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Background Multiple studies have reported on dermoscopic structures in basal cell carcinoma (BCC) and its subtypes, with varying results. Objective To systematically review the prevalence of dermoscopic structures in BCC and its subtypes. Methods Databases and reference lists were searched for relevant trials according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Studies were assessed for the relative proportion of BCC dermoscopic features. Random-effects models were used to estimate summary effect sizes. Results Included were 31 studies consisting of 5950 BCCs. The most common dermoscopic features seen in BCC were arborizing vessels (59%), shiny white structures (49%), and large blue-grey ovoid nests (34%). Arborizing vessels, ulceration, and blue-grey ovoid nests and globules were most common in nodular BCC; short-fine telangiectasia, multiple small erosions, and leaf-like, spoke wheel and concentric structures in superficial BCC; porcelain white areas and arborizing vessels in morpheaform BCC; and arborizing vessels and ulceration in infiltrative BCC. Limitations Studies had significant heterogeneity. Studies reporting BCC histopathologic subtypes did not provide clinical data on pigmentation of lesions. Conclusion In addition to arborizing vessels, shiny white structures are a common feature of BCC. A constellation of dermoscopic features may aid in differentiating between BCC histopathologic subtypes.

Trichoblastoma (TB) is an uncommon benign follicular tumour for which clinical data is limited since most reports originate from pathology studies.To describe the clinical aspects of TB.This is an ancillary study of a prospective multicentre cohort of 2710 clinically suspected basal cell carcinoma (BCC), including 935 nodular BCCs. Sixty-two cases were TB: they were analysed and compared to 935 nodular BCCs.TB mostly occurred in females (61% vs. 43% for BCC, P0.01) of mean age 63 years. They were located on the head and neck, mainly on the nose and forehead, in 87% of cases. The mean size was 8.1mm, 77% were10mm (55% of BCCs, P0.001), 8% were ulcerated (vs. 21% of BCCs, P0.02), and 47% persisted for more than 1 year (34% of BCCs, P0.05). Most cases had a clinical presentation similar to nodular BCC, except for 5 small, flat, white papules and 1 anfractuous plaque.Cases originated from a series of tumours clinically suspected as BCCs.Some 2.6% of tumours clinically diagnosed as BCC are in fact TB. TB occurs on the head, are more frequent in women, and are smaller and of longer duration than BCC. In most cases, clinical diagnosis on clinical grounds is difficult.

Introduction. Basal cell carcinoma (BCC) is one of the most prevalent skin neoplasms with increasing incidence. The grade of BCC malignancy is highly variable and depends on the invasiveness and recur-rence potential. The study was aimed at identification of immunohistochemical (IHC) determinants of BCC recurrence. Materials and methods. The comparative study encompassed 10 cases of primary BCC and 10 cases of recurrent BCC. The panel of immunohistochemical targets included p53, CK8/18, Bcl-2, CK19, Collagen type IV, Desmin, CD8, Ki-67, Vimentin, VEGFR, EGFR and AR. Results. Diffuse expression of vimentin (characteristic of both primary and recurrent BCCs and clearly indicating the border between the tumor stroma and the surrounding dermis) in the recurrent tumors was twice as strong as in the primary tumors. Immunohistochemistry for collagen type IV revealed different nature of the basement membrane alterations in the primary and recurrent tumors. A two-fold increase in the intensity of angiogenesis observed in the recurrent tumors was accompanied by a more than two-fold significant increase in the androgen receptor protein expression. Conclusion.Increasing grade of BCC malignancy is associated with the immunohistochemically revealed reinforcement of the stromal and vascular components of the tumor, as well as progressive destruction of the basement membrane along with the increased expression of androgen receptor protein by tumor cells. Keywords: basal cell carcinoma, recurrence, immunohistochemistry

Purpose: Nodular basal cell carcinoma (nBCC) is mostly treated with surgical excision. Interest in minimally invasive treatment of these low-risk tumors is increasing. We assessed the effectiveness of nBCC treatment with curettage and imiquimod cream compared with surgical excision.Methods: Patients with nBCC included in this randomized, controlled noninferiority trial were randomly assigned to either a curettage and imiquimod cream group or a surgical excision group. The primary endpoint was the proportion of patients free from treatment failure 1 year after the end of treatment. A prespecified noninferiority margin of 8% was used. A modified intention-to-treat and a per-protocol analysis was performed (ClinicalTrials.gov identifier NCT02242929).Results: One hundred forty-five patients were randomized: 73 to the curettage and imiquimod cream group and 72 to the surgical excision group. The proportion of patients free of recurrence after 12 months was 86.3% (63/73) for the curettage and imiquimod group and 100% (72/72) for the surgical excision group. The difference in efficacy was -13.7% (95% confidence interval -21.6% to -5.8%; 1-sided P =.0004) favoring surgical excision.Conclusion: Noninferiority of curettage and imiquimod cream cannot be concluded. Given the still high efficacy of curettage and imiquimod cream and the indolent growth pattern of nBCC, curettage and imiquimod could still be a valuable treatment option with the possibility to prevent overuse of excisions. However, it cannot replace surgical excision.

