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Activating mutations in GNAQ, GNA11, CYSLTR2, and PLCB4 genes are regarded as the main oncogenic drivers of blue nevi (BN) and blue malignant melanocytic tumors. Here we report 4 cases of blue melanocytic neoplasms devoid of these mutations but harboring GRM1 gene fusions. In this short series, there was no gender predominance (sex ratio, 1). The mean age at diagnosis was 40 years (range, 12-72). Tumors were located on the face (n = 2), forearm (n = 1), and dorsum of the foot (n = 1). Clinically, a plaque-like pre-existing BN was found in 2 cases, including a deep location; another case presented as an Ota nevus. Two cases were diagnosed as melanoma ex-BN, one as an atypical BN, and one as a plaque-like BN. Microscopic examination revealed a dermal proliferation of dendritic melanocytes in a sclerotic stroma. A dermal cellular nodule with atypia and mitotic activity was observed in 3 cases. Genetic investigation by whole exome RNA sequencing revealed MYO10::GRM1 (n = 2) and ZEB2::GRM1 (n = 1) fusions. A GRM1 rearrangement was identified by fluorescence in situ hybridization in the remaining case. SF3B1 comutations were present in the 2 melanomas, and both had a MYO10::GRM1 fusion. Array comparative genomic hybridization was feasible for 3 cases and displayed multiple copy number alterations in the 2 melanomas and limited copy number alterations in the atypical BN, all genomic profiles compatible with those of classical blue lesions. GRM1 was overexpressed in all cases compared with a control group of blue lesions with other typical mutations. Both melanomas rapidly developed visceral metastases following diagnosis, with a fatal outcome in one case and tumor progression under palliative care in the other. These data suggest that GRM1 gene fusions could represent an additional rare oncogenic driver in the setting of BN, mutually exclusive of classical canonical mutations, especially in plaque-type or Ota subtypes.
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BACKGROUND: Congenital nail matrix nevi (NMN) are difficult to diagnose because they feature clinical characteristics suggestive of adult subungual melanoma. Nail matrix biopsy is difficult to perform, especially in children. OBJECTIVE: To describe the initial clinical and dermatoscopic features of NMN appearing at birth (congenital) or after birth but before the age of 5 years (congenital-type). METHODS: We conducted a prospective, international, and consecutive data collection in 102 hospitals or private medical offices across 30 countries from 2009 to 2019. RESULTS: There were 69 congenital and 161 congenital-type NMNs. Congenital and congenital-type NMN predominantly displayed an irregular pattern of longitudinal microlines (n = 146, 64%), reminiscent of subungual melanoma in adults. The distal fibrillar ("brush-like") pattern, present in 63 patients (27.8%), was more frequently encountered in congenital NMN than in congenital-type NMN (P = .012). Moreover, congenital NMN more frequently displayed a periungual pigmentation (P = .029) and Hutchinson's sign (P = .027) than did congenital-type NMN. LIMITATIONS: Lack of systematic biopsy-proven diagnosis and heterogeneity of clinical and dermatoscopic photographs. CONCLUSION: Congenital and congenital-type NMN showed worrisome clinical and dermatoscopic features similar to those observed in adulthood subungual melanoma. The distal fibrillar ("brush-like") pattern is a suggestive feature of congenital and congenital-type NMN.
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Melanoma , Enfermedades de la Uña , Nevo , Neoplasias Cutáneas , Adulto , Niño , Preescolar , Dermoscopía , Diagnóstico Diferencial , Humanos , Recién Nacido , Melanoma/diagnóstico por imagen , Melanoma/patología , Enfermedades de la Uña/diagnóstico por imagen , Enfermedades de la Uña/patología , Nevo/diagnóstico , Estudios Prospectivos , Neoplasias Cutáneas/diagnóstico por imagen , Neoplasias Cutáneas/patologíaRESUMEN
PURPOSE: Vismodegib is approved for the treatment of locally advanced basal cell carcinoma (laBCC), but some cases demonstrate intrinsic resistance (IR) to the drug. We sought to assess the frequency of IR to vismodegib in laBCC and its underlying genomic mechanisms. EXPERIMENTAL DESIGN: Response to vismodegib was evaluated in a cohort of 148 laBCC patients. Comprehensive genomic and transcriptomic profiling was performed in a subset of five intrinsically resistant BCC (IR-BCC). RESULTS: We identified that IR-BCC represents 6.1% of laBCC in the studied cohort. Prior treatment with chemotherapy was associated with IR. Genetic events that were previously associated with acquired resistance (AR) in BCC or medulloblastoma were observed in three out of five IR-BCC. However, IR-BCCs were distinct by highly rearranged polyploid genomes. Functional analyses identified hyperactivation of the HIPPO-YAP and WNT pathways at RNA and protein levels in IR-BCC. In vitro assay on the BCC cell line further confirmed that YAP1 overexpression increases the cell proliferation rate. CONCLUSIONS: IR to vismodegib is a rare event in laBCC. IR-BCCs frequently harbor resistance mutations in the Hh pathway, but also are characterized by hyperactivation of the HIPPO-YAP and WNT pathways.
