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Biopsy-based histology has been the foundation of disease diagnosis and management for over a century. A long-sought goal in dermatology is the development of an imaging modality with sufficient resolution and compositional detail to noninvasively interrogate skin histology in vivo. Here, we describe a system that achieves this goal using cross-sectionally scanned, multimodal microscopy (cross-modal). Cross-modal combines multiphoton and reflectance confocal microscopy into one compact system with coordinated three-axis scanning that preserves optical resolution in cross-section. A custom pinhole-free mechanism employing finite-infinite conjugates further simplifies and stabilizes confocal alignment. Evaluated in participants ages 9-81 and Fitzpatrick skin types (FST) 1-5, cross-modal images revealed histological details analogous to those obtained from traditional biopsied tissue. We observed dermal elastosis in sun-damaged skin, elevated melanin in pigmented skin, basaloid nests in basal cell carcinoma, and elongated rete ridges in seborrheic keratosis, supporting cross-modal's potential to deliver histological insights noninvasively., (© 2024. The Author(s).)

Background: The incidence rates of cutaneous squamous cell carcinoma (cSCC) and basal cell carcinoma (BCC) skin cancers are rising, while the current diagnostic process is time-consuming. We describe the development of a novel approach to high-throughput sampling of tissue lipids using electroporation-based biopsy, termed e-biopsy. We report on the ability of the e-biopsy technique to harvest large amounts of lipids from human skin samples., Materials and Methods: Here, 168 lipids were reliably identified from 12 patients providing a total of 13 samples. The extracted lipids were profiled with ultra-performance liquid chromatography and tandem mass spectrometry (UPLC-MS-MS) providing cSCC, BCC, and healthy skin lipidomic profiles., Results: Comparative analysis identified 27 differentially expressed lipids (p < 0.05). The general profile trend is low diglycerides in both cSCC and BCC, high phospholipids in BCC, and high lyso-phospholipids in cSCC compared to healthy skin tissue samples., Conclusion: The results contribute to the growing body of knowledge that can potentially lead to novel insights into these skin cancers and demonstrate the potential of the e-biopsy technique for the analysis of lipidomic profiles of human skin tissues., (© 2024 The Authors. Skin Research and Technology published by John Wiley & Sons Ltd.)

Early detection of skin cancer is of critical importance since the five-year survival rate for early detected skin malignancies is 99% but drops to 27% for cancer that has spread to distant lymph nodes and other organs. Over 2.5 million benign skin biopsies (55% of the total) are performed each year in the US at an alarming cost of USD ~2.5 B. Therefore there is an unmet need for novel non-invasive diagnostic approaches to better differentiate between cancerous and non-cancerous lesions, especially in cases when there is a legitimate doubt that a biopsy may be required. The purpose of this study is to determine whether the differences in the extracellular matrices among normal skin, actinic keratosis (AK), basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) can be assessed non-invasively using vibrational optical coherence tomography (VOCT). VOCT is a new diagnostic technology that uses infrared light and audible sound applied transversely to tissue to measure the resonant frequencies and elastic moduli of cells, dermal collagen, blood vessels and fibrous tissue in skin and lesion stroma without physically touching the skin. Our results indicate that the cellular, vascular and fibrotic resonant frequency peaks are altered in AK, BCC and SCC compared to those peaks observed in normal skin and can serve as physical biomarkers defining the differences between benign and cancerous skin lesions. The resonant frequency is increased from a value of 50 Hz in normal skin to a value of about 80 Hz in pre- and cancerous lesions. A new vascular peak is seen at 130 Hz in cancerous lesions that may reflect the formation of new tumor blood vessels. The peak at 260 Hz is similar to that seen in the skin of a subject with Scleroderma and skin wounds that have healed. The peak at 260 Hz appears to be associated with the deposition of large amounts of stiff fibrous collagen in the stroma surrounding cancerous lesions. Based on the results of this pilot study, VOCT can be used to non-invasively identify physical biomarkers that can help differentiate between benign and cancerous skin lesions. The appearance of new stiff cellular, fragile new vessels, and stiff fibrous material based on resonant frequency peaks and changes in the extracellular matrix can be used as a fingerprint of pre- and cancerous skin lesions.

Dermoscopy and reflectance confocal microscopy (RCM) are two noninvasive, optical imaging tools used to facilitate clinical diagnosis. A biopsy technique that produces exact correlation with optical imaging features is not previously reported. To evaluate the applications of a novel feature-focused 'precision biopsy' technique that correlates clinical-dermoscopy-RCM findings with histopathology. This was a prospective case-series performed during August 2017 and June 2019 at a tertiary care cancer. We included consecutive patients requiring a precise dermoscopy-RCM-histopathologic correlation. We performed prebiopsy dermoscopy and both wide probe and handheld RCM of suspicious lesions. Features of interest were isolated with the aid of paper rings and a 2 mm punch biopsy was performed in the dermoscopy- or RCM-highlighted area. Tissue was processed either en face or with vertical sections. One-to-one correlation with histopathology was obtained. Twenty-three patients with 24 lesions were included in the study. The mean age was 64.6 years (range 22-91 years); there were 16 (69.6%) males, 14 (58.3%) lesions biopsied were on head and neck region. We achieved tissue-conservation diagnosis in 100% (24/24), 13 (54.2%) were clinically equivocal lesions, six (25%) were selected for 'feature correlation' of structures on dermoscopy or RCM, and five (20.8%) for 'correlation of new/unknown' RCM features seen on follow-up. The precision biopsy technique described herein is a novel method that facilitates direct histopathological correlation of dermoscopy and RCM features. With the aids of optical imaging devices, accurate diagnosis may be achieved by minimally invasive tissue extraction., (© 2020. Springer-Verlag GmbH Germany, part of Springer Nature.)

