Vitamin D status in children with congenital melanocytic nevi.

Congenital melanocytic nevi (CMN) are rare, pigmented birthmarks that can predispose patients to melanoma of the central nervous system and skin. Data from non-CMN melanoma cohorts suggest that vitamin D levels may be connected to outcome, prompting this study of 25-hydroxyvitamin D levels in plasma samples from 40 children with CMN. While 27% were insufficient and 13% deficient, this was representative of European populations, and UK supplementation guidelines are already in place. Our data support routine vitamin D supplementation for all CMN patients during winter months, without routine serum measurement.

Presumed incipient choroidal melanoma: proposed diagnostic criteria and management.

AIMS: To propose diagnostic criteria for a presumed incipient choroidal melanoma based on tumour growth rate and tumour doubling time (TDT) and to describe management of such tumours with transpupillary thermotherapy (TTT). METHODS: Retrospective interventional case series of nine consecutive presumed incipient uveal melanomas diagnosed and treated with TTT in 2010-2017. Growth rate in mm/year and per cent/year in largest basal diameter (LBD) and TDT were compared with published data for uveal melanomas and growing naevi that did not transform to melanoma under long-term follow-up. RESULTS: The median LBD and thickness were 1.6 mm (range 0.9-2.3) and 0.20 mm (range 0.15-0.29), respectively. The median age was 57 years (range 47-78). Seven tumours were classified as de novo melanomas and two as transformed naevi. The median time from first observation to diagnosis was 3.3 years (range 2.2-7.3), LBD growth rate 0.25 mm/year (range 0.11-0.72) and 34 per cent/year (range 10-1437), and TDT 609 days (range 97-1612). The estimates matched those reported for uveal melanoma (median TDT 521 days, 90th percentile 2192) and exceeded those for growing naevi (median growth rate 0.04 mm/year, 90th percentile 0.12; 1.1 per cent/year, 90th percentile 2.6). The predicted median age at de novo appearance was 51 years (range 32-63). No tumour grew after TTT during a median follow-up of 2.1 years (range 0.6-8.7). CONCLUSIONS: In this series, relative growth rate and TDT best qualified as diagnostic criteria for an incipient choroidal melanoma. Too small for brachytherapy, they could be managed with TTT.

Successful treatment with MEK-inhibitor in a patient with NRAS-related cutaneous skeletal hypophosphatemia syndrome.

Cutaneous skeletal hypophosphatemia syndrome (CSHS) is caused by somatic mosaic NRAS variants and characterized by melanocytic/sebaceous naevi, eye, and brain malformations, and FGF23-mediated hypophosphatemic rickets. The MEK inhibitor Trametinib, acting on the RAS/MAPK pathway, is a candidate for CSHS therapy. A 4-year-old boy with seborrheic nevus, eye choristoma, multiple hamartomas, brain malformation, pleural lymphangioma and chylothorax developed severe hypophosphatemic rickets unresponsive to phosphate supplementation. The c.182A > G;p.(Gln61Arg) somatic NRAS variant found in DNA from nevus biopsy allowed diagnosing CSHS. We administered Trametinib for 15 months investigating the transcriptional effects at different time points by whole blood RNA-seq. Treatment resulted in prompt normalization of phosphatemia and phosphaturia, catch-up growth, chylothorax regression, improvement of bone mineral density, reduction of epidermal nevus and hamartomas. Global RNA sequencing on peripheral blood mononucleate cells showed transcriptional changes under MEK inhibition consisting in a strong sustained downregulation of signatures related to RAS/MAPK, PI3 kinase, WNT and YAP/TAZ pathways, reverting previously defined transcriptomic signatures. CSHS was effectively treated with a MEK inhibitor with almost complete recovery of rickets and partial regression of the phenotype. We identified "core" genes modulated by MEK inhibition potentially serving as surrogate markers of Trametinib action.

Neonatal Curettage of Large to Giant Congenital Melanocytic Nevi Under Local Anesthetic: A Case Series With Long-Term Follow Up.

BACKGROUND: Neonatal curettage of large to giant congenital melanocytic nevi (L-GCMN) is a simple, minimally invasive procedure typically performed within the first 2 weeks of life. OBJECTIVES: To retrospectively review our experience with serial curettage of L-GCMN in the neonatal period performed under local anesthesia and their long-term outcomes. METHODS: Curettage was performed by a single pediatric dermatologist on nine neonates with L-GCMN under local anesthetic and with oral analgesia between 2002 and 2016 in Red Deer, Alberta, Canada. Patient charts were reviewed retrospectively to assess patient and procedure characteristics, tolerability, safety, cosmetic and functional outcomes, and malignant transformation. RESULTS: Patients were treated with an average of 6 curettage sessions (range 3 to 15) to remove the majority or entirety of the nevus. All patients tolerated local anesthesia well. The most common adverse event of the procedure was transient neutropenia. Two patients developed positive bacterial cultures without clinical signs of infection, treated with antibiotics. All curetted specimens demonstrated benign pathology. Patients were followed annually thereafter, for an average of 6 years. Eight patients with L-GCMN of the trunk had minimal to partial repigmentation with good cosmetic outcome. One patient had recurrence of a facial nevus. None of the patients developed cutaneous malignant melanoma. CONCLUSIONS: Curettage appears to be a safe and effective treatment option for select cases of L-GCMNs of the trunk. We do not recommend the procedure for face or scalp CMN. This procedure can be performed under local anesthesia with serial curettage to avoid potential risks of general anesthesia.

