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This study examines global, regional, and national trends in melanoma and non-melanoma skin cancer (NMSC) burden from 1990 to 2021, their socioeconomic associations, and projects future trends. Data was extracted from the Global Burden of Disease (GBD) 2021 database, focusing on malignant melanoma, basal cell carcinoma (BCC), and squamous cell carcinoma (SCC). Joinpoint regression, age-period-cohort modeling, and decomposition analysis were used to assess temporal trends. The Socio-Demographic Index (SDI) was applied to examine the correlation between skin cancer burden and socioeconomic development, and ARIMA models forecasted future trends. The global burden of skin cancers has shown significant growth over the study period, with the age-standardized incidence rate (ASIR) rising globally (Estimated Annual Percentage Change, EAPC = 1.94%) from 1990 to 2021. This increase was particularly pronounced for BCC and SCC, while the melanoma DALYs rate declined (EAPC = -0.67%). In 2021, the most recent year covered, the global incidence of skin cancers was 6.64 million cases, with an ASIR of 77.66 per 100,000 and a disability-adjusted life years (DALYs) burden of 2.89 million cases. Significant geographic disparities were observed, with Australasia and North America reporting the highest ASIR, while middle-SDI regions exhibited rapid increases. Skin cancer incidence is rising globally, driven by demographic changes, increased UV exposure, and improved detection. The burden of melanoma has decreased, which may be related to advances in treatment. Targeted prevention, equitable access to care, and tailored regional strategies are crucial to mitigating the growing impact of skin cancers worldwide. [ABSTRACT FROM AUTHOR]

Arsenic (As) is a risk factor for non-melanoma skin cancer (NMSC). From a six-year follow-up study on 7000 adults exposed to As, we reported the associations of single-nucleotide variation in tumor tissue and gene expression. Here, we identify the associations of small deletions (DELs) and transcriptomic profiles in NMSC. Comparing the (a) NMSC tissue (n = 32) and corresponding blood samples from each patient, and (b) an independent set of non-lesional, healthy skin (n = 16) and paired blood, we identified NMSC-associated DELs. Differential expressions of certain gene pathways (TGF-β signaling pathway, IL-17 pathway, PD-L1 pathway, etc.) showed significant interactions with these somatic DELs and As exposure. In low-As-exposure cases, the DELs in APC were associated with the up-regulation of inflamed T-Cell-associated genes by a fold change (FC) of 8.9 (95% CI 4.5–17.6), compared to 5.7 (95% CI 2.9–10.8) without APC DELs; in high-As-exposure cases, the APC DELs were associated with an FC of 5.8 (95% CI 3.5–9.8) compared to 1.2 (95% CI −1.3 to 1.8) without APC DELs. We report, for the first time, the significant associations of somatic DELs (many in STR regions) in NMSC tissue and As exposure with many dysregulated gene pathways. These findings may help in selecting groups of patients for potential targeted therapy like PD-L1 inhibitors, IL-17 inhibitors, and TGF-β inhibitors in the future. [ABSTRACT FROM AUTHOR]

Albinos are at great risk for developing cutaneous malignancy. We report a 33-year-old patient of occulocutaneous albinism who presented with multiple actinic keratoses and basal-cell carcinoma. This report highlights the increase in vascular structures seen on dermoscopy as a clue toward malignant transformation. We hereby emphasize the role of dermoscopy for monitoring and screening of skin tumors in albinism and other genodermatosis prone to skin tumors.

Albinos are at great risk for developing cutaneous malignancy. We report a 33-year-old patient of occulocutaneous albinism who presented with multiple actinic keratoses and basal-cell carcinoma. This report highlights the increase in vascular structures seen on dermoscopy as a clue toward malignant transformation. We hereby emphasize the role of dermoscopy for monitoring and screening of skin tumors in albinism and other genodermatosis prone to skin tumors [ABSTRACT FROM AUTHOR]