Recent advances in artificial intelligence, particularly in the field of deep learning, have enabled researchers to create compelling algorithms for medical image analysis. Histological slides of basal cell carcinomas (BCCs), the most frequent skin tumor, are accessed by pathologists on a daily basis and are therefore well suited for automated prescreening by neural networks for the identification of cancerous regions and swift tumor classification.In this proof-of-concept study, we implemented an accurate and intuitively interpretable artificial neural network (ANN) for the detection of BCCs in histological whole-slide images (WSIs). Furthermore, we identified and compared differences in the diagnostic histological features and recognition patterns relevant for machine learning algorithms vs. expert pathologists.An attention-ANN was trained with WSIs of BCCs to identify tumor regions (n = 820). The diagnosis-relevant regions used by the ANN were compared to regions of interest for pathologists, detected by eye-tracking techniques.This ANN accurately identified BCC tumor regions on images of histologic slides (area under the ROC curve: 0.993, 95% CI: 0.990-0.995; sensitivity: 0.965, 95% CI: 0.951-0.979; specificity: 0.910, 95% CI: 0.859-0.960). The ANN implicitly calculated a weight matrix, indicating the regions of a histological image that are important for the prediction of the network. Interestingly, compared to pathologists' eye-tracking results, machine learning algorithms rely on significantly different recognition patterns for tumor identification (p < 10 -4 ).To conclude, we found on the example of BCC WSIs, that histopathological images can be efficiently and interpretably analyzed by state-of-the-art machine learning techniques. Neural networks and machine learning algorithms can potentially enhance diagnostic precision in digital pathology and uncover hitherto unused classification patterns.

Background: The prognosis and treatment of basal cell carcinoma (BCC) are largely dependent on tumor subtype, which is typically determined by punch or shave biopsy. Data regarding concordance between BCC subtype on initial biopsy and final histopathology for Mohs micrographic surgery (MMS) or excision with frozen sections (EFS) are limited., Objectives: To determine the concordance between initial biopsy and final MMS or EFS subtyping of BCC. We aim to investigate the incidence and clinical characteristics of lesions initially diagnosed as superficial BCC (sBCC) that are later found to have a nodular, micronodular, or infiltrative component., Methods: We conducted a retrospective review of all MMS or EFS cases performed at a single academic center from August 1, 2015 to August 31, 2017. Inclusion criteria were a biopsy-proven diagnosis of sBCC and presence of residual tumor following stage I of MMS or EFS. Fisher&rsquo;s exact test was used to evaluate significance of clinical characteristics and outcomes associated with the presence of a nodular, micronodular, or infiltrative BCC component., Results: A total of 164 MMS or EFS cases had an initial biopsy showing sBCC. Of these, 117 had residual BCC on stage I, and 43 (37%) were found to have a nodular, micronodular, or infiltrative component. Significant predictors of reclassified BCC subtype included age over 60 years (P=0.006) and location on the head or neck (P=0.043). Reclassified lesions required significantly more stages of MMS to clear (P=0.036). Shave biopsy was used to diagnose 114 (98%) of the included cases., Conclusions: Over one third of shave biopsies that initially diagnosed sBCC failed to detect a nodular, micronodular, or infiltrative component. Management of biopsy-proven sBCC should take into account the possible presence of an undiagnosed deeper tumor component with appropriate margin-assessment treatment modalities when clinically indicated. J Drugs Dermatol. 2021;20(3):283-288. doi:10.36849/JDD.5383.

Background: Surgery is the best treatment for basal cell carcinoma (BCC); however, incomplete excisions are possible., Objective: Assessment of the accurateness of dermoscopy and clinical evaluation in the detection of borders of BCC and description of dermoscopic findings in clinically healthy tissue surrounding BCC., Materials and Methods: Eighty-eight lesions with clinical dermoscopic diagnosis of BCC were examined clinically and dermoscopically, to delineate the correct site of surgical incision, demarcating the respective margins with colred dermographic pencils. Specific dermoscopic features were searched in the skin adjacent to the demarcated clinical margin., Results: In 29 of 88 lesions, clinical and dermoscopic margins of the tumor coincided. In the remaining 59 (67%), 10 (16.9%) presented, in the lesion area identified under dermoscopy, classical criteria for BCC and 57 (96.6%) nonclassical criteria. Differences between clinical and dermoscopic margins were significantly more frequent in superficial BCCs (p = .006). The frequency was not significantly different (p = .85) in relation to body sites., Conclusion: Dermoscopy improves the identification of margins for surgical excision in BCC. The observation of nontraditional dermoscopic criteria of BCC, mainly pink-white areas and short telangiectasias in the area between clinically and dermoscopically detected margins, helps to define the actual tumoral margins and to achieve a really radical excision., (Copyright © 2020 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Background: The primary endpoint for surgical excision of skin cancer is the positive margin status. Tumor characteristics may explain much of this risk, but other important factors can include physician specialty., Objective: To determine the variables affecting the success of a basal cell carcinoma (BCC) or melanoma in situ (MIS) excision., Methods/materials: An 8-year, multicenter, retrospective study of 5,800 BCC or MIS excisions performed at 13 different Kaiser Permanente medical centers. The margin status was determined by searching final pathology diagnosis texts for phrases associated with positive margins., Results: An incomplete excision rate was found in 23% of all specimens (BCC-22%, MIS-25%). Per specialty, the proportion of specimens with positive tumor margins was 24% for dermatology, 26% for plastic surgery, 28% for otolaryngology, and 12% for general surgery. General surgeons most often excised large tumors and tumors from truncal regions, 2 variables conferring lower odds of an incomplete excision. For non-Mohs procedures, dermatologists were no different than otolaryngologists or plastic surgeons in performing an incomplete BCC or MIS excision in all multivariate models (all p > .05)., Conclusion: Intrinsic tumor characteristics may influence the success of achieving tumor-free resection margins more than the specialty of the provider., (Copyright © 2020 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Background: As the availability of Mohs micrographic surgery (MMS) continues to expand in Australia and incidence of keratinocyte cancer increases in adolescents and young adults, there has been rising interest in the use of MMS in this population., Objective: This study aimed to evaluate the characteristics of MMS cases in patients younger than 40 years., Methods: A review was performed of all MMS cases in patients younger than 40 years at the time of their surgery from 2012 to 2017 at the Skin and Cancer Foundation Australia, with comparison to a control group, aged older than 40 years. Patient, tumor and management characteristics were analyzed., Results: Four hundred ninety-three cases were eligible. Study and control groups differed significantly regarding gender (p < .001), tumor pathology (p < .001), anatomic site of tumor (p < .001), Mohs surgery stages (p = .039), defect size (p < .001), and repair method (p < .001)., Limitations: Retrospective study at a single institution., Conclusion: Mohs micrographic surgery cases in patients younger than 40 years exhibit unique patient and tumor characteristics influencing choice of repair method.