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Antineoplásicos , Carcinoma Basocelular , Neoplasias Cerebelosas , Neoplasias Cutáneas , Anilidas/uso terapéutico , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Carcinoma Basocelular/tratamiento farmacológico , Carcinoma Basocelular/genética , Carcinoma Basocelular/patología , Neoplasias Cerebelosas/tratamiento farmacológico , Proteínas Hedgehog/genética , Proteínas Hedgehog/metabolismo , Humanos , Piridinas , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/patologíaRESUMEN
Although cemiplimab has been approved for locally advanced (la) and metastatic (m) cutaneous squamous-cell carcinomas (CSCCs), its real-life value has not yet been demonstrated. An early-access program enrolled patients with la/mCSCCs to receive cemiplimab. Endpoints were best overall response rate (BOR), progression-free survival (PFS), overall survival (OS), duration of response (DOR) and safety. The 245 patients (mean age 77 years, 73% male, 49% prior systemic treatment, 24% immunocompromised, 27% Eastern Cooperative Oncology Group performance status (PS) ≥ 2) had laCSCCs (35%) or mCSCCs (65%). For the 240 recipients of ≥1 infusion(s), the BOR was 50.4% (complete, 21%; partial, 29%). With median follow-up at 12.6 months, median PFS was 7.9 months, and median OS and DOR were not reached. One-year OS was 73% versus 36%, respectively, for patients with PS < 2 versus ≥ 2. Multivariate analysis retained PS ≥ 2 as being associated during the first 6 months with PFS and OS. Head-and-neck location was associated with longer PFS. Immune status had no impact. Severe treatment-related adverse events occurred in 9% of the patients, including one death from toxic epidermal necrolysis. Cemiplimab real-life safety and efficacy support its use for la/mCSCCs. Patients with PS ≥ 2 benefited less from cemiplimab, but it might represent an option for immunocompromised patients.
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Lipofibromatosis-like neural tumors (LPF-NT) are soft tissue tumors characterized by a lipofibromatosis-like pattern, CD34/PS100 positivity, and recurrent NTRK1 gene rearrangement. It occurs mainly in pediatric patients or young adults. We report here, the first case of LPF-NT in a middle-aged adult initially misdiagnosed as a myoepithelial tumor. LPF-NT may have a locally aggressive course but no recurrence was seen after complete surgeries, whereas metastatic diseases remain exceptional.
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Neoplasias de los Tejidos Blandos/patología , Fibroma/patología , Humanos , Lipoma/patología , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: Teledermoscopy (TDS) improves diagnostic accuracy and decreases the number of unnecessary consultations. OBJECTIVES: To determine the diagnostic concordance in tertiary (dermatologist-to-experts) TDS with histopathology/follow-up-based diagnosis. METHODS: A descriptive retrospective cohort study including 290 requests. RESULTS: Perfect diagnostic concordance was found in 202 (69.7%) cases and partial agreement in 29 (10%). Disagreement was found in 59 (20.3%) cases. Perfect concordance on the benign/malignant nature of the lesion was found in 227 (78.3%) cases and disagreement in 63 (21.7%). In onychology, diagnostic concordance was perfect in 43 (76.8%) cases, partial in 7 (12.5%), and there was disagreement in 6 (10.7%). Final concordance on the benign/malignant nature of the lesion was perfect in 48 (85.7%) and there was disagreement in 8 (14.3%) nail cases. For pediatric requests, diagnostic concordance was perfect in 29 (65.9%) cases, partial in 5 (11.4%), and there was disagreement in 10 (22.7%). Final concordance on the benign/malignant nature of the lesion was observed in 34 (77.3%) cases, disagreement in 10 (22.7%). CONCLUSIONS: This study confirms that tertiary TDS improves diagnostic accuracy of pigmented skin lesions. Moreover, it shows encouraging results in unusual conditions such as ungual and pediatric skin tumors. The main limitation was the retrospective nature and the "real-life" setting of our study that could have created a selection bias toward inclusion of the most difficult cases.
