RESUMEN
Giant congenital melanocytic nevi are NRAS-driven proliferations that may cover up to 80% of the body surface. Their most dangerous consequence is progression to melanoma. This risk often triggers preemptive extensive surgical excisions in childhood, producing severe lifelong challenges. We have presented preclinical models, including multiple genetically engineered mice and xenografted human lesions, which enabled testing locally applied pharmacologic agents to avoid surgery. The murine models permitted the identification of proliferative versus senescent nevus phases and treatments targeting both. These nevi recapitulated the histologic and molecular features of human giant congenital nevi, including the risk of melanoma transformation. Cutaneously delivered MEK, PI3K, and c-KIT inhibitors or proinflammatory squaric acid dibutylester (SADBE) achieved major regressions. SADBE triggered innate immunity that ablated detectable nevocytes, fully prevented melanoma, and regressed human giant nevus xenografts. These findings reveal nevus mechanistic vulnerabilities and suggest opportunities for topical interventions that may alter the therapeutic options for children with congenital giant nevi.
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Melanoma , Nevo Pigmentado , Neoplasias Cutáneas , Animales , Xenoinjertos , Humanos , Melanoma/tratamiento farmacológico , Melanoma/patología , Ratones , Trasplante de Neoplasias , Nevo Pigmentado/congénito , Nevo Pigmentado/tratamiento farmacológico , Nevo Pigmentado/patología , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/prevención & controlRESUMEN
NRAS activating mutations are prevalent in melanocytic neoplasia, occurring in a subset of common acquired melanocytic nevi and â¼30% of cutaneous melanomas. In this study, we described a cohort of 7 distinctive melanocytic tumors characterized by activating point mutations in codon 61 of NRAS with amplification of the mutant NRAS allele and shared clinicopathologic features. These tumors occurred predominantly in younger patients, with a median age of 20 years (range, 6-56 years). They presented as papules on the helix of the ear (4 cases) or extremities (3 cases). Microscopically, the tumors were cellular, relatively well-circumscribed, compound, or intradermal proliferations. The tumor cells often extended into the deep reticular dermis and involved the superficial subcutaneous fat in some cases. The melanocytes were epithelioid to spindled with moderate amounts of cytoplasm and conspicuous nucleoli. They were arranged in short plexiform fascicles, nests, and cords. Some cases had occasional pleomorphic and multinucleated melanocytes. Rare dermal mitotic figures were present in all cases. The dermis contained thick collagen bundles and minimal solar elastosis. Follow-up data were available for 5 patients, with a median period of 4.2 years (range, 1-9 years), during which no recurrences or metastases were reported. Our series highlights a clinicopathologically and molecularly distinctive subset of NRAS-mutated tumors with amplification of the mutant NRAS allele.
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GTP Fosfohidrolasas , Proteínas de la Membrana , Nevo de Células Epitelioides y Fusiformes , Neoplasias Cutáneas , Humanos , GTP Fosfohidrolasas/genética , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/patología , Masculino , Femenino , Persona de Mediana Edad , Proteínas de la Membrana/genética , Adulto , Adolescente , Niño , Adulto Joven , Nevo de Células Epitelioides y Fusiformes/genética , Nevo de Células Epitelioides y Fusiformes/patología , Melanoma/genética , Melanoma/patología , Amplificación de Genes , Melanocitos/patología , Mutación , Nevo Pigmentado/genética , Nevo Pigmentado/patología , Mutación PuntualRESUMEN
AIMS: Plaque-type blue naevi are rare melanocytic tumours presenting as large, pigmented plaques at birth or during childhood. There is a risk for malignant transformation, but no larger comprehensive studies exist and the diagnosis is challenging, especially on limited biopsy material. The aim is to describe the clinicopathological features and behaviour of the disease more comprehensively. METHODS AND RESULTS: We retrieved eight plaque-type blue naevi, presenting as large, pigmented plaques (median = 7 cm; range = 3-26) most frequently affecting the scalp (four) followed by the cheek, arm, abdominal wall and gluteal cleft (one each), with a slight female predilection. Median age at time of biopsy was 39.5 years (range = 15-90), but three tumours had been present at birth and one since childhood. Histopathologically, the tumours were poorly circumscribed and composed of cellular fascicles of uniform spindle cells in a background of variably prominent pigmented dendritic cells affecting dermis and subcutaneous tissues. The majority had mutations in GNAQ. One tumour showed malignant transformation, characterised by an expansile nodule of pleomorphic epithelioid melanocytes with rhabdoid morphology, high mitotic activity and areas of necrosis. This patient developed metastatic melanoma to lymph nodes. All patients are alive with a median follow-up of 60 months. CONCLUSION: Plaque-type blue naevi are diagnostically challenging tumours with risk for malignant transformation. Awareness and familiarity with the salient clinicopathological features are necessary for reliable diagnosis, and long-term clinical follow-up is required to monitor for malignant transformation.