Background and Objectives: Non-melanoma skin cancers (NMSCs) include basal cell carcinoma (BCC) and squamous-cell carcinoma (SCC), as well as a wide range of rare skin tumors. NMSCs is the most frequently diagnosed type of tumor among Caucasians. We aimed at estimating the incidence and mortality of NMSCs in the Salento area (Lecce province, Southern Italy), whose population is assumed to experience heavy and frequent sun exposure due to climatic/environmental factors, both for working and leisure activities. Materials and Methods: We computed the incidence of NMSCs in the Province of Lecce by examining the comprehensive real-world data collected by the local cancer registry, which covers all the 830,000 inhabitants, over a period of fifteen years (from 2003 to 2017), with a focus on the latest 5 years (2013–2017) for the analysis of the different histologic morphologies of these tumors. The incidence of NMSCs has been described in terms of absolute frequencies, crude rates and age-adjusted direct standardized rates (DSR). Joinpoint analysis was used to examine temporal trends in the incidence of NMSCs and estimate annual percent changes (APCs). Results: During the period of 2003–2017, the incidence of NMSCs reached a direct standardized rate (DSR) of 162.62 per 100,000 in men (mortality 1.57 per 100,000) and 89.36 per 100,000 in women (mortality 0.52 per 100,000), respectively. The incidence significantly increased among both men and women across the entire period. Basal cell carcinoma (BCC), with its different morphologies, represented about 67.6% of the NMSCs in men (n = 2139 out of a total of 3161 tumors observed between 2013 and 2017) and about 75.8% of the NMSCs in women (n = 1718 out of a total of 2264 tumors from 2013 to 2017), thus accounting for the vast majority of NMSCs. The results are consistent with the literature data carried out both at national and international level. Conclusions: Proper monitoring of this phenomenon through timely reporting and recording of all new NMSC cases is necessary to develop new preventive strategies.

Background and Objectives: Non-melanoma skin cancers (NMSCs) include basal cell carcinoma (BCC) and squamous-cell carcinoma (SCC), as well as a wide range of rare skin tumors. NMSCs is the most frequently diagnosed type of tumor among Caucasians. We aimed at estimating the incidence and mortality of NMSCs in the Salento area (Lecce province, Southern Italy), whose population is assumed to experience heavy and frequent sun exposure due to climatic/environmental factors, both for working and leisure activities. Materials and Methods: We computed the incidence of NMSCs in the Province of Lecce by examining the comprehensive real-world data collected by the local cancer registry, which covers all the 830,000 inhabitants, over a period of fifteen years (from 2003 to 2017), with a focus on the latest 5 years (2013–2017) for the analysis of the different histologic morphologies of these tumors. The incidence of NMSCs has been described in terms of absolute frequencies, crude rates and age-adjusted direct standardized rates (DSR). Joinpoint analysis was used to examine temporal trends in the incidence of NMSCs and estimate annual percent changes (APCs). Results: During the period of 2003–2017, the incidence of NMSCs reached a direct standardized rate (DSR) of 162.62 per 100,000 in men (mortality 1.57 per 100,000) and 89.36 per 100,000 in women (mortality 0.52 per 100,000), respectively. The incidence significantly increased among both men and women across the entire period. Basal cell carcinoma (BCC), with its different morphologies, represented about 67.6% of the NMSCs in men (n = 2139 out of a total of 3161 tumors observed between 2013 and 2017) and about 75.8% of the NMSCs in women (n = 1718 out of a total of 2264 tumors from 2013 to 2017), thus accounting for the vast majority of NMSCs. The results are consistent with the literature data carried out both at national and international level. Conclusions: Proper monitoring of this phenomenon through timely reporting and recording of all new NMSC cases is necessary to develop new preventive strategies. [ABSTRACT FROM AUTHOR]

Simple Summary: Artificial intelligence (AI) has shown promise in detecting and diagnosing nonmelanoma skin cancer through image analysis. The incidence of skin cancer continues to rise each year, and it is estimated that one in five Americans will have nonmelanoma skin cancer at some point in their lifetime. Non-invasive diagnostic tools are becoming more widely adopted as the standard of care. When integrated with AI, there is the potential to identify skin cancer earlier and more rapidly compared to traditional methods. This review aims to assess the current status of AI diagnostic algorithms in tandem with noninvasive imaging for the detection of nonmelanoma skin cancer. Background: The objective of this study is to systematically analyze the current state of the literature regarding novel artificial intelligence (AI) machine learning models utilized in non-invasive imaging for the early detection of nonmelanoma skin cancers. Furthermore, we aimed to assess their potential clinical relevance by evaluating the accuracy, sensitivity, and specificity of each algorithm and assessing for the risk of bias. Methods: Two reviewers screened the MEDLINE, Cochrane, PubMed, and Embase databases for peer-reviewed studies that focused on AI-based skin cancer classification involving nonmelanoma skin cancers and were published between 2018 and 2023. The search terms included skin neoplasms, nonmelanoma, basal-cell carcinoma, squamous-cell carcinoma, diagnostic techniques and procedures, artificial intelligence, algorithms, computer systems, dermoscopy, reflectance confocal microscopy, and optical coherence tomography. Based on the search results, only studies that directly answered the review objectives were included and the efficacy measures for each were recorded. A QUADAS-2 risk assessment for bias in included studies was then conducted. Results: A total of 44 studies were included in our review; 40 utilizing dermoscopy, 3 using reflectance confocal microscopy (RCM), and 1 for hyperspectral epidermal imaging (HEI). The average accuracy of AI algorithms applied to all imaging modalities combined was 86.80%, with the same average for dermoscopy. Only one of the three studies applying AI to RCM measured accuracy, with a result of 87%. Accuracy was not measured in regard to AI based HEI interpretation. Conclusion: AI algorithms exhibited an overall favorable performance in the diagnosis of nonmelanoma skin cancer via noninvasive imaging techniques. Ultimately, further research is needed to isolate pooled diagnostic accuracy for nonmelanoma skin cancers as many testing datasets also include melanoma and other pigmented lesions. [ABSTRACT FROM AUTHOR]

