Frequent Skin Cancer Research Articles

Differences in peripheral neuropathy in xeroderma pigmentosum complementation groups A and D as evaluated by nerve conduction studies

BackgroundXeroderma pigmentosum (XP) is a rare autosomal recessive genetic disorder with defective DNA nucleotide excision repair and associated with a high frequency of skin cancer. Approximately 25% of patients develop progressive neurological degeneration. Complementation groups XP-A and XP-D are most frequently associated with neurological disorders.Design/methodsThis is a retrospective review of patients with XP who were evaluated at NIH from 1986 to 2015 and had nerve conduction studies (NCS). In the complementation groups with peripheral neuropathy, further comparisons of the NCS were made with audiological, brain imaging, neuropsychological assessments that were also performed on most of the patients. Limited neuropathology of XP-A and XP-D patients were examined..ResultsThe 33 patients had NCS: XP-A (9 patients), XP-C (7 patients), XP-D (10 patients), XP-E (1 patient), XP-V (4 patients), and XP-unknown (2 patients). Peripheral neuropathy based on nerve conduction studies was documented only in two complementation groups: 78% (7/9) of XP-A patients had a sensorimotor neuropathy while 50% (5/10) of XP-D patients had a sensory neuropathy only. Analysis of sural sensory nerve amplitude in both complementation groups XP-A and XP-D correlated with sensorineural hearing loss (SNHL), MRI/CT severity, and Full-scale Intelligence Quotient (IQ). Analysis of fibular motor nerve amplitude in complementation XP-A correlated with SNHL and MRI/CT severity. Limited follow-up studies showed gradual loss of NCS responses compared to an earlier and more rapid progression of the hearing loss.ConclusionsDespite similar brain imaging and audiological findings patients, XP-A and XP-D complementation groups differ in the type of neuropathy, sensorimotor versus sensory alone. A few cases suggest that sensorineural hearing loss may precede abnormal NCS in XP and therefore serve as valuable clinical indicators of XP patients that will later develop peripheral neuropathy.

068 Differential expression of keratins during cutaneous squamous cell carcinoma progression

Squamous cell carcinoma (SCC) is the second most frequent skin cancer after basal cell carcinoma. Actinic keratosis (AK) arises within the sun exposed skin, eventually develops SCC in situ, and invasive SCC. Cancer cells may change their phenotypes along with tumor progression. However, the change of keratin (KRT) expression during this process is not fully understood. Previous studies showed increased expression of KRT6 and KRT16 in SCC, though these keratins are found in proliferating keratinocytes as found in psoriasis, thus not cancer specific. We have previously performed laser capture microdissection on AK, in situ SCC, and invasive SCC tissues. Messenger RNA extracted form those tissues were subjected to genechip analysis. Various keratin expression was altered between AK, in situ SCC, and invasive SCC. KRTs 6A and 6B were the most highly expressed compared to normal epidermis, with increased expression as cancer progression. Whereas KRTs 2 and 10, known as markers for differentiated keratinocytes, were down regulated in SCCs compared to normal epidermis. Among differentially expressed KRTs, KRT13 was slightly but significantly elevated in AK (FCH in AK vs. epidermis; 4.12) and further increased in in situ and invasive SCC (FCHs 30.54 and 40.47, respectively). KRT19 was not differentially expressed in AK region (FCH; 1.17), but increased in in situ and invasive SCC (FCHs; 2.80 and 11.33 respectively). Interestingly, KRT9, positive for differentiated keratinocytes in palms and soles, were detected in AKs (FCH in AK vs. epidermis; 17.25) but decreased in in situ and invasive SCCs. Immunohistochemistry of KRTs 9 and 13 were examined in AK and SCC tissues, as well as BCC and seborrheic keratosis to evaluate the disease specificity. Our results suggested that KRT13 was expressed even earlier stage of this malignancy. In addition, KRT19 might be a novel marker of malignant transformation of epidermal keratinocytes and acquisition of invasion capacity.