Asunto(s)
Melanoma , Nevo Azul , Nevo Pigmentado , Neoplasias Cutáneas , Recién Nacido , Humanos , Femenino , Adolescente , Adulto Joven , Adulto , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Nevo Azul/diagnóstico , Nevo Azul/patología , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/patología , Nevo Pigmentado/patología , Melanoma/patología , Melanocitos/patologíaRESUMEN
PURPOSE OF REVIEW: Congenital melanocytic nevi (CMN) and acquired nevi are prevalent in pediatric populations, with distinct characteristics and management considerations. This chapter aims to equip pediatricians with knowledge to discern between benign and high-risk nevi, facilitating appropriate referrals and management within primary care settings. Risk factors associated with malignant melanoma (MM) underscore the importance of vigilant monitoring and early referral to dermatology for suspicious lesions. RECENT FINDINGS: Recent findings highlight the variability in CMN presentation and the evolving diagnostic strategies, emphasizing the need for multidisciplinary approaches to optimize patient outcomes. SUMMARY: Management of CMN involves tailored surveillance and intervention strategies, with an emphasis on early identification of high-risk features for MM and neurocutaneous melanosis (NCM). Pediatricians play a crucial role in advocating for sun protection practices and facilitating timely referrals, thereby contributing to the overall well being of pediatric patients with nevi.
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Melanoma , Nevo Pigmentado , Derivación y Consulta , Neoplasias Cutáneas , Humanos , Nevo Pigmentado/diagnóstico , Nevo Pigmentado/terapia , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/terapia , Niño , Melanoma/diagnóstico , Melanoma/terapia , Factores de RiesgoRESUMEN
BACKGROUND: Dermoscopic and reflectance confocal microscopy (RCM) correlations between morphologic groups of melanoma have not yet been described. OBJECTIVE: Describe and compare dermoscopic and RCM features of cutaneous melanomas with histopathological confirmation. METHODS: Single center, retrospective analysis of consecutive melanomas evaluated with RCM (2015-2019). Lesions were clinically classified as typical, nevus-like, amelanotic/nonmelanoma skin cancer (NMSC)-like, seborrheic keratosis (SK)-like and lentigo/lentigo maligna (LM)-like. Presence or absence of common facial and nonfacial melanoma dermoscopic and RCM patterns were recorded. Clusters were compared with typical lesions by multivariate logistic regression. RESULTS: Among 583 melanoma lesions, significant differences between clusters were evident (compared to typical lesions). Observation of dermoscopic features (>50% of lesions) in amelanotic/NMSC-like lesions consistently displayed 3 patterns (atypical network, atypical vascular pattern + regression structures), and nevus-like and SK-like lesions and lentigo/LM-like lesions consistently displayed 2 patterns (atypical network + regression structures, and nonevident follicles + heavy pigmentation intensity). Differences were less evident with RCM, as almost all lesions were consistent with melanoma diagnosis. LIMITATIONS: Small SK-like lesions sample, single RCM analyses (no reproduction of outcome). CONCLUSION: RCM has the potential to augment our ability to consistently and accurately diagnose melanoma independently of clinical and dermoscopic features.
