RESUMEN
BACKGROUND: Histopathological examination is adequate for the diagnosis of most cutaneous melanocytic neoplasms. However, there is a subset that is either difficult to definitively diagnose or would have diagnostic disagreement upon review by multiple dermatopathologists if a more exhaustive review was performed. METHODS: Melanocytic lesions underwent an independent, blinded diagnostic histopathological review of hematoxylin and eosin-stained sections. Each lesion was reviewed by three to six dermatopathologists and categorized as benign, malignant, or unknown malignant potential (UMP). Diagnoses were grouped as concordant (all the same designation); opposing (received benign and malignant designations); majority (single designation with the highest number of diagnoses, no benign/malignant opposing designations); and non-definitive (equal number of non-opposing designations [i.e., benign/UMP or malignant/UMP]). Lesions with equivocal designations (concordant or majority UMP, opposing, majority, and non-definitive) were utilized in a patient treatment model of projected surgical treatment discrepancies. RESULTS: In total, 3317 cases were reviewed, and 23.8% of lesions received equivocal diagnoses. Of these, 7.3% were majority benign, 4.8% were majority malignant, 2.7% were majority UMP, 0.5% were concordant UMP, 6.9% were opposing, and 1.6% were non-definitive. Patient treatment models of those with equivocal lesions (n = 788) revealed a potential of overall surgical treatment variations ranging from 18% to 72%, with the highest variation amongst lesions with opposing, non-definitive, or majority UMP (40%-72%) diagnoses. CONCLUSION: Histopathologic review in this large cohort demonstrated substantial diagnostic variation, with 23.8% of cases receiving equivocal diagnoses. We identified diagnostic ambiguity even in lesions where a definitive diagnosis was previously rendered by a single real-world dermatopathologist. The combined clinical impact of diagnostic discordance or a final diagnosis of UMP is highlighted by high diagnosis-dependent treatment variation in the patient treatment model, which could be underreported in a real-world setting, where review by more than one to two dermatopathologists is relatively rare.
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Melanoma , Neoplasias Cutáneas , Humanos , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/diagnóstico , Melanoma/patología , Melanoma/diagnóstico , Femenino , Masculino , Adulto , Persona de Mediana Edad , Melanocitos/patología , Anciano , Diagnóstico DiferencialAsunto(s)
Insulinoma/diagnóstico por imagen , Neoplasias Pancreáticas/diagnóstico por imagen , Anciano , Femenino , Humanos , Insulinoma/patología , Insulinoma/cirugía , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/cirugía , Tomografía Computarizada por Tomografía Computarizada de Emisión de Fotón ÚnicoRESUMEN
BACKGROUND: Among the diverse roles of the Type III secretion-system (T3SS), one of the notable functions is that it serves as unique nano machineries in gram-negative bacteria that facilitate the translocation of effector proteins from bacteria into their host. These effector proteins serve as potential targets to control the pathogenicity conferred to the bacteria. Despite being ideal choices to disrupt bacterial systems, it has been quite an ordeal in the recent times to experimentally reveal and establish a concrete sequence-structure-function relationship for these effector proteins. This work focuses on the disease-causing spectrum of an effector protein, HopS2 secreted by the phytopathogen Pseudomonas syringae pv. tomato DC3000. RESULTS: The study addresses the structural attributes of HopS2 via a bioinformatics approach to by-pass some of the experimental shortcomings resulting in mining some critical regions in the effector protein. We have elucidated the functionally important regions of HopS2 with the assistance of sequence and structural analyses. The sequence based data supports the presence of important regions in HopS2 that are present in the other functional parts of Hop family proteins. Furthermore, these regions have been validated by an ab-initio structure prediction of the protein followed by 100 ns long molecular dynamics (MD) simulation. The assessment of these secondary structural regions has revealed the stability and importance of these regions in the protein structure. CONCLUSIONS: The analysis has provided insights on important functional regions that may be vital to the effector functioning. In dearth of ample experimental evidence, such a bioinformatics approach has helped in the revelation of a few structural regions which will aid in future experiments to attain and evaluate the structural and functional aspects of this protein family.
