. Two-sample MR analyses were conducted using summary data from genome-wide association study (GWAS) meta-analyses of childhood BMI, melanoma, cutaneous squamous cell carcinoma (cSCC), and basal cell carcinoma (BCC). We used the inverse-variance-weighted (IVW) methods to obtain a pooled estimate across all genetic variants for childhood BMI. We performed multiple sensitivity analyses to evaluate the potential influence of various assumptions on our findings. We found no evidence that genetically predicted childhood BMI was associated with risks of developing melanoma, cSCC, or BCC in adulthood (OR, 95% CI: melanoma: 1.02 (0.93-1.13), cSCC 0.94 (0.79-1.11), BCC 0.97 (0.84-1.12)). Our findings do not support the conclusions from observational studies that childhood BMI is associated with increased risks of melanoma, cSCC, or BCC in adulthood. Intervening on childhood adiposity will not reduce the risk of common skin cancers later in life.

Primary basal cell carcinoma of the caruncle: case report and review of the literature.

We present a rare case of primary caruncle basal cell carcinoma (BCC), a condition with limited occurrences. Our patient, an 80-year-old woman without prior ocular pathological history, presented a 2x2mm pedunculated blackish nodular lesion on the caruncle of her left eye, without local conjunctival or cutaneous involvement. Histological analysis following complete excision confirmed the presence of basal cell carcinoma within the caruncle. Over a span of 30 months, no recurrence has been observed. While scant cases are documented in the literature, we conducted a review of these instances. Despite its infrequent manifestation, this condition should be taken into account when evaluating caruncular tumors, given its tendency to invade the orbit. Complete excision with free surgical margins is the treatment of choice, and adjuvant radiotherapy or chemotherapy might be considered.

Excision pathways for keratinocyte cancers diagnosed by teledermatology: a retrospective review.

Introduction The New Zealand population has one of the highest incidences of skin cancer in the world. Hospital waiting lists for surgical excision of keratinocytic skin cancers (basal cell carcinoma and squamous cell carcinoma) are lengthy, and increasingly, excisions are undertaken in primary care. Teledermatology, in response to general practitioners' electronic referrals (e-referrals), can improve clinical communication between general practitioners and dermatologists. Aim The aim of this study was to evaluate an excision pathway for keratinocytic cancers diagnosed by teledermatology. Methods A retrospective observational descriptive review of a 3-month cohort of primary care e-referrals was undertaken. Results Three hundred and fifty eight suspected keratinocytic cancers (KCs) were diagnosed by teledermatology; histology reports confirmed KC in 201 of 267 excisions (75%). The majority (77.2%) were excised by general practitioners an average of 25 days after the dermatologist's recommendation. The rest were excised by plastic surgeons in private (3.4%) or at a public hospital (19.5%) after an average of 40 or 134 days, respectively. Discussion E-referral pathways are now widely implemented. However, the ideal workflow for skin cancer management is unknown. We have demonstrated in New Zealand that surgery can be undertaken in primary care within a month of a teledermatology diagnosis and excision recommendation. Conclusion This study reports prompt excision of KCs by general practitioners after an e-referral and a teledermatology response.

Efficacy of photodynamic therapy using ALAHCl in gel with a lipid nanoemulsion and MALHCl in cream in superficial basal cell carcinoma.

INTRODUCTION AND OBJECTIVE: Photodynamic therapy (PDT) is a therapeutic option for low-risk basal cell carcinoma (BCC). The aim of the study was to assess the efficacy of topical PDT in the treatment of superficial BCC (sBCC) using two different photosensitizers: aminolevulinic acid hydrochloride (ALA-HCl) in a gel formulation with a lipid nanoemulsion (ALA-HCl in gel) and ALA methyl ester hydrochloride (MAL-HCl) in a cream formulation (MAL-HCl in cream). MATERIAL AND METHODS: 21 patients were treated twice with a one week interval between treatments. The formulations were applied onto lesions: 10 patients were treated with MAL-HCl in cream, and 11 with ALA-HCl in gel. After three hours of incubation and removing the preparations, fluorescence was assessed. The skin areas were then irradiated with red light 630 ± 5 nm. RESULTS: At the follow-up visit 12 weeks after the second treatment, complete clinical remission was found in 82% after ALA-HCl in gel and in 80% after MAL-HCl in cream. An excellent cosmetic result was found in 96% of patients after MALHCl in cream and in 100% after ALA-HCl in gel. Faster skin healing and less post-inflammatory hyperpigmentation during follow-up visits was observed after treatment with ALA-HCl in gel. CONCLUSIONS: Both formulations - ALA-HCl in gel and MAL-HCl in cream - were highly effective photosensitisers for PDT. The advantage of ALA-HCl in a gel formulation with a lipid nanoemulsion was faster skin healing, resulting in better cosmetic results.

Expression of Early Growth Response 3 in Skin Cancers.

OBJECTIVE: To assess the expression of early growth response 3 (EGR3) in normal skin and different types of skin tumors: cutaneous squamous cell carcinoma (cSCC), basal cell carcinoma (BCC), melanoma (MM), and cutaneous adnexal tumors containing sebaceous carcinoma (SC), trichoepithelioma (TE) and clear cell hidradenoma (CCH). BACKGROUND: EGR3, expressed in multiple organs, including skin, plays an important role in cell differentiation and tumor growth. Previous studies have shown that EGR3 suppresses tumor growth and is downregulated in various malignancies. However, its distribution in normal skin and its expression especially in skin tumors have not been studied. MATERIALS AND METHODS: Samples of normal cases (n = 4), cSCC (n = 12), BCC (n = 12), MM (n = 12), SC (n = 4), TE (n = 4), and CCH (n = 4) were collected from patients treated in our department between 2018 and 2023. Immunohistochemistry was used to investigate the expression of EGR3. The results were analyzed with the description of the staining pattern and the histochemical score. RESULTS: Immunohistochemical staining showed that EGR3 was uniquely expressed in normal skin in the granular layer and upper part of the stratum spinosum, as well as in sebaceous glands and hair follicles, but not in sweat glands. In skin cancers, BCC, SC, and TE showed positive EGR3 staining, whereas cSCC, MM, and CCH were negative. CONCLUSIONS: EGR3 has a specific expression pattern in normal skin and in skin tumors, which is important for the differential diagnosis of skin tumors, in particular for cSCC and sebaceous gland carcinoma.

Treatments on the horizon for locally advanced basal cell carcinoma.

Basal cell carcinoma (BCC) is one of the most common human cancers. Most cases of BCC are amenable to surgical and topical treatments with excellent prognosis if diagnosed timely and managed appropriately. However, in a small percentage of cases, it could be locally advanced BBC (laBCC) and not amenable to surgery or radiation, including recurrent, large tumors or tumors that invade deeper tissue. Hedgehog inhibitors (vismodegib and sonidegib) are approved as the first-line treatment of laBCC. PD-1 inhibitor immunotherapy (cemiplimab) is indicated for cases that progressed on or could not tolerate hedgehog inhibitors or when hedgehog inhibitors are contraindicated. Given the modest response and bothersome side effects of some of the agents above, there are reports of novel treatments, and clinical trials are currently evaluating multiple agents.