Background: Keratinocyte cancer (KC) patients benefit from early diagnosis. We describe here the anatomy of head/neck KCs to help guide screening efforts., Objective: To examine lesion frequency and anatomic distribution of head and neck KC., Methods: This retrospective cohort study of 4,770 consecutive pathology reports, 1998 to 2015, analyzes 5,463 head and neck KCs (3,664 basal cell carcinoma [BCC], 1,259 squamous cell carcinoma [SCC], and 540 SCC in situ) from 3,581 patients., Results: Basal cell carcinoma relative tumor density (RTD) was highest on the nose; SCC RTD was highest on the cheek. Basal cell carcinoma-to-SCC ratio was highest on eyelid and lowest on scalp. Temple, ear, and neck SCC predominated in men; nose and cheek SCC in women. Scalp, temple, and ear BCC showed male predominance, while cheek, nose, and chin predominated in women. Left-sided ear SCC in situ and BCC were more common than right-sided ear lesions., Conclusion: This study demonstrates gender- and laterality-specific differences that comport with patterns of solar exposure.

Basosquamous carcinoma (BSC) is a malignant and aggressive neoplasm with unclear molecular etiology. It is often misdiagnosed as basal cell carcinoma (BCC) or squamous cell carcinoma (SCC) on biopsy as there are unclear histologic criteria for this neoplasm. It has been interchangeably referred to as metatypical BCC and collision tumor, although these entities are different. On histology, BSC consists of basal cells with areas with nests of squamous cells and an intermediate transition zone. The nature of this transition zone is not clearly defined in literature; however, Ber-EP4 staining is diagnostic for BSC. A gradation of Ber-EP4 staining from strongly positive in basaloid areas to weakly positive in an intermediate zone is demonstrated (no staining of squamous areas). Treatment with an array of modalities including wide local excision, Mohs surgery, radiotherapy, and palliative chemotherapy has been performed. We recommend further molecular studies in understanding the genetic mechanisms leading to BSC. For the purpose of good clinical practice, multiple biopsies and immunohistochemical studies should be performed to avoid sampling error that can lead to a misdiagnosis of BSC.

Background: Basal cell carcinoma (BCC) recurrence and metastatic rates are known to be very low. The risk factors for these rare outcomes are subsequently not well studied., Objective: To identify risk factors independently associated with local recurrence (LR) and metastasis and/or death (M/D) in large (≥2 cm) BCC., Methods: BCCs histologically confirmed between 2000 and 2009 were retrospectively screened for tumor diameter at 2 academic centers. Medical records of all large BCCs and an equal number of randomly selected small BCCs were reviewed for LR and M/D., Results: Included were 248 large BCC and 248 small BCC tumors. Large BCCs had a significantly higher risk of LR and M/D than small BCCs (LR: 8.9% vs 0.8%, P < .001; M/D: 6.5% vs. 0%, P < .001). Because the risks were so low in small BCCs, they were excluded from further analysis. On multivariable logistic regression, head/neck location (odds ratio [OR], 9.7; 95% confidence interval [CI], 3.0-31.3) and depth beyond fat (OR, 3.1; 95% CI, 1.0-9.6) were associated with LR in large BCCs. Risk of LR was lower with Mohs micrographic surgery (OR, 0.14; 95% CI, 0.04-0.5). Head/neck location (OR, 5.3; 95% CI, 1.2-23.2), tumor diameter ≥4 cm (OR, 11.9; 95% CI, 2.4-59.4), and depth beyond fat (OR, 28.6; 95% CI, 6.7-121) were significant predictors of M/D in large BCCs., Limitations: Retrospective cohort design., Conclusions: Large BCCs, particularly those with additional risk factors, have a high enough risk of recurrence and metastasis to warrant further investigation to optimize management., (Copyright © 2019 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 2020 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background/aim: Squamous cell carcinoma (SCC) is highly prevalent in kidney transplant patients (KT). It is characterized by the presence of an inflammatory infiltrate. In this study, we examined the presence of similar infiltrates in intact skin, which could be regarded as a precancerous step., Patients and Methods: We retrospectively analyzed skin biopsies of 19 non-transplanted patients with a diagnosis of SCC or basal cell carcinoma (BCC) and 17 KT with either SCC or BCC., Results: KT showed increased inflammatory infiltrate in the subepithelial region, compared to non-transplanted patients. The density of basal cell nuclei was also different among the four groups with an interaction effect between tumor type and transplantation. The extent of inflammatory infiltrates did not correlate with the eGFR and proteinuria., Conclusion: KT with a non-melanoma skin cancer show increased intact skin inflammatory infiltrate and alterations in the density of the basal cell layer compared to non-transplanted patients., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: The Mohs Appropriate Use Criteria (MAUC) have come into question recently regarding the most appropriate treatment for superficial basal cell carcinoma (sBCC). At the heart of this debate is the limited body of evidence describing tumor behavior of sBCC based on clinical factors relevant to the MAUC., Objective: To determine whether sBCC is more likely to harbor aggressive subtypes in high-risk anatomical locations and in immunocompromised patients., Materials and Methods: A single institution retrospective review produced 133 evaluable Mohs cases performed on sBCC over a 10-year period. All slides from the respective cases were reviewed for the presence of histologic patterns other than known sBCC. Cases were then grouped by both MAUC anatomical zone (H, M, and L) and patient immune status for statistical analysis., Results: A significantly higher rate of mixed histology (MH) was observed when comparing Zone H with Zone L across all patients, healthy patients, and immunocompromised patients. The same was true when comparing Zone M with Zone L for all patients and healthy patients (immunocompromised did not reach significance)., Conclusion: The authors' data very clearly demonstrate a higher rate of MH in sBCC of the head and neck which provides strong support to the current MAUC scoring.