Small Molecules in the Treatment of Squamous Cell Carcinomas: Focus on Indirubins.

Simple SummaryIn this review, the genetic landscape of squamous cell carcinoma is related to the potential targets of indirubin-based small molecules in cancer therapy. Being a component of traditional Chinese medicine, indirubins are used to treat chronic or inflammatory diseases, and have received increasing attention in cancer treatment due to their proapoptotic and antiproliferative activity. Frequent genetic alterations of squamous cell carcinomas are summarized, and it is discussed how these may render tumors susceptible to indirubin-based small molecule inhibitors.Skin cancers are the most common malignancies in the world. Among the most frequent skin cancer entities, squamous cell carcinoma (SCC) ranks second (~20%) after basal cell carcinoma (~77%). In early stages, a complete surgical removal of the affected tissue is carried out as standard therapy. To treat advanced and metastatic cancers, targeted therapies with small molecule inhibitors are gaining increasing attention. Small molecules are a heterogeneous group of protein regulators, which are produced by chemical synthesis or fermentation. The majority of them belong to the group of receptor tyrosine kinase inhibitors (RTKIs), which specifically bind to certain RTKs and directly influence the respective signaling pathway. Knowledge of characteristic molecular alterations in certain cancer entities, such as SCC, can help identify tumor-specific substances for targeted therapies. Most frequently, altered genes in SCC include TP53, NOTCH, EGFR, and CCND1. For example, the gene CCND1, which codes for cyclin D1 protein, is upregulated in nearly half of SCC cases and promotes proliferation of affected cells. A treatment with the small molecule 5′-nitroindirubin-monoxime (INO) leads to inhibition of cyclin D1 and thus inhibition of proliferation. As a component of Danggui Longhui Wan, a traditional Chinese medicine, indirubins are used to treat chronic diseases and have been shown to inhibit inflammatory reactions. Indirubins are pharmacologically relevant small molecules with proapoptotic and antiproliferative activity. In this review, we discuss the current literature on indirubin-based small molecules in cancer treatment. A special focus is on the molecular biology of squamous cell carcinomas, their alterations, and how these are rendered susceptible to indirubin-based small molecule inhibitors. The potential molecular mechanisms of the efficacy of indirubins in killing SCC cells will be discussed as well.

Vulvar Basal Cell Carcinoma: Clinical and Histopathologic Features.

Basal cell carcinoma (BCC) is the most frequent skin cancer but <1% of the cases develop in the vulva. Histoprognostic features of vulvar BCCs are not recognized and, consequently, the treatment of the disease is not well codified. To overcome this lack of knowledge, we have performed a retrospective analysis of vulvar BBCs to assess the value of various histological features regarding the disease outcome. In all, 19 patients surgically treated for a vulvar BCC in the Centre Hospitalier Intercommunal de Créteil from March 1, 2000 to September 26, 2019 were retrieved. Clinical and histologic features were reviewed in all cases and analyzed in comparison with disease recurrence and patient's survival. The median age of the patients was 74 (range 54-99) yr. Tumor location on the labium majus was the most frequent (68%). None presented with a medical condition related to BCC. All the patients were treated by surgery alone, except one who benefited from additional radiotherapy. We found a significant association between tumor size and recurrences (P=0.031). Other features associated with disease outcome were tumor thickness, treatment type, and surgical margins. Recurrence was observed for tumors larger than 20 mm with a surgical margin of less than 3 mm. A combination of tumor size, thickness, and surgical margin are histoprognostic factors more significant than tumor subtype.