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Peca Melanótica de Hutchinson , Queratosis Seborreica , Lentigo , Melanoma , Nevo Pigmentado , Nevo , Neoplasias Cutáneas , Humanos , Melanoma/patología , Dermoscopía , Estudios Retrospectivos , Neoplasias Cutáneas/patología , Peca Melanótica de Hutchinson/patología , Queratosis Seborreica/diagnóstico , Nevo/diagnóstico por imagen , Nevo Pigmentado/patología , Lentigo/diagnóstico , Microscopía Confocal , Diagnóstico DiferencialRESUMEN
An 11-year-old female was referred from an outside institution after a diagnostic biopsy and subsequent excision of a progressively enlarging reddish-brown nodule demonstrated features concerning for a balloon cell nevus with severe atypia versus a high-grade melanocytoma. Upon review of the initial biopsy specimen and molecular data, we favored the diagnosis to be consistent with a high-grade melanocytoma with balloon cell changes while considering the possibility of balloon cell melanoma due to concerning histopathologic and genetic abnormalities. In this case study, we discuss critical diagnostic considerations in this rare pediatric case and highlight important pathologic and clinical features of melanocytomas and balloon cell melanoma.
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Melanoma , Nevo Pigmentado , Neoplasias Cutáneas , Humanos , Femenino , Melanoma/diagnóstico , Melanoma/patología , Niño , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/diagnóstico , Nevo Pigmentado/patología , Nevo Pigmentado/diagnóstico , Diagnóstico Diferencial , Melanocitos/patologíaRESUMEN
Nevus lipomatosus still imposes diagnostic, categorization, and etiologic challenges. Even though an intradermal adipose tissue is a histopathologic prerequisite, the lesions are clinically divided into classic multiple forms and a solitary variant, which some consider a separate so-called lipofibroma clinicopathologic entity. This further complicates the true prevalence, classification and etiopathogenesis of nevus lipomatosus. Case reports and series studies have reflected either consistent or variable and sometimes conflicting clinicopathologic findings. A few have reported electron microscopic findings. Immunohistochemistry is lacking. We report two multiple and four solitary forms of nevus lipomatosus in six patients, highlighting their salient histopathologic features and immunohistochemical profile. Both forms showed intradermal groups of perivascular S100+ lipogenic and CD34+ mesenchymal cells intermixed with scattered CD1a+ and FXIIIa+ dendrocytes, CD3 lymphocytic and CD117 mast cells in a fibromyxoid milieu. Epidermal nevoid and comedonal follicular alterations, attenuated dermal connective tissue and adnexal structures were variably present in both forms. We compared our findings with seven series of studies reporting classic and solitary forms. Both forms showed similar histopathologic findings, comparable clinicopathologic features, predominantly pelvic, and shoulder girdle distribution patterns in bimodal age onsets. Even though some lipomatous skin lesions clinically and histopathologically overlap with nevus lipomatosus, certain findings are helpful distinguishing features. Small intradermal islands of lipocytic fibroplasia have characteristic perivascular milieu that may function as a niche of preadipose CD34 mesenchymal stem cells. They are most likely represented in the dermis of the pelvic and shoulder areas in certain individuals prone to maintain these embryonic reservoirs, which are clinically manifested at different ages. Some may have unifocal or multifocal residues reflecting multiple and solitary forms.