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Proteínas Bacterianas/química , Biología Computacional/métodos , Pseudomonas syringae/metabolismo , Secuencia de Aminoácidos , Proteínas Bacterianas/metabolismo , Enlace de Hidrógeno , Modelos Moleculares , Simulación de Dinámica Molecular , Análisis de Componente Principal , Estructura Secundaria de Proteína , Reproducibilidad de los Resultados , Análisis de Secuencia de Proteína , Relación Estructura-ActividadRESUMEN
Fewer than half of patients with systemic sclerosis demonstrate modified Rodnan skin score improvement during mycophenolate mofetil (MMF) treatment. To understand the molecular basis for this observation, we extended our prior studies and characterized molecular and cellular changes in skin biopsies from subjects with systemic sclerosis treated with MMF. Eleven subjects completed ≥24 months of MMF therapy. Two distinct skin gene expression trajectories were observed across six of these subjects. Three of the six subjects showed attenuation of the inflammatory signature by 24 months, paralleling reductions in CCL2 mRNA expression in skin and reduced numbers of macrophages and myeloid dendritic cells in skin biopsies. MMF cessation at 24 months resulted in an increased inflammatory score, increased CCL2 mRNA and protein levels, modified Rodnan skin score rebound, and increased numbers of skin myeloid cells in these subjects. In contrast, three other subjects remained on MMF >24 months and showed a persistent decrease in inflammatory score, decreasing or stable modified Rodnan skin score, CCL2 mRNA reductions, sera CCL2 protein levels trending downward, reduction in monocyte migration, and no increase in skin myeloid cell numbers. These data summarize molecular changes during MMF therapy that suggest reduction of innate immune cell numbers, possibly by attenuating expression of chemokines, including CCL2.
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Inmunosupresores/uso terapéutico , Ácido Micofenólico/uso terapéutico , Células Mieloides/efectos de los fármacos , Esclerodermia Sistémica/tratamiento farmacológico , Adulto , Biopsia , Estudios de Casos y Controles , Recuento de Células , Quimiocina CCL2/inmunología , Quimiocina CCL2/metabolismo , Femenino , Perfilación de la Expresión Génica , Humanos , Inmunosupresores/farmacología , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Ácido Micofenólico/farmacología , Células Mieloides/inmunología , Estudios Prospectivos , Esclerodermia Sistémica/inmunología , Esclerodermia Sistémica/patología , Piel/citología , Piel/efectos de los fármacos , Piel/inmunología , Piel/patología , Transcriptoma/efectos de los fármacos , Transcriptoma/inmunología , Resultado del TratamientoAsunto(s)
Antígenos CD34/metabolismo , Cirugía de Mohs , Neoplasias de Tejido Fibroso/cirugía , Neoplasias Cutáneas/cirugía , Anciano , Femenino , Humanos , Neoplasias de Tejido Fibroso/metabolismo , Neoplasias de Tejido Fibroso/patología , Neoplasias Cutáneas/metabolismo , Neoplasias Cutáneas/patologíaRESUMEN
PURPOSE: To assess the utility of 18F-fluoroethyl-L-tyrosine (FET) positron emission tomography/magnetic resonance imaging (PET/MRI) in distinguishing recurrence from radionecrosis. MATERIALS AND METHODS: Thirty-two patients (25 males, 7 females) of glioma who had already undergone surgery/chemoradiotherapy and had enhancing brain lesions suspicious of recurrence were evaluated using integrated 18F-FET PET/MRI, and followed up with histopathology or clinical follow-up and/or MRI/PET/MRI imaging. Manually drawn regions of interest over areas of maximal enhancement or FET uptake were used to calculate tumor to background ratios [TBRmax, TBRmean], choline: creatine ratio [Cho: Cr ratio], normalized relative cerebral blood volume [N rCBVmean] and apparent diffusion coefficient [ADCmean]. Correlations were evaluated using Pearson's coefficient. Accuracy of each parameter was calculated using independent t-test and receiver operator curve (ROC) analysis while utility of all four parameters together using multivariate analysis of variance (MANOVA) for differentiating recurrence vs. radionecrosis was evaluated. Positive histopathology and imaging/clinical follow up served as the gold standard. RESULTS: Twenty-four of the 32 patients were diagnosed with recurrent disease and 8 with radiation necrosis. Significant correlations were observed between TBRmaxand N rCBVmean (ρ =0.503; P = 0.003), TBRmean, and N rCBVmean (ρ =0.414; P = 0.018), TBRmaxand ADCmean (ρ = -0.52; P = 0.002), and TBRmeanand ADCmean(ρ = -0.518; P = 0.002). TBRmax, TBRmean, ADCmean, Cho: Cr ratios, and N rCBVmeanwere significant in differentiating recurrence from radiation necrosis with an accuracy of 94.1%, 88.2%, 80.4%, 96.4%, and 89.9%, respectively. MANOVA indicated that combination of all parameters demonstrated better evaluation of recurrence vs. necrosis than any single parameter. The diagnostic accuracy, sensitivity, and specificity using all MRI parameters were 93.75%, 96%, and 85.7%, and using all FET PET/MRI parameters was 96.87%, 100%, and 85.7%, respectively. CONCLUSIONS: Synergetic effect of multiple MR parameters evaluated together in addition to FET PET uptake highlights the fact that integrated 18F-FET PET/MRI might have the potential to impact management of patients with glioma by timely and conclusive recognition of true recurrence from radiation necrosis.