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PURPOSE: Vismodegib is a hedgehog pathway inhibitor indicated for the treatment of locally advanced basal cell carcinoma (laBCC), with an objective response rate of 65%, including a 32% complete response (CR). However, adverse effects often lead to drug discontinuation. The objective of our study was to evaluate long-term responses, predictive factors, and management of relapse after vismodegib discontinuation. METHODS: An observational retrospective study was conducted in nine French oncodermatology units. We included patients with laBCC with CR on vismodegib who discontinued treatment between March 2012 and January 2016; we reviewed charts up to June 2016. The primary objective was to evaluate median relapse-free survival (RFS). Secondary objectives were risk factors associated with RFS, relapse, and death and treatment modalities after relapse and their efficacy. RESULTS: One hundred sixteen patients with laBCC were included. The median RFS was 18.4 months (95% CI, 13.5 to 24.8 months). The RFS rate at 36 months was 35.4% (95% CI, 22.5% to 47.9%) for the total population and 40.0% (95% CI, 25.7% to 53.7%) for patients without Gorlin syndrome. LaBCC to the limbs and trunk was the only variable independently associated with a higher risk of relapse (hazard ratio, 2.77; 95% CI, 1.23 to 6.22; P = .019). Twenty-seven patients (50%) who experienced relapse during follow-up were retreated with vismodegib, with an objective response in 23 (objective response rate, 85%; CR rate, 37%; partial response rate, 48%) and eligibility for surgery in 24 (42%). CONCLUSION: Long-term response after vismodegib discontinuation is frequent. Most patients who experience a relapse still respond to vismodegib rechallenge.
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Anilidas/administración & dosificación , Antineoplásicos/administración & dosificación , Carcinoma Basocelular/tratamiento farmacológico , Piridinas/administración & dosificación , Neoplasias Cutáneas/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Anilidas/efectos adversos , Antineoplásicos/efectos adversos , Carcinoma Basocelular/mortalidad , Carcinoma Basocelular/patología , Progresión de la Enfermedad , Esquema de Medicación , Femenino , Francia , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Supervivencia sin Progresión , Piridinas/efectos adversos , Retratamiento , Estudios Retrospectivos , Factores de Riesgo , Neoplasias Cutáneas/mortalidad , Neoplasias Cutáneas/patología , Factores de TiempoRESUMEN
Background: MITF encodes an oncogenic lineage-specific transcription factor in which a germline mutation ( MITFE318K ) was identified in human patients predisposed to both nevus formation and, among other tumor types, melanoma. The molecular mechanisms underlying the oncogenic activity of MITF E318K remained uncharacterized. Methods: Here, we compared the SUMOylation status of endogenous MITF by proximity ligation assay in melanocytes isolated from wild-type (n = 3) or E318K (n = 4) MITF donors. We also used a newly generated Mitf E318K knock-in (KI) mouse model to assess the role of Mitf E318K (n = 7 to 13 mice per group) in tumor development in vivo and performed transcriptomic analysis of the tumors to identify the molecular mechanisms. Finally, using immortalized or normal melanocytes (wild-type or E318K MITF, n = 2 per group), we assessed the role of MITF E318K on the induction of senescence mediated by BRAF V600E . All statistical tests were two-sided. Results: We demonstrated a decrease in endogenous MITF SUMOylation in melanocytes from MITF E318K patients (mean of cells with hypoSUMOylated MITF, MITF E318K vs MITF WT , 94% vs 44%, difference = 50%, 95% CI = 21.8% to 67.2%, P = .004). The Mitf E318K mice were slightly hypopigmented (mean melanin content Mitf WT vs Mitf E318K/+ , 0.54 arbitrary units [AU] vs 0.36 AU, difference = -0.18, 95% CI = -0.36 to -0.007, P = .04). We provided genetic evidence that Mitf E318K enhances BRaf V600E -induced nevus formation in vivo (mean nevus number for Mitf E318K , BRaf V600E vs Mitf WT , BRaf V600E , 68 vs 44, difference = 24, 95% CI = 9.1 to 38.9, P = .006). Importantly, although Mitf E318K was not sufficient to cooperate with BRaf V600E alone in promoting metastatic melanoma, it accelerated tumor formation on a BRaf V600E , Pten-deficient background (median survival, Mitf E318K/+ = 42 days, 95% CI = 31 to 46 vs Mitf WT = 51 days, 95% CI = 50 to 55, P < .001). Transcriptome analysis suggested a decrease in senescence in tumors from Mitf E318K mice. We confirmed this hypothesis by in vitro experiments, demonstrating that Mitf E318K impaired the ability of human melanocytes to undergo BRAF V600E -induced senescence. Conclusions: We characterized the functions of melanoma-associated MITF E318K mutations. Our results demonstrate that MITF E318K reduces the program of senescence to potentially favor melanoma progression in vivo.