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Lipomatosis , Nevo Pigmentado , Nevo , Neoplasias Cutáneas , Humanos , Neoplasias Cutáneas/patología , Lipomatosis/patología , Nevo/patología , Piel/patologíaRESUMEN
Nevus-associated lentigo maligna and lentigo maligna melanoma (NALMM) are rarely described in the literature and are considered an incidental finding. This study aimed to evaluate the frequency of NALMM and its clinicopathological features. A total of 201 histopathology reports were reviewed and among them 20% of the samples corresponded to NALMM, with females overrepresented in this group (p = 0.02). A significant association was also observed between NALMM with the presence of multiple nevi (p = 0.01), and dysplastic nevi (p = 0.04). Moreover, the risk of developing a second melanoma of nevus-associated type was 4.3 times higher in patients with NALMM. These results indicate that NALMM is more frequent than previously reported, suggesting that the associated nevus could interact or even act as a precursor for LM/LMM. Future studies with larger samples allied to techniques like confocal microscopy and molecular analysis are essential to determine this biological link between nevus and LM/LMM.
Asunto(s)
Peca Melanótica de Hutchinson , Melanoma , Nevo Pigmentado , Nevo , Neoplasias Cutáneas , Femenino , HumanosRESUMEN
BACKGROUND: Congenital melanocytic naevi (CMN) are the result of aberrations in the mitogen-activated protein kinase signal transduction pathway. The risk of melanoma is the most important concern among patients with CMN because of its poor prognosis. However, as a result of the great variability between studies, the reported risk of melanoma varies considerably, making it difficult to provide reliable information. OBJECTIVES: To evaluate the prevalence, incidence density and standardized morbidity ratio (SMR) of melanoma among patients with CMN. METHODS: We conducted a systematic literature search of studies providing data on the risk of melanoma in patients with CMN following our registered and published protocol (PROSPERO: CRD42022383009). RESULTS: Overall, 27 studies with a total of 11 480 patients with CMN and 82 patients developing melanoma were included for analysis. The prevalence of melanoma was 1.84% [95% confidence interval (CI) 1.13-2.99] in patients with CMN and 2.73% (95% CI 1.67-4.43) in the subgroup of patients with large CMN (LCMN). The incidence of melanoma was 237.56 (95% CI 97.79-575.96) per 100 000 person-years in patients with CMN and 585.73 (95% CI 315.39-1085.29) per 100 000 person-years in the LCMN subgroup. The SMR of melanoma was 122.27 (95% CI 11.84-1262.88) among all patients with CMN and 285.97 (95% CI 50.65-1614.59) in the subgroup of patients with LCMN. CONCLUSIONS: Our research suggests that the risk of melanoma in the CMN population seems to have been overestimated in previous studies, but it is still significantly higher than that in the general population. In addition to the risk of melanoma, aesthetic improvement and mental health should also be taken into account when making management decisions.
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Melanoma , Nevo Pigmentado , Neoplasias Cutáneas , Humanos , Melanoma/epidemiología , Neoplasias Cutáneas/epidemiología , Prevalencia , Incidencia , Nevo Pigmentado/epidemiología , Nevo Pigmentado/congénito , Factores de RiesgoRESUMEN
BACKGROUND: S100A8 is a melanoma biomarker expressed in the melanoma-associated epidermal keratinocytes, but its diagnostic utility has not been compared with other biomarkers, including PRAME. OBJECTIVES: To compare the utility of S100A8 and PRAME immunohistochemistry (IHC) in the differential diagnosis of melanoma and naevi in a case-control study. METHODS: A previously described cohort of 209 melanomas (case samples) and naevi (control samples) dual-immunostained for S100A8 and PRAME were included. For S100A8, previously reported scores indicating the proportion of tumour-associated epidermis stained (0 = indeterminate; 1 = 0-4%; 2 = 5-25%; 3 = 26-50%; 4 = 51-75%; 5 = > 75%) were utilized. PRAME IHC was reviewed by at least two reviewers and a consensus score assigned, with score indicating the proportion of tumour stained (0 = indeterminate; 1 = 0%; 2 = 1-50%; 3 = > 50%). A positive test was defined as > 50% staining. RESULTS: The area under the receiver operating characteristic curves for S100A8 (0.833) and PRAME (0.874) were not significantly different from each other (P = 0.22). The diagnostic sensitivity and specificity were 42.4% [95% confidence interval (CI) 32.6-52.8%] and 98.2% (95% CI 93.6-99.8%) for S100A8, and 79.8% (95% CI 70.5-87.2%) and 87.3% (95% CI 79.6-92.9%) for PRAME, respectively. A combined test requiring both S100A8 and PRAME IHC positivity had a sensitivity of 39.4% (95% CI 29.7-49.7%) and specificity of 99.1% (95% CI 95.0-100.0%). CONCLUSIONS: S100A8 and PRAME have utility in the diagnostic workup of melanoma, with S100A8 being more specific and PRAME being more sensitive when using this threshold. Our findings suggest that these two immunohistochemical markers may favourably complement one another to improve the detection of melanoma.
