Analysis of 141 cases clinically misdiagnosed as melanoma / 中华皮肤科杂志

Objective:To analyze 141 cases clinically misdiagnosed as melanoma, and to improve the understanding and diagnosis of diseases.Methods:Totally, 141 cases preliminarily diagnosed as melanoma, which was finally excluded according to histopathological examination results, were collected from the pathological database of Department of Dermatology, Xijing Hospital, The Fourth Military Medical University from November 2001 to September 2019, and their clinical and histopathological data were analyzed retrospectively.Results:Among the 141 cases clinically misdiagnosed as melanoma, 64 were males and 77 were females. Their median age at the time of misdiagnosis was 51 years, and the average disease duration was 103.4 months. The patients mainly presented with patches and papules, most of which were black in color. Based on histopathological manifestations, 35 patients were diagnosed with pigmented nevi, 29 with basal cell carcinoma, 15 with seborrheic keratosis, 7 with Bowen′s disease, 6 with nail melanin spots, 5 with epidermal cysts, 4 with poroma, 4 with hemorrhage, 4 with dermatofibroma, and 23 with other skin diseases.Conclusions:In clinical practice, some diseases with characteristics of melanoma are liable to be misdiagnosed. It is necessary to grasp their clinical features and actively carry out auxiliary examinations such as dermoscopy and histopathological examinations to confirm the diagnosis and reduce the misdiagnosis rate.

Gut microbiota and immune checkpoint inhibitor treatment of melanoma / 中华皮肤科杂志

A growing number of studies have shown that gut microbiota affects the development of melanoma through various mechanisms, and plays a vital role in the treatment of melanoma. This review summarizes the relationship between gut microbiota and the development of melanoma, the effect of gut microbiota on the checkpoint blockade immunotherapy of melanoma and related adverse effects.

Clinicopathological analysis of primary nasopharyngeal melanomas in elderly patients / 中华老年医学杂志

Objective:To investigate the clinicopathologic features and molecular genetics characteristics of sinonasal tract mucosal malignant melanomas(STMMMs)in elderly patients.Methods:The clinicopathological features, immunohistochemical features and BRAF, C-KIT, NRAS mutations of STMMM in ten elderly patients were retrospectively analyzed.Results:Among the 10 patients, 5 were female and 5 were male.The patients were aged 65-81 years, with an average age of(72.5 ± 8.5)years.The lesions in 7 cases were located in the nasal cavity and paranasal sinuses, and in the other 3 cases were located in the nasopharynx.The morphologies of tumor cells under microscope was complex and diverse, showing plasma cell-like, rhabdomyoblast-like, small cell-like, epithelial-like, and spindle cell-like morphologies.Immunohistochemically, HMB-45 and S-100 were generally positive in 10 cases, and the positive rate of Melan A was 70.0%.The genes detection data showed no mutations in BRAF or NRAS genes in all the 10 cases, while C-KIT exon 11 c. 1666_1667insA mutation was found in one case, and the remaining 9 cases were wild-type for C-KIT.All the 10 cases were followed up for 4~50 months.Three cases survived so far.Conclusions:STMMM in elderly patients are rare and easy to be misdiagnosed.Immunohistochemistry and genetic testing provide guidance for accurate diagnosis and targeted therapy.

Clinical and histopathological analysis of five cases of solitary dermal melanoma / 中华皮肤科杂志

Objective:To analysis clinical and histopathological features of solitary dermal melanoma (SDM) .Methods:Clinical and histopathological data were collected from 5 patients with SDM, and analyzed retrospectively.Results:The 5 patients with SDM presented with black, skin-colored or red papules or nodules without any specific anatomic predilection. These lesions pathologically manifested as localized dermal/subcutaneous solitary nodules with characteristics of malignancy but no obvious capsules, and the epidermis was not involved.Conclusion:Detailed clinical data and skin histopathological examination are the key to accurate diagnosis of SDM.