Purpose To compare the expression of cytotoxic T-lymphocyte-associated protein-4 (CTLA-4) and lymphocyte activation gene-3 (LAG-3) in nodular and orbitally-invasive forms of basal cell carcinoma (BCC). Methods Immunohistochemical staining for CTLA-4 and LAG-3 was performed on the pathology specimens of BCC from orbital exenteration and nodular forms. The numbers of positively-staining cells/×40 field were counted across 5 consecutive fields of each specimen and statistical analysis was performed to calculate the difference in expression between the 2 groups. Results Nine cases of orbitally-invasive BCC and 6 cases of nodular BCC were studied. The mean numbers of CTLA-4-positively staining cells were 11.51 cells/×40 field (median = 6.60 cells/×40 field, range = 0.4-31.8 cells/×40 field) in invasive BCC and 0.90 cells/×40 field (median = 0.60 cells/×40 field, range = 0.0-2.8 cells/×40 field) in nodular specimens. The difference between the 2 groups was statistically significant (p = 0.0030). The mean number of LAG-3-positively staining cells was 0.58 cells/×40 field (median = 0.0, range = 0.0-2.8 cells/×40 field) in invasive BCC and 3.13 cells/×40 field (median = 0.0, range = 0.0-18.18 cells/×40 field). There was no significant difference in LAG-3 positivity between tumor groups (p = 0.5564). Conclusions CTLA-4 expression was enriched in orbitally invasive BCC compared with nodular forms of BCC, whereas LAG-3 expression did not differ between these entities. CTLA-4 mediated immune suppression may facilitate the development of orbitally invasive BCC. Treatment strategies that use existing medications to target CTLA-4 may decrease the requirement for orbital exenteration and provide enhanced survival outcomes.

Photodynamic therapy (PDT) has been reported as an excellent option for the treatment of small nodular basal cell carcinomas (nBCC). The standard protocol consists of two sessions, one week apart. Sometimes, returning to the hospital after one week can be impractical for elderly patients, due to comorbidities and mobility issues. Therefore, a new technique performed in one day could be superior for those patients.Evaluate the effectiveness of a PDT Single-visit protocol comparing to the standard protocol, as well as pain and long-term recurrence-free follow-up for nBCC.A total of 120 nBCC were treated through a Standard PDT protocol(two sessions, one week apart), and 120 nBCC were treated through a Single-visit PDT(two sessions in one day). A 30-day-after biopsy was performed in order to evaluate the results after the treatment. The lesions that had successful treatment were clinically and dermoscopically evaluated every 6 months up to 60 months. The pain score was compared between the groups(assessed every 3 min during PDT).A complete response at 30-days-after PDT biopsy was observed in 85% of Standard PDT and in 93.3% of Single-visit PDT. Regarding the pain during the illumination, less pain was observed during the second session of the Single-visit PDT. The recurrence-free follow up showed, after 60 months, an 69.0% cumulative probability of recurrence-free for Standard PDT and 80.6% for Single-visit PDT.The suggested Single-visit PDT protocol resulted in better outcomes at 30-day-after PDT biopsy and in lower recurrence rates than the Standard PDT protocol. A more comfortable and more efficient treatment was offered for the patients, with lower pain.

6 pags., 3 figs., 3 tabs., Background: The increase in the number of basal cell carcinoma (BCC) lesions has prompted use of minimally invasive therapies, including Photodynamic therapy (PDT). . The objective of the present work was to analyze the efficacy of methyl aminolevulinate-mediated photodynamic therapy (MAL-PDT) in patients suffering from superficial or nodular BCCs. Methods: A total of 220 BCC lesions (76 superficial and 144 nodular), clinically diagnosed and confirmed by histopathology analysis, were treated in 174 patients (mean age 72.5). Debulking using curettage was performed before two or three MAL-PDT sessions (λ = 630 nm; 90 J/cm; 23 min) at 4-week intervals. Analyses of clinical clearance and cosmetic outcome were carried out by direct examination, dermoscopy, photographs, as well as by fluorescence diagnosis using a Wood's lamp. Evaluations were carried out at the different PDT sessions and follow-ups over a 3-year period. Results: MAL-PDT was safe and highly tolerated. After an average of 2.6 MAL-PDT sessions, the overall clearance rate at 3-year follow-up was 96.1 % (95 % confidence interval [CI] 100 %–92 %) for superficial BCCs and 95.2 % (95 % [CI] 99 %-92 %) for nodular BCCs after an average of 2.7 sessions. Minimal side effects such as crushing, erythema and edema were reported. All BCC lesions showed excellent or good cosmetic results. Conclusion: The protocol followed in the present study has shown that MAL-PDT is a safe and effective treatment for superficial and nodular types of BCC., This research was supported by a grant from the Eugenio Rodríguez Pascual Foundation (Madrid, Spain) and by the Spanish Research Project MINECO (Ref.: MAT 2017-83856-C3).

Background Surgical excision is considered standard treatment for nodular basal cell carcinoma (nBCC). However, patients who reject or are unsuited for surgery may benefit from imiquimod (IMQ) 5% cream as an alternative treatment. Objectives The objective of this study was to conduct a systematic review on the efficacy and safety of IMQ for the treatment of nBCC. Materials and Methods The terms basal cell carcinoma AND imiquimod OR Aldara were searched on Ovid-MEDLINE, EMBASE, and Cochrane Library databases. Articles were included if they reported the efficacy or side effects of IMQ for nBCC. Primary outcomes included clearance (clinical and histological), recurrence rates, and adverse events. Number of lesions/subjects, treatment regimens, length of treatment, and time to recurrence were secondary outcomes. Results Thirty-nine publications, totaling 738 lesions, revealed a 77.4% (335/433 lesions) clinical and 72.9% (390/535 lesions) histological clearance rate. Regimens ranged from once daily 2 days a week to twice daily 7 days a week. Average treatment duration was 8.81 (±3.49) weeks. There was a 1.80% recurrence rate after an average follow-up period of 13.03 (±15.09) months. Common adverse effects included erythema (77.2%), crusting (50.5%), pruritus (34.1%), tenderness/irritation (27.3%), ulceration (25.4%), burning (22.1%), and erosion (21.7%). Unforeseen side effects included conjunctivitis, keratitis, depigmentation, comedone formation, and ruptured epidermoid cysts. Conclusion Imiquimod showed clinical and histological clearance rates of over 70% for nBCC, with a recurrence rate of 1.80%. Although clearance rates are lower than surgery, IMQ can be considered as a treatment option for nBCC in those who decline or are unfit for surgical intervention.

