Definición del pronóstico del carcinoma epidermoide cutáneo mediante la combinación de factores clínico-patológicos, marcadores proteicos y expresión de miRNAs

Trabajo realizado por D. Javier Cañueto Álvarez para optar al grado de Doctor en Medicina por la Universidadd de Salamanca.La presente tesis doctoral ha sido parcialmente subvencionada por los siguientes proyectos de investigación: GRS 612/A/11, Q3718001E y SA078A09 de la Junta de Castilla y León y por la Fundación Eugenio Rodríguez Pascual.Peer Reviewe

Cutaneous collagenous vasculopathy: papular form

Cutaneous collagenous vasculopathy is a rare clinicopathological entity, first described in 2000. Cutaneous collagenous vasculopathy has been considered a form of microangiopathy of superficial dermal vessels and produce lesions that appear as telangiectasia. We present a patient with histopathologic features of cutaneous collagenous vasculopathy and scattered erythematous papules on the trunk with a striking dermatoscopic finding. We propose the term of 'cutaneous papular collagenous vasculopathy' as a new clinical manifestation of this disease

A Novel Approach for the Shape Characterisation of Non-Melanoma Skin Lesions Using Elliptic Fourier Analyses and Clinical Images

[EN] The early detection of Non-Melanoma Skin Cancer (NMSC) is crucial to achieve the best treatment outcomes. Shape is considered one of the main parameters taken for the detection of some types of skin cancer such as melanoma. For NMSC, the importance of shape as a visual detection parameter is not well-studied. A dataset of 993 standard camera images containing different types of NMSC and benign skin lesions was analysed. For each image, the lesion boundaries were extracted. After an alignment and scaling, Elliptic Fourier Analysis (EFA) coefficients were calculated for the boundary of each lesion. The asymmetry of lesions was also calculated. Then, multivariate statistics were employed for dimensionality reduction and finally computational learning classification was employed to evaluate the separability of the classes. The separation between malignant and benign samples was successful in most cases. The best-performing approach was the combination of EFA coefficients and asymmetry. The combination of EFA and asymmetry resulted in a balanced accuracy of 0.786 and an Area Under Curve of 0.735. The combination of EFA and asymmetry for lesion classification resulted in notable success rates when distinguishing between benign and malignant lesions. In light of these results, skin lesions’ shape should be integrated as a fundamental part of future detection techniques in clinical screening.SIJunta de Castilla y Leó

Patterns of incidental perineural invasion and prognosis in cutaneous squamous cell carcinoma: A multicenter, retrospective cohort study

To the Editor: Perineural invasion (PNI) is rare and usually incidental in cutaneous squamous cell carcinoma (SCC), with an incidence of 2.5% to 14%.1 Incidental PNI is associated with poor prognosis in cutaneous SCC,2 and some evidence suggests its outcome differs, depending on the PNI pattern. We evaluated patterns of incidental PNI, using a multicenter retrospective cohort of 140 cutaneous SCCs with incidental PNI to determine the influence of nerve involvement on cutaneous SCC prognosis.Dr Canueto is partially supported ~ by grants PI18/000587 (Instituto de Salud Carlos III, cofinanced by Fondo Europeo de Desarrollo Regional) and GRS 1835/A/18 (Gerencia Regional de Salud de Castilla y Leon)

Outcome of cutaneous squamous cell carcinoma with microscopic residual disease after surgery and usefulness of postoperative radiotherapy: a retrospective cohort study