The incidence and clinical analysis of non-melanoma skin cancer

Non-melanoma skin cancers (NMSCs) are the most common malignancies diagnosed in Caucasian populations. Basal cell carcinoma (BCC) is the most frequent skin cancer, followed by squamous cell carcinoma (SCC). Unfortunately, most European cancer registries do not record individual types of NMSC. To evaluate the incidence of primary BCCs and SCCs regarding age, sex, tumour site and tumour subtype to determine trends in epidemiology of both cancers. Retrospective analysis of BCCs and SCCs diagnosed and treated across seven sites in Poland from 1999 to 2019. We recorded 13,913 NMSCs occurring in 10,083 patients. BCC represented 85.2% of all cases. SCC patients were older than BCC patients (77.1 ± 11.3 years vs. 70.1 ± 12.3 years, p < 0.01). The nodular subtype was the most common subtype of BCC, followed by the superficial and infiltrative subtypes. The superficial BCC subtype was more common on photoprotected areas (p < 0.01), whereas the nodular BCC subtype occurred on the face (p < 0.01). The high-risk SCC subtypes were more common on face compared to low-risk SCC subtypes (p < 0.01). BCC and SCC are common malignancies developing at various ages and anatomical sites. These data underline the need for better registration policies regarding NMSC in order to improve prevention and treatment strategies for these tumours.

Environmental factors’ contribution in skin cancer etiology

Skin cancers are the most frequent types of malignant tumors worldwide, being mostly found in light-skinned populations, with a ratio of 30%. Approximately 3 million non-melanoma skin cancers and 132000 melanoma cases are diagnosed globally each year. The most frequent skin cancers are the basal cell carcinoma, squamous cell carcinoma and malignant melanoma. The incidence, morbidity and mortality of skin cancers are on the rise and have become a major public health concern. We aim to review the most important environmental factors involved in the development of skin cancers, along with the incidence rates and preventive behaviors or strategies (including personal behavioral changes and public educational initiatives). Ultraviolet radiation (UVR) is a well-known physical hazard, responsible for photoaging, photoallergy and phototoxic reactions, being heavily involved in carcinogenesis, including melanoma development. Overexposure to natural and artificial UVR is a public health problem. Sunburns, especially in childhood, are an important risk factor for melanoma development. Excessive exposure causes cumulative damage which determines immune suppression and skin cancer initiation. Transplant patients and AIDS patients have an increased incidence of skin cancer. Some treatment methods, including radiotherapy, phototherapy and psoralen and ultraviolet A (PUVA) therapy can lead to skin cancer development. Viral infections such as those with human papilloma virus can trigger the initiation of squamous cell carcinoma. Patients with familial genetic syndromes are highly sensitive to certain types of skin cancers. Ionising radiation, environmental pollutants, chemical carcinogenic agents and work exposure have been associated with skin cancer. Artificial UV radiation exposure (tanning beds and lamps), aging, skin color, personal diet and smoking are important risk factors. Ultraviolet radiation is the main etiological agent in skin cancer development. A better understanding of the causative factors is an essential step in skin cancer prevention.

Epidermal activation of Hedgehog signaling establishes an immunosuppressive microenvironment in basal cell carcinoma by modulating skin immunity.

Genetic activation of hedgehog/glioma-associated oncogene homolog (HH/GLI) signaling causes basal cell carcinoma (BCC), a very frequent nonmelanoma skin cancer. Small molecule targeting of the essential HH effector Smoothened (SMO) has proven an effective therapy of BCC, though the frequent development of drug resistance poses major challenges to anti-HH treatments. In light of recent breakthroughs in cancer immunotherapy, we analyzed the possible immunosuppressive mechanisms in HH/GLI-induced BCC in detail. Using a genetic mouse model of BCC, we identified profound differences in the infiltration of BCC lesions with cells of the adaptive and innate immune system. Epidermal activation of Hh/Gli signaling led to an accumulation of immunosuppressive regulatory T cells, and to an increased expression of immune checkpoint molecules including programmed death (PD)-1/PD-ligand 1. Anti-PD-1 monotherapy, however, did not reduce tumor growth, presumably due to the lack of immunogenic mutations in common BCC mouse models, as shown by whole-exome sequencing. BCC lesions also displayed a marked infiltration with neutrophils, the depletion of which unexpectedly promoted BCC growth. The study provides a comprehensive survey of and novel insights into the immune status of murine BCC and serves as a basis for the design of efficacious rational combination treatments. This study also underlines the need for predictive immunogenic mouse models of BCC to evaluate the efficacy of immunotherapeutic strategies invivo.

