Estudio de la expresión de telomerasa en una serie de neoplasias melanocíticas / Telomerase Expression in a Series of Melanocytic Neoplasms

Introducción y objetivos: La telomerasa es una enzima implicada en el mantenimiento de los telómeros y la senescencia celular. Numerosos estudios han demostrado que en más del 90% de las neoplasias malignas se detecta actividad telomerásica. El objetivo del presente estudio es analizar la expresión de telomerasa por inmunohistoquímica en una serie de neoplasias melanocíticas. Material y métodos: Estudio observacional retrospectivo realizado en una serie de 85 melanomas primarios, 12 metastásicos y 22 nevus melanocíticos. La expresión de telomerasa se analizó empleando el anticuerpo monoclonal hTERT (Rockland). El análisis de los datos se realizó con el programa SPSS. Resultados: En todas las neoplasias melanocíticas analizadas se demostró expresión de telomerasa. En el caso de los melanomas predominó el patrón de expresión heterogéneo, y la expresión moderada o intensa. En los nevus resultó más frecuente una expresión homogénea con intensidad leve. El patrón de expresión heterogéneo se asoció a los melanomas de rápido crecimiento (p = 0,028), con Breslow > 4 mm (p = 0,004), con mitosis (p = 0,032), y con mutaciones en el gen TERT (p = 0,002). En el caso de los nevus, la intensidad fue menor en los nevus intradérmicos, seguidos de los compuestos y de los diplásicos (p = 0,054). Conclusiones: La expresión de telomerasa está presente en la totalidad de las neoplasias melanocíticas, con mayor expresión en los melanomas que en los nevus. En el caso de los melanomas, la expresión de forma heterogénea se asocia a un fenotipo de mayor agresividad

Background and objectives: Telomerase is an enzyme involved in maintaining the length of telomeres and cell senescence. Numerous studies have shown that in more than 90% of malignant tumors telomerase activity is detected. Material and methods: Retrospective observational study in a series of 85 cases of primary melanomas, 12 metastatic melanomas, and 22 melanocytic nevi. We used the monoclonal antibody hTERT (human telomerase reverse transcriptase, Rockland) to assess telomerase activity. The SPSS software package was used to analyze data. Results: Telomerase expression was present in all the melanocytic neoplasms analyzed. Expression was heterogenous and moderate or high in the melanomas. In contrast, expression was homogeneous and lower in the nevi. Heterogeneous expression was associated with rapid melanoma growth (P = .028), a Breslow thickness of more than 4 mm (P = .004), mitosis (P = .032), and mutations in the TERT gene (P = .002). Activity was less intense in intradermal nevi, and more intense in compound and dysplastic nevi (P = .054). Conclusions: Telomerase expression is found in all melanocytic neoplasms but is higher in melanomas than in nevi. A heterogeneous pattern of expression in melanomas is associated with more aggressive tumors

Telomerase Expression in a Series of Melanocytic Neoplasms. / Estudio de la expresión de telomerasa en una serie de neoplasias melanocíticas.

BACKGROUND AND OBJECTIVES: Telomerase is an enzyme involved in maintaining the length of telomeres and cell senescence. Numerous studies have shown that in more than 90% of malignant tumors telomerase activity is detected. MATERIAL AND METHODS: Retrospective observational study in a series of 85 cases of primary melanomas, 12 metastatic melanomas, and 22 melanocytic nevi. We used the monoclonal antibody hTERT (human telomerase reverse transcriptase, Rockland) to assess telomerase activity. The SPSS software package was used to analyze data. RESULTS: Telomerase expression was present in all the melanocytic neoplasms analyzed. Expression was heterogenous and moderate or high in the melanomas. In contrast, expression was homogeneous and lower in the nevi. Heterogeneous expression was associated with rapid melanoma growth (P=.028), a Breslow thickness of more than 4 mm (P=.004), mitosis (P=.032), and mutations in the TERT gene (P=.002). Activity was less intense in intradermal nevi, and more intense in compound and dysplastic nevi (P=.054). CONCLUSIONS: Telomerase expression is found in all melanocytic neoplasms but is higher in melanomas than in nevi. A heterogeneous pattern of expression in melanomas is associated with more aggressive tumors.

Aberrant DNA methylation is associated with aggressive clinicopathological features and poor survival in cutaneous melanoma.