Abstract Background Information about global and local epidemiology and trends of skin cancers is limited, which increases the difficulty of cutaneous cancer control. Methods To estimate the global spatial patterns and temporal trends of skin cancer burden. Based on the GBD 2019, we collected and analyzed numbers and age‐standardized rates (ASR) of skin cancer incidence, disability‐adjusted life years (DALYs) and mortality (ASIR, ASDR, and ASMR) in 204 countries from 1990 through 2019 were estimated by age, sex, subtype (malignant skin melanoma [MSM], squamous‐cell carcinoma [SCC], and basal‐cell carcinoma [BCC]), Socio‐demographic Index (SDI), region, and country. Temporal trends in ASR were also analyzed using estimated annual percentage change. Results Globally, in 2019, there were 4.0 million BCC, 2.4 million SCC, and 0.3 million MSM. There were approximately 62.8 thousand deaths and 1.7 million DALYs due to MSM, and 56.1 thousand deaths and 1.2 million DALYs were attributed to SCC, respectively. The men had higher ASR of skin cancer burden than women. The age‐specific rates of global skin cancer burden were higher in the older adults, increasing trends observed from 55 years old. Geographically, the numbers and ASR of skin cancers varied greatly across countries, with the largest burden of ASIR in high SDI regions. However, an unexpected increase was observed in some regions from 1990 to 2019, such as East Asia, and Sub‐Saharan Africa. Although there was a slight decrease of the ASMR and ASDR, the global ASIR of MSM dramatically increased, 1990–2019. Also, there was a remarkable increase in ASR of BCC and SCC burden. Conclusions Skin cancer remains a major global public health threat. Reducing morbidity and mortality strategies such as primary and secondary prevention should be reconsidered, especially in the most prevalent and unexpected increased regions, especially for those areas with the greatest proportions of their population over age 55.

Abstract Treatment of choice for nodular basal-cell carcinomas (BCCs) is complete excision, implying that small lesions are of minor concern. Metastasis is very rare (

ABSTRACT Polypoid basal-cell carcinoma (BCC) is a rare tumor, considered a clinical and histopathological variant of the nodular BCC, presenting broad exophytic or pedunculated base that connects to the surface of the skin and histopathologically displays the neoplastic aggregations restricted to the polypoid zone. We report a clinical case of BCC, with a bibliographical review, highlighting the clinical similarity of such malignant tumor with other benign and malignant tumors of the skin, besides the importance of dermoscopy for the diagnostic aid.

Background: Information about global and local epidemiology and trends of skin cancers is limited, which increases the difficulty of cutaneous cancer control. Methods: To estimate the global spatial patterns and temporal trends of skin cancer burden. Based on the GBD 2019, we collected and analyzed numbers and age‐standardized rates (ASR) of skin cancer incidence, disability‐adjusted life years (DALYs) and mortality (ASIR, ASDR, and ASMR) in 204 countries from 1990 through 2019 were estimated by age, sex, subtype (malignant skin melanoma [MSM], squamous‐cell carcinoma [SCC], and basal‐cell carcinoma [BCC]), Socio‐demographic Index (SDI), region, and country. Temporal trends in ASR were also analyzed using estimated annual percentage change. Results: Globally, in 2019, there were 4.0 million BCC, 2.4 million SCC, and 0.3 million MSM. There were approximately 62.8 thousand deaths and 1.7 million DALYs due to MSM, and 56.1 thousand deaths and 1.2 million DALYs were attributed to SCC, respectively. The men had higher ASR of skin cancer burden than women. The age‐specific rates of global skin cancer burden were higher in the older adults, increasing trends observed from 55 years old. Geographically, the numbers and ASR of skin cancers varied greatly across countries, with the largest burden of ASIR in high SDI regions. However, an unexpected increase was observed in some regions from 1990 to 2019, such as East Asia, and Sub‐Saharan Africa. Although there was a slight decrease of the ASMR and ASDR, the global ASIR of MSM dramatically increased, 1990–2019. Also, there was a remarkable increase in ASR of BCC and SCC burden. Conclusions: Skin cancer remains a major global public health threat. Reducing morbidity and mortality strategies such as primary and secondary prevention should be reconsidered, especially in the most prevalent and unexpected increased regions, especially for those areas with the greatest proportions of their population over age 55. [ABSTRACT FROM AUTHOR]