Background: Initial biopsy of basal cell carcinoma (BCC) may fail to show aggressive histologic subtypes. Additionality, the clinical evaluation of BCC before surgery can miss subclinical extension. Reflectance confocal microscopy (RCM) and optical coherence tomography (OCT) are emerging tools that can help in the presurgical evaluation of BCCs., Objective: To assess the feasibility of a combined RCM-OCT imaging modality for presurgical evaluation of biopsy-proven BCCs for residual tumor, margin status, and depth., Methods: Thirty-eight BCCs in 35 patients referred to a tertiary cancer center for Mohs micrographic surgery (MMS) were imaged with combined RCM-OCT. Images were correlated to MMS frozen sections., Results: Thirty-eight BCCs were analyzed. The mean age of patients was 67.34 years (range, 36-84 years), and 20 patients were female (57.14%). Twenty four BCCs were located on the head (63.16%) , and the mean size was 8.58 mm (range, 3-30 mm). RCM-OCT showed an overall agreement of 91.1% with MMS frozen sections. A sensitivity of 82.6% (95% confidence interval [CI], 69%-92%), specificity of 93.8% (95% CI, 88%-97%), and receiver operating characteristic curve of 0.88 (95% CI, 0.82-0.94) was found. OCT depth was highly correlated with MMS depth (r 2 = 0.9)., Limitations: Small sample size and difficulty evaluating certain challenging anatomic sites., Conclusions: Combined RCM-OCT may emerge as a useful tool for presurgical evaluation of BCCs., (Copyright © 2019 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Benign cutaneous lesions, so-called cysts, are frequently seen in clinics and might evoke cosmetic and psychosocial concerns., Aim: This study aimed to demonstrate the clinicopathologic findings of these lesions and also the importance of histological evaluation for prevention of misdiagnosing a benign-appearing malignant lesion., Methods: A descriptive study was conducted of 2,438 cases who had a diagnosis of cyst confirmed with pathology. The data of patients over the 6-year period between 2011 and 2017, including gender, age, location, prevalence, complications, and microscopic evaluation, were gathered., Results: From a total of 2,438 records with a clinical diagnosis of mucocutaneous cyst, 2077 had the pathologic diagnosis of cysts. They consisted of 910 women (43.8%) and 1167 men (56.1%) with a mean age of 42. The most common mucocutaneous cysts were epidermal cyst 994 (47.8%) followed by trichilemmal cyst 495 (23.8%). In 479 (19.6%) records, the clinical diagnosis was not congruent with histopathological diagnosis including 45 malignant cases. Basal cell carcinoma in 22 (48.9%) was the most common one., Conclusions: This study reports on clinical characteristics of cutaneous cysts and the need for a decent diagnostic investigation, like histopathology, for achieving a reliable diagnosis regarding the benign mimicking malignant lesions, especially high risk ones., (© 2020 The International Society of Dermatology.)

Background: Pathologists sometimes include commentary on margin involvement in shave biopsy reports of keratinocyte carcinoma (KC). This practice can lead to confusion regarding the need for further treatment. There is limited literature evaluating the reliability of reported histologic margin status in shave biopsies of KC., Objective: To evaluate the negative predictive value (NPV) of reported clear shave biopsy margins in basal and squamous cell carcinomas to determine whether this assessment is a reliable predictor of complete tumor removal., Methods: A literature review was performed using the PubMed database. The data were compiled, NPVs were calculated by the tumor subgroup, and a statistical analysis was performed., Results: Four studies met inclusion criteria. Two hundred twenty-one KCs were identified (n = 221). All specimens had negative-reported histologic margins (39 squamous cell carcinoma [SCC] and 182 BCC). Fifty-five cases initially noted to have negative margins on biopsy were found to have residual tumor on subsequent analysis: 5 SCC and 50 BCC, translating to 12.8% of all SCC (5/39) and 27.5% for BCC (50/182). Negative predictive values were found to be 75.1% for all KCs, 87.2% for SCC, and 72.5% for BCC., Conclusion: Negative histologic margin status on shave biopsy specimens of KC has a poor NPV and is an inadequate predictor for complete tumor removal.

Background: The histological subtype of basal-cell carcinoma (BCC) is often based on a punch biopsy; only a small part is evaluated, possibly leading to misclassification. Consensus on the optimal approach to process punch biopsies is lacking, though accurate subtyping is important for appropriate treatment., Objective: The aim is to investigate whether evaluating 4 levels of a punch biopsy instead of 1 or 2 levels leads to more accurate subtyping of BCC., Methods: In a retrospective study we evaluated 87 punch biopsies of histologically confirmed BCCs. The primary outcome was the proportion of "more aggressive" BCCs (nonsuperficial vs. superficial, infiltrative vs. nodular subtype) that was missed by evaluation on 1 or 2 levels, using 4-level diagnosis as reference standard., Results: Eighty-five cases were available for analysis. Subtyping based on 1 level resulted in discrepancies with 4-level diagnosis in 16.5% of all cases. Underdiagnosis occurred in 14 of 58 nonsuperficial BCCs (24.1%, 95% CI: 13.9-37.2). Seven of 38 nodular BCCs (18.4%, 95% CI: 7.74-34.3) were diagnosed as superficial in 1 level, and 7 of 20 infiltrative BCCs (35%, 95% CI: 15.4-59.2) were diagnosed as superficial (n = 2) or nodular (n = 5) in 1 level., Conclusion: In order to maximize correct subtyping and plan appropriate treatment, we advise to evaluate at least 2, but preferably more, levels of a punch biopsy to determine the BCC subtype., (© 2019 The Author(s) Published by S. Karger AG, Basel.)

Background and Objectives: Many cutaneous drug-delivery techniques rely on passive diffusion to deliver topical compounds to the skin. When attempting to deliver drugs to thicker lesions, such as skin tumors, modalities that do not rely on diffusion may serve as a better drug-delivery method. In this histological study, we aim to investigate the cutaneous delivery patterns of an electronic pneumatic needle-free injection device., Study Design/materials and Methods: Needle-free-injection was investigated in 24 ex vivo porcine skin samples and one basal cell carcinoma (BCC) tissue sample. A needle-free injection device with a nozzle size of 200 μm delivered 80 μl compound ink (0.1 cc black ink: 5.0 cc saline) at low (30%/3.1 bar; n = 6 porcine skin; n = 1 BCC tissue), medium (50%/3.9 bar; n = 6 porcine skin), high (65%/4.6 bar; n = 6 porcine skin), and stacked (30 + 50%/3.1 + 3.9 bar; n = 6 porcine skin) pressures. Depth, width, and depth of maximum width of ink deposition were evaluated on histological slides., Results: Depositions with small ink-lined vacuoles were seen intra-dermally in all samples, including the BCC tissue. Deposition depth was similar at low and medium pressures (924 vs. 994 μm; P = 0.873) but increased significantly with high pressure (1,564 μm; P = 0.010). When injections were stacked (3.1 + 3.9 bar), the depth remained similar to that of a single injection (931 μm; P = 1.000). The width of the deposition stayed comparable for low, medium, and high pressures when a single needle-free injection was performed (30% = 2,394 μm; 50% = 2,226 μm; and 65% = 2,757 μm; P = 0.09), but increased significantly with stacking (2,979 μm; P = 0.037). The depth of maximal width was superficially located in the papillary dermis at low and medium pressures (321 and 305 μm; P = 0.748) but shifted to the deeper reticular dermis with high pressure (950 μm; P = 0.004) and with stacking (734 μm; P = 0.004)., Conclusions: In conclusion, with an electronically controlled, pneumatic needle-free injector, depth and width of a cutaneous deposition can be influenced by pressure and stacking, respectively. The pneumatic needle-free injection can potentially serve as a viable drug-delivery technique for cutaneous pathologies where dermal deposition is essential. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc., (© 2019 Wiley Periodicals, Inc.)

