[Infantile hepatic cholestatis: An unusual case of Langerhans cells histiocytosis associated with advanced fibrosis]. / Colestasis hepática infantil: presentación de un caso inusual de histiocitosis de células de Langerhans asociado a fibrosis avanzada.

Neonatal cholestasis is a clinical metabolic alteration requiring investigation of its eitiology. It is characterized by elevation of liver enzymes with cholestasis pattern and, in some cases, with acute liver failure. Its etiology is variable although the most frequent cause is atresia of extrahepatic bile ducts. We present a case of a 23-month-old boy who presented with cholestasis and was finally diagnosed with systemic Langerhans cell histiocytosis.

Colestasis hepática infantil: presentación de un caso inusual de histiocitosis de células de Langerhans asociado a fibrosis avanzada / Infantile hepatic cholestatis: An unusual case of Langerhans cells histiocytosis associated with advanced fibrosis

La colestasis neonatal es una situación clinicoanalítica que requiere una determinación urgente de su etiología. Se caracteriza por elevación de enzimas hepáticas con patrón de colestasis y en algunos casos con situación de fallo hepático agudo. Su etiología es variable aunque la causa más frecuente es la atresia de vías biliares extrahepáticas. En el presente caso describimos el caso de un niño de 23 meses de vida que presentó comienzo colestásico y que finalmente fue diagnosticado de histiocitosis de células de Langerhans sistémica.(AU)

Neonatal cholestasis is a clinical metabolic alteration requiring investigation of its eitiology. It is characterized by elevation of liver enzymes with cholestasis pattern and, in some cases, with acute liver failure. Its etiology is variable although the most frequent cause is atresia of extrahepatic bile ducts. We present a case of a 23-month-old boy who presented with cholestasis and was finally diagnosed with systemic Langerhans cell histiocytosis.(AU)

Gangliogliomas in the pediatric population.

BACKGROUND: Gangliogliomas are neoplastic lesions composed by a mixed population of neoplastic glial and dysplastic neural cells. They represent around 5% of all CNS tumors in the pediatric population. These usually are well-differentiated, slow-growing tumors, meaning that complete resection could cure most of these patients. Although most lesions remain stable over time after incomplete resection, some patients develop progression of the residual lesions: the optimal approach to treat these tumors is still to be defined. METHODS: This is a retrospective study in which we obtained data from medical records of pediatric patients who had a histological diagnosis of ganglioglioma following surgical treatment at a single center between 2001 and 2020. RESULTS: We included 17 pediatric subjects with gangliogliomas. The median age at diagnosis was 6.7 years, and the median follow-up duration was 60 months. The most common clinical presentation was epileptic seizures (41.1%). Hydrocephalus was present in 29.4% of cases. 52.9% of tumors involved exclusively the cerebral hemispheres, with the temporal lobe being the most affected location. Gross total tumor resection (GTR) was accomplished in 47% of all cases and in 75% of hemispheric tumors. Of patients, 33% in whom GTR could not be achieved showed progression of the residual tumor. BRAF V600E mutation was present in 44.4% of cases. CONCLUSION: Gangliogliomas are typically grade I tumors that occasionally affect children. They classically localize in the cerebral hemisphere but may involve deep structures like the basal ganglia, brain stem, and cerebellum, which seems to be particularly frequent in the pediatric population, implying further challenge to achieve adequate oncological control with surgery as the only treatment modality. Although most cases in which GTR could not be performed remained stable over the follow-up, significant progression of the tumor remains was observed in some patients. BRAF inhibitors should be considered as a feasible treatment option in this setting.

MicroRNAs expression associated with aggressive clinicopathological features and poor prognosis in primary cutaneous melanomas.

Several studies have focused on identifying microRNAs involved in the pathogenesis of melanoma. However, its association with clinicopathological features has been scarcely addressed. The aim of this study is to identify microRNAs expression profiles related to aggressive clinicopathological and molecular features, and to analyze the association with melanoma survival. A retrospective and observational study was performed in a series of 179 formalin-fixed paraffin embedded primary cutaneous melanomas. First, a screening analysis on a discovery set (n = 22) using miRNA gene chip array (Affymetrix, Santa Clara, California, USA) was performed. Differentially expressed microRNAs were detected employing the software Partek Genomic Suite. Validation of four microRNAs was subsequently performed in the entire series (n = 179) by quantitative real time PCR (qRT-PCR). MicroRNAs expression screening analysis identified 101 microRNAs differentially expressed according to Breslow thickness (≤1 mm vs. >1 mm), 79 according to the presence or absence of ulceration, 78 according to mitosis/mm2 (<1 mitosis vs. ≥1 mitosis) and 97 according to the TERT promoter status (wt vs. mutated). Six microRNAs (miR-138-5p, miR-130b-3p, miR-30b-5p, miR-34a-5p, miR-500a-5p, miR-339-5p) were selected for being validated by qRT-PCR in the discovery set (n = 22). Of those, miR-138-5p, miR-130b-3p, miR-30b-5p, miR-34a-5p were selected for further analysis in the entire series (n = 179). Overexpression of miR-138-5p and miR-130b-3p was significantly associated with greater Breslow thickness, ulceration, and mitosis. TERT mutated melanomas overexpressed miR-138-5p. Kaplan-Meier survival analysis showed poorer survival in melanomas with miR-130b-3p overexpression. Our findings provide support for the existence of a microRNA expression profile in melanomas with aggressive clinicopathological features and poor prognosis.