The electron microscopic study represent the changes in the skin layers in the malignant tumor, the nodular basal cell epithelioma. Comparisons were made between normal cells found in the normal skin at the periphery of the tumor, the cells located near the tumor and the tumors located in the depth of the carcinoma. The microscopic analysis of the tumor formation revealed the characteristics of the pigmented nodular basal cell epitheliu. To the exterior of the carcinoma were evidenced numerous globular formations limiting the peripheral extension of the tumor, which explains its evolution in years.

Purpose: To describe a posterior lamella-sparing technique to resect nodular basal cell carcinoma involving the inferior part of the tarsal skin of the lower eyelid. Surgical Technique: Excision of nodular basal cell carcinoma of the tarsal skin using a grey-line-splitting technique with preservation of the posterior lamella. Specimen was sent for frozen section control. Additional excision was performed in caseof irradicality. The defect was closed with a free skin graft from the ipsi- or contralateral upper eyelid. Results: We show a case series of three patients with lower eyelid basal cell carcinoma and investigated radicality on histology, aesthetic outcome and clinical recurrence during a follow-up of 18 months. Pre, intra, and postoperative photographs were obtained. In all cases radicality was reached. In all patients, the skin graft was viable, with no recurrence after 18 months. Excellent aesthetic results were obtained. Conclusion: Anterior lamellar resection of nodular basal cell carcinomas involving the tarsal lower eyelid skin using a grey line lid-splitting technique is a simple and one-step technique with good clinical outcome. It may avoid the morbidity associated with full thickness eyelid resection and might be useful for other, nonmalignant eyelid lesions.

Introduction Basal cell carcinoma (BCC) is the most commonly occurring cancer worldwide, and the overall incidence is still rising. Unfortunately, the cancer registry in Poland does not record BCC individually. Thus, the incidence of BCC in a defined population is unknown. Aim Analysis of incidence rates of primary BCC in central Poland during 16 years considering sex, site distribution and age to determine trends. Material and methods We retrospectively included all cases of BCC which were diagnosed and treated in the Department of Dermatology and Venereology, Medical University of Lodz, during the 16-year period from 1999 to 2015. Results We recorded 945 BCCs occurring in 890 patients (504 females - 57%, 386 males - 43%). Patient's age was between 21 and 94. A distinct increase in BCC was observed after 1999, while after 2010 during the next 2-year period a slight decrease was noted. A statistically significant correlation was observed between histopathological types of BCC and the location of the lesions. The superficial type predominates on photoprotected areas, especially on the trunk, while the nodular type occurs mainly in facial areas. No statistically significant correlation was observed between histopathological types of BCC and sex. We found a significant increase in incidence for superficial BCC among middle-age patients, while the nodular type was observed more frequently among elderly subjects. Conclusions Basal cell carcinoma is quite common in Poland and predominantly develops in the facial area. In middle-age patients the most common is superficial BCC, while in elderly people the nodular type is most common. Based on our results we assume that there is a strong need to educate general physicians to enable them to diagnose BCC in the early stages.

Nodular amelanotic melanoma has been always a great challenge in dermatology. Because of lack of melanin pigment, tumors are diagnosed usually in advanced stage. Amelanotic melanoma can mimic basal cell carcinoma. Knowledge of typical dermoscopic structures helps to establish diagnosis and to plan surgery with appropriate safety margins. In amelanotic melanoma we can see typical vessels, white streaks or milky red globules on pink-reddish background. Vessels are typically thin and polymorphous in thick amelanotic melanoma. We had a case when vessels were polymorphous but thick. It can be confusing with nodular basal cell carcinoma where vessels are typically thick and arborizing. Nodular basal cell carcinoma is the most common form of basal cell carcinoma. Dermoscopy is a valuable tool for the diagnosis of basal cell carcinoma. Typical dermoscopic structures are arborizing vessels, possible sites of ulceration and/or pigmentation. We describe a case report of patient with typical dermoscopic structures seen in nodular basal cell carcinoma.

With over 4.3 million new cases in the U.S. every year, basal cell carcinoma (BCC), is the most common form of skin cancer. Pathologists must examine pathology images to diagnose BCC, potentially resulting in delay, error, and inconsistency. To address the need for standardized, expedited diagnosis, we created an automated diagnostic machine to identify BCC given pathology images. In MATLAB, we adapted a deep neural network image segmentation model, UNet, to train on BCC images and their corresponding masks, which can learn to highlight these nodules in pathology images by outputting a computer-generated mask. We trained the U-Net on one image from the dataset and compared the computer-generated mask output from testing on three types of images: an image from a different region of the same image taken with the same microscope, an image from a different tissue sample with a different microscope, and an image taken with a confocal microscope. We observed good, medium and poor results, respectively, illustrating that performance depends on the similarity between test and training data. In subsequent tests using data augmentation, we achieved sensitivity of 0.82±0.07 and specificity of 0.87±0.16 on N = 6 sample sections from 3 different BCCs imaged with the same microscope system. These data show that the U-Net performed well with a relatively few number of training images. Examining the errors raised interesting questions regarding what the errors mean and how they possibly arose. By creating a surgeon interface for rapid pathological assessment and machine learning diagnostics for pathological features, the BCC diagnosis process will be expedited and standardized.

