Basal Cell Carcinoma Patients Research Articles

Basal cell carcinoma: what new can be learned about the most common human cancer? A cross-sectional prospective study of 180 cases in a single centre.

IntroductionBasal cell carcinoma (BCC) is the most common cancer in humans, but the reporting of patients with BCC is still not complete. There are a limited number of analyses in the literature on BCC epidemiology.AimTo study the epidemiological as well as clinical aspects of BCC by analysing a single centre’s experience in the Lower Silesia region of Poland.Material and methodsWe investigated 180 patients with BCC treated in the Unit of Dermatosurgery, Department of Dermatology, Venereology, and Allergology of Wroclaw Medical University between September 2017 and December 2019.ResultsThe mean age of patients with BCC was 70.5 ±11.9 years. The most frequently diagnosed type of BCC was nodular type, at 72% of all patients. BCC occurred most commonly on the face and neck area, at 132 (73.3%), without a statistical difference between males and females. The vast majority of cancers were located on the nose. There was a personal history of skin cancer in 29% of our patients. In 127 (70.6%) subjects, the diameter of the BCC on the day of excision was less than 2 cm.ConclusionsThe clinical characteristics of our cohort of BCC patients has some similarities with that reported from central Poland and other European countries. However, we found an increase in the incidence of BCC among females.

MTOR promotes basal cell carcinoma growth through atypical PKC.

Advanced basal cell carcinomas (BCCs) are driven by the Hedgehog (HH) pathway and often possess inherent resistance to SMO inhibitors. Identifying and targeting pathways that bypass SMO could provide alternative treatments for patients with advanced or metastatic BCC. Here, we use a combination of RNA-sequencing analysis of advanced human BCC tumor-normal pairs and immunostaining of human and mouse BCC samples to identify an MTOR expression signature in BCC. Pharmacological inhibition of MTOR activity in BCC cells significantly reduces cell proliferation without affecting HH signalling. Similarly, treatment of the Ptch1fl/fl ; Gli1-CreERT2 mouse BCC tumor model with everolimus reduces tumor growth. aPKC, a downstream target of MTOR, shows reduced activity, suggesting that MTOR promotes tumor growth by activating aPKC and demonstrating that suppressing MTOR could be a promising target for BCC patients.

Evaluation of ultrahigh-resolution optical coherence tomography for basal cell carcinoma, seborrheic keratosis, and nevus.

Basal cell carcinoma, seborrheic keratosis, and nevus are common skin conditions. Though most of the skin diseases can be distinguished from each other by physician's naked eyes, the diagnostic accuracy is not 100%. The accurate diagnosis and assessment of three diseases make a big difference on the clinical management. Nowadays, biopsy is still the gold standard for diagnosis even it is invasive, time-consuming, and painful. Ultrahigh-resolution optical coherence tomography is an emerging technology that can produce in situ, cellular-resolution, real-time, continuous, 3D images in a noninvasive way. In our study, four basal cell carcinoma patients, five seborrheic keratosis patients, and 10 nevus patients who were diagnosed by histology were studied by ultrahigh-resolution optical coherence tomography after visual examination by experienced dermatologists. Cellular contrast was utilized to clearly identify the features of the three skin diseases. The features including such as hyperkeratosis (horn pseudocysts), papillomatosis, intraepidermal nests, elongated, and expanded rete ridge can be visualized in seborrheic keratosis. Tumor nodular, mucin surrounding with tumor (retraction space in histopathology), tumor subtype, and necrosis were featured in basal cell carcinoma. Pigment was characterized in epidermis and dermis. The comparison of ultrahigh-resolution optical coherence tomography images reveals a strong correlation with histological images. Ultrahigh-resolution optical coherence tomography can complement existing diagnostic techniques for investigating seborrheic keratosis, basal cell carcinoma and nevus, and show enormous potential in vivo applications for the three skin diseases in the future.

The Synthetic Flavonoid Derivative GL-V9 Induces Apoptosis and Autophagy in Cutaneous Squamous Cell Carcinoma via Suppressing AKT-Regulated HK2 and mTOR Signals.