Care of Congenital Melanocytic Nevi in Newborns and Infants: Review and Management Recommendations.

A pediatric dermatology expert working group performed a narrative review to describe care related to congenital melanocytic nevi (CMN) in neonates and infants. There are no published guidelines for most aspects of care, including routine skin care and visit intervals. Few guidelines exist for surgical management; newer recommendations favor conservative practice. Emerging evidence contributes to recommendations for screening MRI to evaluate for neural melanosis and related central nervous system complications, however, more research is needed. Risk for melanoma is generally low, but those with large, giant, or multiple CMN have a higher risk. Multidisciplinary care, with a focus on family and patient preferences, is of paramount importance. Without standardized screening and management guidelines, questions abound regarding appropriate physical examination intervals, potential treatment including full or partial excision, timing and frequency of imaging, melanoma risk, and assessment for neural melanosis. This review highlights the current state of knowledge concerning care of patients with CMN, reveals gaps in the literature surrounding skin care, and provides management recommendations. We additionally discuss cutaneous complications of CMN, such as pruritus, hypertrichosis, and wound healing. Resources and references for families and providers can help patients navigate this sometimes challenging diagnosis. Finally, we contribute expert care recommendations to the current body of literature as a foundation for the development of future, more comprehensive care guidelines.

Differential Immunoexpression of BRAF/V600E, Senescence Markers, PTEN, and T-type Calcium Channels in Acquired Naevi According to their Histopathological and Dermoscopic Classification.

BRAF/V600E mutation and other cell growth/growth-control mechanisms are involved in naevogenesis and melanomagenesis. Immunoexpression of BRAF/V600E and other molecules (p16, phosphatase and tensin homologue (PTEN), Ki67, hTERT and Cav3.1 and 3.2 calcium channels) were investigated in 80 histopatho-logically and dermoscopically classified acquired naevi. Regarding BRAF/V600E, dysplastic naevi showed lower immunostaining than common naevi, which was significant in comparison with intradermal naevi, which showed the highest BRAF/V600E histoscore. Junctional naevi showed the lowest BRAF/V600E levels. Globular/cobblestone and reticular dermoscopic patterns were consistently associated with high and low BRAF/V600E immunoexpression, respectively, but Zalaudek's peripheral globule pattern (CR/PG) showed the highest BRAF/V600E immunoexpression. Among global patterns, the previously not investigated multicomponent pattern showed the lowest BRAF/V600E immunoexpression. Regarding the remaining biomarkers, new immunohistochemical features were found, in particular p16 and PTEN low expression in multicomponent pattern; and Ki67, hTERT and Cav.3.1 high expression in CR/PG. In conclusion, histopathology and dermoscopy provide complementary information regarding the biology of melanocytic naevi.

Nevu agminado en síndrome de nevus displásico / Agminated nevus in dysplastic nevus syndrome

Los nevus melanocíticos agminados (NMA) son poco reportados en la bibliografía mundial. El nevus agminado (NA), puede presentar varios orígenes, dependiendo de ello pueden desarrollar características displásicas, con riesgo potencial de desarrollar melanoma y entrar a formar parte del Síndrome de Nevus Displásico (SND) de acuerdo a su diagnóstico clínico, dermatoscópico, histológico e historia familiar. El objetivo del presente trabajo es presentar y discutir el caso clínico de un paciente masculino de 26 años de edad sin antecedentes patológicos, evaluado en la Clínica Dermatológica Skinlaser en Quito Ecuador en mayo 2020, que presentó múltiples nevus en la superficie corporal, especialmente en la espalda a nivel posterior e interescapular. El estudio enfatiza la importancia de los controles dermatoscópicos y el seguimiento para hacer el reconocimiento de signos de atipia y cambios que hacen sospechar de malignización(AU)

Agminate melanocytic nevus (AMN) are little reported in the world literature. The agminated nevus (NA) can have various origins, depending on it, they can develop dysplastic characteristics, with a potential risk of developing melanoma and become part of Dysplastic Nevus Syndrome (SND) according to its clinical, dermoscopic, histological and history diagnosis. family. The objective of this work is to present and discuss the clinical case of a 26-year-old male patient with no pathological history, evaluated at the Clinica Dermatologica Skinlaser in Quito Ecuador in May 2020, who presented multiple nevi on the body surface, especially in the back at posterior and interscapular level. The study emphasizes the importance of dermoscopic controls and follow-up are essential to recognize signs of atypia and changes that lead to suspicion of malignancy(AU)