141 All-trans Retinoic Acid Inhibits Cell Proliferation through Upregulation of TET2 in Squamous Cell Cancer

Cutaneous squamous cell carcinoma (cSCC) is the second most frequent non-melanoma skin cancer. All-trans retinoic acid (ATRA) has been previously proposed anti-tumor potential via inhibiting cancer cell growth by binding to the intracellular retinoic acid receptors (RAR). The ten-eleven translocation 2 (TET2) proteins oxidize the epigenetic mark 5-methylcytosine to 5-hydroxymethylcytosine (5hmC) and loss-functions of TET2 leading to hypermethylation have been established in various cancers. However, its role in cSCC remains unknown. In the present study, we detected the expression of 5hmC, TET2 and retinoic acid receptor B (RARb) in normal skin, actinic keratosis (AK), Bowen disease and cSCC clinical samples by immunohistochemical staining. It’s significant downregulation of 5hmC and TET2 were observed in the AK, Bowen disease and cSCC tissues compared with normal skin, while expression of RARb was reduced. Human primary keratinocytes and cSCC cell lines (Scl-1 and HSC-1) were cultured in vitro, receiving stimulation of retinoic acid. The results showed that treatment with ATRA inhibited the proliferation of cSCC cell lines and increased the expressions of TET2 and RARb in cSCC cell lines. Moreover, ectopic overexpression of TET2 in cSCC cell lines induce upregulation of RARB while no obvious expression changes of TET2 were observed in RARB overexpressed cSCC cell lines. Our results suggest that TET2 and 5hmC were decreased in cSCC tissue and cSCC cell lines compared to normal tissues and human primary keratinocytes. In addition, ATRA promotes the expression of TET2 in cSCC cell lines, which is closely related to RARb. This study provides evidence that 5hmC and TET2 have the potentials to serve as biomarkers that identified presence and progression of cSCC. It identified a novel function of ATRA in promoting a TET-mediated epigenetic regulation suggesting that the availability of ATRA in cancer cells will have various effects on different epigenetic targets.

Pattern of response of unresectable and metastatic cutaneous squamous cell carcinoma to programmed death-1 inhibitors: A review of the literature.

Cutaneous squamous cell carcinoma (cSCC) is the second most frequent nonmelanoma skin cancer (NMSC). The majority of in situ cSCC [cSCC (Tis)] can be cured surgically, while local advanced and metastatic ones require other treatments, but there are no therapies approved by U.S. Food and Drug Administration (FDA). Available treatments for these stages included radiotherapy, chemotherapy as cisplatin, but responses to these treatments are usually of short duration. Programmed death-1 (PD-1) inhibitors (pembrolizumab, nivolumab, and cemiplimab) are an innovative immunologic treatment that now has been shown to be useful for the treatment of advanced cSCC. Nowadays, data about the response rate with the use of PD-1 inhibitors in cSCC are still few and, especially, the duration of the response after the start of treatment is short. Moreover, the number of cases is too small to express the beneficial effects of these treatments, although most data reported in the literature show quite good response rates. This review focused on some of the studies and associated results through an interesting research on search engines of all the cases about these systemic drugs, analyzing effects and side effects, and the research has been conducted considering published cases since March 2016 to October 2019.

Basal cell carcinoma within rhinophyma: coincidence or relationship?

