Clinical, histopathological and molecular features of dedifferentiated melanomas: An EORTC Melanoma Group Retrospective Analysis.

PURPOSE: Dedifferentiated melanoma (DedM) poses significant diagnostic challenges. We aimed to investigate the clinical, histopathological and molecular features of DedM. Methylation signature (MS) and copy number profiling (CNP) were carried out in a subgroup of cases. PATIENTS AND METHODS: A retrospective series of 78 DedM tissue samples from 61 patients retrieved from EORTC (European Organisation for Research and Treatment of Cancer) Melanoma Group centres were centrally reviewed. Clinical and histopathological features were retrieved. In a subgroup of patients, genotyping through Infinium Methylation microarray and CNP analysis was carried out. RESULTS: Most patients (60/61) had a metastatic DedM showing most frequently an unclassified pleomorphic, spindle cell, or small round cell morphology akin to undifferentiated soft tissue sarcoma, rarely associated with heterologous elements. Overall, among 20 successfully analysed tissue samples from 16 patients, we found retained melanoma-like MS in only 7 tissue samples while a non-melanoma-like MS was observed in 13 tissue samples. In two patients from whom multiple specimens were analysed, some of the samples had a preserved cutaneous melanoma MS while other specimens exhibited an epigenetic shift towards a mesenchymal/sarcoma-like profile, matching the histological features. In these two patients, CNP was largely identical across all analysed specimens, in line with their common clonal origin, despite significant modification of their epigenome. CONCLUSIONS: Our study further highlights that DedM represents a real diagnostic challenge. While MS and genomic CNP may help pathologists to diagnose DedM, we provide proof-of-concept that dedifferentiation in melanoma is frequently associated with epigenetic modifications.

Profiles of Maladjustment and Interpersonal Risk Factors in Adolescents.

The individual's adaptation problems can lead to risky behaviors such as drug use. This study aimed to analyze the existence of different adaptation profiles (personal, school, and social) in adolescents. Thus, the study aimed to analyze the existence of significant differences in interpersonal risk factors depending on the degree of adaptation. The study participants were 1,201 students of Compulsory Secondary Education (M = 14.43, SD = 1.43), and 50.6% were girls. The TAMAI Test (multifactorial adaptation self-evaluation test) and the FRIDA questionnaire (Interpersonal Risk Factors for Drug Use in Adolescence) were used. A latent class analysis (LCA) revealed three different types of adaptation: maladjusted group, at-risk group, and adjusted group. The results showed the existence of significant differences between the different adaptation profiles based on interpersonal risk factors. The data obtained will help school and mental health plans to prevent misbehaving or risky behaviors.

Profiles of Perfectionistic Ruminations in Undergraduates: Impact on the Spontaneous Use of Mental Images.

Perfectionistic Automatic Thoughts (PAT) negatively affects people who present it. Hence the importance of their study to determine possible ways of reduction. The current study tried to identify PAT profiles and specify the statistically significant differences in the Spontaneous Use of Mental Imaging in 647 undergraduates. For this the Perfectionism Cognitions Inventory and the Spontaneous Use of Imagery Scale were used. The cluster analyses showed three groups of PATs; low (LPAT), moderate (MPAT) and high (HPAT). An analysis of variance revealed moderate size differences in the visual-spatial capacity as well as in the total of the Spontaneous Use of Mental Images for MPAT and LPAT. Implications for the training of future teachers related to the use of mental imagery that can reduce maladaptive PAT are discussed.

Early Detection of Academic Performance During Primary Education Using the Spanish Primary School Aptitude Test (AEI) Battery.

The aim of this study was to assess the predictive capacity of some of the most relevant cognitive skills pertaining to the academic field as measured by the Spanish Primary School Aptitude Test Battery. This psychometric tool was applied to all students who were enrolled in the final year of Early Childhood Education (631 students) in the public schools of the province of Alicante (in the South-East of Spain) and a follow-up of their academic progress was carried out when they completed Primary Education (6 school years). The results obtained show that medium-high and high scores in Verbal Aptitude and Numerical Aptitude tests in Early Childhood Education (5 years of age), can predict academic success at the end of Primary Education (12 years of age) in instrumental subjects such as: (1) Language (Verbal Aptitude Odds Ratio = 1.39 and Numerical Aptitude Odds Ratio = 1.39) and (2) Mathematics (Verbal Aptitude Odds Ratio = 1.47 and Numerical Aptitude Odds Ratio = 1.52). We have determined the importance of developing pedagogical programs that stimulate the development of these skills during Early Childhood Education, while implementing support strategies during Primary Education, for those students who present underdeveloped aptitudes in these areas. In this way, school difficulties would be prevented in the instrumental subjects that provide access to other academic areas.