Cutaneous squamous-cell carcinoma (cSCC) is one of most common type of non-black skin cancer. The malignancy degree and the death risk of cSCC patients are significantly higher than basal cell carcinoma patients. GL-V9 is a synthesized flavonoid derived from natural active ingredient wogonin and shows potent growth inhibitory effects in liver and breast cancer cells. In this study, we investigated the anti-cSCC effect and the underlying mechanism of GL-V9. The results showed that GL-V9 induced both apoptosis and autophagy in human cSCC cell line A431 cells, and prevented the growth progression of chemical induced primary skin cancer in mice. Metabolomics assay showed that GL-V9 potentially affected mitochondrial function, inhibiting glucose metabolism and Warburg effect. Further mechanism studies demonstrated that AKT played important roles in the anti-cSCC effect of GL-V9. On one hand, GL-V9 suppressed AKT-modulated mitochondrial localization of HK2 and promoted the protein degradation of HK2, resulting in cell apoptosis and glycolytic inhibition. On the other hand, GL-V9 induced autophagy via inhibiting Akt/mTOR pathway. Interestingly, though the autophagy induced by GL-V9 potentially antagonized its effect of apoptosis induction, the anti-cSCC effect of GL-V9 was not diluted. All above, our studies suggest that GL-V9 is a potent candidate for cSCC treatment.

Recurrence of Basal Cell Carcinoma After Mohs Micrographic Surgery: A 4-Year Retrospective Analysis

Background: Among non-melanoma skin cancers (NMSC), Basal cell carcinoma (BCC) is one of the most common. Objectives: We endeavored to assess the recurrence rate of BCC after surgery and compare tumors recurrence based on different aspects. Methods: This was a retrospective and observational study which was analyzed medical records of 154 patients who had Mohs micrographic surgery (MMS) from March 2013 to February 2017 in two clinical centers. For finding if the clinical characteristics of the patients have related to tumoral recurrence, we gathered them, including gender and age of the patient, tumor size, site, and its histological type plus the existence of ulcer in malignancy. Data were analyzed using SPSS 22 statistical software. Statistical difference between proportions was determined by χ2 analysis. Results: The majority of patients (74%) were female (57%) older than 60 years old. Most tumors, based on the histopathological diagnosis, were Infiltrating (43.5%) and nodular and infiltrating (40.3%), respectively. The mean tumor size was 1.81 cm and most of them (74%) were larger than 1 cm. The tumor site was mostly in the nasal (56.5%) followed by the cheek (11%). Most patients (96.8%) had one lesion. The recurrence rate was 1.9%. The mean interval between surgeries to recurrence was 13 months. There was no significant difference between recurrence rate and age, sex, tumor type in terms of clinical diagnosis, tumor location, tumor size, number of lesions, and type of tumor (P < 0.05). Conclusions: the rate of recurrence of BCC in patients treated with MMS is low (1.9%). We recommend the utilization of the MMS technique for the treatment of BCC.

Assessment of sun-related behavior and serum vitamin D in basal cell carcinoma: Preliminary results.

Ultraviolet radiation (UV), mainly from sunlight, is the main risk factor of the most common human skin cancer, basal cell carcinoma (BCC). A positive effect of UV on the skin is its contribution to the synthesis of vitamin D, which is important in sustaining general health, but having high levels of vitamin D is considered a risk factor for BCC. However, vitamin D receptor has antagonistic effects to UV radiation in regulating Sonic Hedgehog pathway. This is a pilot study aimed at characterizing the sun-related behavior and vitamin D status of 52 BCC patients and 59 controls from our geographical area. Patients were included in 4 subgroups: Single, multiple, recurrent, and both multiple and recurrent BCCs. Patients, more than controls, had at least one sunburn in childhood and lentigines (P<0.001). Also, they spent daily, on average, more time in the sun than controls (P<0.001) (3.00-8.00 and 1.50-4.00 h respectively). Outdoor work was similar in both groups. Participants had lower vitamin D serum levels than expected. Due to the small number of cases, no statistically significant differences were found between the subgroups but some tendencies were noted. Patients with only one recurrent BCC had less sunburns than the ones who also developed tumors at multiple sites (P=0.2). Patients with multiple and recurrent tumors had slightly lower vitamin D levels compared with single BCC patients (P=0.1) although they used more vitamin D supplements after the BCC diagnosis (P=0.2). Having a diagnosis of BCC, made patients more compliant to the use of sunscreen cream, but even so, half of them still did not use it. In conclusion, more effort should be invested in sun-related education and public health actions should focus on vitamin D deficiencies.