Desenvolvimento e validação de rede neural artificial para suporte ao diagnóstico de melanoma em imagens dermatoscópicas / Development and validation of an artificial neural network to support the diagnosis of melanoma from dermoscopic images

Introdução: Com o avanço da análise digital de imagens, análises preditivas e métodos de aprendizagem de máquina, surgiram estudos referentes ao uso da inteligência artificial nos exames de imagem como a dermatoscopia. Objetivo: Construção, teste e implementação de uma rede neural artificial baseada em características de imagens dermatoscópicas. Métodos: Foram incluídas 1949 imagens de nevos melanocíticos e melanomas, tanto de arquivos dos autores, quanto de bancos de imagens dermatoscópicas disponíveis na internet, e desenvolvidas rotinas e plugins para a extração de 58 características aplicadas a um algoritmo de construção de rede neural multicamadas. Quarenta imagens aleatórias foram também avaliadas por 52 dermatologistas e os acertos comparados. Resultados: O treinamento e o teste da rede neural obtiveram uma porcentagem correta de classificação de 78,5 e 79,1%, respectivamente, com uma curva ROC abrangendo 86,5% da área. A sensibilidade e especificidade dos dermatologistas foi de 71,8 e 52%. Para as mesmas imagens e um ponto de corte de 0,4 (40%) do valor de saída, o aplicativo obteve valores de 62 e 56%, respectivamente. Conclusões: Modelos de rede neural multicamada podem auxiliar na avaliação dermatoscópica de nevos melanocíticos e melanomas, quanto ao diagnóstico diferencial entre eles.

Introduction: With the advancement of digital image analysis, predictive analysis, and machine learning methods, studies have emerged regarding the use of artificial intelligence in imaging tests such as dermoscopy. Objective: Construction, testing, and implementation of an artificial neural network based on characteristics of dermoscopic images. Methods: 1949 images of melanocytic nevi and melanomas were included, both from the authors' files and from dermoscopic image banks available on the internet, and routines and plugins were developed to extract 58 features applied to a multilayered neural network construction algorithm. Also, 52 dermatologists assessed 40 random images and compared the results compared. Results: The training and testing of the neural network obtained a correct percentage of classification of 78.5% and 79.1%, respectively, with a ROC curve covering 86.5% of the area. The sensitivity and specificity of dermatologists were 71.8% and 52%. For the same images and a cutoff point of 0.4 (40%) of the output value, the application obtained 62% and 56% values, respectively. Conclusions: Multilayer neural network models can assist in the dermoscopic evaluation of melanocytic nevi and melanomas regarding the differential diagnosis between them

Dermoscopic features of 266 cases of melanonychia / 中华皮肤科杂志

Objective:To investigate dermoscopic manifestations and features of melanonychia.Methods:A retrospective analysis was carried out on dermoscopic images of 4 common types of melanonychia collected in Department of Dermatology, Xijing Hospital, the Fourth Military Medical University from January 2016 to July 2020.Results:A total of 266 cases of melanonychia were collected, including 64 (24.1%) of subungual melanoma, 52 (19.5%) of nail matrix nevi, 89 (33.5%) of subungual hemorrhage, and 61 (22.9%) of onychomycosis. Subungual melanoma and nail matrix nevi mostly occurred in the fingernails. To be specific, subungual melanoma most frequently occurred in the thumbnails (62.8%) , while nail matrix nevi mostly involved the 2 nd - 5 th fingernails (73.9%) . Subungual hemorrhage and onychomycosis mostly occurred in the toenails, and there were 51 (57.3%) cases of subungual hemorrhage of the toenails and 46 (75.4%) cases of onychomycosis of the toenails. Subungual melanoma mostly occurred in patients aged over 40 years (49 cases, 76.8%) , while the other 3 types of melanonychia mostly affected patients aged under 40 years. Dermoscopic manifestations of subungual melanoma mainly included regular longitudinal bands (35 cases, 54.7%) or irregular bands (25 cases, 39.0%) whose width was greater than 3 mm in 87.5% cases, Hutchinson sign (36 cases, 56.3%) , and ruptures (15 cases, 23.4%) which mainly were black-brown in color; dermoscopic manifestations of nail matrix nevi mainly were a single regular pigmented band (52 cases, 100%) whose width was less than 3 mm in 36 (69.2%) cases, and Hutchinson sign (26 cases, 50%) , while no ruptures were observed in nail matrix nevus lesions; subungual hemorrhage dermoscopically manifested as diffuse macules (74 cases, 83.1%) , and globular dark red or black hemorrhagic structures were observed in 85 (95.5%) cases; fungal melanonychia was dermoscopically characterized by irregular dark brown longitudinal bands (54 cases, 88.5%) . Conclusions:Subungual melanoma was dermoscopically characterized by regular longitudinal bands with a width of greater than 3 mm, nail matrix nevi by regular longitudinal bands, subungual hemorrhage by diffuse macules, and onychomycosis by irregular longitudinal bands. Dermatoscopy can be used to identify melanonychia lesions and provide a basis for auxiliary diagnosis of subungual melanoma.