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Lesiones Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/diagnóstico por imagen , Glioma/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Recurrencia Local de Neoplasia/diagnóstico por imagen , Tomografía de Emisión de Positrones/métodos , Traumatismos por Radiación/diagnóstico por imagen , Tirosina/análogos & derivados , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Lesiones Encefálicas/etiología , Lesiones Encefálicas/patología , Neoplasias Encefálicas/patología , Femenino , Glioma/patología , Humanos , Masculino , Persona de Mediana Edad , Imagen Multimodal , Necrosis/diagnóstico por imagen , Necrosis/patología , Recurrencia Local de Neoplasia/patología , Estudios Prospectivos , Traumatismos por Radiación/patología , Adulto JovenRESUMEN
Lipoblastoma is a rare neoplasm of embryonal adipose tissue most often encountered on the trunk and extremities of children. It commonly presents as a painless subcutaneous soft tissue mass, but there are other unique clinical presentations that are important to recognize. The differential is broad and includes sarcoma, vascular tumor, myofibroma, and other fibromatoses. We present three varied, distinct cases of pediatric lipoblastoma and review the literature on this condition.
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Lipoblastoma/patología , Neoplasias Cutáneas/patología , Preescolar , Femenino , Humanos , Lactante , Lipoblastoma/terapia , Masculino , Neoplasias Cutáneas/terapiaRESUMEN
The natural history of atypical Spitz neoplasms remains poorly understood, resulting in significant patient and clinician anxiety. We sought to better characterize outcomes that correlated with molecular features by performing a prospective cohort study of pediatric atypical spitzoid neoplasms in which fluorescence in situ hybridization studies were obtained for diagnosis. Cases with sufficient tissue underwent additional retrospective assessment for translocations in ALK, NTRK1, BRAF, RET, and ROS1. Among 246 total patients assessed, 13% had a positive fluorescence in situ hybridization result. Follow-up data was available in 85 patients. Two patients had a recurrence of whom 1 had distant metastasis. Both patients had homozygous deletions in 9p21. Homozygous deletions in 9p21 significantly correlated with recurrence of disease (P = 0.027). Fifteen (36%) of 42 cases were found to have a kinase fusion protein. However, the presence of kinase fusions was nonprognostic of recurrence (P > 0.99). This study was limited by the availability and length of follow-up data and the number of adverse outcomes. The majority of atypical spitzoid neoplasms in childhood have indolent behavior. Although the subgroup of patients with homozygous deletions in 9p21 is at higher risk for aggressive clinical behavior, their prognosis seems considerably better than similarly staged conventional melanoma.