Efficacy and Safety of Laser-Assisted Combination Chemotherapy: An Explorative Imaging-Guided Treatment With 5-Fluorouracil and Cisplatin for Basal Cell Carcinoma.

Rising incidences of basal cell carcinoma (BCC) have increased the need for effective topical therapies. By enhancing cutaneous uptake of the chemotherapeutic agents, cisplatin and 5-fluorouracil (5-FU), laser-assisted delivery may provide a new combination treatment for BCC. Accordingly, this study aimed to evaluate tumor response, safety, and drug biodistribution in tumors and blood after topical laser-assisted 5-FU + CIS treatment in BCC patients. This open-label, proof-of-concept trial investigated laser-assisted combination cisplatin + 5-FU treatment in 20 patients with histologically verified, low-risk superficial or nodular BCCs on the face (<20 mm) or trunk/extremities (<50 mm). After tumor demarcation guided by optical coherence tomography (OCT), BCCs were exposed to ablative fractional CO2 laser followed by 60 minutes topical cisplatin solution and 7-day exposure to 5% 5-FU cream under occlusion. After 30 days, treatment was repeated if any tumor residual was identified. Tumor response at day 30 and month 3 was assessed clinically as well as by OCT, reflectance confocal microscopy, and ultrasound, supplemented by histological verification at 3 months. Local skin reactions (LSRs) and side effects were evaluated on days 1, 3-5, 14, 30, and month 3. Drug detection in tumors and blood was performed in a subset of patients 1- and 24 hours after treatment. Nineteen patients completed the trial, with 32% (6/19) receiving a single treatment and 68% (13/19) treated twice. At 3 months, clinical clearance was seen in 18/19 patients with a corresponding 94% (17/18) achieving histological clearance. Baseline tumor thickness and subtype did not influence treatment number or clearance rate (P ≥ 0.61). LSRs were well-tolerated and consisted of erythema, edema, and erosion, followed by crusting by day 14. Erythema declined gradually by month 3, with 94% of patients and 79% of physicians rating cosmesis as "good" or "excellent." Scarring or hyperpigmentation was noted in 50% and 56%, respectively, while pain and infection were not observed during the follow-up period. Although chemotherapy uptake was visualized extending to deep skin layers, no systemic exposure to cisplatin or 5-FU was detected in patient blood. Laser-assisted cisplatin + 5-FU shows potential as an effective and tolerable treatment option for low-risk BCC, particularly in instances where self-application is not possible or where in-office, non-surgical therapy is preferred. Lasers Surg. Med. © 2020 Wiley Periodicals LLC.

Shining a Light on Skin Cancer in Inflammatory Bowel Disease: A Role for Prevention.

Risks of nonmelanoma skin cancer in patients with inflammatory bowel disease (IBD) have been well described. Newer data have classified risks of subsequent squamous cell carcinoma or basal cell carcinoma in patients with IBD after an initial skin cancer excision. In this editorial, risks of continuing medical therapy for IBD after a skin cancer diagnosis are discussed in the context of a holistic preventive care approach for patients with IBD.

Evaluation of the effect of surgical treatment on quality of life with the Dermatology Life Quality Index in patients with facial nonmelanoma skin cancer.