Treatment of choice for nodular basal-cell carcinomas (BCCs) is complete excision, implying that small lesions are of minor concern. Metastasis is very rare (< 1%). However, locally advanced basal-cell carcinomas (laBCCs), which are ineligible for surgery or radiation, are a therapeutic challenge. First-generation Smoothened (SMO) inhibitors (vismodegib, sonidegib) have been approved for treatment, but common side effects limit their use. Numerous new compounds are being investigated in clinical trials as potential therapeutic alternatives, among them second-generation SMO inhibitors, other Hedgehog signaling pathway inhibitors, immune-checkpoint inhibitors and intralesional modalities such as oncolytic viruses. Neoadjuvant treatment regimens open another field. This article deals with the clinical management of laBCCs, based on the description of an illustrative case from our department featuring multiple extensive lesions of the scalp. In this short review we will discuss therapeutic options and implications for the future. Some of the new strategies might potentially evolve as alternatives in the management of genodermatoses such as basal-cell carcinoma syndrome, if proven effective and safe. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Basal-cell carcinoma (BCC) rarely occurs on the lip. We herein report a case of an 89-year-old male, who presented with a blackish nodule on the vermilion border and the outer mucosa of the right side of the upper lip. A diagnosis of pigmented BCC was made by histopathological examination. The patient was successfully treated by Abbe flap with excellent esthetic and functional results. We have reviewed 64 cases of lip BCCs previously reported. There was no gender predominance, and the upper lip was involved 1.5 times higher than the lower lip. There was no lymph node metastasis, and thus, lip BCC had a good prognosis.

Skin malignancies usually take the form of basal cell carcinoma, squamous cell carcinoma and malignant melanoma. The head and neck malignant tumor pathology can be addressed by multiple medical specialists: maxillofacial surgeons, dermatologists and plastic surgeons. Although considered a less aggressive type of malignancy, the basal-cell carcinoma can extend to profound regions and require extensive surgery and immediate reconstructions of the defect area with regional or distant flaps. The treatment does not end with the surgical phase, the follow-up being as equally important, as there is a 50% higher risk for developing a second skin malignancy in the next 5-10 years postoperatively. [ABSTRACT FROM AUTHOR]

Skin cancers are the most common type of cancer worldwide, with increasing incidence and prevalence in the past decades. It has been aimed to determine the recurrence rates after different treatment options, and the results proved that surgical excision and radiotherapy had the lowest relapse rates, whereas curettage and photodynamic therapy resulted in five-year relapse rates of up to 70%(1). The axial paramedian forehead is the flap of choice for extensive nose defects reconstruction due to its great variability in terms of size and shape of the donor and recipient site. When used as a three-dimensional pattern flap, it will restore not only the dimensions of the defect, but also the proportion and contour of the nose by replacing skin with tissue of similar color, texture and thickness. [ABSTRACT FROM AUTHOR]

Gorlin-Goltz syndrome (GGS) is a genetic disease of autosomal dominant inheritance. It is characterized by the presence of multiple basal-cell carcinoma foci, odontogenic keratocysts and anomalies of the skin, eyes, bones, nervous and endocrine system. Patients are predisposed to various neoplasms, such as medulloblastoma and fibrosarcoma. Rare incidence of the syndrome and multi-organ manifestations require providing patients with multi-specialist care, in particular, with dermatologists, dentists and surgeons. This is a case report of a 63-year-old patient with Gorlin-Goltz syndrome treated for odontogenic keratocysts of the mandible and basal-cell carcinoma. The report includes an extensive review of the GGS with regard to its etiology, features, clinical examination, diagnostic criteria and treatment modalities. [ABSTRACT FROM AUTHOR]

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Background: Benign lichenoid keratosis (BLK, LPLK) is often misdiagnosed clinically as superficial basal-cell carcinoma (BCC), especially when occurring on the trunk. However, BCCs undergoing regression may be associated with a lichenoid interface dermatitis that may be misinterpreted as BLK in histopathologic sections. Methods: In order to assess the frequency of remnants of BCC in lesions interpreted as BLK, we performed step sections on 100 lesions from the trunk of male patients that had been diagnosed as BLK. Results: Deeper sections revealed remnants of superficial BCC in five and remnants of a melanocytic nevus in two specimens. In the original sections of cases in which a BCC showed up, crusts tended to be more common, whereas vacuolar changes at the dermo-epidermal junction and melanophages in the papillary dermis tended to be less common and less pronounced. Conclusions: Lesions from the trunk submitted as BCC and presenting histopathologically as a lichenoid interface dermatitis are not always BLKs. Although no confident recommendations can be given on the basis of this limited study, deeper sections may be warranted if lesions are crusted and/or associated with only minimal vacuolar changes at the dermo-epidermal junction and no or few melanophages in the papillary dermis.