Utilidad del dermatoscopio en la correlación clínica e histológica de nevus pigmentados / Usefulness of Dermatoscopy in the clinical and histological correlation of Pigmented Nevi

Introducción: La precisión diagnóstica de los nevus pigmentados ha sido una constante preocupación por los dermatólogos. Objetivo: Identificar la utilidad del dermatoscopio en la correlación de las características clínicas y los patrones dermatoscópicos de nevus pigmentados y su asociación con el diagnóstico histológico. Métodos: Se realizó una investigación observacional, analítica, de tipo correlacional, con pacientes de la zona sur de Ciego de Ávila que acudieron a la consulta de dermatología del Hospital Provincial General Docente Dr. Antonio Luaces Iraola en el periodo de abril 2017 a diciembre 2019. Resultados: Predominó el sexo femenino, el grupo de edad de 21 a 30 años, el fototipo II de piel y la zona expuesta (cara y V del escote) (18 ;35,3 por ciento) sin relación entre estas variables. El diagnóstico histológico de nevus de la unión se encontró asociado a la simetría (p < 0,004), la pigmentación homogénea (p < 0,000), así como al patrón dermatoscópico reticular (p < 0,000), globular (p < 0,002) y homogéneo (p < 0,008). El nevus intradérmico se observó asociado a la característica clínica de pigmentación homogénea (p < 0,007), y al patrón dermatoscópico reticular (p < 0,000) y homogéneo (p < 0,005). El nevus compuesto no presentó relación con las características clínicas ni dermatoscópicas. El nevus azul solo se correlacionó con el patrón dermatoscópico homogéneo (p < 0,025). Conclusión: Los patrones dermatoscópicos fueron útiles para el diagnóstico clínico e histológico de los nevus pigmentados(AU)

Introduction: The diagnostic precision of pigmented nevi has been a constant concern of dermatologists. Objective: To determine the usefulness of the Dermatoscope in the correlation of the clinical characteristics and the dermoscopic patterns of pigmented nevi and their association with the histological diagnosis. Methods: An analytical observational investigation of a correlational type was carried out in patients from the southern area of Ciego de Ávila who attended the Dermatology consultation at the Antonio Luaces Iraola Provincial Hospital in the period from April 2017 to December 2019. Results: The female sex, the age group of 21 to 30 years, skin phototype II and the exposed area (face and V of the neckline) (18; 35.3 percent) predominated with no relationship between these variables. The histological diagnosis of junctional nevus was found associated with symmetry (p <0.004), homogeneous pigmentation (p <0.000), as well as the reticular dermoscopic pattern (p <0.000), globular (p <0.002) and homogeneous (p <0.008). The intradermal nevus was observed associated with the clinical characteristic of homogeneous pigmentation (p <0.007), and with the reticular (p <0.000) and homogeneous (p <0.005) dermoscopic pattern. The composite nevus was not related to clinical or dermoscopic characteristics. The blue nevus only correlated with the homogeneous dermoscopic pattern (p <0.025). Conclusions: The dermoscopic patterns were useful for the clinical and histological diagnosis of pigmented nevi(AU)

Treatment of maxillofacial congenital melanocytic nevus with percutaneous radiofrequency thermal ablation: A case series study.

When congenital melanocytic nevus (CMN) is in the maxillofacial region, a safer, more effective and fewer side-effects treatment is needed for patients with high requirement for appearance. The objective of this study was to investigate the effectiveness of radiofrequency thermal ablation (RFA) for CMN in the maxillofacial region. We reviewed 21 patients treated with RFA for CMN followed by a blinded retrospective analysis of serial photographs taken during the course of their therapy. Questionnaires were used to evaluate perceived therapeutic response and complications of this treatment. Most CMNs stopped growing, faded in color and became smaller. Reduction in size of 90% to 100% was obtained in two patients (10%), 75% to 90% in six patients (29%), 50% to 75% in two patients (10%), <50% in eight patients (38%), and three had no reduction (13%). Clear effect of clinical response score was obtained in two patients (10%), excellent in four patients (19%), good in 14 patients (67%), and fair in one patient (4%). No serious complication, severe hypertrophic scarring, and evidence of recurrence was observed in any case. Percutaneous RFA, as a minimally invasive and safe treatment, may provide an alternative treatment for maxillofacial CMN.

Clinical Follow-Up of Patients with Neurocutaneous Melanosis in a Tertiary Center; Proposed Modification in Diagnostic Criteria.