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Antígenos de Neoplasias , Biomarcadores de Tumor , Calgranulina A , Inmunohistoquímica , Melanoma , Nevo Pigmentado , Neoplasias Cutáneas , Humanos , Melanoma/diagnóstico , Melanoma/metabolismo , Melanoma/patología , Calgranulina A/metabolismo , Calgranulina A/análisis , Estudios de Casos y Controles , Diagnóstico Diferencial , Biomarcadores de Tumor/metabolismo , Biomarcadores de Tumor/análisis , Nevo Pigmentado/diagnóstico , Nevo Pigmentado/metabolismo , Nevo Pigmentado/patología , Antígenos de Neoplasias/metabolismo , Antígenos de Neoplasias/análisis , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/metabolismo , Neoplasias Cutáneas/patología , Curva ROC , Sensibilidad y Especificidad , Masculino , Femenino , Persona de Mediana Edad , AdultoRESUMEN
BACKGROUND: Limited research exists on laser treatment of giant congenital melanocytic nevus (GCMN). OBJECTIVE: We sought to elucidate the efficacy of the Erbium: YAG laser on GCMN and the histologic factors associated with a positive clinical response. METHODS AND MATERIALS: Between 2019 and 2022, we enrolled 30 medium-to-giant CMN patients who underwent Er: YAG laser treatment. All patients received biopsies before and after laser treatments. Clinical efficacy outcomes were evaluated by the investigator's global assessment (IGA), 5-point scale of depigmentation, and Vancouver Scar Scale (VSS) scores at least 6 months after treatment. RESULTS: Of the 30 cases, 18 (60.0%) showed improvement (IGA score ≥3). Eight (26.7%) patients showed repigmentation. Eight (26.7%) patients developed hypertrophic scars. The average IGA, depigmentation, and VSS scores were 2.93, 3.57, and 3.20. The IGA score was higher (3.24 ± 1.18 vs. 2.22 ± 0.97, p = 0.031) and a lower repigmentation rate (14.3% vs. 55.6%, p = 0.032) was observed in the cases with Grenz zone. The IGA score was higher (3.33 ± 1.24 vs. 2.13 ± 0.89, p = 0.023) and the repigmentation rate was lower (11.1% vs. 50.0%, p = 0.034) also in the cases with the melanocytes nests with aggregation of melanin. Lesions with superficial ablation resulted in less hypertrophic scar formation than those with deep ablation (5.9% vs. 53.8%, p < 0.05). CONCLUSION: The Er: YAG laser demonstrated effective clinical results for GCMNs. The grenz zone and the melanocytes nests with aggregation of melanin are promising predictors of laser efficacy.