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Nevo de Células Epitelioides y Fusiformes/genética , Nevo de Células Epitelioides y Fusiformes/patología , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/patología , Adolescente , Biomarcadores de Tumor/análisis , Niño , Preescolar , Deleción Cromosómica , Cromosomas Humanos Par 9/genética , Estudios de Cohortes , Análisis Mutacional de ADN , Femenino , Estudios de Seguimiento , Humanos , Inmunohistoquímica , Hibridación Fluorescente in Situ , Lactante , MasculinoRESUMEN
AIM: The aim of the present study was to investigate the ability of operators using The Canary System and DIAGNOdent to detect natural pit and fissure caries under four commonly-used opaque dental sealants. METHODS: Mixed sound and carious pits/fissures (N = 105) selected from 40 human teeth were randomly assigned (10 teeth/group) to one of four opaque sealant groups (Delton, Embrace WetBond, Helioseal F, UltraSeal XT Plus). Selected pits/fissures sites on occlusal surfaces were scanned with The Canary System and DIAGNOdent, sealed, re-scanned, and subjected to polarized light microscopy to confirm whether the scanned regions were sound or carious. Sensitivities and specificities for each detection method before and after sealant placement were calculated. RESULTS: The Canary System and DIAGNOdent were able to distinguish between sound and carious tissue beneath opaque sealants with an accuracy of 76% and 59%, respectively. CONCLUSIONS: The Canary System can serve as a clinical tool to aid dental professionals to detect and monitor the status of caries lesions and tooth structure underneath sealant. The increased likelihood of false-positive diagnoses with DIAGNOdent due to intrinsic auto-fluorescence of sealant filler and opacifying agents might limit its usefulness as an aid to detect caries underneath opaque sealants.
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Caries Dental/diagnóstico , Selladores de Fosas y Fisuras , Técnicas y Procedimientos Diagnósticos , Humanos , Técnicas In Vitro , Rayos LáserRESUMEN
Recent studies have identified translocations involving the kinase domains of ALK, NTRK1, BRAF, RET, and ROS in spitzoid neoplasms. Subsequent studies have also characterized morphologic features corresponding to ALK and NTRK1 translocations. In this study, we sought to further compare morphologic features across a range of 49 genetically defined spitzoid neoplasms with ALK, NTRK1, BRAF, or RET fusions to determine discriminating features. We also compared them with a group of 22 spitzoid neoplasms, which were confirmed to be negative for fusions in ALK, NTRK1, BRAF, and RET. Features with the highest discriminatory value included diameter of the lesion, dermal architecture, and certain cytomorphologic features. Specifically, cases with a large diameter (≥9 mm) and wedge-shaped, plexiform dermal architecture of nests of large, spindle-shaped cells were most likely to have an ALK fusion. NTRK1-fused cases were most likely of the fusions to have Kamino bodies and were typically arranged in smaller nests with smaller predominantly spindle-shaped cells, occasionally forming rosettes. BRAF fusion cases were the only fusion subtype to have a predominance of epithelioid cells, were less organized in nests, and commonly had a sheet-like growth pattern or dysplastic Spitz architecture. BRAF fusion cases were most likely to have high-grade nuclear atypia, to be diagnosed as spitzoid melanoma, to have a positive result by melanoma fluorescence in situ hybridization assay, and to develop copy number gains in the kinase domain of the fusion protein. On the basis of experience from this cohort, BRAF-fused cases appear most likely to progress to melanoma.