IntroductionRhinophyma is a relatively rare form of rosacea, while basal cell carcinoma (BCC) is the most frequent skin cancer in humans – both diseases prevail in the elderly.AimTo analyse patients with rhinophyma treated surgically in the Dermatosurgery Unit and look for possible cases with BCC within the rhinophyma.Material and methodsWe performed a retrospective review of all treated rhinophymas in the Dermatosurgery Unit in 2004–2019.ResultsAmong 140 rhinophyma patients 2 (1.4%) subjects with concomitant clinically diagnosed and histologically confirmed BCC were found, with BCC located in the hypertrophic tissue of the nose. There were no patients with BCC located in other anatomical regions of the skin. Both of these patients were in more advanced age.ConclusionsTaking into consideration these two conditions: advanced age and anatomical location, typical for BCC, one may speculate that the development of BCC within rhinophyma is rather a simple coincidence. However, more numerous series of patients with rhinophyma are needed to clear the controversy of BCC within rhinophyma hypertrophic tissue.

Update in the Management of Basal Cell Carcinoma.

Basal cell carcinomas are the most frequent skin cancers in the fair-skinned adult population over 50 years of age. Their incidence is increasing throughout the world. Ultraviolet (UV) exposure is the major carcinogenic factor. Some genodermatosis can predispose to formation of basal cell carcinomas at an earlier age. Basal cell carcinomas are heterogeneous, from superficial or nodular lesions of good prognosis to very extensive difficult-to-treat lesions that must be discussed in multidisciplinary committees. Recent guidelines have updated the management of basal cell carcinoma. The prognosis is linked to the risk of recurrence of basal cell carcinoma or its local destructive capacity. Characteristic molecular events in these tumours are: (i) activation of the hedgehog pathway, which has allowed the development of hedgehog inhibitors for difficult-to-treat lesions that are not accessible to surgery or radiotherapy; (ii) high mutational burden, which suggests that hedgehog inhibitor refractory tumours could be offered immunotherapy; some trials are ongoing. The standard treatment for most basal cell carcinomas is surgery, as it allows excision margin control and shows a low risk of recurrence. Superficial lesions can be treated by non-surgical methods with significant efficacy.

Surgical Outcomes of More Than 1300 Cases of Mohs Micrographic Surgeries from a Private Mohs Clinic in Romania.

Background: Basal cell carcinoma (BCC) and Squamous cell carcinoma (SCC) are the most frequent skin cancers with a continuous increasing incidence and a cause of economic impact. Mohs micrographic surgery (MMS) is known as the gold-standard of treatment of non-melanoma skin cancer. Methods: The files of the patients treated with MMS were analysed during a 6 year period (2014-2019) and demographic information was extracted in addition to the information on tumor histology, localization of tumors, number of stages required for a complete removal of the tumors, and the evolution of the patients. We also analysed the information regarding the number and type of reconstructions performed. Results: Over the course of 6 years, 1,356 cutaneous tumors were treated in our clinic by means of MMS. BCC represented 80.5%, SCC 17.6%, and other tumors such as melanoma in situ, DFSP, Extramammary Paget's Disease - being 1.9% of the number of other treated tumors. During the period under review, only 4 cases of post-Mohs Micrographic Surgery recurrence have been recorded, with a cure rate of over 99.7%. Conclusions: Mohs micrographic surgery is an efficient treatment method in removing cutaneous carcinoma as well as tumors with special indications with a low recurrence rate therefore reducing the need of successive surgical interventions.

The epidemiology of skin cancer at Dr. Cipto Mangunkusumo National Central General Hospital from 2014 to 2017

Background: The incidence of skin cancer has been increasing over the past decades globally. At present, there is no valid national cancer data in Indonesia. The purpose of this study is to evaluate the increment of skin cancer cases at Dr. Cipto Mangunkusumo National General Hospital, Jakarta. Methods: In this retrospective descriptive study, we evaluated all pigmented skin tumor cases from June 2014 to June 2017. Data were obtained from the Department of Anatomical Pathology and medical records at Dr. Cipto Mangunkusumo National General Hospital. Data were compared with previous reports. Results: From 263 skin cancer cases, the most frequent skin cancer was basal cell carcinoma (BCC; 66.9%), followed by squamous cell carcinoma (SCC; 27.4%), and malignant melanoma (MM; 5.7%). Most of the skin cancer w ere predominantly in the female population. In BCC and SCC, most of the patients were within the age group above 60 years (n = 106 and 18, respectively). In MM, the incidence is greater in age group of 41–50 years (n = 5). For BCC and SCC, the distribution sites of lesions were mostly in sun-exposed areas, whereas the distribution sites of MM were mostly in non-sun-exposed areas. Median diameters of BCC, SCC, and MM were 2, 4, and 6.5 cm, respectively. There was an increase of BCC incidence from 1996 to 2017. Conclusion: In comparison with other types, the incidence of BCC in Dr. Cipto Mangunkusumo National General Hospital is increasing. A well-documented skin cancer registry is required to establish national data of skin cancer in Indonesia. Keywords: epidemiology, incidence, basal cell carcinoma, malignant melanoma, squamous cell carcinoma