A 58-year-old patient presented for a newly developing small non-pigmented lesion, located on the left cheek. The patient had a previous history of melanoma, Breslow thickness 1.2 mm, located on the back, and excision of nodular basal cell carcinoma on the scalp. Dermoscopic examination revealed a discrete red pseudo-network, the so-called strawberry pattern, intersected by whitish hair follicles and covered by fine scales giving clues for actinic keratoses.

An 81-year-old patient was presented for three nodular apigmented lesions located on the face.

A 66-year-old patient presented for two nodular apigmented lesions located on the right lateral part of the nose and the right nasolabial line. The dermoscopic examination of the apigmented nodular lesion on the right side of the nose displayed arborizing vessels and multifocal blue-gray globules and dots. Dermoscopic evaluation of the second nodular apigmented lesion showed numerous arborizing vessels throughout the lesion. Dermoscopic features of both lesions corresponding to the diagnosis of two nodular basal cell carcinomas, which were surgically excised and histopathologically verified.

A 72-year old lady was referred due to excessive growth of nodular pigmented lesion located on the right lateral side of the nose. Clinically, a large bluish pigmented lesion, 2 × 1 cm in diameter, located on the right side of the nose was ugly duckling positive suggesting the possible diagnosis of nodular pigmented melanoma. Fortunately, dermoscopic examination revealed thick arborizing vessels associated with numerous erosions covered by hemorrhagic crusts, indicating the diagnosis of pigmented nodular basal cell carcinoma, afterward confirmed by pathohistology.

A 46-year-old patient presented for nodular highly pigmented lesion suspected for diagnosis of melanoma, located on the back. Although the clinical appearance was highly suspicious of melanoma, dermoscopic examination revealed different dermoscopic features, namely thick arborizing vessels, numerous blue-gray globules, and dots, indicating the diagnosis of pigmented nodular basal cell carcinoma, which was excised and confirmed by pathohistology.

Clinical Image Basal cell carcinoma is a frequent disease that can be caused by chronic exposition to UV radiation. Dermoscopy is a very helpful device that can lead to diagnosis. Mr. M.G is 63-years-old man that presents a rough pigmented plaque on the back since more than 5 years. Recently it becomes slightly itchy. Clinically: A 3 cm pigmented oval plaque on the back. On dermoscopy screening maple leaf-like area, spoke wheel areas, blue-gray nests, gray-blue globules, pink white area, digitiform structures seen. We removed the lesion with 5 mm of margin. The histopathology concluded to a nodular basal cell carcinoma with healthy margin. The patient was advised to apply photo protection measures and a follow-up once a year. Keywords: Pigmented basal cell carcinoma; Diagnosis; Dermoscopy

Aim: To describe the ultrasonographic findings of surface and nodular basal cell skin cancer (BCC) using high frequency ultrasonography.Materials and methods: We examined 60 primary BCCs in different locations with the High Frequency Ultrasound (HFU) system DUB Skin Scanner using 75 MHz and 30 MHz probes. Epidermis, dermis, and depth of tumors spread in the region of interest (ROI) were measured. Visually unchanged, contralateral skin areas were examined as the control. Results: The surface BCC most often had elongated contours, clear margins and hypoechoic structure, while the nodular BCC had round or oval outlines and diffusely hypo-heterogeneous structure with clear margins. Sclerodermiform BCCs were visualized as hypoechoic areas of irregular shape penetrating in the dermis, with wavy fuzzy margins. The average thickness of the surface BCC in the US examination was 556.28±136.95 μ, the nodular BCC thickness was 2439.71±865.92 μ and the sclerodermiform thickness was 1500±325.33 μ. A statistically significant increase in the average thickness of tumors of the nodularand scleroderma forms was observed in comparison with the surface clinical variant (p0.05), respectively. In the surface BCC, they were mainly located along the periphery of the hypoechoic zones. In nodular BCC, the inclusions had a peripheral and combined (center and peripheral) distribution.Conclusions: Ultrasound allows differentiating BCC as diffuse-heterogeneous, hypoechoic, formations in the dermis with distinct contours. Depending on the clinical picture, they differ in form, depth of bedding, as well as in the quantitative ratio and distribution of the point hyperechoic structures in them.