[Background]: Microscopic residual disease (MRD) after surgery can be a challenging situation in cutaneous squamous cell carcinoma (CSCC) and there is a lack of evidence concerning its management. [Objective]: To evaluate the prognosis of CSCC with MRD and the usefulness of postoperative radiotherapy (PORT) in CSCC with MRD. [Methods]: Retrospective cohort study of CSCC with MRD through a 10-year period (2010–2019) (n = 244). Disease-free survival and event-free survival were assessed using R (v.3.4.1), considering competing risks. Evaluated outcomes were local recurrence (LR), nodal metastases (NMs), and disease-specific death (DSD). [Results]: Median age was 88y (IQR: 10.5). A total of 145 (59.43%) were men and 69 (28.28%) were immunosuppressed. Median tumour diameter and thickness were 19 and 6.4 mm (IQR 11 and 5.5 mm). Patients treated by re-excision had a relapse rate of 4.3% compared with 11.30% and 29.71% in those who received PORT and observation (P = 0.045). The use of PORT was associated with a lower risk of LR compared with observation (HR = 0.206 [0.049–0.859], P = 0.030), but not with a lower risk of NMs or DSDs. In the multivariable models, PORT was again associated with a lower risk of LR than observation (HR = 0.167 [0.039–0.708], P = 0.014), but not with lower risk of metastasis and death. [Conclusions]: We always should try to obtain clear margins after surgery. PORT improves local control in CSCC with MRD, but when administered to the tumour bed, it does not reduce the risk of NM and DSD.Javier Cañueto is partially supported by the grants GRS2139/A/20 (Gerencia Regional de Salud de Castilla y León), PI18/00587 and PI21/01207 (Instituto de Salud Carlos III, confanciado con fondos FEDER) and by the ‘Programa de Intensificación of the ISCIII’, grant number INT20/00074

A New Case of Schindler Disease

Lysosomal storage disorders (LSDs) are a group of genetic disorders caused by mutations in genes encoding enzymes involved in lysosomal function. Schindler disease is an autosomal recessive, inherited LSD caused by defective or non-existent activity of the enzyme α-N-acetylgalactosaminidase (α-NAGA). To date, three main phenotypes of Schindler disease have been described. We report the case of a 68-year-old man presenting with axonal and demyelinating polyneuropathy, sensorineural hearing loss, chronic lymphoedema, angiokeratoma corporis diffusum and bilateral carpal tunnel syndrome. Genetic testing (PCR) for α-galactosidase revealed the c.577G>T (p.Glu193*) mutation in the NAGA gene, confirming Schindler disease, which is clinically compatible with Kanzaki disease and Schindler disease type II

Evolutionary origins of metabolic reprogramming in cancer

Metabolic changes that facilitate tumor growth are one of the hallmarks of cancer. These changes are not specific to tumors but also take place during the physiological growth of tissues. Indeed, the cellular and tissue mechanisms present in the tumor have their physiological counterpart in the repair of tissue lesions and wound healing. These molecular mechanisms have been acquired during metazoan evolution, first to eliminate the infection of the tissue injury, then to enter an effective regenerative phase. Cancer itself could be considered a phenomenon of antagonistic pleiotropy of the genes involved in effective tissue repair. Cancer and tissue repair are complex traits that share many intermediate phenotypes at the molecular, cellular, and tissue levels, and all of these are integrated within a Systems Biology structure. Complex traits are influenced by a multitude of common genes, each with a weak effect. This polygenic component of complex traits is mainly unknown and so makes up part of the missing heritability. Here, we try to integrate these different perspectives from the point of view of the metabolic changes observed in cancer.This work was supported in JPL’s lab by Grant PID2020-118527RB-I00 funded by MCIN/AEI/10.13039/501100011039; Grant PDC2021-121735-I00 funded by MCIN/AEI/10.13039/501100011039 and by the “European Union Next Generation EU/PRTR.”, the Regional Government of Castile and León (CSI234P18 and CSI144P20). SCLl was the recipient of a Ramón y Cajal research contract from the Spanish Ministry of Economy and Competitiveness and was supported by grant RTI2018-094130-B-100 funded by MCIN/AEI/10.13039/501100011039 and by “ERDF A way of making Europe.” RCC and AJN are funded by fellowships from the Spanish Regional Government of Castile and León. NGS is a recipient of an FPU fellowship (MINECO/FEDER). MJPB is funded by grant PID2020-118527RB-I00 funded by MCIN/AEI/10.13039/501100011039. J.C. is partially supported by grant GRS2139/A/20 (Gerencia Regional de Salud de Castilla y León) and by the Instituto de Salud Carlos III (PI18/00587 and PI21/01207), co-financed by FEDER funds, and by the “Programa de Intensificación” of the ISCIII, grant number INT20/00074. We thank Phil Mason for English language support