Pembrolizumab and concurrent hypo-fractionated radiotherapy for advanced non-resectable cutaneous squamous cell carcinoma.

Cutaneous squamous cell carcinoma (cSCC) is the second most frequent non-melanoma skin cancer. Treatment options for inoperable advanced cSCC cases are limited. The efficacy of anti-programmed cell death-1 (PD-1) monoclonal antibodies (mAb) has been reported recently in some patients with cSCC. To evaluate the efficacy of anti-PD-1 mAb in a case series of inoperable advanced cSCC and to analyse the efficacy of concurrent radiotherapy. We retrospectively analysed the files of all patients with advanced inoperable cSCC treated with anti-PD-1 mAb and concurrent radiotherapy outside clinical trials in our skin cancer centre before December 31, 2017. A total of four patients with locally or regionally advanced cSCC were identified. All patients received pembrolizumab at 2mg/kg every three weeks and concurrent radiotherapy. Two patients who received pembrolizumab as first-line therapy with concurrent radiotherapy (one with skull and leptomeningeal invasion and one with rapidly progressing regional cSCC) had a complete response, allowing treatment discontinuation, without recurrence after a median of 11 months off treatment. All other patients experienced progressive disease. The median progression-free survival and overall survival were 14.4 and 15.6 months, respectively. No toxicity was observed. There appears to be a place for pembrolizumab as first-line treatment for unresectable or advanced cSCC. Further studies are needed to evaluate concomitant radiotherapy with anti-PD1 antibodies.

Non-invasive imaging techniques for the in vivo diagnosis of Bowen's disease: Three case reports.

Bowen's disease (BD) is a relatively frequent non-melanoma skin cancer occurring mostly in elderly people. Until now, the usual way to establish the diagnosis is histopathological examination of a skin biopsy. Dermoscopy and reflectance confocal microscopy (RCM) are modern alternative methods that can be used as quick and non-invasive diagnostic techniques and as follow-up instruments in cases in which a conservative treatment is chosen for the management of BD. There are no very specific dermoscopic criteria for the diagnosis of this disease, but some dermoscopic features (scaly surface, vascular structures and pigmentation) can be found more frequent and can be helpful for the diagnosis. RCM of BD shows an acanthotic epidermis with two types of targetoid cells: the first, a large cell with bright center and dark peripheral halo, the second, a cell with dark center and a bright rim surrounded by a dark hallo, related with dyskeratotic cells on histological examination. BD management could be improved by using non-invasive, in vivo imaging techniques that allow a fast and easy diagnosis and can be used as follow-up tools. However, larger studies are necessary for the validation of our observations.

Children with malignant melanoma: a single center experience from Turkey.