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Cicatriz Hipertrófica , Terapia por Láser , Láseres de Estado Sólido , Nevo Pigmentado , Neoplasias Cutáneas , Humanos , Erbio , Melaninas , Láseres de Estado Sólido/uso terapéutico , Terapia por Láser/métodos , Resultado del Tratamiento , Nevo Pigmentado/radioterapia , Nevo Pigmentado/cirugía , Cicatriz Hipertrófica/patología , Inmunoglobulina ARESUMEN
BACKGROUND: Acquired melanocytic nevi are common benign skin lesions that require removal under certain circumstances. Shave removal is a straightforward treatment modality with a risk of recurrence. OBJECTIVE: To evaluate the outcome of dermoscopy-guided shave removal of acquired melanocytic nevi in the face of dark-skinned individuals who are more liable to postsurgical complications. METHODS: The study was conducted on 64 patients with acquired facial melanocytic nevi. Serial shave removal using a razor blade guided by dermoscopic examination was done until nevus-free tissue was seen, followed by electrocauterization of the base. Cosmetic outcome, patients' satisfaction, and recurrence rate were evaluated during follow-up. RESULTS: Excellent cosmetic outcome was achieved in 54.69% of patients, while 39.06% had an acceptable outcome, and 6.25% of patients had poor cosmetic outcome. Meanwhile, the recurrence rate was noticed in 5 cases only (7.8%). CONCLUSION: Dermoscopic-guided shave removal provides an easy procedure of treating common melanocytic nevi with an acceptable cosmetic result and a lower rate of recurrence even in patients with darker skin phenotypes.
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Dermoscopía , Nevo Pigmentado , Neoplasias Cutáneas , Humanos , Nevo Pigmentado/cirugía , Nevo Pigmentado/patología , Femenino , Masculino , Neoplasias Cutáneas/cirugía , Neoplasias Cutáneas/patología , Adulto , Persona de Mediana Edad , Adolescente , Adulto Joven , Neoplasias Faciales/cirugía , Neoplasias Faciales/patología , Recurrencia Local de Neoplasia/cirugía , Pigmentación de la Piel , Satisfacción del Paciente , Resultado del Tratamiento , Anciano , NiñoRESUMEN
ABSTRACT: Nevus sebaceus is a rare congenital hamartoma with clinical and histopathological features that change with puberty. It has been associated with a number of secondary neoplasms, most of which are thought to derive from follicular germ cells. In this article, the authors describe a total of 3 cases of combined melanocytic nevus and nevus sebaceus to highlight this rare finding.
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Nevo Pigmentado , Neoplasias Cutáneas , Humanos , Nevo Pigmentado/patología , Nevo Pigmentado/congénito , Neoplasias Cutáneas/patología , Masculino , Femenino , Adolescente , Niño , Hamartoma/patología , Hamartoma/congénito , AdultoRESUMEN
ABSTRACT: Melanocytic nevi can show a great number of morphological, cytoarchitectural, and stromal variations. Some of these histopathological patterns, infrequent or unusual, can occasionally produce diagnostic doubts or problems. A 22-year-old female patient presented a poorly pigmented cutaneous polypoid lesion of the scalp. Histopathological examination showed an intradermal melanocytic nevus composed of aggregates, nests, and cords of benign melanocytes, with collagenous stroma and large lipomatous areas. In the lipidized portion of the lesion, nevus cells, arranged in clusters, nests, and cords, were intimately associated with mature-appearing adipocytes, CD34-positive spindle cells, Alcian Blue-positive fibromyxoid stroma, and eosinophilic collagen bundles, findings resembling those typically seen in spindle cell lipoma. Spindle cell lipomatous metaplasia, rarely observed in some benign nonmelanocytic skin lesions, can be considered an additional unusual, not previously described, stromal variation occurring in melanocytic nevi.
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Metaplasia , Nevo Pigmentado , Neoplasias Cutáneas , Humanos , Femenino , Metaplasia/patología , Nevo Pigmentado/patología , Neoplasias Cutáneas/patología , Adulto Joven , Lipoma/patología , Cuero Cabelludo/patología , InmunohistoquímicaRESUMEN
ABSTRACT: Close relationship between melanocytes and neural cells is accepted to reflect their common derivation from the neural crest and tumors combining both elements. We present a series of 10 patients with giant congenital melanocytic nevi (CMN) in which a secondary proliferation (11 lesions) with schwannian and/or perineuriomatous differentiation developed in the course of the disease. The age of the patients (4 male and 6 female) at the time of surgery and histological assessment varied from 3 months to 57 years. Histopathologically, the following subgroups were delineated: (1) nodular/tumoriform "neurotization" in CMN, (2) diffuse neurofibroma-like proliferation within CMN, (3) plexiform neurofibroma-like proliferation within CMN, and (4) diffuse perineuriomatous (hybrid schwannomatous-perineuriomatous) differentiation in CMN. We review the pertinent literature, including the role of recently identified Schwann cell precursors which are believed to represent the nerve-associated state of neural crest-like cells that persists into later developmental stages.