Introduction: Giant basal cell carcinoma (GBCC) is a tumor ≥5 cm in size, with aggressive biological behavior, that represents 1% of basal cell carcinomas (BCC), and studies regarding it are scarce. Our objective was to investigate the clinical-histopathological characteristics of GBCC and the risk factors associated with its development., Methods: A retrospective study over 8 years included patients with the clinical and histopathological diagnosis of GBCC. Age, sex, localization, size, evolution time, risk factors, and histological variants were compared to conventional BCC. Descriptive and inferential statistics were used, and a value of P < 0.05 was considered statistically significant., Results: Of 5958 patients with BCC, 115 (2%) of them corresponded to GBCC. The average patient age was 73 ± 11 years, and the male sex (52%) and localization on the head and neck (63%) predominated. Average tumor size was 6.6 ± 2.2 cm, evolution time was 96 ± 86 months, and high-grade histological variants (51%) predominated. The group with GBCC had higher age (P < 0.01), greater frequency in the male sex (P = 0.01), longer evolution time (P < 0.01); a greater prevalence of risk factors (24% vs. 16%, P = 0.01), antecedents of other types of cancer (P = 0.03), and of burns (P = 0.03); and a greater frequency of high-grade histological variants (51% vs. 29%, P < 0.01)., Conclusions: This is the largest series of GBCC published to date. Findings are similar to those previously reported, although the prevalence found here was greater., (© 2019 The International Society of Dermatology.)

Background: Basal cell carcinoma (BCC) is a common tumor but rarely presents on nonexposed skin. We sought to identify and characterize the traits of the malignancy over a 10-year period., Methods: A retrospective chart review of all BCCs between 2007 and 2017 was performed. Clinical characteristics and histological features were evaluated., Results: Of all BCCs biopsied in a 10-year period, 53 tumors in 50 patients were diagnosed in the groin or buttocks. This accounts for 0.094% of all BCCs during this time period. None of the cases had genetic diseases prone to skin cancer development or were immunosuppressed. The most common location was the buttocks, and the most frequently diagnosed histological subtype was nodular (49%)., Conclusion: To our knowledge, this is the largest report of BCC of the groin and buttocks. In this rare presentation of a common tumor, the histological characteristics of it are not more aggressive than other sites on the body., (© 2019 The International Society of Dermatology.)

Basal cell carcinoma (BCC) is the most frequent malignant neoplasm in the Caucasian population. There are several therapeutic options for BCC, but surgical excision is considered gold standard treatment. As BCCs often have poorly defined borders, the clinical assessment of the tumor margins can be challenging. Therefore, there is an increasing demand for efficient in vivo imaging techniques for the evaluation of tumor borders prior to and during surgeries. In the near future, nonlinear microscopy techniques might meet this demand. We measured the two-photon excitation fluorescence (TPEF) signal of nicotinamide adenine dinucleotide hydride (NADH) and elastin and second harmonic generation (SHG) signal of collagen on 10 ex vivo healthy control and BCC skin samples and compared the images by different quantitative image analysis methods. These included integrated optical density (IOD) measurements on TPEF and SHG images and application of fast Fourier transform (FFT), CT-FIRE and CurveAlign algorithms on SHG images to evaluate the collagen structure. In the BCC samples, we found significantly lower IOD of both the TPEF and SHG signals and higher collagen orientation index utilizing FFT. CT-FIRE algorithm revealed increased collagen fiber length and decreased fiber angle while CurveAlign detected higher fiber alignment of collagen fibers in BCC. These results are in line with previous findings which describe pronounced changes in the collagen structure of BCC. In the future, these novel image analysis methods could be integrated in handheld nonlinear microscope systems, for sensitive and specific identification of BCC.

Background: Lichen planus-like keratosis (LPLK) is a frequent skin lesion usually biopsied to rule out basal cell carcinoma (BCC). Because of overlapping histopathological characteristics, LPLK is frequently muddled with lichen planus (LP), lichenoid actinic keratosis (LAK), and lupus erythematosus (LE)., Objective: To investigate the clinical and histopathological characteristics of LPLK., Methods: A clinicopathologic review was performed of all LPLK cases (1366) signed in one calendar year in a busy academic practice., Results: LPLK occurs mostly as a single lesion (97%) with the chest (41.4%) being the most common site. It is almost equally present in women and men (51.5%-48.5%). The most common clinical concern (65%) is basal cell carcinoma. Parakeratosis, red blood extravasation, and presence of dermal eosinophils and plasma cells, usually not seen in lichen planus, are helpful signs to suggest LPLK but are seen only in a minority of cases., Conclusion: Clinicopathologic correlation is necessary to diagnose lichen planus-like keratosis, as the most consistent feature is a clinical history of a lesion/neoplastic process rather than an inflammatory process. There are histopathologic features that can help distinguish lichen planus-like keratosis from lichen planus; however, these features are nonspecific and lacking in almost half of the cases., (© 2018 The International Society of Dermatology.)