Clinical and histopathological analysis of three cases of nevoid melanoma / 中华皮肤科杂志

Objective:To investigate clinical and histopathological characteristics of nevoid melanoma.Methods:A retrospective analysis was carried out on clinical and histopathological data collected from 3 patients with nevoid melanoma diagnosed in Department of Dermatology, Xijing Hospital from 2000 to 2020.Results:Among the 3 patients with nevoid melanoma, 2 were females and 1 was male. Skin lesions initially manifested as black macules and papules. After surgical resection, 2 patients developed new nodular lesions or recurrent skin lesions which enlarged into plaques. Histopathological examination showed proliferation of epithelioid melanocytes in the epidermis and dermis, with cytological atypia and some deeply stained nuclei. Immunohistochemical study revealed positive staining for Melan-A and S100 in tumor cells in the skin lesions, diffusely positive staining for HMB45 in dermal tumor cells, locally negative staining for HMB45 in the deep dermis, increased Ki67 proliferation index, and active expression of cyclin D1.Conclusion:Nevoid melanoma is easy to be misdiagnosed as pigmented nevi or seborrheic keratosis; when recurrence or metastasis occurs in patients with histologically diagnosed pigmented nevi, attention should be paid to the possibility of nevoid melanoma.

Screening of DNA methylation sites associated with melanoma and construction of an aberrant methylation profile: a preliminary study / 中华皮肤科杂志

Objective:To screen aberrant DNA methylation sites associated with melanoma using gene chip technology, and to preliminarily construct a melanoma-specific methylation profile.Methods:The Illumina Human Methylation 450K whole-genome methylation chip was used to detect the whole-genome DNA in 6 melanoma tissues and their paralesional skin tissues, and DNA differentially methylated sites were obtained. Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) -based pathway analysis were carried out to investigate gene functions.Results:Gene chip testing showed that there were 27 779 differentially methylated sites between melanoma tissues and paralesional tissues, of which 16 673 were hypermethylated sites and 11 106 were hypomethylated sites in melanoma tissues. According to more stringent screening criteria " P < 0.01 and |Δβ| > 0.2", a total of 4 883 differentially methylated sites were screened out after filtering out all single nucleotide polymorphism-related probes, probes located on the XY chromosomes and cross-reactive probes, 1 459 (30%) of which were located in the promoter region including TSS1500, TSS200, 5′UTR and 1st Exon. GO enrichment analysis showed that differentially methylated genes were involved in many biological processes, including cell growth, differentiation, adhesion, movement and migration, signal transduction, transcriptional regulation, etc. KEGG-based pathway analysis showed that differentially methylated genes were mainly involved in signaling pathways, such as focal adhesion pathway, cancer pathways, transforming growth factor-β signaling pathway, phosphatidylinositol signaling pathway, melanogenesis pathway, chemokine signaling pathway, adhesion junction pathway, calcium signaling pathway, cell adhesion molecule pathway, mitogen-activated protein kinase signaling pathway, Wnt signaling pathway, Janus kinase-signal transducer and activator of transcription signaling pathway. Based on the criteira "the top 16 most differentially methylated genes related to hypermethylated sites in the promoter region, the genes with the highest methylation frequency (CpG sites ≥ 7) , the genes with certain functions or involved in a certain signaling pathway", 8 genes (KAAG1, DGKE, SOCS2, TFAP2A, GNMT, GALNT3, ANK2 and HOXA9) were selected as candidate biomarkers for melanoma. Conclusion:There are many hypermethylated genes in melanoma tissues, and 8 differentially methylated genes may serve as biomarkers for melanoma.