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Diferenciación Celular , Nevo Pigmentado , Células de Schwann , Neoplasias Cutáneas , Humanos , Nevo Pigmentado/patología , Nevo Pigmentado/congénito , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/congénito , Masculino , Femenino , Lactante , Células de Schwann/patología , Niño , Adolescente , Adulto , Preescolar , Persona de Mediana Edad , Adulto JovenRESUMEN
BACKGROUND: In vivo reflectance confocal microscopy (RCM) enables the study of architectural and cytological aspects in horizontal sections, which closely correlate with histologic features. However, traditional histopathological vertical sections cannot totally reproduce the image of the in vivo RCM horizontal section. OBJECTIVE: To evaluate the concordance between in vivo RCM and histopathologic transverse sections for melanocytic lesions, basal cell carcinoma and seborrheic keratoses. METHODS: Prospectively collected benign melanocytic and non-melanocytic tumours diagnosed by dermoscopy were evaluated for common RCM features and compared to histopathology in horizontal sections with haematoxylin and eosin staining. RESULTS: A total of 44 skin tumours including 19 melanocytic lesions (nine compound, five junctional and five intradermal nevi), 12 basal cell carcinomas and 13 seborrheic keratoses were collected in the Department of Dermatology of Hospital Clinic of Barcelona. The RCM features that had statistically significant agreement with the histopathological horizontal sections were the preserved and visible honeycomb pattern, well defined DEJ, small bright particles, dermal nests, tumour islands and dark silhouettes, clefting, collagen bundles, thickened collagen bundles and cytologic atypia. CONCLUSIONS: Histopathology evaluation of horizontal sections of skin tumours can be correlated with main RCM findings. The results of this study have improved the understanding and interpretation of RCM features in relation to skin tumours, thus reinforcing the utility of RCM as a diagnostic tool.
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Carcinoma Basocelular , Queratosis Seborreica , Melanoma , Nevo Pigmentado , Neoplasias Cutáneas , Humanos , Melanoma/patología , Queratosis Seborreica/diagnóstico por imagen , Nevo Pigmentado/patología , Dermoscopía/métodos , Microscopía Confocal/métodos , Neoplasias Cutáneas/patología , Carcinoma Basocelular/diagnóstico por imagen , ColágenoRESUMEN
BACKGROUND: Studies on the interaction between tumour-infiltrating immune cells (TIICs) and tumour cells in melanoma arising from congenital melanocytic nevus (CMN) are lacking. OBJECTIVE: The aim of this study was to determine the intratumoral immune landscape of TIICs and tumour cells during invasion and metastasis. METHODS: Tissue specimens were obtained from patients with melanoma originating from CMN. Differential gene expression in melanoma cells and TIICs during invasion and metastasis was determined using spatial transcriptomics. RESULTS: As invasion depth increased, the expression of LGALS3, known to induce tumour-driven immunosuppression, increased in melanoma cells. In T cells, the expression of genes that inhibit T-cell activation increased with increasing invasion depth. In macrophages, the expression of genes related to the anti-inflammatory M2 phenotype was upregulated with increasing invasion depth. Compared to primary tumour cells, melanoma cells in metastatic lesions showed upregulated expression of genes associated with cancer immune evasion, including AXL and EPHA2, which impede T-cell recruitment, and BST2, associated with M2 polarization. Furthermore, T cells showed increased expression of genes related to immunosuppression, and macrophages exhibited increased expression of genes associated with the M2 phenotype. CONCLUSIONS: The interaction between melanomas arising from CMN and TIICs may be important for tumour progression and metastasis.