Background: Skin tumors surgery is common and well established. There is discrepancy between recommendations on macroscopic margins to apply and therapeutic decisions taken on histological margins. The purpose of this study is to examine skin shrinkage upon exeresis, then in formalin, to understand the anatomo-clinical discrepancy, which is often found., Material and Methods: It was a prospective study, lasting a month, including patients receiving skin surgery. For each tumor, the surgeon carried out 4 margins measurements before and after exeresis ; margins measured again in histology. The evaluation criterion was the difference between preoperative, postoperative and histological margins measurement. These data was weighting according to factors linked to the patient and the tumor., Results: Seventy-nine tumors for 61 patients had been studied. The study showed a significant shrinkage between preoperative measurements and postoperative, from 0.4 to 0.6mm. It is correlated with no one tested factors. Significant shrinkage between 0.4 and 0.5mm was also established between preoperative and histological measurements. However, there is a significant augmentation between postoperative and histological measurements., Conclusion: This last result could be linked to the inflammatory peri-wound skin that surgeon consider as tumoral process so exclude of his margin, while histology could show a healthy area. In front of these results, an expert committee leading a more important study could include histological margins recommendations to the actual clinical recommendations., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Basaloid tumors of the skin pose a diagnostic challenge to pathologists, because the differential diagnosis is broad, sometimes with subtle differentiating features. We evaluated SOX10 expression in 120 primary cutaneous tumors with epidermal, sweat glandular, neuroendocrine/neuroectodermal, follicular, and sebaceous lineages. Our findings were compared with those of previous studies that evaluated SOX10 in tumors of the skin. SOX10 staining was seen in the majority of sweat gland tumors with the exception of syringoma and microcystic adnexal carcinoma. There were no immunoreactive cases among epidermal, neuroendocrine/neuroectodermal, follicular, or sebaceous tumors. These findings are comparable to reported in previous studies, and show SOX10 can be a useful adjunct in the differential diagnosis of nodular basaloid skin tumors. That marker has less utility in the assessment of sclerosing basaloid cutaneous neoplasms, because such tumors are almost uniformly nonreactive for it.

Cutaneous nerve hyperplasia is characterized by the presence of increased and hypertrophic myelinated and unmyelinated nerve fibers in the dermis. We report a case of periadnexal nerve hyperplasia as an asymptomatic and infrequent reactive histopathological change, with no associated risk of malignancy that can be seen in scars, in patients with no syndromic stigmata.

Introduction: Skin tumors are not uncommon in the Nepalese community. Accurate diagnosis and categorization of these into different types is important because of its effect on prognosis and management. We conducted this study to find out the frequency of different histological types of skin tumors, correlate with their clinicopathologic profile and to determine the stage of malignant tumors., Methods: This is a descriptive cross-sectional study of skin tumors during the period February 2015 to January 2017. All the patients who were subjected to skin biopsy for skin tumors were included in this study. The biopsies taken were fixed in 10% formalin and then processed. Four microns thick sections were taken and stained with Haematoxylin and Eosin stain (H&E)., Results: Total of 108 cases of skin tumors were included of which 68 (62.97%) cases were histologically diagnosed as benign and 40 (37.03%) cases were diagnosed as malignant tumors. Keratinocytic tumors were predominant among both benign and malignant skin tumors., Conclusions: Histopathological examination is the gold standard for accurate diagnosis and prognostic assessment of the patient. Staging of the malignant tumors in excision biopsy specimen needs to be emphasized since it is a predictor of prognosis.

Chondrodermatitis nodularis helicis (CNH) is a benign auricular disease whose differentiation with nonpigmented tumors is mandatory. Clinical characteristics of CNH are well known, but there is no information about the dermoscopic features that could help differentiate CNH from squamous cell carcinoma and other non-melanoma skin cancers. To describe the dermoscopic appearance of CNH and to formulate a differential diagnostic model, we conducted  a retrospective, single center, observational dermoscopic study on a sample of 189 biopsy-proven lesions: 25 CNH; 26 squamous cell carcinomas; 62 basal cell carcinomas and 76 other benign and malignant tumors. Univariate and multivariate analyses were conducted by logistic regression. The most significant dermoscopic finding for CNH was a peculiar global configuration (daisy pattern), consisting of white thick lines, radially arranged, converging to a central rounded yellow/brown clod (an erosion covered by keratin or sero-crust). This pattern achieved 92 and 98% of specificity for discriminating CNH with squamous cell carcinoma and basal cell carcinoma, respectively. In conclusion, dermoscopy is valuable for the diagnosis of CNH as a first screening tool because of a consistent global dermoscopic configuration (daisy pattern), consisting of radially arranged white thick lines surrounding a central rounded yellow/brown clod.

The diagnosis of infiltrative basal cell carcinoma (BCC) can be delayed owing to its often subtle clinical findings. A 90-year-old woman presented with an asymptomatic annular pink plaque on her left shin that was clinically diagnosed as tinea corporis. After years of not responding to topical anti-fungal therapy, biopsies confirmed a diagnosis of infiltrative BCC. We discuss the differential diagnosis of the case, the difficulties in identifying infiltrative BCC, and the pathologic features of infiltrative BCC.

Objective: A vascular cause is found in around 85% of leg ulcer patients, but non-vascular causes are also observed. Their diagnosis is based on a set of clinical arguments and skin biopsy with histological analysis. The aim of this study was to analyze the results of these biopsies and to find common criteria for ulcers whose skin biopsies had led to the diagnosis of a non-vascular ulcer., Material and Method: A retrospective study was carried out on the analysis of 143 skin biopsies of leg ulcers. The reasons for the biopsy were mainly atypical clinical signs and/or the lack of improvement in care after 6 months, as advocated by the French health authorities., Results: The skin biopsies led to a diagnosis of non-vascular ulcer in 4.9% of cases (7/143), including skin cancer (n=5, 3.5%), cutaneous leishmaniasis (n=1, 0.7%) and Pyoderma gangrenosum (n=1, 0.7%). The univariate statistical analysis revealed that an elevated rim and abnormal excessive granulation tissue were significantly more frequently found in these ulcers. All patients with a positive skin biopsy had associated vascular involvement., Conclusion: This study found a 5% rate of non-vascular causes of ulcers, mainly skin cancer. Elevated rims and abnormal excessive granulation tissue were the unusual features most commonly found in these ulcers. All patients whose skin biopsy revealed a non-vascular cause had associated vascular involvement. This information confirms the need to perform a skin biopsy, even in the presence of a vascular disease., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Bazex syndrome (BS) is a rare paraneoplastic syndrome most frequently associated with squamous cell carcinomas of the upper aerodigestive tractand other tumours. Characteristically, cutaneous lesions precede the diagnosis of malignancy. We report a 72-year-old patient with 1-year history of acral dermatitis. The diagnosis of BS was based on the presence of psoriasiform acral dermatitis and the evidence of two simultaneous tumors (prostate adenocarcinoma and undifferentiated carcinoma ofthe submandibular gland). It is important to have this syndrome in mind since cutaneous features usually precede an underlying neoplasm.