Aim:Malignant melanoma is the most frequent skin cancer in children and adolescents. It comprises 1–3% of all malignancies. In this study, we aimed to evaluate the clinical aspects, histopathologic features, and treatment outcomes of our patients with malignant melanoma.Material and Methods:Patients aged <15 years who were treated between 2003 and 2018 for malignant melanoma were retrospectively analyzed.Results:Seventeen patients (10 females, 7 males), with a median age of 7 years (range, 7 months-13 years) were evaluated. Five patients had congenital melanocytic nevi. All had cutaneous melanoma except one with mucosal (conjunctival) melanoma. The most frequent primary tumor site was the lower extremities (35%). Sentinel lymphoscintigraphy, sentinel node biopsy, and PET/CT were performed as the staging procedures at initial diagnosis. Localized disease was present in eight patients; nine had regional lymph node metastasis. The only treatment was surgery in localized disease; surgery and adjuvant interferon treatment was given in patients with regional lymph node metastasis. Three developed distant metastasis (bone, lung, brain) at a median of 9 months. A three-year-old patient received a BRAF inhibitor (vemurafenib), and a 13-year-old patient received a check point inhibitor (ipilimumab); both died of progressive disease. The median follow-up for all patients was 25 months. The 5-year overall survival was 76.6%.Conclusion:Although malignant melanoma is rare in children, prognosis is good if diagnosed early. Physicians should be aware of skin lesions and full-layer biopsy should be obtained in suspicious skin lesions. Patients with congenital melanocytic nevi should also be followed up cautiously.

Synergistic cross‐talk of hedgehog and interleukin‐6 signaling drives growth of basal cell carcinoma

Persistent activation of hedgehog (HH)/GLI signaling accounts for the development of basal cell carcinoma (BCC), a very frequent nonmelanoma skin cancer with rising incidence. Targeting HH/GLI signaling by approved pathway inhibitors can provide significant therapeutic benefit to BCC patients. However, limited response rates, development of drug resistance, and severe side effects of HH pathway inhibitors call for improved treatment strategies such as rational combination therapies simultaneously inhibiting HH/GLI and cooperative signals promoting the oncogenic activity of HH/GLI. In this study, we identified the interleukin‐6 (IL6) pathway as a novel synergistic signal promoting oncogenic HH/GLI via STAT3 activation. Mechanistically, we provide evidence that signal integration of IL6 and HH/GLI occurs at the level of cis‐regulatory sequences by co‐binding of GLI and STAT3 to common HH‐IL6 target gene promoters. Genetic inactivation of Il6 signaling in a mouse model of BCC significantly reduced in vivo tumor growth by interfering with HH/GLI‐driven BCC proliferation. Our genetic and pharmacologic data suggest that combinatorial HH‐IL6 pathway blockade is a promising approach to efficiently arrest cancer growth in BCC patients.

Frequent basal cell cancer development is a clinical marker for inherited cancer susceptibility.

Innate DNA repair mechanisms play a critical role in protecting skin keratinocytes from UV mutagenesis and skin cancer development. We hypothesized that individuals who develop frequent skin cancers may harbor germline defects in DNA repair genes and have increased predisposition to internal malignancies. We enrolled 61 patients with unusually frequent basal cell carcinoma (BCC) development, seen at Stanford Hospital and Clinics from January 2005 until December 2015, for germline analysis of 29 DNA repair genes. In parallel, a case-control retrospective review was performed to interrogate the association of malignancies with frequent BCC development in a large US medical insurance claims database (Truven), which included 13,264 individuals with 6 or more BCCs from 2007 to 2011. 19.7% of the frequent BCC cohort harbored pathogenic mutations in DNA repair genes: APC, BARD1, BRCA1, BRCA2, CDH1, CHEK2, MLH1, MSH2, MSH6, MUTYH, NBN, and PALB2. Individuals with 6 or more BCCs had an increased risk of other malignancies, with a 3.5-fold increase in the frequent BCC cohort and a 3.2-fold increase in the Truven database. Individuals who developed frequent BCCs have an increased prevalence of germline mutations in DNA repair genes and increased malignancy risk. Our data implicate frequent BCC development as an external marker of inherited cancer risk.