Skin cancers are the most common type of cancer. Nonmelanoma skin cancers (NMSCs) are more common than melanoma. Although the mortality rate is low, cancer word can be frightening for patients. Surgery is the main treatment. As skin cancers are most commonly located on the face, undesirable cosmetic results can occur as a result of treatments or due to primary disease. Therefore, the quality of life of patients could be affected. To determine the effect of surgical treatment on quality of life of the patients with facial NMSC using the Dermatology Life Quality Index (DLQI) at baseline and 3 months after surgery. We aimed to see if there was any improvement in quality of life scores after surgery, and to identify factors affecting quality of life. A total of 255 patients; 174 basal cell carcinoma (BCC) (68.2%) and 81 squamous cell carcinoma (SCC) (31.8%) were included in our study. All participants completed DLQI at baseline and 3 months after surgery. The mean total DLQI scores were 6.37 ± 6.28 in patients with BCC, and 6.35 ± 6.16 in patients with SCC. The mean total DLQI scores were 3.96 ± 5.14 in patients with BCC (P < .001), and 4.49 ± 5.24 in patients with SCC (P < .001) 3 months after surgery. In patients with primary skin cancer, all subscale scores and total DLQI scores were worse than the recurrent skin cancer group in both BCC and SCC at baseline. According to the treatment modalities, total DLQI scores and all subscales were worse in the graft group in BCC and SCC patients at baseline. Interestingly, the sex and the type of skin cancer did not affect quality of life, but tumor localization ([auricula OR: 6.45 [95% CI: 1.28-37.47] and eyelid OR:0.20 [95% CI: 0.04-0.96]) treatment procedure ([flap procedure OR: 7.90 [95% CI: 2.64-23.62] and graft procedure OR: 5.47 [95% CI: 1.60-18.71]) and, primary tumor OR:3.86 (95% CI: 1.01-14.78) were significant. The quality of life of skin cancer patients was affected by tumor localization, treatment procedure, primary, or recurrent tumor. The quality of life showed a significant improvement in patients with facial NMSC after surgical treatment. However, the type of NMSC seems to have no effect on the quality of life.

Interleukin-6 -174 G/C polymorphism is associated with the risk of basal cell carcinoma in a Chinese Han population.

To explore the association between the IL-6 -174 G/C polymorphism and the risk of basal cell carcinoma (BCC) in a Chinese population, we performed a case-control study involving 265 BCC patients and 341 controls. Genotyping was performed using polymerase chain reaction with sequence-specific primers. The data showed that the GG+CG and GG genotypes were associated with an increased risk of BCC. The G allele increased the risk of BCC. Moreover, stratified analyses indicated the risk was higher in males, smokers, drinkers, and those aged ≥ 60 years. Cross-over analysis confirmed that the combined effects of the GG or CG genotype and environmental factors (smoking and alcohol consumption) contribute to an increased risk of BCC. In addition, the IL-6 -174 G/C polymorphism was related to larger tumors and multiple lesions. These findings indicate that the IL-6 -174 G/C polymorphism is associated with an increased risk of BCC in a Chinese population. This locus is thus a potential diagnostic marker for predicting susceptibility to BCC.

Association study indicates combined effect of interleukin-10 and angiotensin-converting enzyme in basal cell carcinoma development.

Cytokines involved in inflammatory and immune response have been associated with risk for development of basal cell carcinoma (BCC). In this study, three functional DNA polymorphisms affecting gene expression were investigated in 54 BCC patients and 111 healthy controls: interleukin-1b (IL-1b) +3953C/T, interleukin-10 (IL-10) -1082G/A and angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphisms. Significant increase of the variant alleles was observed in IL-10 -1082G (P = 0.019) and in ACE D (P = 0.003) in BCC patients in comparison to controls. Multivariate logistic regression models evaluated the contribution of homozygous and heterozygous variant polymorphisms to the risk for BCC development. The studied polymorphisms influencing the expression of IL-10 and ACE genes were recognized as potential predictive factors for BCC. These findings suggest a possible molecular mechanism leading to BCC development that is likely to involve the activation of angiotensin receptors in combination with increased plasma levels of IL-10 in patients.

Impairment of Base Excision Repair in Dermal Fibroblasts Isolated From Nevoid Basal Cell Carcinoma Patients.