The aim of this study was to compare the expressions of mRNA for metalloproteinases (MMP-2 and MMP-9) and type IV collagen in two different histological types of basal-cell carcinoma (BCCs; nodular and infiltrative) and in normal tissues from the tumor interface. The study included biopsy specimens of the skin involved with BCC and normal skin adjacent the lesion. The expressions of mRNA for MMP-2, MMP-9 and type IV collagen were determined by means of RT-PCR (Reverse transcription polymerase chain reaction). The level of type IV collagen mRNA in nodular and infiltrative BCCs turned out to be significantly lower, and the expressions of MMP-2 and MMP-9 mRNA significantly higher than in normal tissues adjacent to these tumors. The expression of mRNA for MMP-9 but not for MMP-2 was significantly higher in infiltrative BCCs than in the nodular BCCs. In turn, normal tissues adjacent to nodular BCCs showed significantly higher levels of mRNA for MMP-2 and significantly lower levels of type IV collagen mRNA than the normal tissues from the interface of infiltrative BCCs. The findings suggest that MMP-2 and MMP-9 could be used as prognostic factors of BCCs. [ABSTRACT FROM AUTHOR]

Basal-cell carcinoma (BCC) rarely occurs on the lip. We herein report a case of an 89-year-old male, who presented with a blackish nodule on the vermilion border and the outer mucosa of the right side of the upper lip. A diagnosis of pigmented BCC was made by histopathological examination. The patient was successfully treated by Abbe flap with excellent esthetic and functional results. We have reviewed 64 cases of lip BCCs previously reported. There was no gender predominance, and the upper lip was involved 1.5 times higher than the lower lip. There was no lymph node metastasis, and thus, lip BCC had a good prognosis. [ABSTRACT FROM AUTHOR]

Radiotherapy (RT) has been used for the treatment of skin cancers since very early after the discovery of X-rays. Indications for radiotherapy in non-melanoma cancers are controversial, and are usually decided according to the tumor type and the possibility of curing the patient with surgery. The introduction of sophisticated surgery techniques and the information of the general population on potential late radiation-induced toxicity and carcinogenesis have led to limiting radiation indications in the dermatologist community. However, radiotherapy has undergone considerable development, including technological advances, to enable limiting doses to the organs at risk. Thus, side effects due to high doses and/or the use of old radiotherapy (RT) techniques have been significantly decreased. In this systematic review we aim to discuss indications of radiotherapy in non-melanoma skin cancers and focus on new advances that may lead to rehabilitating this treatment option according to the tumor’s radiosensitivity and the clinical benefit/risk ratio. Finally, for each type of cancer, we suggest “the best RT practice”. [ABSTRACT FROM AUTHOR]

Basal-cell carcinomas may show irregular, asymmetric subclinical growth. This study analyzed the efficacy of 'breadloaf' microscopy (serial sectioning) and three-dimensional ( 3D) microscopy in detecting positive tumor margins. Two hundred eighty-three (283) tumors (51.2%) were put into the breadloaf microscopy group; 270 tumors (48.8%) into the 3D microscopy group. The position of any detected tumor outgrowths was identified in clock face fashion. The time required for cutting and embedding the specimens and the examination of the microscopic slides was measured. Patient/tumor characteristics and surgical margins did not differ significantly. Tumor outgrowths at the excision margin were found in 62 of 283 cases (21.9%) in the breadloaf microscopy group and in 115 of 270 cases (42.6%) in the 3D microscopy group, constituting a highly significant difference (p < 0.001). This difference held true with incomplete excision of fibrosing (infiltrative/sclerosing/morpheaform) tumors [32.9% in the breadloaf microscopy group and 57.5% in the 3D microscopy group (p = 0.003)] and also with solid (nodular) tumors [16.1 and 34.2%, respectively (p < 0.001)]. The mean overall examination time required showed no important difference. In summary, for detection of tumor outgrowths, 3D microscopy has almost twice the sensitivity of breadloaf microscopy, particularly in the situation of aggressive/infiltrative carcinomas. [ABSTRACT FROM AUTHOR]