High nevus counts confer a favorable prognosis in melanoma patients.

A high number of nevi is the most significant phenotypic risk factor for melanoma and is in part genetically determined. The number of nevi decreases from middle age onward but this senescence can be delayed in patients with melanoma. We investigated the effects of nevus number count on sentinel node status and melanoma survival in a large cohort of melanoma cases. Out of 2,184 melanoma cases, 684 (31.3%) had a high nevus count (>50). High nevus counts were associated with favorable prognostic factors such as lower Breslow thickness, less ulceration and lower mitotic rate, despite adjustment for age. Nevus count was not predictive of sentinel node status. The crude 5- and 10-year melanoma-specific survival rate was higher in melanomas cases with a high nevus count compared to those with a low nevus count (91.2 vs. 86.4% and 87.2 vs. 79%, respectively). The difference in survival remained significant after adjusting for all known melanoma prognostic factors (hazard ratio [HR] = 0.43, confidence interval [CI] = 0.21-0.89). The favorable prognostic value of a high nevus count was also seen within the positive sentinel node subgroup of patients (HR = 0.22, CI = 0.08-0.60). High nevus count is associated with a better melanoma survival, even in the subgroup of patients with positive sentinel lymph node. This suggests a different biological behavior of melanoma tumors in patients with an excess of nevi.

Evaluation of the Roche COBAS® TaqMan® HIV-1 test for quantifying HIV-1 RNA in infected cells and lymphoid tissue.

Lymphoid tissue is the main reservoir of HIV-1 in infected individuals. In this study the COBAS® TaqMan® HIV-1 test was evaluated for use with the High Pure System (HPS), for quantifying HIV-1 RNA in infected cells and lymphoid tissue specimens. Serial dilutions of 8E5-LAV1 infected T-cells into SUP-T1 cells and 44 tonsil specimens were examined. Some modifications of the test were required, such as the removal of residual DNA and the HIV-1 RNA output copies were adjusted to the sample input and expressed as HIV-1 RNA copies/µg of total RNA. The Roche COBAS® TaqMan HIV-1® (HPS) test proved to be a robust, sensitive, specific and reproducible method for quantifying HIV-1 RNA in infected cells and lymphoid tissue. Linearity and reproducibility were observed in serial dilutions of 8E5-LAV1 infected T-cells (R²>0.86). High reproducibility was found in clinical tonsil specimens (Wilcoxon test p > 0.05). rDNase I treatment was essential to avoid false positives caused by residual HIV-1 DNA, mainly in tonsil specimens obtained from infected patients receiving effective antiretroviral treatment. Probit analysis determined the limit of detection as 22HIV-1 RNA copies/µg of total RNA. The Roche COBAS® TaqMan® HIV-1 (HPS) test thereby proved to be a helpful tool for measuring the HIV-1 viral load in infected cells and lymphoid tissue reservoirs.

Polydimethylsiloxane versus polytetrafluoroethylene for vocal fold medialization: histologic evaluation in a rabbit model.

The objective is to study the tissue reaction of the paralyzed vocal cord in response to the injection of particulate plastics in a rabbit model. Forty-five New Zealand rabbits with surgical vocal-fold paralysis were used in the study. Histologic reactions of the larynx and the regional lymph nodes were analyzed by a single blinded pathologist at 6 weeks and 6 months after a vocal-cord injection of Teflon or of silicone elastomer. Macroscopic studies of the liver, lungs, spleen, kidney, and brain were performed. The histological study showed a greater proportion of chronic granulomatous inflammation in animals injected with silicone than in those injected with Teflon. The immunohistochemical study showed a higher degree of phagocytosis of Teflon particles than of the silicone particles. The silicone group presented a more severe fibrous reaction than the Teflon group, but the difference was not significant. No migration particles were found. It is concluded that silicone, having a greater viscosity than Teflon because of the size of its particles, induces more fibrosis and a larger proportion of foreign giant cells in the host. Due to this histological reaction, silicone particles present greater anchorage and stability.