BACKGROUND: Promoter methylation of tumour suppressor genes (TSGs) has recently been implicated in the pathogenesis of several types of cancer. Regarding melanoma, over 100 genes that contribute to its pathogenesis have been identified to be aberrantly hypermethylated. OBJECTIVES: This is a retrospective observational study that aims to analyse the prevalence of CpG island methylation in a series of primary melanomas, to identify the associations with the main clinicopathological features, and to explore the prognostic significance of methylation in melanoma survival. MATERIALS AND METHODS: DNA methylation was analysed using methylation-specific multiplex ligation-dependent probe amplification in a series of 170 melanoma formalin-fixed paraffin-embedded tumour samples. The relationship between the methylation status, known somatic mutations and clinicopathological features was evaluated. Disease-free survival (DFS) and overall survival (OS) were displayed by the Kaplan-Meier method. RESULTS: In the entire cohort, one or more genes were detected to be methylated in 55% of the patients. The most prevalent methylated genes were RARB 31%, PTEN 24%, APC 16%, CDH13 16%, ESR1 14%, CDKN2A 6% and RASSF1 5%. An association between aberrant methylation and aggressive clinicopathological features was observed (older age, increased Breslow thickness, presence of mitosis and ulceration, fast-growing melanomas, advancing stage and TERT mutations). Furthermore, Kaplan-Meier survival analysis showed a correlation of methylation and poorer DFS and OS. CONCLUSIONS: Aberrant methylation of TSGs is a frequent event in melanoma. It is associated with aggressive clinicopathological features and poorer survival. Epigenetic alterations may represent a significant prognostic marker with utility in routine practice.

Histiocitosis de células indeterminadas en edad pediátrica: a propósito de un caso / Indeterminate Cell Histiocytosis in Children: A Case Report

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Accuracy of magnetic resonance enterography in the preoperative assessment of patients with Crohn's disease of the small bowel.

AIM: To assess the accuracy of magnetic resonance enterography in predicting the extension, location and characteristics of the small bowel segments affected by Crohn's disease. METHOD: This is a prospective study including a consecutive series of 38 patients with Crohn's disease of the small bowel who underwent surgery at a specialized colorectal unit of a tertiary hospital. Preoperative magnetic resonance enterography was performed in all patients, following a homogeneous protocol, within the 3 months prior to surgery. A thorough exploration of the small bowel was performed during the surgical procedure; calibration spheres were used according to the discretion of the surgeon. The accuracy of magnetic resonance enterography in detecting areas affected by Crohn's disease in the small bowel was assessed. The findings of magnetic resonance enterography were compared with surgical and pathological findings. RESULTS: Thirty-eight patients with 81 lesions were included in the study. During surgery, 12 lesions (14.8%) that were not described on magnetic resonance enterography were found. Seven of these were detected exclusively by the use of calibration spheres, passing unnoticed at surgical exploration. Magnetic resonance enterography had 90% accuracy in detecting the location of the stenosis (75.0% sensitivity, 95.7% specificity). Magnetic resonance enterography did not precisely diagnose the presence of an inflammatory phlegmon (accuracy 46.2%), but it was more accurate in detecting abscesses or fistulas (accuracy 89.9% and 98.6%, respectively). CONCLUSION: Magnetic resonance enterography is a useful tool in the preoperative assessment of patients with Crohn's disease. However, a thorough intra-operative exploration of the entire small bowel is still necessary.

La enfermedad de Castleman: entidad poco frecuente en pediatría y de presentación variable / Castleman’s disease: a rare entity and variable presentation in children

La enfermedad de Castleman (EC) es un trastorno linfoproliferativo infrecuente. Su etiología es desconocida, pero se cree que en ella pueden estar implicados procesos autoinmunes, inflamaciones crónicas, infecciones e inmunodeficiencias. Afecta a pacientes jóvenes y se diferencian clínicamente dos formas, una localizada, que se presenta como una masa única, asintomática, de buen pronóstico, más prevalente en pediatría, y otra multicéntrica, con afectación sistémica y peor pronóstico. Histológicamente, existen dos variantes: la hialinovascular, que suele corresponder a las formas localizadas, y la de células plasmáticas, que suele ser multicéntrica. La resección es curativa en las formas localizadas; sin embargo, en las formas multicéntricas se ha ensayado multitud de tratamientos sin éxito. Presentamos el caso de un paciente de 7 años de edad con una forma localizada de EC en la región cervical, en la que la resección quirúrgica resultó ser diagnóstica y terapéutica. Tras 2 años de seguimiento, se mantiene asintomático (AU)

Castleman's disease (CD) is an uncommon lymphoproliferative disorder. The etiology is unknown, but autoimmune processes, chronic inflammations, infections and immunodeficiencies are postulated to be involved. CD usually affects young patients and is classified into two clinical groups: a localized variant, the more frequent type in children, presented as a solitary asymptomatic mass, with good prognosis; and the multicentric variant, associated with systemic symptoms and a more aggressive clinical evolution. There are two histological variants, the hyaline-vascular type, which usually appears as localized forms, and the plasma-cell type, which is often multicentric. Resection is curative in localized forms; however, several treatments have been tried in multicentric forms without success. We report the case of a 7-year-old boy with the localized form of CD in the neck, in which the excision was both diagnostic and therapeutic. He remains asymptomatic after 2 years of follow-up (AU)