Nodular basal cell carcinoma is a deep skin lesion and one of the most common cancers. Conventional photodynamic therapy is limited to treatment of superficial skin lesions. The parenteral administration of near-IR preformed photosensitizers suffers from poor selectivity and may result in prolonged skin photosensitivity. Microneedles (MNs) can provide localized drug delivery to skin lesions. Intradermal delivery of the preformed near-IR photosensitizer; 5,10,15,20-tetrakis(2,6-difluoro-3-N-methylsulfamoylphenyl bacteriochlorin (Redaporfin™) using dissolving MN was successful in vitro and in vivo. MN demonstrated complete dissolution 30 min after skin application and showed sufficient mechanical strength to penetrate the skin to a depth of 450 μm. In vitro deposition studies illustrated that the drug was delivered and detected down to 5 mm in skin. In vivo biodistribution studies in athymic nude mice Crl:NU(NCr)-Foxn1nu showed both fast initial release and localized drug delivery. The MN-treated mice showed a progressive decrease in the fluorescence intensity at the application site over the 7-day experiment period, with the highest and lowest fluorescence intensities measured being 9.2 × 1010 ± 2.5 × 1010 and 3.8 × 109 ± 1.6 × 109 p/s, respectively. By day 7, there was some migration of fluorescence away from the site of initial MN application. However, the majority of the body surfaces showed fluorescence levels that were comparable to those seen in the negative control group. This work suggests utility for polymeric MN arrays in minimally invasive intradermal delivery to enhance photodynamic therapy of deep skin lesions.

Basal cell carcinoma is a slow-growing malignant skin tumor and its often found in elderly patients on sun exposed areas that confirming chronic UV radiation. Demographic, clinical and histological characteristics of the patients have been analyzed of nodular type of basal cell carcinoma in order to determine correlation between localization, duration and tumor size. Database was searched for medical records of patients with nodular BCC evaluated in Health Center of Kosovska Mitrovica and Clinical Center of Nis during the period of 2006 through 2008 year with the focus on demographic characteristics, localization, duration, size and clinical and histological characteristics of the tumor. Results: 36 patients with nodular BCC, 14 female and 22 male, in average old between 72.5±7.26 years of age. Two thirds of patients is older than 60 years and only 3 (8.33%) male patients are younger than 60 years of age. 72.11% of patients living in rural areas unlike 27.77% that lives in urban areas. Nodular type is occurring more often in males on skin of frontal and zygomatical region and in females on zygomatic and nose region. We found that the size of the tumor is in close correlation with length of duration of illness. Nodal BCC is more common in elderly male patients. Nodular type is occurring more often in males on skin of frontal and zygomatical region with a different distribution among women.

Trichoblastoma is a benign cutaneous neoplasm that is clinically and histologically similar to basal cell carcinoma. We report the dermoscopic features seen in 2 cases of facial trichoblastoma. One case presented with very short, delicate, scarcely branching telangiectases against a pearly white background. In the second case, the veins were also short and scarcely branching, but they were arranged in a crown pattern, with white striae and milia-like cysts. Although dermoscopic evidence of fine, scarcely branching telangiectases is not specific to a diagnosis of trichoblastoma, these features may be useful for differentiating this neoplasm from nodular basal cell carcinoma.

We report a case of a 46-year-old female who presented with a persistent lesion on the inferior right breast. The lesion was located within the scar from a breast augmentation procedure 12 years ago. The lesion had been treated as several conditions with no improvement. Biopsy revealed a superficial and nodular basal cell carcinoma, and the lesion was successfully removed with Mohs micrographic surgery. Basal cell carcinoma arising in a surgical scar is exceedingly rare with only 13 reported cases to date. This is the first reported case of basal cell carcinoma arising in a breast augmentation scar. We emphasize the importance of biopsy for suspicious lesions or those refractory to treatment, particularly those lesions that form within a scar. Level of Evidence V This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Surgical excision is the first-choice treatment for basal cell carcinoma (BCC). Other treatments with topical agents such as 5-fluorouracil or imiquimod have also been suggested for use in superficial BCC (sBCC). Ingenol mebutate (IM) is a novel agent employed in the treatment of superficial actinic keratoses. The drug has been also successfully used in the treatment of sBCC. A case of large nodular BCC (nBCC) of the face in a 100-year-old inoperable woman is described. IM 0.015% gel was applied once daily for three consecutive days. This dose regimen was repeated for seven rounds within 11 months, with complete cure of the tumor. Mild local skin reactions, which were tolerated well, were observed. Selected cases of nBCC could be treated with IM gel, but the optimal concentration of the drug and the standard dose regimen of treatment are yet to be determined.

Purpose The programmed death-1 pathway negatively regulates the immune system. Previous reports have indicated worse tumor-related outcomes with increased expression of the ligand for this pathway. This study was undertaken to assess the role of the PD pathway in cutaneous malignancies that invade the orbit. Methods Immunohistochemical staining for the programmed death-1 receptor and ligand was performed on exenteration specimens of invasive cutaneous orbital malignancies (n = 12) and nodular basal cell carcinoma (n = 10). The numbers of positively-staining cells/40× field were counted across 5 consecutive fields, and statistical analyses were performed to compare the differences between the 2 groups. Results Programmed death-1 receptor positivity was seen in means of 30.9 cells/40× field and 62.4 cells/40× field for nodular basal cell carcinomas and invasive malignancies, respectively (p = 0.0046). A mean of 4.54 cells/40× field stained positively for the programmed death-1 ligand in nodular basal cell carcinoma, whereas a mean of 46.4 cells/40× field stained positively for programmed cell death ligand-1 in orbital invasive cutaneous carcinomas (p = 0.0015). Both of these differences were statistically significant. Conclusions Both the programmed death-1 receptor and its ligand are enriched in invasive cutaneous malignancies. This finding indicates that negative regulation of the immune system likely prohibits tumor surveillance, and facilitates increasing aggressiveness and invasion of cutaneous malignancies.