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Melanoma/genética , Factor de Transcripción Asociado a Microftalmía/genética , Factor de Transcripción Asociado a Microftalmía/metabolismo , Nevo/genética , Proteínas Proto-Oncogénicas B-raf/genética , Neoplasias Cutáneas/genética , Adulto , Anciano , Animales , Línea Celular Tumoral , Senescencia Celular/genética , Modelos Animales de Enfermedad , Mutación de Línea Germinal , Humanos , Melanocitos , Ratones , Persona de Mediana Edad , Fosfohidrolasa PTEN/genética , Cultivo Primario de Células , Sumoilación , TranscriptomaAsunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Azetidinas/efectos adversos , Azetidinas/uso terapéutico , Transformación Celular Neoplásica/inducido químicamente , Dermoscopía , Indoles/efectos adversos , Indoles/uso terapéutico , Melanoma/inducido químicamente , Melanoma/tratamiento farmacológico , Proteínas Quinasas Activadas por Mitógenos/antagonistas & inhibidores , Nevo Pigmentado/tratamiento farmacológico , Nevo Pigmentado/patología , Piperidinas/efectos adversos , Piperidinas/uso terapéutico , Transducción de Señal/efectos de los fármacos , Neoplasias Cutáneas/inducido químicamente , Neoplasias Cutáneas/tratamiento farmacológico , Sulfonamidas/efectos adversos , Sulfonamidas/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , VemurafenibRESUMEN
The nosology of bullous lesions or equivalents (vesicles, erosions, and crusts) in patients with lupus erythematosus (LE) is rarely addressed.The primary aim of this study was to draw up a precise phenotypic inventory of such skin lesions; the secondary objective was to assess a potential relationship between the different types of loss of epidermis and extracutaneous lupus manifestations.We conducted a retrospective multicenter study including 22 patients with definite LE and bullous lesions or equivalents. All biopsies were reviewed. Patients were recruited in the dermatology departments of 6 centers. Patients were included if they met the diagnosis of systemic LE according to American College of Rheumatology and/or Systemic Lupus International Collaborating Clinics criteria or diagnosis of cutaneous LE based on classic clinical criteria and/or histological ascertainment of LE. Patients were recruited through clinician's memory and photographic collections.Three clinico-pathological patterns could be individualized. First, toxic epidermal necrolysis (TEN)-like, sheet-like, skin detachment; sun-exposure, mild mucosal involvement, and dermal mucin deposition allow differential diagnosis with classical Lyell syndrome. Second, vesiculo-bullae and/or crusting occurring on typical lesions of subacute cutaneous lupus erythematosus or chronic cutaneous lupus erythematosus. Third, tense vesicles and/or blisters with an underlying neutrophilic dermatosis and a usual response to dapsone.A careful analysis of 22 LE patients with epidermal detachment reveals 2 main pathomechanisms: a classic LE interface dermatitis, which can be hyperacute and lead to TEN-like skin detachment; and a neutrophilic dermatosis, with tense vesicles and/or blisters, including classic bullous LE.