Vismodegib, a highly selective inhibitor of hedgehog ( Hh) pathway, is an approved treatment for basal-cell carcinoma. Patients on treatment with vismodegib often report profound alterations in taste sensation. The cellular mechanisms underlying the alterations have not been studied. Sonic Hh ( Shh) signaling is required for cell growth and differentiation. In taste buds, Shh is exclusively expressed in type IV taste cells, which are undifferentiated basal cells and the precursors of the three types of taste sensing cells. Thus, we investigated if vismodegib has an inhibitory effect on taste cell turnover because of its known effects on Hh signaling. We gavaged C57 BL/6J male mice daily with either vehicle or 30 mg/kg vismodegib for 15 weeks. The gustatory behavior and immunohistochemical profile of taste cells were examined. Vismodegib-treated mice showed decreased growth rate and behavioral responsivity to sweet and bitter stimuli, compared to vehicle-treated mice. We found that vismodegib-treated mice had significant reductions in taste bud size and numbers of taste cells per taste bud. Additionally, vismodegib treatment resulted in decreased numbers of Ki67- and Shh-expressing cells in taste buds. The numbers of phospholipase C β2- and α-gustducin-expressing cells, which contain biochemical machinery for sweet and bitter sensing, were reduced in vismodegib-treated mice. Furthermore, vismodegib treatment resulted in reduction in numbers of T1R3, glucagon-like peptide-1, and glucagon-expressing cells, which are known to modulate sweet taste sensitivity. These results suggest that inhibition of Shh signaling by vismodegib treatment directly results in alteration of taste due to local effects in taste buds. [ABSTRACT FROM AUTHOR]

Vismodegib (Erivedge) is a first-in-class small-molecule hedgehog pathway inhibitor for the treatment of adults with advanced basal-cell carcinoma. Because this pathway is known to play key roles in patterning and growth during vertebrate development, vismodegib was anticipated to be embryotoxic. To support marketing applications, an embryofetal development study was completed in which a limited number of pregnant rats ( n = 6/group) was administered vismodegib by oral gavage on gestation days 6 to 17. When vismodegib was administered at ≥60 mg/kg/day, doses associated with evidence of pharmacologic activity in previous rat toxicity studies, all conceptuses were resorbed at an early embryonic stage in the absence of significant maternal toxicity. When administered at 10 mg/kg/day, corresponding to an exposure (AUC0-24h) approximately 15% of the median in patients at steady state, a variety of malformations were observed, including absent/fused digits in the hindlimb of multiple fetuses, multiple craniofacial abnormalities in one fetus, and an anorectal defect in one fetus. In addition, the incidence of variations, including dilated renal pelvis or ureter and incompletely or unossified skeletal elements, was significantly greater when compared with the controls. These results confirmed that vismodegib is likely to be embryotoxic at clinically relevant maternal exposures, and doses ≥60 mg/kg/day resulted in a 100% incidence of embryolethality that likely resulted from severe defects in early embryonic development. In contrast, craniofacial defects typically associated with hedgehog pathway inhibition were only observed in one fetus at the low dose of 10 mg/kg/day, which likely reflected minimal or intermittent pathway inhibition at low exposures. [ABSTRACT FROM AUTHOR]

There is a paucity of data on basal-cell carcinoma (BCC) in the United States, since most national registries do not collect information on BCC. We evaluated BCC incidence trends and associated risk factors for BCC in 140,171 participants from a US female cohort, the Nurses' Health Study (1986-2006), and a US male cohort, the Health Professionals' Follow-up Study (1988-2006). Age-adjusted BCC incidence rates increased from 519 cases per 100,000 person-years to 1,019 cases per 100,000 person years for women and increased from 606 cases per 100,000 person-years to 1,488 cases per 100,000 person-years for men during the follow-up period. Cox proportional hazards analysis identified the following phenotypic risk factors for BCC in both cohorts: family history of melanoma, blond or red hair colors, higher number of extremity moles, higher susceptibility to sunburn as a child/ adolescent, and higher lifetime number of severe/blistering sunburns. The multivariate-adjusted risk ratio for the highest quintile of cumulative midrange ultraviolet B flux exposure versus the lowest quintile was 3.18 (95% confidence interval: 2.70, 3.76) in women and 1.90 (95% confidence interval: 1.57, 2.29) in men. BCC incidence was generally higher in men than in women, and BCC risk was strongly associated with several phenotypic and exposure factors, including midrange ultraviolet B radiation, in our study populations. [ABSTRACT FROM AUTHOR]

Sonic hedgehog (Shh) pathway impairment plays a key role in the pathogenesis of basal-cell carcinomas (BCC), the most frequent skin tumor among Caucasians. Shh, Smo, and Gli2 family proteins are necessary for adequate and controlled cell proliferation. The aim of this study was to evaluate Shh, Smo, and Smo expression in BCC skin biopsies taken from sun-exposed areas. 41 BCC skin biopsies and 22 healthy skin specimens (the control group) taken from the same areas served as material for the study. All specimens were immunohistochemically stained with monoclonal antibodies directed against the chosen proteins. Shh and Smo expression (cytoplasmic pattern) were recorded semiquantitatively using a four-grade score (0-3). Gli2 expression (nuclear pattern) was determined using an image analysis system (semiautomatic function). The immunoexpression of the Shh and Smo proteins significantly increased in the BCC group, as compared with the normal controls (for Shh, the mean intensity was 1.67 in BCC vs. 1.17 in the control group, p < 0.001; for Smo, the mean intensity was 1.46 in BCC vs. 0.99 in the control group, p < 0.001). The staining for Gli2 in the BCC group was completely negative, but indicated the presence of Gli2 in the control patients (1.15 Gli2+ cells/100 cells). Sonic hedgehog pathway dysregulation may play an important role in skin cancerogenesis leading to BCC development. [ABSTRACT FROM AUTHOR]