Basal cell carcinoma preferentially occurs in the face where the surgical excision with adequate margin is curative. Sometimes basal cell carcinoma is also reported rarely in other sites especially associated with basal cell carcinoma syndrome. The histological variants are Nodular basal cell carcinoma, Keratotic basal cell carcinoma, Adenoid basal cell carcinoma, Basal cell carcinoma with sebaceous differentiation. Of these variants, Basal cell carcinoma with eccrine differentiation is practically very rare.

BACKGROUND: The management of basal cell carcinoma (BCC) depends, among other factors, on its histopathologic subtype. Although dermoscopic criteria of BCC have been investigated, the possible role of dermoscopy in predicting the tumor subtype remains unclear. OBJECTIVES: We sought to assess the diagnostic accuracy of dermoscopic criteria for differentiating superficial BCC (sBCC) from other BCC subtypes. METHODS: Dermoscopic images of histopathologically confirmed BCCs were retrospectively evaluated for the presence of predefined criteria. Univariate and adjusted odds ratios were calculated. Discriminant functions were used to plot receiver operating characteristic curves. RESULTS: In all, 77 sBCCs and 258 non-sBCCs were included. Maple leaf-like areas, short fine superficial telangiectasia, multiple small erosions, and shiny white-red structureless areas were potent predictors of sBCC, each making its diagnosis over 5-fold more likely. Conversely, the presence of arborizing vessels, blue-gray ovoid nests, and ulceration gave 11-fold, 15-fold, and 3-fold increased possibility for the diagnosis of non-sBCCs, respectively. Based on the results of the multivariate analysis, we propose a diagnostic algorithm that can predict the diagnosis of sBCC with a sensitivity of 81.9% and a specificity of 81.8%. LIMITATIONS: The retrospective design and the inclusion of only Caucasian patients are limitations. CONCLUSION: Dermoscopy is reliable in differentiating sBCC from other BCC subtypes.

The major limitation of photodynamic therapy with 5-aminolevulinic acid (ALA-PDT) is proper photosensitizer penetration. The nodular form of BCC (nBCC) is perceived as a contraindication to ALA-PDT because the tumor layer is thicker than 2 mm. We have improved on the results of previous studies that used an ablative laser to limit tumor thickness. A fractional laser produces skin microtubules that can improve the penetration of ALA into tumors.To evaluate the use of a fractional laser as pretreatment before ALA-PDT for nBCC treatment in an 18-month single-blind clinical trial.Fifty-six verified nBCCs were ablated using a diode laser under ultrasound control. Half of the tumors were treated 3 weeks later using a fractional carbon dioxide laser, and the other half were treated using curettage (control). We then immediately treated with ALA-PDT. Fluorescence and photography were evaluated and compared each month, and a final histopathologic examination was performed.Fifty-two of 56 nBCCs in the fractional laser treatment group responded to ALA-PDT, compared with only 45 of 56 in the control group. Fluorescence was higher in 53 cases in the treatment group; 3 cases demonstrated the same fluorescence level in both groups. Healing took longer in the treatment group, and there were more side effects.Fractional laser pretreatment increases the fluorescence and clinical effectiveness of ALA-PDT for the treatment of nBCC.

Background: Although effective in superficial basal cell carcinoma (BCC), the treatment effect of photodynamic therapy (PDT) in nodular BCC (nBCC) is still questionable. The relation between tumor thickness and PDT failure is unclear. Objective: We sought to compare long-term effectiveness of fractionated 20% 5-aminolevulinic acid (ALA)-PDT with prior partial debulking versus surgical excision in nBCC. The effect of tumor thickness on ALA-PDT failure was analyzed. Methods: 173 primary, histologically proven nBCCs in 151 patients were randomized to fractionated ALA-PDT (n = 85) or surgical excision (n = 88). Two PDT illuminations were performed with a 1-hour interval. Follow-up was at least 5 years posttreatment. Clinical recurrences were confirmed histologically. Results: A total of 171 nBCCs were treated and had a median follow-up of 67 months (range 0-106). At 60 months, 23 tumors had recurred in the ALA-PDT group and 2 tumors in the surgical excision group. Cumulative recurrence probabilities 5 years posttreatment were 30.7% (95% confidence interval [CI] 21.5%-42.6%) for ALA-PDT and 2.3% (95% CI 0.6%-8.8%) for surgical excision (P

BACKGROUND The aim of this study is to measure and compare the dynamic thiol/disulphide homeostasis of patients with basal cell carcinoma and healthy subjects with a newly developed and original method. OBJECTIVE Thirty four patients attending our outpatient clinic and clinically and histopathologically diagnosed as nodular basal cell carcinoma, and age and gender matched 30 healthy individuals have been involved in the study. Thiol/disulphide homeostasis tests have been measured with a novel automatic spectrophotometric method developed and the results have been compared statistically. RESULTS Serum native thiol and disulphide levels in the patient and control group show a considerable variance statistically (p = 0.028, 0.039, respectively). Total thiol levels do not reveal a considerable variation (p = 0.094). Disulphide/native thiol ratios and native thiol/total thiol ratios also show a considerable variance statistically (p = 0.012, 0.013, 0.010, respectively). CONCLUSIONS Thiol disulphide homeostasis in patients with basal cell carcinoma alters in the way that disulphide gets lower and thiols get higher. Thiol/disulphide level is likely to have a role in basal cell carcinoma pathogenesis.