The nevoid basal cell carcinoma syndrome (NBCCS), also called Gorlin syndrome is an autosomal dominant disorder whose incidence is estimated at about 1 per 55,600–256,000 individuals. It is characterized by several developmental abnormalities and an increased predisposition to the development of basal cell carcinomas (BCCs). Cutaneous fibroblasts from Gorlin patients have been shown to exhibit an increased sensitivity to ionizing radiations. Mutations in the tumor suppressor gene PTCH1, which is part of the Sonic Hedgehog (SHH) signaling pathway, are responsible for these clinical manifestations. As several genetic mutations in the DNA repair genes are responsible of photo or radiosensitivity and high predisposition to cancers, we hypothesized that these effects in Gorlin syndrome might be due to a defect in the DNA damage response (DDR) and/or the DNA repair capacities. Therefore, the objective of this work was to investigate the sensitivity of skin fibroblasts from NBCCS patients to different DNA damaging agents and to determine the ability of these agents to modulate the DNA repair capacities. Gorlin fibroblasts showed high radiosensitivity and also less resistance to oxidative stress-inducing agents when compared to control fibroblasts obtained from healthy individuals. Gorlin fibroblasts harboring PTCH1 mutations were more sensitive to the exposure to ionizing radiation and to UVA. However, no difference in cell viability was shown after exposure to UVB or bleomycin. As BER is responsible for the repair of oxidative DNA damage, we decided to assess the BER pathway efficacy in Gorlin fibroblasts. Interestingly, a concomitant decrease of both BER gene expression and BER protein activity was observed in Gorlin fibroblasts when compared to control. Our results suggest that low levels of DNA repair within Gorlin cells may lead to an accumulation of oxidative DNA damage that could participate and partly explain the radiosensitivity and the BCC-prone phenotype in Gorlin syndrome.

High Carbohydrate 19-9 Antigen Serum Levels in Patients with Nonmelanoma Skin Cancer and Primary Occult Cancer.

Background: Non-melanoma skin cancers (NMSC), despite having a favourable prognosis, present an increased risk of occult malignancies. The aim of this study was the evaluation of the usefulness of the mucinous marker carbohydrate 19-9 antigen (CA 19-9) in the diagnosis of occult cancers. (1) Patients and Methods: This is a case control study in which 480 patients with NMSC and 480 matched control subjects with dermatitis were enrolled; 208 patients with NMSC showed upper-normal CA 19-9 values, and 272 showed under-normal CA 19-9 values. (2) Results: The 208 patients positive for CA 19-9 included 87 with basal cell carcinoma (BCC) and 121 with squamous cell carcinoma (SCC). The 272 patients negative for CA 19-9 included 107 with BCC and 165 with SCC. For the SCC patients, CA 19-9 serum levels were significant in 121 of the patients (positive), 66 of which were affected by cancer; CA 19-9 was within the normal range in 165 patients, of which 30 were diagnosed with cancer. In the SCC patients, the CA 19-9 sensitivity was 68%, the specificity was 70%, the positive predictive value (PPV) was 54% (95%) and the negative predictive value (NPV) was 81%. In the BCC patients, the CA 19-9 sensitivity was 70%, the specificity was 66%, the PPV was 48% and the NPV was 83%. In the dermatitis patients (controls), we observed 121 patients that were CA 19-9 positive, with 15 malignancies, and 359 CA 19-9-negative patients, with three malignancies. (3) Conclusions: To confirm the association between CA 19-9 and an elevated risk of malignancies in NMSC, prospective cohort studies should be performed.

Sparsity of dendritic cells and cytotoxic T cells in tumor microenvironment may lead to recurrence in basal cell carcinoma.

Antitumor immune response affects tumor growth. The effect of antitumor immune response on recurrence has been poorly studied in basal cell carcinoma (BCC). To investigate the effects of the peritumoral immune infiltrate on BCC recurrence. A total of 30 BCC patients without recurrence and 29 BCC patients with recurrence were included in this retrospective study. Non-recurrent tumor samples as well as primary and recurrent tumor samples from the recurrent group were stained immunohistochemically with anti-CD4, CD8, CD25, FOXP3, CD68, CD163, and CD1a antibodies. Immune infiltrates were semiquantitatively evaluated. BCC tumor microenvironment was rich in CD4+ cells. CD163 expression was higher than CD68. In primary tumors of the recurrent group, CD8 expression was significantly lower than CD4 expression. CD1a expression was lower in primary tumors of the recurrent group than in nonrecurrent tumors. Our results suggest the existence of an immunosuppressive microenvironment in BCC. Lower CD8+ T-cell numbers and sparsity of dendritic cells in primary tumors of recurrent patients suggest further immunosuppression in the tumor microenvironment and an increase in recurrence risk. This is the first study that evaluates and compares tumor immune microenvironments of primary and recurrent BCC lesions with several markers and investigates the role of antitumor immunity on BCC recurrence.