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Biomarcadores de Tumor/genética , Fusión Génica , Melanoma/genética , Nevo de Células Epitelioides y Fusiformes/genética , Proteínas Proto-Oncogénicas B-raf/genética , Proteínas Tirosina Quinasas Receptoras/genética , Receptor trkA/genética , Neoplasias Cutáneas/genética , Translocación Genética , Adolescente , Adulto , Anciano , Quinasa de Linfoma Anaplásico , Biomarcadores de Tumor/análisis , Estudios de Casos y Controles , Núcleo Celular/patología , Niño , Preescolar , Variaciones en el Número de Copia de ADN , Progresión de la Enfermedad , Femenino , Dosificación de Gen , Predisposición Genética a la Enfermedad , Humanos , Inmunohistoquímica , Hibridación Fluorescente in Situ , Lactante , Masculino , Melanoma/enzimología , Melanoma/patología , Persona de Mediana Edad , Clasificación del Tumor , Nevo de Células Epitelioides y Fusiformes/enzimología , Nevo de Células Epitelioides y Fusiformes/patología , Fenotipo , Valor Predictivo de las Pruebas , Proteínas Proto-Oncogénicas B-raf/análisis , Proteínas Proto-Oncogénicas c-ret/genética , Proteínas Tirosina Quinasas Receptoras/análisis , Receptor trkA/análisis , Neoplasias Cutáneas/enzimología , Neoplasias Cutáneas/patología , Carga Tumoral , Adulto JovenRESUMEN
Nisin is a well-recognised antimicrobial peptide (AMP) used in food industry. However, efficacy of the peptide has been compromised due to development of resistance in different bacterial strains. Here, efficacy of the peptide upon assembly at a silver nanoparticle (AgNP) interface has been characterized. To this end, experimental and simulation studies are done to characterize the interfacial assembly of nisin and underlie antibacterial mechanism. Being an AMP, efficacy of an intact nisin is explored against Gram-positive and Gram-negative bacteria, and compared with antibacterial propensity of the interfacially assembled nisin. Antibacterial propensity, upon the assembly, increases against both kinds of bacteria. Interestingly, the growth inhibition studies of the interfacially assembled nisin indicate that the originally nisin resistant Gram-negative bacteria become sensitive to the nanomolar nisin concentrations. Furthermore, reactive oxygen species (ROS) measurements together with confocal microscopy imaging indicate that the increase in interfacial and intracellular ROS production upon the treatment is underling mechanism of enhanced antibacterial propensity of the assembled nisin. Thus, the study observed that the interfacial assembly of nisin at AgNP interface enhances the efficacy of nisin against different spectrum of bacteria, where the intact nisin is largely ineffective for the studied concentrations.
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Antibacterianos/farmacología , Nanopartículas/química , Nisina/farmacología , Especies Reactivas de Oxígeno/agonistas , Plata/farmacología , Antibacterianos/química , Bacillus subtilis/efectos de los fármacos , Bacillus subtilis/crecimiento & desarrollo , Bacillus subtilis/ultraestructura , Escherichia coli/efectos de los fármacos , Escherichia coli/crecimiento & desarrollo , Escherichia coli/ultraestructura , Pruebas de Sensibilidad Microbiana , Viabilidad Microbiana/efectos de los fármacos , Nanopartículas/ultraestructura , Nisina/química , Proteus vulgaris/efectos de los fármacos , Proteus vulgaris/crecimiento & desarrollo , Proteus vulgaris/ultraestructura , Especies Reactivas de Oxígeno/metabolismo , Plata/química , Staphylococcus aureus/efectos de los fármacos , Staphylococcus aureus/crecimiento & desarrollo , Staphylococcus aureus/ultraestructura , Propiedades de SuperficieRESUMEN
Mammary analog secretory carcinoma (MASC) is a recently described tumor of the salivary glands named for its morphological and molecular similarity to secretory carcinoma of the breast. Many primary carcinomas arising from the adnexal glands also share similar morphology to those arising from the breast. Brandt et al first described primary cutaneous MASC in 2009 and since then only 2 other cases have been reported. Herein, we describe a long-standing mass on the arm of an otherwise healthy 40-year-old female. Histologic examination revealed a circumscribed but unencapsulated, nodular tumor composed of bland epithelial cells arranged in solid and microcystic growth patterns. The cells showed vacuolated cytoplasm and round to oval nuclei with vesicular chromatin. Intraluminal homogenous eosinophilic secretions were present. Mitotic figures were not identified. The tumor cells stained positive for CK8/18, CK7, and S100 but were negative for other markers performed, including estrogen receptor, progesterone receptor, HER2/neu, paired box 8 (PAX8), and thyroid transcription factor 1 (TTF1). As the patient clinically had no other masses or known carcinomas, a diagnosis of primary cutaneous MASC was rendered. The ETV6-NTRK3 fusion transcript was subsequently detected by reverse transcriptase polymerase chain reaction amplification, further supporting the diagnosis. We present this case to review the histologic features of MASC and highlight the importance of recognizing this lesion not only as a possible cutaneous metastasis but also as a primary cutaneous tumor.