Surgical treatment strategies and outcomes of early-stage nail apparatus melanoma: a retrospective analysis of 115 cases / 中华皮肤科杂志

Objective:To explore surgical treatment strategies and prognosis of early-stage nail apparatus melanoma.Methods:A total of 115 patients with early-stage nail apparatus melanoma receiving surgical treatment were collected from Department of Dermatology, Xijing Hospital, the Fourth Military Medical University from July 2011 to December 2019, and surgical treatment strategies and outcomes were analyzed retrospectively.Results:According to the modified ABCDEF criteria and clinical manifestations (such as deformation of the nail plate, ulcers, nodules) , 73 patients with early-stage nail apparatus melanoma received extended surgical resection based on the resection principles of melanoma in situ, 22 based on the resection principles of stage I and II melanoma, 20 based on the resection principles of stage I and II melanoma with invasion risks. During the follow-up period of 6 months to 9 years, there was no recurrence of the primary tumors in any patients; no abnormalities were observed by the ultrasound examination of lymph nodes in 101 patients; metastases occurred in 2 patients receiving finger amputation, 1 of whom died; 12 patients were lost to follow-up. Conclusion:To select extended surgical resection strategies for early-stage nail apparatus melanoma based on clinical manifestations, can ensure adequate treatment and preserve the normal function of the extremities to the greatest extent without recurrence of the primary tumors.

Considerations in the diagnosis and treatment of several nail diseases / 中华皮肤科杂志

In recent years, some progress has been made in the diagnosis and treatment of nail diseases, but there are still many challenges, such as longitudinal melanonychia, rare nail unit-specific tumors and nail dystrophy. Longitudinal melanonychia may develop into melanoma. Besides, biopsy and surgery are triggering factors for acral melanoma, so it is important to decide whether to operate and how to apply operating principles in clinic. In addition, the diagnosis and treatment should be based on patients′ age, clinical evaluation results, dermoscopic findings and pathological examinations, so as to avoid missed diagnosis of malignant melanonychia and deformities from treatment of benign melanonychia as far as possible. There are few summaries of clinical manifestations and pathological features of rare nail unit-specific tumors, and their diagnosis is difficult. In particular, onychocytic carcinoma and onycholemmal carcinoma are malignant tumors with great harm, so this article focuses on the two kinds of tumors to remind clinicians to avoid missed diagnoses. The etiology of nail dystrophy is complex. Nail dystrophy caused by inflammatory diseases can be treated with topical or systemic drugs, while various nail deformities caused by genetic factors, toe deformities, improper walking posture, mechanical injuries, and chronic inflammation of the nail groove are in need of physical or surgical correction. This article gives insight into challenges and strategies for the diagnosis and treatment of the above nail diseases.

Nevo azul no aparato ungueal: relato de um caso / Blue nevus of the nail apparatus: a case report

A discromia azul das unhas possui vários diagnósticos diferenciais. Crescimento da lesão, distrofia ungueal associada e extensão periungueal requerem avaliação para excisão cirúrgica. Mulher, 27 anos, apresentava mancha azulada, semicircular, ocupando cerca de 50% da lúnula, sem alteração da lâmina suprajacente, com pequena alteração da porção distal da unha, com camadas do tipo "onicosquizia localizada", sem história prévia de trauma ou sangramento. Realizada avulsão parcial da placa e biópsia excisional por saucerização da lesão fortemente pigmentada. O exame histopatológico foi compatível com nevo azul. Sugere-se que, neste caso, o nevo se situasse em posição submatricial, não interferindo, portanto, na coloração da lâmina ungueal