Retinol and α-Tocopherol Levels in the Serum and Subcutaneous Adipose Tissue of Newly Diagnosed Basal Cell Carcinoma Patients

Nonmelanoma skin cancers are the most frequently occurring skin cancers. Vitamin A is involved in epithelial cell differentiation and may control skin tumor development. Vitamin E is a powerful lipophilic antioxidant that can quench and scavenge reactive oxygen species. However, there is little consistent evidence considering micronutrients and the development of basal cell carcinoma (BCC). Therefore, we aimed to investigate the possible difference between retinol and α-tocopherol in BCC patients and controls in Iranian population. This case-control study was conducted on adults with newly diagnosed BCC referred to Razi Hospital, Tehran, Iran in 2015. Serum and subcutaneous fat tissue retinol and α-tochopherol were measured by HPLC method. Overall, serum retinol level was lower significantly in BCC patients (0.237±0.01 μg/ml) in comparison with control group (0.27±0.02 μg/ml, P-value: 0.038). However serum α-tocopherol level was not significantly different between BCC patients (4.41±0.33 μg/ml) and control subjects (4.06±0.35 μg/ml, P-value=0.18). Sub-cutaneous adipose tissue retinol was lower significantly in BCC patients (38.60±3.30 ng/mg) compared with control group (54.78±3.49 ng/mg, P-value=0.002). Furthermore, results revealed lower subcutaneous adipose tissue α-tocopherol in BCC patients (4.41±0.33 μg/ml) in comparison with control group (4.06±0.35 μg/ml, P-value=0.18). Skin tissue concentration of retinol and α-tocopherol and serum retinol level was lower in BCC patients in comparison with control group but serum α-tocopherol was not different between groups.

A comparative study of long interspersed element-1 protein immunoreactivity in cutaneous malignancies

BackgroundSkin cancer is the most common cancer worldwide and commonly classified into malignant melanoma (MM) and Nonmelanoma skin cancers (NMSCs), which mainly include basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). The extent to which Long Interspersed Element-1 (LINE-1, L1) ORF1p is expressed in cutaneous malignancies remains to be evaluated. This study aimed to assess LINE-1 ORF1p immunoreactivity in various skin cancer subtypes.MethodThe expression level of LINE-1 ORF1p was evaluated in 95 skin cancer specimens comprising 36 (37.9%) BCC, 28 (29.5%) SCC, and 31 (32.6%) melanoma using the tissue microarray (TMA) technique. Then the association between expression of LINE-1 encoded protein and clinicopathological parameters was analyzed.ResultsWe showed that LINE-1 ORF1p expression level was substantially higher in BCC and SCC patients compared with melanoma samples (p < 0.001). BCC cases had a higher LINE-1 histochemical score (H-score) compared with SCC cases (p = 0.004). In SCC samples, a lower level of LINE-1 ORF1p expression was associated with age younger than the mean (p = 0.041). At the same time, no significant correlation was found between LINE-1 ORF1p expression and other clinicopathological parameters (all p > 0.05).ConclusionsAccording to our observation, LINE-1 ORF1p immunoreactivity in various skin tumor subtypes extends previous studies of LINE-1 expression in different cancers. LINE-1ORF1p overexpression in NMSCs compared with MM can be considered with caution as a tumor-specific antigen for NMSCs.

Intradermal Delivery of an Immunomodulator for Basal Cell Carcinoma; Expanding the Mechanistic Insight into Solid Microneedle-Enhanced Delivery of Hydrophobic Molecules.