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Biomarcadores de Tumor/genética , Neoplasias de la Mama/genética , Carcinoma/genética , Proteínas de Fusión Oncogénica/genética , Neoplasias Cutáneas/genética , Translocación Genética , Adulto , Biomarcadores de Tumor/análisis , Biopsia , Neoplasias de la Mama/química , Neoplasias de la Mama/patología , Neoplasias de la Mama/cirugía , Carcinoma/química , Carcinoma/patología , Carcinoma/cirugía , Humanos , Inmunohistoquímica , Valor Predictivo de las Pruebas , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Neoplasias Cutáneas/química , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/cirugíaRESUMEN
A 33-year-old female with a 7-year history of CD8-positive hypopigmented mycosis fungoides (MF) involving the trunk and extremities presented with a large well-defined alopecic patch on her frontal scalp. Clinically, this area resembled alopecia areata (AA) and was without hypopigmentation or erythema. A scalp biopsy revealed a non-scarring inflammatory alopecia and a superficial band-like atypical lymphoid infiltrate with prominent epidermotropism. Atypical, predominately CD8-positive lymphocytes were seen surrounding and infiltrating the bulb portion of several hair follicles. Treatments for her MF lesions have included topical bexarotene, topical corticosteroids and phototherapy. Her alopecia has been treated with high potency topical corticosteroids and multiple intralesional triamcinolone injections with very minimal hair regrowth to date. Alopecia due to cutaneous lymphoma is an uncommon phenomenon but can occur in erythrodermic MF or Sezary syndrome. AA-like changes have most often been reported in conventional patch/plaque stage MF and folliculotropic MF. In these cases, the atypical lymphoid infiltrate is comprised predominately of CD4-positive lymphocytes. This is a rare report of a CD8-positive MF causing AA-like changes. This case highlights the importance of a scalp biopsy in patients with a history of cutaneous lymphoma presenting with alopecia in order to evaluate the nature of their hair loss.
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Alopecia Areata/etiología , Linfocitos T CD8-positivos/patología , Micosis Fungoide/complicaciones , Neoplasias Cutáneas/complicaciones , Adulto , Femenino , Humanos , Micosis Fungoide/patología , Recurrencia Local de Neoplasia/complicaciones , Recurrencia Local de Neoplasia/patología , Neoplasias Cutáneas/patologíaRESUMEN
BACKGROUND: Nevi of special sites display aberrant clinical and histologic features that can be difficult to distinguish from melanoma, leading to unnecessarily high rates of excision with poor cosmetic or functional results. Dermoscopy can improve clinical assessment of melanocytic lesions by visualizing morphologic structures beyond the epidermis. OBJECTIVE: We sought to assess the value of specific dermoscopic features for diagnosing melanocytic neoplasms arising on the breast area in females. METHODS: In this retrospective cohort study, we collected clinical and dermoscopic information for 104 nevi and 13 melanomas removed from the breast, chest, and areola, and evaluated the diagnostic performance of each dermoscopic feature. RESULTS: Melanomas from the breast area were larger (P = .0175) than nevi and occurred in older women (P = .0117). Irregular blotches, nonuniform radial streaks, blue-gray veil, and regression were highly specific for melanoma, whereas atypical network and irregular dots and globules had low to moderate specificity. LIMITATIONS: This study was retrospective with a small sample size. CONCLUSION: Compared to melanocytic neoplasms from other sites, atypical network and irregular dots and globules were poor indicators for breast melanoma. Irregular blotches, nonuniform radial streaks, blue-gray veil, and regression were highly specific and should heighten clinical suspicion for melanoma arising on the breast.
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Neoplasias de la Mama/patología , Dermoscopía , Melanoma/patología , Nevo/patología , Neoplasias Cutáneas/patología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Diagnóstico Diferencial , Femenino , Humanos , Persona de Mediana Edad , Estudios Retrospectivos , Adulto JovenRESUMEN
Genital melanomas (GM) are the second most common cancer of the female external genitalia and may be confused with atypical genital nevi (AGN), which exhibit atypical histological features but have benign behavior. In this study, we compared the clinical, histological, and molecular features of 19 GM and 25 AGN. We described chromosomal copy number aberrations and the mutational status of 50 oncogenes and tumor suppressor genes in both groups. Our study showed that a pigmented lesion occurring in mucosal tissue, particularly in postmenopausal women, was more likely to be a melanoma than a nevus. GM had high levels of chromosomal instability, with many copy number aberrations. Furthermore, we found a completely nonoverlapping pattern of oncogenic mutations when comparing GM and AGN. In GM, we report somatic mutations in KIT and TP53. Conversely, AGN had frequent BRAF V600E mutations, which were not seen in any of the GM. Our results show that GM and AGN have distinct clinical and molecular changes and that GM have a different mutational pattern compared with AGN.