Background The macrophages associated with solid tumors are related to the progression or regression of tumors, depending on the differentiation in M1 or M2. M2 subtype promotes angiogenesis, remodeling, and tissue repair (tumor proliferation). In contrast, M1 produces toxic mediators and presents antigens, destroying microorganisms and tumor cells. The microenvironment of most aggressive forms of basal cell carcinoma (BCC) shows an increase in macrophages due to M2 phenotype compared to noninvasive forms. The treatment of nodular BCC by Mohs micrographic surgery (MMS) provides high cure rates, but relapses can occur. Aims To compare the total population of macrophages and their subpopulations M1 and M2 in cases of recurrent and nonrecurrent nodular BCC after excision by MMS. Materials & Methods Histological sections obtained from paraffin blocks of nine cases of recurrent nodular BCC after MMS and 18 cases of nonrecurrent nodular BCC operated by MMS were immunostained for iNOS, CD204, CD163, and CD68. The expression of these markers was analyzed by image analysis. Results No significant differences were found between the groups in relation to the average percentage of M1 cells, M2 cells, and total cells. Discussion and Conclusion A relationship was not seen between tumor-associated macrophages (TAM) and tumor recurrence.

BACKGROUND/AIM Nodular and superficial are the most common subtypes of basal cell carcinoma (BCC). Signaling pathways such as Hedgehog (HH) and Wingless (WNT) signaling are associated with BCC phenotypic variation. The aim of the study was to evaluate of the expression profiles of 84 genes related to the WNT and HH signaling pathways in patients with nodular and superficial BCC. MATERIALS AND METHODS A total of 58 BCCs and 13 samples of normal skin were evaluated by quantitative real-time polymerase chain reaction (qPCR) to detect the gene-expression profile. RESULTS qPCR array showed segregation in BCC subtypes compared to healthy skin. PRKX, WNT3 and WNT16 were significantly (p

SummaryBackground Surgical excision (SE) is a first-line treatment for basal cell carcinoma (BCC). Topical photodynamic therapy (PDT) has also been used and has cosmetic advantages over surgery. The latest European guidelines for topical PDT recommended that it be used to treat nodular basal cell carcinoma (nBCC) but a consensus has not been reached. Our study was to evaluate the efficacy of PDT versus SE for the treatment for nBCC by a meta-analysis. Materials and methods We searched PubMed, EMBASE, the Cochrane Library, CKNI, VIP, and relevant references up to October 2014 including randomized controlled trials (RCTs) that compared PDT with SE for treatment of nBCC patients. A meta-analysis was conducted by using the Cochrane Collaboration's revman 5.0 software. Results We selected five studies that covered 596 of pathologically confirmed nBCC. We compared complete response rate (RR) of PDT and SE at 3 months and 1, 2, 3, 4, and 5 years. We found that the RR was 0.95 (0.90, 1.00), 0.89 (0.80, 0.99), 0.83 (0.69, 1.00), 0.73 (0.63, 0.85), 0.84 (0.65, 1.08), and 0.79 (0.61, 1.03), respectively, for those time points, the cumulative probability of recurrence for the time points post-treatment, with an estimate at RR 5.28 (1.85, 15.12), 6.48 (2.46, 17.09), 9.67 (3.02, 30.99), 7.73 (2.81, 21.28), and 8.25 (3.01–22.62), respectively. Conclusion We observed no significant differences between PDT and SE for the complete RR, but there was an increased cumulative probability of recurrence. More large-scale RCTs are required to verify our findings.

Cryosurgery is a surgical technique that employs freezing to destroy target tumor tissue. While the main objective during a cryosurgical procedure is to ensure tissue destruction within the cryolesion, the greatest challenge is how to spare the surrounding healthy tissues from cryoablation. In this work, a historical review of the field of cryosurgery is presented followed by a theoretical study where a mathematical model is developed for cryosurgery on a basal cell carcinoma (BCC) using liquid nitrogen ( LN2) spray. The model takes into consideration the anatomic structure of skin tissue and the irregular geometry of BCC. In particular, a methodology for quantitatively determining the extent of the intracellular ice formation ( IIF) zone based on the tissue temperature and cooling rate (CR) is proposed, which can directly relate to the necrosis of the cancer cells after cryosurgery. The model is then used to analyze formation of the IIF zone during cryosurgery on a BCC and quantification is provided for the volume of the final IIF zone. A parametric study is also carried out to investigate the effect of various protocol parameters on the final IIF zone. The results should be useful for dermatologists for pre-treatment surgery planning.

Background Photodynamic therapy (PDT) is an attractive modality for the treatment of BCC, based on its generally favorable efficacy, adverse effect profile and its excellent cosmetic outcome. Objectives The purpose of the study is to compare the efficacy and cosmetic outcome of photodynamic therapy with topical 5-aminolaevulinic acid (ALA-PDT) vs. simple excision surgery for superficial and nodular basal cell carcinoma (BCC). Methods A total of 72 patients, 32 with 48 lesions, were treated with ALA- PDT, and 40 with 46 lesions treated by excision were included in this prospective, comparative, controlled, clinical study. The patients have been followed for 16–37 months (mean 25 months). The PDT was performed in combination with 5-aminolaevulinic acid twice, one month apart. Surgical excision was performed under local anesthesia with a 3-mm margin, followed by histological examination. The cosmetic outcome was evaluated by the physician according to a 4-point scale. Results Overall 94 BCC were treated. Complete healing rates did not differ significantly between groups, P = 0.64 (46/48 [95.83%] lesions treated with PDT vs. 44/46 [95.65%] lesions with surgery). In the first 12 months of follow-up, 4 lesions had recurred, 2 of which were in the PDT group while 2 lesions after surgery. The mean follow-up was 25 months. The recurrence rate in the ALA-PDT group was 4.16% vs. 4.34% in the surgery group, p = 0.64. The cosmetic outcome was superior for ALA-PDT at all time points. At 12 months, 100% lesions treated with ALA-PDT had an excellent or good cosmetic outcome, according to the investigator, compared with 88.86% with surgery, P = 0.01. Conclusion ALA-PDT offers a similarly high efficacy, and a better cosmetic outcome than simple excision surgery in the treatment of BCC.