Basal cell carcinoma (BCC) is the most common cutaneous malignancy in humans. One of the most efficacious drugs used in the management of BCC is the immunomodulator, imiquimod. However, imiquimod has physiochemical properties that limit its permeation to reach deeper, nodular tumor lesions. The use of microneedles may overcome such limitations and promote intradermal drug delivery. The current work evaluates the effectiveness of using an oscillating microneedle device Dermapen either as a pre- or post-treatment with 5% w/w imiquimod cream application to deliver the drug into the dermis. The effectiveness of microneedles to enhance the permeation of imiquimod was evaluated ex vivo using a Franz cell setup. After a 24-h permeation experiment, sequential tape strips and vertical cross-sections of the porcine skin were collected and analyzed using time-of-flight secondary ion mass spectrometry (ToF-SIMS). In addition, respective Franz cell components were analyzed using high-performance liquid chromatography (HPLC). Analysis of porcine skin cross-sections demonstrated limited dermal permeation of 5% w/w imiquimod cream. Similarly, limited dermal permeation was also seen when 5% w/w imiquimod cream was applied to the skin that was pretreated with the Dermapen, this is known as poke-and-patch. In contrast, when the formulation was applied first to the skin prior to Dermapen application, this is known as patch-and-poke, we observed a significant increase in intradermal permeation of imiquimod. Such enhancement occurs immediately upon microneedle application, generating an intradermal depot that persists for up to 24 h. Intradermal colocalization of isostearic acid, an excipient in the cream, with imiquimod within microneedle channels was also demonstrated. However, such enhancement in intradermal delivery of imiquimod was not observed when the patch-and-poke strategy was used with a non-oscillating microneedle applicator, the Dermastamp. The current work highlights that using the patch-and-poke approach with an oscillating microneedle pen may be a viable approach to improve the current treatment in BCC patients who would prefer a less invasive intervention relative to surgery.

Gorlin-Goltz Syndrome: Multiple Basal Cell Carcinoma, Bifid Rib, Palmar and Plantar Pits in a 50-Year-Old Woman

Gorlin-Goltz Syndrome: Multiple Basal Cell Carcinoma, Bifid Rib, Palmar and Plantar Pits in a 50-Year-Old Woman

Coding and noncoding somatic mutations in candidate genes in basal cell carcinoma

Basal cell carcinoma (BCC) represents the most commonly diagnosed human cancer among persons of European ancestry with etiology mainly attributed to sun-exposure. In this study we investigated mutations in coding and flanking regions of PTCH1 and TP53 and noncoding alterations in the TERT and DPH3 promoters in 191 BCC tumors. In addition, we measured CpG methylation within the TERT hypermethylated oncological region (THOR) and transcription levels of the reverse transcriptase subunit. We observed mutations in PTCH1 in 58.6% and TP53 in 31.4% of the tumors. Noncoding mutations in TERT and DPH3 promoters were detected in 59.2% and 38.2% of the tumors, respectively. We observed a statistically significant co-occurrence of mutations at the four investigated loci. While PTCH1 mutations tended to associate with decreased patient age at diagnosis; TP53 mutations were associated with light skin color and increased number of nevi; TERT and DPH3 promoter with history of cutaneous neoplasms in BCC patients. Increased reverse transcriptase subunit expression was observed in tumors with TERT promoter mutations and not with THOR methylation. Our study signifies, in addition to the protein altering mutations in the PTCH1 and TP53 genes, the importance of noncoding mutations in BCC, particularly functional alterations in the TERT promoter.

Photoacoustic imaging for three-dimensional visualization and delineation of basal cell carcinoma in patients

BackgroundPhotoacoustic (PA) imaging is an emerging non-invasive biomedical imaging modality that could potentially be used to determine the borders of basal cell carcinomas (BCC) preoperatively in order to reduce the need for repeated surgery. MethodsTwo- and three-dimensional PA images were obtained by scanning BCCs using 59 wavelengths in the range 680–970 nm. Spectral unmixing was performed to visualize the tumor tissue distribution. Spectral signatures from 38 BCCs and healthy tissue were compared ex vivo. Results and discussionThe PA spectra could be used to differentiate between BCC and healthy tissue ex vivo (p < 0.05). Spectral unmixing provided visualization of the overall architecture of the lesion and its border. ConclusionPA imaging can be used to differentiate between BCC and healthy tissue and can potentially be used to delineate tumors prior to surgical excision.