INTRODUCTION: Neurocutaneous melanosis (NCM) is a rare congenital syndrome. Except for some retrospective studies, information on clinical follow-up and management of these patients are limited. This study aimed to review our experience on diagnostic protocol and clinical follow-up of patients with NCM in a referral children's hospital in Iran. METHODS: Between 2012 and 2019, eight patients with NCM were consecutively managed in our center. Brain magnetic resonance imaging and cutaneous biopsy were done in all patients at diagnosis. Follow-up surveillance and characteristics of the disease are described. RESULTS: The mean follow-up period was 25.75 ± 13.81 months, and 75% of patients were male. Most magnetic resonance imaging findings were hypersignal lesions in the temporal lobe (75%), cerebellum (62.5%), brainstem (50%), and thalamus (12.5%). Dandy-Walker syndrome was found in 4 patients (50%), and shunt-dependent hydrocephalus was found in 3 patients (37.5%). Cutaneous malignant melanoma and malignant involvement of the central nervous system were found in 2 (25%) and 3 cases (37.5%), respectively. The mortality rate was 37.5%. CONCLUSIONS: There are no specific guidelines for management of NCM due to the rarity of the disease. This study proposed modifications in diagnostic criteria, as well as recommendations for follow-up surveillance.

Nódulo proliferativo en nevus melanocítico congénito gigante / Proliferative nodule in giant congenital melanocytic nevus

El nevus melanocítico gigante es una entidad poco frecuente. En los primeros meses o años de vida, pueden aparecer nódulos dérmicos pequeños o grandes, muy pigmentados, que pueden crecer rápidamente o incluso ulcerarse. Esto obliga a realizar diagnóstico diferencial con el melanoma. Se presenta el caso de una paciente de 3 años de edad, con gran lesión pigmentada en pierna izquierda, con nódulos de rápido crecimiento, compatibles con nódulo proliferativo.

Giant melanocytic nevi are rare. In the fi rst few months or even years of life, they may develop small or large dermic nodules, very pigmented, with rapid growth o even ulcer formation. This forces the diff erential diagnosis with melanoma. We present a case of a 3 year old female patient, with a large pigmented lesion on the left leg, with nodules compatible with proliferative nodules.

Pediatric Laser Therapy in Pigmented Conditions.

Advances in laser therapy have led to novel therapeutic approaches to common pediatric skin conditions. As a non-invasive alternative to surgical options, laser therapy is efficacious in treating a broad range of conditions, from vascular and pigmented lesions to tattoo and hair removal. This paper reviews the basic mechanics of laser therapy, its role in common pigmented pediatric dermatoses, and special considerations for this unique age group.

Phototherapy-induced blistering reaction and eruptive melanocytic nevi in a child with transient neonatal porphyrinemia.

Neonatal blue-light phototherapy induced a blistering reaction followed by eruption of melanocytic nevi on the exposed skin surface of a child with transient neonatal porphyrinemia. New nevi are still developing 4 years after the triggering event. The role of phototoxicity-induced epidermal injury, that of porphyrins and the influence of neonatal blue-light therapy, in this unique phenomenon are discussed.

FR - Nevus melanocíticos eruptivos asociados a medicamentos / Drug-Induced Eruptive Melanocytic Nevi

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Medium-sized nevus spilus of the neck treated with pulsed dye laser.

Patients with large benign melanocytic lesions located on the neck represent a therapeutic challenge since the neck is a high-risk area for hypertrophic scarring and/or retraction. When treating a benign, extensive and visible melanocytic lesion, the choice of therapy mainly depends on the likelihood of improved cosmesis. We report a case of a 33-year-old woman with a medium-sized Nevus Spilus located on the neck, successfully treated with four sessions of pulsed dye laser. We achieved an excellent clinical and cosmetic result in such a challenging area. No scarring, distortion or significant dyscromia were observed after 24 months.

Mosaic NRAS Q61R mutation in a child with giant congenital melanocytic naevus, epidermal naevus syndrome and hypophosphataemic rickets.

The association of hypophosphataemic rickets with verrucous epidermal naevus (EN) and elevated fibroblast growth factor 23 levels is known as cutaneous-skeletal hypophosphataemia syndrome (CSHS), and can be caused by somatic activating mutations in RAS genes. We report a unique patient with CSHS associated with giant congenital melanocytic naevus (CMN), neurocutaneous melanosis and EN syndrome, manifesting as facial linear sebaceous naevus, developmental delay and ocular dermoids. An activating mutation Q61R in the NRAS gene was found in affected skin and ocular tissue but not blood, implying that the disparate manifestations are due to a multilineage activating mutation (mosaic RASopathy). We speculate on the apparently rare association of CSHS with CMN compared with EN. We also report the favourable outcome of this patient at the age of 8 years after extensive neonatal curettage of the giant CMN and use of vitamin D and phosphate supplementation.