Evidence of the high prevalence of neurological disorders in nonsyndromic X-linked recessive ichthyosis: a retrospective case series

[Background]: X-linked recessive ichthyosis (XLI) is a relatively common type of ichthyosis caused by a deficiency in the steroid sulfatase (STS) enzyme. It is the only type of ichthyosis that can be both syndromic and nonsyndromic. Typical clinical features include dark-brown scale of variable size favouring the extensor surfaces of the extremities.[Objectives]: To characterize clinically nonsyndromic XLI, with a particular focus on extracutaneous manifestations.[Methods]: This was a multicentre retrospective review of clinical findings from a case series of patients with a clinical and genetic diagnosis of XLI.[Results]: We identified 30 patients with XLI belonging to 25 different families carrying a deletion in the STS locus. All patients had dark scales of variable size on the extensor surfaces of the extremities. Lack of flexural involvement and pruritus were common but inconsistent findings, whereas palmoplantar hyperlinearity was absent in all but one patient. A history of orchiopexy was present in 10% and thus was more common than expected vs. the general population (3%). Neurological disorders including epilepsy (13%) and attention deficit hyperactivity disorder (ADHD; 30%) were over-represented in patients with XLI.[Conclusions]: This was a retrospective study with a limited number of patients. In the absence of confirmatory genetic testing and family history of the disease, dark-brown scale of the extensor surfaces and the absence of palmoplantar hyperlinearity appear to be the most reliable clinical findings supporting a diagnosis of XLI. Dermatologists should be aware of the high prevalence of ADHD and epilepsy in patients with nonsyndromic XLI

Hyperspectral imaging and robust statistics in non-melanoma skin cancer analysis

Non-Melanoma skin cancer is one of the most frequent types of cancer. Early detection is encouraged so as to ensure the best treatment, Hyperspectral imaging is a promising technique for non-invasive inspection of skin lesions, however, the optimal wavelengths for these purposes are yet to be conclusively determined. A visible-near infrared hyperspectral camera with an ad-hoc built platform was used for image acquisition in the present study. Robust statistical techniques were used to conclude an optimal range between 573.45 and 779.88 nm to distinguish between healthy and non-healthy skin. Wavelengths between 429.16 and 520.17 nm were additionally found to be optimal for the differentiation between cancer types.Gerencia Regional de Salud de Castilla y León (GRS 2139/A/20); Spanish Ministry of Science, Innovation and Universities (PRE2019-089411); Instituto de Salud Carlos III (PI18/00587); Ibderdrola Spain; Junta de Castilla y León (GRS 1837/A/18). This project was funded by the Junta de Castilla y Leon, under the title project HYPERSKINCARE (Ref. GRS 1837/A/18). Lloyd Austin Courtenay is funded by the Spanish Ministry of Science, Innovation and Universities with an FPI Predoctoral Grant (Ref. PRE2019-089411) associated to project RTI2018-099850-B-I00 and the University of Salamanca. Susana Lagüela and Susana del Pozo are both funded by the Iberdrola Spain through the initiative Cátedra Iberdrola VIII Centenario of the University of Salamanca. Javier Cañueto is partially supported by the PI18/00587(Instituto de Salud Carlos III cofinanciado con fondos FEDER) and GRS 2139/A/20 (Gerencia Regional de Salud de Castilla y León

Hyperspectral imaging and robust statistics in non-melanoma skin cancer analysis

[EN] Non-Melanoma skin cancer is one of the most frequent types of cancer. Early detection is encouraged so as to ensure the best treatment, Hyperspectral imaging is a promising technique for non-invasive inspection of skin lesions, however, the optimal wavelengths for these purposes are yet to be conclusively determined. A visible-near infrared hyperspectral camera with an ad-hoc built platform was used for image acquisition in the present study. Robust statistical techniques were used to conclude an optimal range between 573.45 and 779.88 nm to distinguish between healthy and non-healthy skin. Wavelengths between 429.16 and 520.17 nm were additionally found to be optimal for the differentiation between cancer typesSIGerencia Regional de Salud de Castilla y LeónSpanish Ministry of Science, Innovation and UniversitiesInstituto de Salud Carlos IIIJunta de Castilla y Leó