Abstract: Objective: The paper addresses the problem of finding visual patterns in histology image collections. In particular, it proposes a method for correlating basic visual patterns with high-level concepts combining an appropriate image collection representation with state-of-the-art machine learning techniques. Methodology: The proposed method starts by representing the visual content of the collection using a bag-of-features strategy. Then, two main visual mining tasks are performed: finding associations between visual-patterns and high-level concepts, and performing automatic image annotation. Associations are found using minimum-redundancy-maximum-relevance feature selection and co-clustering analysis. Annotation is done by applying a support-vector-machine classifier. Additionally, the proposed method includes an interpretation mechanism that associates concept annotations with corresponding image regions. The method was evaluated in two data sets: one comprising histology images from the different four fundamental tissues, and the other composed of histopathology images used for cancer diagnosis. Different visual-word representations and codebook sizes were tested. The performance in both concept association and image annotation tasks was qualitatively and quantitatively evaluated. Results: The results show that the method is able to find highly discriminative visual features and to associate them to high-level concepts. In the annotation task the method showed a competitive performance: an increase of 21% in f-measure with respect to the baseline in the histopathology data set, and an increase of 47% in the histology data set. Conclusions: The experimental evidence suggests that the bag-of-features representation is a good alternative to represent visual content in histology images. The proposed method exploits this representation to perform visual pattern mining from a wider perspective where the focus is the image collection as a whole, rather than individual images. [Copyright &y& Elsevier]

Abstract: In a long-term cohort study, we calculated cancer incidences and survival rates after the development of these cancers in kidney-transplant recipients. The cancer incidences were compared with those in the general population. The occurrence of cancer was recorded in all patients who received kidney transplantation between 1966 and 2006. The median follow-up time was more than 9 years with a maximum of almost 40 years. Altogether 327 (17%) of 1906 patients developed cancer after transplantation: 142 (7%) had non-cutaneous malignancies; 178 (9%) cutaneous squamous-cell carcinomas and 138 (7%) basal-cell carcinomas. The cumulative incidence of any cancer was 13%, 33% and 47% after 10, 20 and 30 years, respectively. The incidences of cancers of the oral cavity, stomach, female genital organs, kidney, thyroid gland, leukemias and lymphomas, and cutaneous squamous-cell carcinoma were significantly increased with a highest standardized morbidity ratio of 40 for cutaneous squamous-cell carcinomas. Survival rates after non-cutaneous malignancies were 57%, 43% and 36% and after non-melanocytic skin cancer 99%, 90% and 77% after 1, 3 and 5 years, respectively. The increased incidence of non-cutaneous malignancies after kidney transplantation is associated with a high mortality. Prevention of cancer after kidney transplantation should be a major focus of future research. [Copyright &y& Elsevier]

Purpose: This retrospective, case-control study aimed at evaluating the influence of patient-, tumor-, and management-related factors on the outcome of surgical therapy for facial basal-cell carcinoma (BCC) employing a multivariate analysis. Methods: One hundred one patients who underwent ablative surgery for BCC of the face at the Department of Oral and Maxillofacial Surgery/ Plastic Surgery, University Hospital Jena, between April 2005 and January 2009, were analyzed. Patients' charts were screened for anamnestic features as well as management- and follow-up-related details. Standardized photographs were subjected to an esthetic evaluation. Logistic regression was used to identify factors associated with postsurgical wound healing disorders, recurrence, and esthetic impairment. Results: Following surgical BCC treatment, age and tumor location in the area of the eyes, nose, lips, and ears were independent predictors of wound healing disorders. Tumor location in the area of the eyes, nose, lips, and ears, subtype and class were independent predictors of recurrence. Female gender and location in the area of the eyes, nose, lips, and ears were independent predictors of esthetic impairment. Micrographic surgery and distant reconstruction technique were management-related predictors of wound healing disorders and esthetic outcome, respectively. Conclusions: The identified negative predictors of treatment outcome should be included in the informed consent to objectify the patient's preoperative expectations. [ABSTRACT FROM AUTHOR]