Summary Background Imiquimod 5% cream can reduce or clear superficial and small nodular basal cell carcinoma (BCC). It could be used as a pretreatment of Mohs micrographic surgery (MMS) to decrease defect size. Objectives To study if a pretreatment with imiquimod 5% cream decreases defect size after MMS. In addition, to study the effect on the number of Mohs stages and reconstruction time. Methods Seventy patients aged >18 years with a primary nodular BCC in the face were included. The imiquimod group used imiquimod 5% cream for 4 weeks, before MMS. The control group was treated with MMS only. Tumour and defect sizes were measured. We noted the number of Mohs stages, reconstruction time and side-effects. Results The median percentage increase in area from tumour size at baseline to the post-MMS defect for the imiquimod group was significantly less compared with the control group, 50% vs. 147% (P

We describe the use of modified Tripier flap for reconstruction of a surgical defect in the lower eyelid region, after excision of nodular basal cell carcinoma.

Nodular basal cell carcinoma, especially when pigmented, can be in differential diagnosis with nodular melanomas, clinically and dermoscopically. Reflectance confocal microscopy is a relatively new imaging technique that permits to evaluate in vivo skin tumors with a nearly histological resolution. Here, we present four cases of challenging nodular lesions where confocal microscopy was able to clarify the diagnosis.

Background Fast and simple microscopic evaluation of basal cell carcinoma (BCC) together with its subtype determination would accelerate diagnostic and therapeutic procedures in dermatology including Mohs surgery. Objectives Assessing whether simplified 3-criteria-based ex vivo confocal microscopic (CM) examination can reliably predict BCC diagnosis and subtype. Analyzing interobserver agreement between expert and novice examiner. Methods CM images of 235 skin samples from 150 patients were prospectively evaluated by 2 blinded examiners for the presence of 3 predefined BCC criteria namely presence of tumor mass, peripheral palisading and clefting. Results Out of 235 skin samples 116 showed histological presence of BCC, confocally expert diagnosed a BCC in 110 and novice examiner in 107 samples. The overall sensitivity and specificity of detecting residual BCC was 96.6% and 98.7%, respectively. Confocally, examiners diagnosed correctly nodular BCC in 96.6%, respectively, 98.3%, superficial BCC in 96.8%, respectively, 93.5%, infiltrating BCC in 88.9%, respectively, 83.3% and other BCC subtype in 22.2%, respectively, 0% (expert and novice examiner, respectively). Conclusion Ex vivo CM allowed intraoperative examination of BCC based on only 3-criteria with high sensitivity and specificity, provided useful information on tumor subtype and showed that both experienced and non-experienced examiners may use this diagnostic approach with excellent results.

Nonmelanoma skin cancers (NMSC) are the most frequent cancers in fair-skinned adult patients. Among NMSC, basal cell carcinoma (BCC) are the most common. While the gold standard treatment of NMSC is surgery, alternative methods such as photodynamic therapy have been developed. The main advantage of photodynamic therapy is optimal healing, offering ad integrum skin restitution. This alternative treatment can be proposed for low-risk BCC. This is of particular interest for superficial BCC, which is often multiple and located in body sites (trunk and limbs) on which surgery often leaves dystrophic scars. Patients must be followed carefully to make appropriate decisions in case of failure.

BACKGROUND Curettage and electrodesiccation (C&D) is a widely used method to treat nodular basal cell carcinoma (BCC). However, residual tumor is present immediately after the procedure in approximately 20 to 40% of cases. Imiquimod, a topical immune response modifier that targets Toll-like receptor 7, is currently approved for superficial BCC. OBJECTIVE In a double-blind, vehicle-controlled study, the administration of imiquimod after C&D was investigated to determine if the combination regimen would reduce the frequency of residual tumor compared with C&D alone in patients with nodular BCC. METHODS Twenty patients received three cycles of C&D followed by imiquimod 5% or vehicle cream once daily for 1 month as adjunctive therapy. The primary end point was the frequency of residual tumor. The secondary end points included the time to heal and cosmetic appearance. RESULTS Twenty patients were randomized to imiquimod (n=10) or vehicle (n=10) treatment group. At 8 weeks, the proportion of patients with residual tumor was substantially decreased with imiquimod therapy (10%) compared with vehicle (40%). Wounds in the vehicle group healed more quickly than those in the imiquimod group, although by 8 weeks, all excision sites were healed. The majority of scars in the control group were atrophic and hypopigmented, whereas most scars in the imiquimod group were at and slightly pink. CONCLUSION Imiquimod 5% cream once daily for 1 month as adjunctive therapy after C&D substantially reduced the frequency of residual tumor and improved the cosmetic appearance compared with C&D alone. These preliminary results suggest that further studies to investigate imiquimod adjunctive therapy are warranted.