Folliculocystic and collagenous hamartoma of tuberous sclerosis complex, not always a single cutaneous lesion.

Folliculocystic and collagenous hamartoma (FCCH) is a rare cutaneous manifestation characterized by the presence of single plaques studded with comedo-like openings and cysts. Although its pathophysiology is still unknown, it has generally been described in men with tuberous sclerosis complex (TSC). We report a case of a one-year-old child with two FCCH in the abdominal wall associated with TSC. In our case, a TSC2 mutation was identified.

Cutaneous and mucocutaneous leishmaniasis: experience of a Mediterranean hospital.

BACKGROUND: Leishmaniasis, considered by the World Health Organization as one of the most important tropical diseases, is endemic in the Mediterranean Basin. The aim of this study was to evaluate epidemiological and clinical characteristics of cutaneous (CL) and mucocutaneous leishmaniasis (MCL) in La Fe University Hospital, Valencia, Spain. The particular focus was on diagnosis techniques and clinical differences according to the immunological status of the patients. METHODS: An eleven-year retrospective observational study of CL and MCL episodes at the hospital was performed. Epidemiological, clinical and therapeutic variables of each case, together with the microbiological and anatomopathological diagnosis, were analyzed. RESULTS: A total of 42 patients were included, 30 of them were male and 28 were immunocompetent. Most of the cases (36/42) were diagnosed in the last 5 years (2013-2017). The incidence of CL and MCL increased from 3.6/100,000 (2006-2012) to 13.58/100,000 (2013-2017). The majority of the patients (37/42) exhibited CL, in 30 cases as single lesions (30/37). Ulcerative lesions were more common in immunosuppressed patients (13/14) than in immunocompetent patients (20/28), (P = 0.2302). The length of lesion presence before diagnosis was 7.36 ± 6.72 months in immunocompetent patients and 8.79 ± 6.9 months in immunosuppressed patients (P = 0.1863). Leishmania DNA detection (92.3%) was the most sensitive diagnostic technique followed by Giemsa stain (65%) and histopathological examination (53.8%). Twelve patients (12/42) had close contact with dogs or were living near to kennels, and 10 of them did not present underlying conditions. Intralesional glucantime (21/42) and liposomal amphotericin B (7/42) were the most common treatments administered in monotherapy. All patients evolved successfully and no relapse was reported. CONCLUSIONS: Some interesting clinical and epidemiological differences were found in our series between immunocompetent and immunosuppressed patients. Future studies can take these results further especially by studying patients with biological therapy. Skin biopsies combining NAAT with histological techniques are the most productive techniques for CL or MCL diagnosis.

Placa necrótica frontal rápidamente progresiva en paciente inmunodeprimido / Rapidly progressive frontal necrotic plaque in an immunosuppressed host

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Placas violáceas y necróticas rápidamente progresivas en un niño de 5 años de edad / Rapidly progressive violaceous and necrotic plaques in a 5 years-old boy

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Towards Personalized Medicine in Melanoma: Implementation of a Clinical Next-Generation Sequencing Panel.

Molecular diagnostics are increasingly performed routinely in the diagnosis and management of patients with melanoma due to the development of novel therapies that target specific genetic mutations. The development of next-generation sequencing (NGS) technologies has enabled to sequence multiple cancer-driving genes in a single assay, with improved sensitivity in mutation detection. The main objective of this study was the design and implementation of a melanoma-specific sequencing panel, and the identification of the spectrum of somatic mutations in a series of primary melanoma samples. A custom panel was designed to cover the coding regions of 35 melanoma-related genes. Panel average coverage was 2,575.5 reads per amplicon, with 92,8% of targeted bases covered ≥500×. Deep coverage enabled sensitive discovery of mutations in as low as 0.5% mutant allele frequency. Eighty-five percent (85/100) of the melanomas had at least one somatic mutation. The most prevalent mutated genes were BRAF (50%;50/199), NRAS (15%;15/100), PREX2 (14%;14/100), GRIN2A (13%;13/100), and ERBB4 (12%;12/100). Turn-around-time and costs for NGS-based analysis was reduced in comparison to conventional molecular approaches. The results of this study demonstrate the cost-effectiveness and feasibility of a custom-designed targeted NGS panel, and suggest the implementation of targeted NGS into daily routine practice.