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Síndrome del Nevo Displásico/genética , Neoplasias de los Genitales Femeninos/genética , Melanoma/genética , Mutación Missense , Neoplasias Cutáneas/genética , Adulto , Anciano , Anciano de 80 o más Años , Biopsia con Aguja , Diagnóstico Diferencial , Síndrome del Nevo Displásico/patología , Femenino , Neoplasias de los Genitales Femeninos/patología , Humanos , Inmunohistoquímica , Hibridación Fluorescente in Situ , Melanoma/patología , Persona de Mediana Edad , Neoplasias Cutáneas/patologíaRESUMEN
BACKGROUND: Dermoscopy allows for visualization of morphologic structures beyond the epidermis, including features that may indicate early malignant transformation. However, dermoscopic features are rarely considered during routine histologic sectioning, and areas of clinical concern may be missed during microscopic evaluation. OBJECTIVE: We assessed the diagnostic impact of a dermoscopy-guided micropunch score for the evaluation of melanocytic lesions. METHODS: In this case-control study, we evaluated 150 scored melanocytic lesions. Original tissue specimens were reprocessed to create a control group, in which a new score was introduced elsewhere in the lesion to guide an alternative plane of section. Slides were reviewed in a randomized, double-blinded manner to assess histologic features and render a diagnosis. Dermoscopy was also reviewed. RESULTS: The proportion of cases with a higher grade in the original, dermoscopy-guided section was statistically significant. Four invasive melanomas were exclusively identified using the scoring protocol. The presence of regression structures, negative pigment network, radial streaming or pseudopods, and irregular blotches were highly specific for a higher diagnostic grade. LIMITATIONS: This study is retrospective and reprocessing tissue does not perfectly mimic routine sectioning. CONCLUSION: Dermoscopy can identify important, histologically high-grade areas, and this information can be used to optimize the sectioning of melanocytic neoplasms.
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Dermoscopía/métodos , Síndrome del Nevo Displásico/patología , Biopsia Guiada por Imagen/métodos , Melanoma/patología , Nevo Pigmentado/patología , Neoplasias Cutáneas/patología , Adulto , Anciano , Estudios de Casos y Controles , Bases de Datos Factuales , Dermoscopía/estadística & datos numéricos , Diagnóstico Diferencial , Síndrome del Nevo Displásico/diagnóstico , Femenino , Humanos , Biopsia Guiada por Imagen/estadística & datos numéricos , Inmunohistoquímica , Masculino , Melanoma/diagnóstico , Persona de Mediana Edad , Nevo Pigmentado/diagnóstico , Neoplasias Cutáneas/diagnósticoRESUMEN
OBJECTIVE: This study investigated the accuracy of the Canary System (CS) to detect proximal caries lesions in vitro, and compared it with conventional methods: International Caries Detection and Assessment System (ICDAS) II and bitewing radiography (BW). METHODS: Visible proximal surfaces of extracted human teeth were assessed by ICDAS-II before setting them in five manikin mouth models. Then contacting proximal surfaces in mouth models were assessed by BW and CS. Histological validation with polarized-light microscopy served as a gold standard. Pairwise comparisons were performed on area under the curve (AUC), sensitivity, and specificity of the three methods, and corrected using Bonferroni's method. Sensitivities and specificities were compared using a test of proportions and AUC values were compared using DeLong's method. RESULTS: The CS presented significantly higher sensitivity (0.933) than ICDAS-II (0.733, P = 0.01) and BW (0.267, P < 0.001), and ICDAS-II higher sensitivity than BW (P < 0.001). There were no significant differences between their specificity values: 0.825 (CS), 0.65 (ICDAS-II), and 0.875 (BW). The AUC of CS (0.862) was significantly higher than of ICDAS-II (0.681, P < 0.001) and BW (0.577, P < 0.001). CONCLUSION: The CS demonstrated greater accuracy in detecting proximal lesions than ICDAS-II and BW, although without significantly higher specificity.