An increased level of mutagenesis, partially caused by imbalanced activities of error prone DNA polymerases, is a key symptom of cell malignancy. To clarify the possible role of incorrect DNA polymerase ι (Pol ι) function in increased frequency of mutations in mammalian cells, the activity of this enzyme in extracts of cells of different mouse organs and human eye (melanoma) and eyelid (basal-cell skin carcinoma) tumor cells was studied. Both Mg2+, considered as the main activator of the enzyme reaction of in vivo DNA replication, and Mn2+, that activates homogeneous Pol ι preparations in experiments in vitro more efficiently compared to all other bivalent cations, were used as cofactors of the DNA polymerase reaction in these experiments. In the presence of Mg2+, the enzyme was active only in cell extracts of mouse testicles and brain, whereas in the presence of Mn2+ the activity of Pol ι was found in all studied normal mouse organs. It was found that in cell extracts of both types of malignant tumors (basal-cell carcinoma and melanoma) Pol ι activity was observed in the presence of either Mn2+ or Mg2+. Manganese ions activated Pol ι in both cases, though to a different extent. In the presence of Mn2+ the Pol ι activity in the basal-cell carcinoma exceeded 2.5-fold that in control cells (benign tumors from the same eyelid region). In extracts of melanoma cells in the presence of either cation, the level of the enzyme activity was approximately equal to that in extracts of cells of surrounding tumor-free tissues as well as in eyes removed after traumas. The distinctive feature of tissue malignancy (in basal-cell carcinoma and in melanoma) was the change in DNA synthesis revealed as Mn2+-activated continuation of DNA synthesis after incorrect incorporation of dG opposite dT in the template by Pol ι. Among cell extracts of different normal mouse organs, only those of testicles exhibited a similar feature. This similarity can be explained by cell division blocking that occurs in all normal cells except in testicles and in malignant cells. [ABSTRACT FROM AUTHOR]

We directly compared risk factors between 214 histologically confirmed melanomas (CMM), 215 basal-cell carcinomas (BCC) and 139 squamous-cell carcinomas (SCC) in a multiple case-case-control study with 349 controls from patients without dermatological disease admitted to the same hospitals. Subjects with fair hair had a significant risk increase for all types of tumours at a comparable level (OR(adj) for blonde hair: CMM 2.3; SCC 2.4; BCC 2.3). The effect of pale eyes was significant and similar for CMM and BCC (OR(adj) 2.6). Intermittent sun exposure measured in hours spent at beach during holidays was significant for both CMM (OR(adj) 2.6 for more than 7000 lifelong hours) and BCC (OR(adj) 2.1 for more than 7000 lifelong hours), while SCC exhibited a significant risk increase for chronic exposure to sunlight measured in hours of outdoor work (OR(adj) 2.2 for more than 6000 lifelong hours). In the case-case comparison using a multinomial logistic regression model, we found a statistically significant risk difference for pale eyes, and number of naevi in the CMM group, compared to other skin cancers. For intermittent sun exposure, there was a significant risk difference of BCC when compared to the risk of SCC. Factors influencing risk of SCC are different, with chronic exposure to sun playing a major role in causing this type of carcinoma. [ABSTRACT FROM AUTHOR]

Expression of human leukocyte elastase inhibitor, elafin, otherwise known as skin-derived antileukoproteinase inhibitor (SKALP), was investigated in normal and abnormal oral tissues using a specific anti-SKALP rabbit antiserum. Weak staining was observed in keratinizing epithelia of normal oral mucosa but not in non-keratinizing mucosa. Increased expression was also observed in the suprabasal layers of dysplastic oral epithelia and in well-differentiated squamous cell carcinoma, but not in basal cell carcinoma. A uniform strong expression was observed in all supra-basal layers of odontogenic keratocyst epithelia, except in regions where inflammatory infiltrate was adjacent to keratocyst epithelia. In contrast, elafin expression in a small number of dentigerous cysts and ameloblastomas was more patchy. The increased levels of elafin in keratocyst epithelia and dysplastic tissue may be a cellular homoeostatic response to generate a protective barrier preventing proteolytic degradation of underlying elastic tissue. [ABSTRACT FROM AUTHOR]

A "window of expression" of a 38-kD cell-surface glycoprotein MH99 (KS 1/4 antigen) has been observed in dysplastic oral tissues using an MH99-specific monoclonal antibody. It appeared that expression of this epitope increases from baseline levels in normal oral epithelium to that of high levels in mild, moderate and severe dysplasia. In invasive squamous cell carcinoma, relatively low levels of expression were observed. In contrast, high levels of expression were demonstrated in basal cell carcinomas. Antibody reactivity could clearly distinguish between the margins of histologically normal and dysplastic tissues. It is envisaged that the expression of this cell-surface glycoprotein, which is possibly related to nidogen, a matrix-adhesion molecule with receptor-like function, could be used in monitoring progression or regression of these lesions and assessment of surgical excision margins. It could also be useful in in vivo and in vitro investigations into molecular changes underlying the formation of dysplastic lesions. [ABSTRACT FROM AUTHOR]