Context: - Basal cell carcinoma (BCC) is the most common human malignant neoplasm and is a frequently encountered diagnosis in dermatopathology. Although BCC may be locally destructive, it rarely metastasizes. Many diagnostic entities display morphologic and immunophenotypic overlap with BCC, including nonneoplastic processes, such as follicular induction over dermatofibroma; benign follicular tumors, such as trichoblastoma, trichoepithelioma, or basaloid follicular hamartoma; and malignant tumors, such as sebaceous carcinoma or Merkel cell carcinoma. Thus, misdiagnosis has significant potential to result in overtreatment or undertreatment., Objective: - To review key features distinguishing BCC from histologic mimics, including current evidence regarding immunohistochemical markers useful for that distinction., Data Sources: - Review of pertinent literature on BCC immunohistochemistry and differential diagnosis., Conclusions: - In most cases, BCC can be reliably diagnosed by histopathologic features. Immunohistochemistry may provide useful ancillary data in certain cases. Awareness of potential mimics is critical to avoid misdiagnosis and resulting inappropriate management.

A half-space electromagnetic model of human skin over the band 30-300 GHz was constructed and used to model radiometric emissivity. The model showed that the radiometric emissivity rose from 0.4 to 0.8 over this band, with emission being localized to a layer approximately one millimeter deep in the skin. Simulations of skin with differing water contents associated with psoriasis, eczema, malignancy, and thermal burn wounds indicated radiometry could be used as a non-contact technique to detect and monitor these conditions. The skin emissivity of a sample of 30 healthy volunteers, measured using a 95 GHz radiometer, was found to range from 0.2 to 0.7, and the experimental measurement uncertainty was ±0.002. Men on average were found to have an emissivity 0.046 higher than those of women, a measurement consistent with men having thicker skin than women. The regions of outer wrist and dorsal forearm, where skin is thicker, had emissivities 0.06-0.08 higher than the inner wrist and volar forearms where skin is generally thinner. Recommendations are made to develop a more sophisticated model of the skin and to collect larger data sets to obtain a deeper understanding of the signatures of human skin in the millimeter wave band. Bioelectromagnetics. 38:559-569, 2017. © 2017 The Authors. Bioelectromagnetics published by Wiley Periodicals, Inc., (© 2017 The Authors. Bioelectromagnetics Published by Wiley Periodicals, Inc.)

Skin is a highly plastic tissue that undergoes tissue turnover throughout life, but also in response to injury. YAP and Hedgehog signalling play a central role in the control of epidermal stem/progenitor cells in the skin during embryonic development, in postnatal tissue homeostasis and in skin carcinogenesis. However, the genetic contexts in which they act to control tissue homeostasis remain mostly unresolved. We provide compelling evidence that epidermal YAP and Hedgehog/GLI2 signalling undergo positive regulatory interactions in the control of normal epidermal homeostasis and in basal cell carcinoma (BCC) development, which in the large majority of cases is caused by aberrant Hedgehog signalling activity. We report increased nuclear YAP and GLI2 activity in the epidermis and BCCs of K14-CreER/Rosa-SmoM2 transgenic mouse skin, accompanied with increased ROCK signalling and ECM remodelling. Furthermore, we found that epidermal YAP activity drives GLI2 nuclear accumulation in the skin of YAP2-5SA-ΔC mice, which depends on epidermal β-catenin activation. Lastly, we found prominent nuclear activity of GLI2, YAP and β-catenin, concomitant with increased ROCK signalling and stromal fibrosis in human BCC. Our work provides novel insights into the molecular mechanisms underlying the interplay between cell signalling events and mechanical force in normal tissue homeostasis in vivo, that could potentially be perturbed in BCC development.

Malignant changes arising on the previously traumatized or chronically inflamed skin are defined as Marjolin ulcers. They can develop on many different lesions but frequently they are detected on burn scars. Histopathologically, Marjolin ulcers are mostly diagnosed as squamous cell carcinoma and they need special attention when especially located on the lower extremities. In this study, 63 patients treated for Marjolin ulcers between January 2000 and March 2015 were evaluated according to etiology, histological differentiation, primary tumor size, patient age and anatomical localization. Medical records of these patients were reviewed retrospectively. Mean age was 49.7 years. Average interval between the first injury and carcinoma development was 37.9 years. Most frequent etiologic factor was burn scars with 82.5%. Foot was the most frequently affected site with 28.6% and scalp was the second most frequent localization with 25.4%. Squamous cell carcinomas were detected in 88.9% of the patients and basal cell carcinomas were detected in 11.1% of the patients. For treatment, excision and grafting was performed for 48 patients (76.2%), excision and local flaps were used for 10 patients (15.9%) and excision and free flaps were used for five patients (7.9%). Regional lymph node dissection was performed for 12 patients (19%). Average follow up period was 46.5 months. Local recurrences were detected in nine patients (14.3%). In conclusion, Marjolin ulcers are aggressive tumors that require special care. In order to prevent life threatening sequelas of this entity, it is important to know basic aspects of clinical progress, prognostic factors and treatment modalities., (Copyright © 2017. Published by Elsevier Taiwan.)

Non-melanomatous skin cancers (NMSCs), which include basal and squamous cell carcinoma (BCC and SCC respectively), represent a significant burden on the population, as well as an economic load to the health care system; yet treatments of these preventable cancers remain ineffective. Studies estimate that there has been a 2-fold increase in the incidence of NMSCs between the 1960s and 1980s. The increase in cases of NMSCs, as well as the lack of effective treatments, makes the need for novel therapeutic approaches all the more necessary. To rationally develop more targeted treatments for NMSCs, a better understanding of the cell of origin, in addition to the underlying pathophysiological mechanisms that govern the development of these cancers, is urgently required. Research over the past few years has provided data supporting both a "bottom up" and "top down" mechanism of tumourigenesis. The "bottom up" concept involves a cancer stem cell originating in the basal compartment of the skin, which ordinarily houses the progenitor cells that contribute towards wound healing and normal cell turnover of overlying epidermal skin layers. The "top down" concept involves a more differentiated cell undergoing genetic modifications leading to dedifferentiation, giving rise to cancer initiating cells (CICs). This review explores both concepts, to paint a picture of the skin SCC cell of origin, the underlying biology, and also how this knowledge might be exploited to develop novel therapies., Competing Interests: The authors declare no conflict of interest.