Carcinoma de células escamosas de piel. Serie de casos

Introduction: Squamous skin cancer (SSC) is the second most frequent skin cancer, nevertheless reports about this issue are not published in Chile. Objetive: To investigate social, demographics, and clinic characteristics of SSC in semidesertic Coquimbo Region, Chile. Material and Methods: serie of patients diagnosed and treated in Coquimbo hospital between January 2006 and December 2015. Inclussion criteria: 1.- histopathological confirmation of SSC. Exclusion criteria: 1.- follow up lesser than 12 months; 2.- operated in another hospital; 3.- submitted to another treatment prior to surgery; 4.- skin metastasis of mucous squamous carcinoma; 5.- patients with distant metastasis. Independent variables: age, gender, tumor site, tumor size, clinical lymph nodes, shore or valley residency. Dependent variable: recurrency frecuence, factors of recurrency, letality. Statistical analysis: descriptive and analytical by SSPS program. Results: 2.202 skin cancer cases were registered, 1.487 basal cells carcinoma (67.5%), 181 melanoma (8.2%) and 534 squamous cells carcinoma (24.2%). 236 patients with complete data are included in this report. There were 153 men (64.8%), and 83 women (35.2%). Mean age was 75.5 years old ± 11.7 (range 46-94). Primary site was: head 158 patients (66.9%), other sun exposed areas 47 patients (20%), and non exposed areas 31 patients. Cheek and front were the most frequents head site with 40 cases (25%) and 29 cases (12.3%), respectively. In 119 cases (50.4%) SCC was ulcerated, and 117 cases was not; primary tumor diameter was 22 millimeters (range 3-100). Clinical lymph nodes were primarily positives in 10 patients, (4.2%). In 12 cases with negative lymph nodes, sentinel limph node was resected. 2 were positives. Histological borders were tumor free in 201 patients (85.2%) and, 35 cases (14.8%) had positive histological borders. Local recurrence incidence was 8.5% (20 cases). Limph nodes recurrence was 2.1% (5 cases). Cancer recurrence was associated with histological positive borders P = 0.001, IC 95% 3.12- 12.19, and ulcerated tumor p = 0.01, OR 4.63; IC 1.59-13.50. Letality was 2.56%. Mean follow up was 36 months (range 12-228 months). Conclusions: SSC has a good prognosis when primary tumor is resected early, with free histological borders resection.

Cutaneous squamous carcinoma in a patient with diabetic foot: an unusual evolution of a frequent complication.

SummaryAfter basal cell carcinoma, the cutaneous squamous cell carcinoma (cSCC) is the second most frequent non-melanoma skin cancer worldwide, and, classically, arises from the upper coats of the epidermis of sun-exposed areas or from skin areas constantly exposed to a chronic inflammatory stimulus. The occurrence of cSCC seems to be linked to several factors, including exposure to sunlight (or other ultraviolet radiations), immunosuppression, chronic scarring conditions and some familial cancer syndromes. Although the majority of cSCCs are adequately eradicated by surgical excision, a subgroup of cSCC may be linked with an increased risk of recurrence, metastasis and death. The incidence of type 2 diabetes mellitus is constantly increasing worldwide. Importantly, diabetes mellitus is a strong risk factor for cancers (including cutaneous tumors) and is highly related with poor cancer outcomes. At present, in the literature, squamous cell carcinoma developing in association with diabetic foot ulcers has been already reported in some reports; however, additional data are needed to make the clinicians aware of this rare, although possible, complication. Therefore, we herein report an unusual case of an elderly man with T2DM and a positive oncological history, presenting a cSCC involving the skin overlying the first toe of left foot. The growing cSCC appeared approximately 3 years after the appearance of a diabetic ulcer.Learning points:Diabetic foot ulcers are an important and severe complication of diabetes mellitus and often can result in foot amputation.Chronic and non-healing diabetic foot ulcers are often observed in clinical practice.Clinicians should always take into consideration the malignant degeneration (e.g., cutaneous squamous cell carcinoma) of any chronic non-healing diabetic foot ulcer in elderly T2DM individuals.Timely surgical resection of a chronic, non-healing diabetic foot ulcer might preclude the development of a cutaneous squamous cell carcinoma.