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Vesícula/etiología , Epidermis/patología , Lupus Eritematoso Cutáneo/patología , Enfermedad Aguda , Adolescente , Adulto , Anciano , Vesícula/inmunología , Vesícula/patología , Niño , Epidermis/inmunología , Femenino , Humanos , Lupus Eritematoso Cutáneo/inmunología , Lupus Eritematoso Discoide/inmunología , Lupus Eritematoso Discoide/patología , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Adulto JovenRESUMEN
BACKGROUND: Vismodegib therapy achieves a breakthrough in patients with locally advanced basal cell carcinoma (BCC). Yet, long-term safety of hedgehog pathway inhibitors remains to be established, while drug resistance is becoming a new challenging issue. CASE REPORT: We report the case of a 90-year-old male initially referred for a locally advanced BCC of the nose. He had been previously treated by topical 5-fluorouracil for an adjacent microinvasive squamous cell carcinoma (SCC), with complete clinical response. Afterwards, vismodegib was initiated to treat his BCC. At week 16, both tumor and tumor ulceration obviously progressed. Palliative rhinectomy was performed. Histological examination found a deeply invasive SCC. CONCLUSION: Although our case must be interpreted with caution, a role of vismodegib as a promoter of cutaneous SCC should be considered, consistently with recently published evidence. Physicians should perform new biopsies whenever in doubt about new and/or progressive skin lesions in patients receiving hedgehog pathway inhibitors.
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Anilidas/efectos adversos , Antineoplásicos/efectos adversos , Carcinoma Basocelular/tratamiento farmacológico , Carcinoma de Células Escamosas/inducido químicamente , Neoplasias Faciales/inducido químicamente , Neoplasias Nasales/tratamiento farmacológico , Piridinas/efectos adversos , Neoplasias Cutáneas/terapia , Anciano de 80 o más Años , Antimetabolitos Antineoplásicos/uso terapéutico , Carcinoma Basocelular/patología , Carcinoma de Células Escamosas/patología , Neoplasias Faciales/patología , Fluorouracilo/uso terapéutico , Humanos , Masculino , Neoplasias Nasales/patología , Neoplasias Cutáneas/patologíaRESUMEN
BACKGROUND: Vemurafenib is a BRAF inhibitor that has become the cornerstone of metastatic or inoperable melanoma therapy since its approval in 2011 in the United States and 2012 in Europe. This targeted therapy has shown impressive results in terms of increased progression-free and overall survival as compared to dacarbazine. The safety profile did not include any renal manifestations at that time. METHODS: This report is the first case series of 8 patients who experienced significant to severe renal insufficiency under vemurafenib treatment. RESULTS: This case series shows that vemurafenib may induce potentially severe acute renal failure, including renal sequelae and persistent kidney disease in some cases. CONCLUSIONS: Further studies are needed to investigate the effects of vemurafenib on the kidneys. Meanwhile, renal function should be closely monitored in treated patients for early detection of any renal dysfunction occurrence. Cancer 2014;120:2158-2163. © 2014 American Cancer Society.
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Lesión Renal Aguda/inducido químicamente , Antineoplásicos/efectos adversos , Indoles/efectos adversos , Riñón/efectos de los fármacos , Proteínas Proto-Oncogénicas B-raf/antagonistas & inhibidores , Sulfonamidas/efectos adversos , Lesión Renal Aguda/diagnóstico , Lesión Renal Aguda/fisiopatología , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/administración & dosificación , Esquema de Medicación , Femenino , Humanos , Indoles/administración & dosificación , Riñón/fisiopatología , Pruebas de Función Renal , Masculino , Melanoma/tratamiento farmacológico , Persona de Mediana Edad , Índice de Severidad de la Enfermedad , Neoplasias Cutáneas/tratamiento farmacológico , Sulfonamidas/administración & dosificación , Insuficiencia del Tratamiento , Resultado del Tratamiento , VemurafenibRESUMEN
Second primary melanomas (SPMs) induced by vemurafenib have been recently described. The aim of this study was to define the dermoscopical signs of melanoma in this context. Patients underwent a total body examination before receiving vemurafenib. Each single melanocytic lesion was registered before therapy by digital dermoscopy (DD), and then repeated monthly until therapy disruption. Forty-two patients were included, the mean duration of follow-up was 6.7 months, and a mean number of 51 lesions per patients were captured and followed. A total number of 2,155 lesions were recorded, of which 56.1% presented at least one change during the study. More common changes concerned the color of the lesions (up to 15%) and appearance or disappearance of globules (14.6%). Thirty-six of the melanocytic lesions were surgically excised, 21 were classified as a nevus, 1 was a lentigo, and 14 as a second new primary melanoma (occurring in 21% of our patients). DD allowed us to excise only 36/2,155 (1.6%) of the lesions and permitted us to detect 14 SPM in the 42 patients with a highly efficient malignant/benign ratio of 63.6%. Although vemurafenib is now tested in an adjuvant setting DD should be systematically used in order to accurately detect SPM and reduce the number of unnecessary excisions.