Indocyanine green (ICG) is a near-IR fluorescent dye with a great potential for application as photosensitizer in topical photodynamic therapy (PDT) of skin diseases. Despite its merits, its use has been hampered by its high degradation rate. Therefore, in the current article, ICG was encapsulated in a vesicular colloidal nanocarrier (transfersomes), with the aim of enhancing its therapeutic efficacy. Transfersomes were characterized for their entrapment efficiency, particle size, zeta potential, morphology, in vitro release and histopathological effect on mice skin. A pilot clinical study was conducted to test its therapeutic potential for PDT of basal cell carcinoma (BCC). Transfersomal ICG displayed particle size (∼125 nm) and a negative zeta potential (∼-31 mV). Transfersomes were also able to sustain the release of ICG >2 h. Upon incorporation of transfersomal ICG in gel form, it was found to maintain the normal histology of mice skin post-irradiation with diode laser 820 nm. Moreover, ICG transfersomal PDT achieved 80% clearance rate for BCC patients with minimal pain reported during treatment. The previous findings suggest that transfersomal nanoencapsulated ICG is a promising treatment modality for BCC.

Cancer-associated fibroblasts (CAFs) play important roles in cancer progression through their complex interactions with cancer cells. The secreted bone morphogenetic protein antagonist, gremlin1 (GREM1) is expressed by the CAFs of basal cell carcinomas (BCCs), and promotes the growth of cancer cells. In this study, we investigated the expression of GREM1 mRNAs in various benign and malignant skin tumors, including various BCC subtypes. Analysis by RNA in situ hybridization (ISH) revealed that fibroblasts in the scar tissue expressed GREM1 and α-smooth muscle actin (α-SMA), whereas resident fibroblasts in the dermis of the normal skin did not express GREM1. Real-time polymerase chain reaction analysis showed significantly higher GREM1 expression in skin cancers and pilomatricomas (PMCs) than in other benign skin tumors. Tissue microarrays analyzed by RNA ISH for GREM1 expression also demonstrated that 23% of BCCs, 42% of squamous cell carcinomas, 20% of melanomas, and 90% of PMCs were positive for GREM1 expression, whereas trichoepitheliomas, eccrine poromas, hidradenomas, and spiradenomas were negative for GREM1 expression. Most BCCs that were GREM1 expression positive were of desmoplastic or mixed subtypes, and GREM1 expression was localized to activated myofibroblasts at the tumoral-stromal interface. Interestingly, most PMCs harbored GREM1-expressing fibroblasts, probably because of the inflammatory responses caused by foreign body reactions to keratin. Additionally, in BCCs, stromal GREM1 expression had a strong correlation with CD10 expression. In conclusion, GREM1 is frequently expressed by myofibroblasts in scars or in the stroma of basal cell carcinomas, suggesting that GREM1 expression can be a marker for activated myofibroblasts in the cancer stroma or in scar tissue.

There are three major types of skin cancer: melanoma, basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). BCC and SCC are often referred to as non-melanoma skin cancer (NMSC). NMSCs are relatively non-lethal and curable by surgery, hence are not reportable in most cancer registries all over the world. Melanoma is the deadliest skin cancer. Its incidence rate (case number) is about 1/10th of that for NMSC, yet its death toll is ~8 fold higher than NMSC.Melanomas arise from melanocytes which are normally located on the basement membrane with dendrites extending into the epidermal keratinocytes. A major known function of melanocytes is to produce pigments which are enclosed by lipid membrane (termed melanosomes) and distribute them into keratinocytes, thus give different shade of skin colors. BCCs arise from basal cells, which are a layer of cells located at the deepest part of epidermis. Basal cells are recently considered to be skin stem cells as they are constantly proliferating and generating keratinocytes which are continuously pushed to the surface and eventually become a dead layer of stratum corneum. Squamous cells are the keratinocytes which resembles fish scale shape, ie, those initiated from basal cells and differentiated into squamous cells. Both basal cells and squamous cells belong to keratinocytes, therefore sometimes BCC and SCC are termed keratinocyte cancer.These three types of cancer share many characteristics, yet they are very different from etiology to progression. One shared characteristic of skin cancer is that, according to the current views, they all are caused by solar or artificial ultraviolet radiation (UVR). UVA and UVB from solar UVR are the major UV bands reaching the earth surface. Both UV types cause DNA damage and immune suppression which play crucial roles in skin carcinogenesis. UVB can be directly absorbed by DNA molecules and thus causes UV-signature DNA damages; UVA, on the other hand, may function through inducing cellular ROS which then causes oxidative DNA damages [1-4]. This chapter will discuss the molecular signaling differences of UVR in melanoma and NMSC.

Background: Diagnosis of suspected basal cell carcinoma (BCC) is typically confirmed with incisional biopsy before referral to final surgery., Objective: To investigate the clinical confidence and accuracy of physicians making a diagnosis of BCC based on dermoscopic and reflectance confocal microscopy (RCM) features., Methods: This study was designed as a simulation to determine the certainty and willingness to refer to surgery without previous biopsy confirmation of BCC. Study subjects were identified with suspected BCC. Dermoscopic and RCM lesion images were obtained before biopsy. Eight clinicians with various expertise levels blindly interpreted these images and chose among four hypothetical treatment options: definite BCC, refer directly to surgery without biopsy; other malignancy, perform biopsy for diagnosis; uncertain diagnosis, perform biopsy; benign, do not biopsy. Decisions for treatment were based on dermoscopic images alone and, subsequently, on dermoscopic and RCM images combined., Results: The sensitivity for referral to surgery without biopsy was 67.6% with the use of dermoscopy; the positive predictive value (PPV) was 97.0%. Adding RCM increased the sensitivity to 76.5% and the PPV to 98.6%., Conclusions: Dermoscopy provides a high PPV for BCC. The addition of RCM to dermoscopy increases diagnostic sensitivity, particularly in less experienced dermoscopists. Physician behavior might be different if actual referrals were made for surgery without biopsy., (© 2016 The International Society of Dermatology.)