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Melanoma , Nevo Pigmentado , Neoplasias Cutáneas , Humanos , Melanoma/genética , Melanoma/inmunología , Melanoma/patología , Nevo Pigmentado/genética , Nevo Pigmentado/inmunología , Nevo Pigmentado/patología , Nevo Pigmentado/metabolismo , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/inmunología , Perfilación de la Expresión Génica , Linfocitos Infiltrantes de Tumor/inmunología , Invasividad Neoplásica , Masculino , Macrófagos/metabolismo , Macrófagos/inmunología , Femenino , Galectina 3/genética , Galectina 3/metabolismo , Linfocitos T/inmunología , Transcriptoma , Tirosina Quinasa del Receptor Axl , Comunicación Celular , Persona de Mediana Edad , Galectinas/genética , Galectinas/metabolismo , Receptor 2 Celular del Virus de la Hepatitis A/genética , Receptor 2 Celular del Virus de la Hepatitis A/metabolismo , Proteínas SanguíneasRESUMEN
BACKGROUND: Early melanoma detection is the main factor affecting prognosis and survival. For that reason, non-invasive technologies have been developed to provide a more accurate diagnosis. Recently, line-field confocal optical coherence tomography (LC-OCT) was developed to provide an in vivo, imaging device, with deep penetration and cellular resolution in three dimensions. Combining the advantages of conventional OCT and reflectance confocal microscopy, this tool seems to be particularly suitable for melanocytic lesions. OBJECTIVES: The objective of this study was to identify and describe the correlation between specific dermoscopic criteria and LC-OCT features in three dimensions associated with melanocytic lesions. METHODS: Dermoscopic and LC-OCT images of 126 melanocytic lesions were acquired in three different centres. The following dermoscopic criteria have been considered: reticular pattern, dots and globules, structureless areas, blue-whitish veil, regression structures, negative network, homogeneous pattern, streaks and blotches. RESULTS: 69 (55%) benign and 57 (45%) malignant lesions were analysed. A regular reticular pattern was found associated in the 75% of the cases with the presence of elongated rete ridges with pigmented cells along the basal layer, while atypical reticular pattern showed an irregular organization of rete ridges with melanocytic hyperplasia, broadened and fused ridges and elongated nests. Both typical and atypical dots and globules were found associated with melanocytic nests in the dermis or at the dermoepidermal junction (DEJ), as well as with keratin cysts/pseudocysts. Grey globules corresponded to the presence of melanin-containing dermal inflammatory cells (melanophages) within the papillae. Structureless brown/black areas correlated with alterations of the DEJ. We observed the same DEJ alterations, but with the presence of dermal melanophages, in 36% of the cases of blue/white/grey structureless areas. A description of each LC-OCT/dermoscopy correlation was made. CONCLUSIONS: LC-OCT permitted for the first time to perform an in vivo, 3D correlation between dermoscopic criteria and pathological-like features of melanocytic lesions.
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Dermoscopía , Melanoma , Neoplasias Cutáneas , Tomografía de Coherencia Óptica , Humanos , Dermoscopía/métodos , Tomografía de Coherencia Óptica/métodos , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/diagnóstico por imagen , Melanoma/diagnóstico por imagen , Melanoma/patología , Masculino , Femenino , Persona de Mediana Edad , Nevo Pigmentado/diagnóstico por imagen , Nevo Pigmentado/patología , Adulto , AncianoRESUMEN
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.
Asunto(s)
Melanoma , Nevo Pigmentado , Neoplasias Cutáneas , Niño , Humanos , Neoplasias Cutáneas/congénito , Nevo Pigmentado/congénito , Piel , Vitamina DRESUMEN
Congenital melanocytic nevi (CMN) are special types of moles. CMN happen when extra pigment-making cells (melanocytes) grow in a baby's skin while the baby is forming before birth. They are not caused by anything their parent did or didn't do during pregnancy. These moles are there when the baby is born, stay on the skin for life, and grow as the child grows.