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Indoles/efectos adversos , Melanoma , Neoplasias Primarias Secundarias/inducido químicamente , Neoplasias Primarias Secundarias/patología , Neoplasias Cutáneas , Sulfonamidas/efectos adversos , Adulto , Anciano , Anciano de 80 o más Años , Dermoscopía , Inhibidores Enzimáticos/administración & dosificación , Inhibidores Enzimáticos/efectos adversos , Femenino , Estudios de Seguimiento , Humanos , Indoles/administración & dosificación , Lentigo/inducido químicamente , Lentigo/patología , Estudios Longitudinales , Masculino , Melanocitos/efectos de los fármacos , Melanocitos/patología , Melanoma/inducido químicamente , Melanoma/tratamiento farmacológico , Melanoma/patología , Persona de Mediana Edad , Nevo Pigmentado/inducido químicamente , Nevo Pigmentado/patología , Estudios Prospectivos , Neoplasias Cutáneas/inducido químicamente , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Cutáneas/patología , Pigmentación de la Piel/efectos de los fármacos , Sulfonamidas/administración & dosificación , VemurafenibRESUMEN
Although dermoscopy reflects the anatomy, skin anatomy is different on facial and acral skin as well as in the nail unit. Malignant patterns on acral sites include the parallel ridge pattern and irregular diffuse pigmentation, whose presence should lead to a biopsy. Malignant patterns on the face include features of follicular invasion (signet-ring images, annular granular images, and rhomboidal structures) and atypical vessels. Malignant patterns on the nail unit include the micro-Hutchinson sign and irregular longitudinal lines.
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Dermoscopía , Dermatosis Facial/diagnóstico , Melanoma/diagnóstico , Enfermedades de la Uña/diagnóstico , Neoplasias Cutáneas/diagnóstico , Diagnóstico Diferencial , Dermatosis Facial/patología , Humanos , Melanoma/patología , Enfermedades de la Uña/patología , Neoplasias Cutáneas/patologíaAsunto(s)
Indoles/uso terapéutico , Melanoma/secundario , Neoplasias Primarias Secundarias , Neoplasias Cutáneas/secundario , Sulfonamidas/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Dermoscopía/métodos , Femenino , Humanos , Masculino , Melanoma/diagnóstico , Melanoma/tratamiento farmacológico , Microscopía Confocal , Persona de Mediana Edad , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/tratamiento farmacológico , VemurafenibRESUMEN
BACKGROUND: Reflectance confocal microscopy (RCM)'s interest has been well established for the non-invasive diagnosis of skin cancers, especially melanocytic, and in the differential diagnosis between benign and malignant cutaneous lesions. However, its diagnostic interest in inflammatory skin diseases still needs to be demonstrated. Our purpose was to evaluate the correlation between RCM and conventional histopathology in a series of pustular eruptions of different pathogeny. METHODS: Reflectance confocal microscopy analysis was performed in eight consecutive unselected patients in whom the diagnoses of pustular psoriasis, bacterial sur-infection, herpes-type virus skin sur-infection, Sneddon-Wilkinson subcorneal putulosis and Hailey-Hailey disease have been made and images were compared to conventional histopathology. RESULTS: Neutrophils within the epidermis exhibited never reported earlier specific features, with either a shiny granular sludge or polylobated particules with a bright granular content. Moreover, some specific etiologies could be identified, such as acantholysis and herpes-type virus-infected keratinocytes. CONCLUSION: Our studies show a good correlation between RCM and conventional histopathology in pustular eruptions. Reflectance confocal microscopy may play an important role in the differential diagnosis of pustular eruptions; as most of the pathologic clues are epidermal, narrow thickness of the field of imaging, its main technical limitation, is indeed of lesser importance.