Blue nail dyschromia has several differential diagnoses. Lesion growth, associated nail dystrophy, and nail extension require evaluation for surgical excision. We report the case of a 27-year-old woman presenting a bluish, semicircular stain, occupying about 50% of the lunula. The patient presented no changes in the overlying lamina, small alteration of the distal nail portion, localized onychoschizia-type layers, and no previous trauma or bleeding history. We performed partial avulsion of the plaque and shave biopsy, evidencing an intensely pigmented lesion. Histopathological examination was compatible with blue nevus. In this case, the nevus should be located in the sub-matricial position, thus not interfering with the nail plate color

Nevo melanocítico congénito gigante, Caso Clínico / Giant Congenital Melanocytic Nevus, Clinical Case

Introducción:Los Nevos Melanocíticos Congénitos (NMC) son lesiones cutáneas que frecuentemente están presentes desde el nacimiento, sin embargo,la presencia de un NMC gigante mayor a 20 cm es infrecuente, motivo de presentación del caso. Caso: Niño de 2 años y 5 meses, quien presentó Nevos congénitas de diferente diámetro dispersos en toda el área de la piel, siendo el más grande uno de color oscuro en el área de tórax posterior en línea media dorsal, abollonada que se eleva de la piel e inicia desde el occipucio y se prolonga por la línea media hasta llegar a la región sacra y glúteos, cubre hombros de forma triangular inversa con diámetros de 27 por 25 centímetros. Se acompañade numerosos nevos satelitales de 3 milímetros hasta 15 centímetros. La presencia de dos neurofibromasenlos dedos. Evolución: Una interconsulta a Neurología Pediátrica concluyó en un examen neurológico sin alteración, el estudio de Resonancia Magnética Nuclear Cerebral y del canal espinal,fueron normales, así como los exámenes complementarios de biometría hemática, química sanguínea, perfil hepático, perfil tiroideoy eco abdominal. La biopsia de piel reportó un patrón histológico de Nevo Melanocítico. Debido a la extensión de la lesión se decidió la observación. El prurito fue tratado sintomáticamente. Conclusión:El Síndrome del Nevo Melanocítico Congénito se asocia con múltiples hallazgos fenotípicos clásicos, dentro de los cuales se encuentran patrones de pigmentación que ocupan las líneas de Blaschko, neurofibromas y múltiples melanomas satélites. Su diagnóstico es clínico y para su tratamiento se requieren procedimientos quirúrgicos a consideración de la extensión de la lesión. El manejo integral de manera interdisciplinaria es fundamental en su tratamiento

Introduction: Congenital Melanocytic Nevi (CMN) are skin lesions that are frequently present from birth, however, the presence of a giant CMN greater than 20 cm is infrequent, reason for the presentation of the case. Case: A boy of 2 years and 5 months, who presented congenital nevi of different diameter scattered throughout the skin area, the largest being a dark-colored one in the posterior thorax area in the mid-dorsal line, embossed that rises from the skin and starts from the occiput and extends through the midline until it reaches the sacral region and buttocks, it covers shoulders in an inverse triangular shape with diameters of 27 by 25 centimeters. It is accompanied by numerous satellite nevi from 3 millimeters to 15 centimeters. The presence of two neurofibromas on the fingers. Evolution: A consultation with Pediatric Neurology concluded in a neurological examination without alteration, the study of Brain Nuclear Magnetic Resonance and of the spinal canal, were normal, as well as the complementary tests of hematic biometry, blood chemistry, liver profile, thyroid profile and abdominal echo . The skin biopsy reported a histological patternof Melanocytic Nevus. Due to the extent of the injury, observation was decided. The pruritus was treated symptomatically. Conclusion: Congenital Melanocytic Nevus Syndrome is associated with multiple classic phenotypic findings, among which are pigmentation patterns that occupy Blaschko's lines, neurofibromas and multiple satellite melanomas. Its diagnosis is clinical and its treatment requires surgical procedures, taking into account the extent of the lesion. Comprehensive management in an interdisciplinary manner is essential in its treatment

Melanoma primário múltiplo sincrônico sobre nevo congênito: relato de caso / Synchronous multiple primary melanomas on congenital nevus: Case report

Pacientes com nevo melanocítico congênito gigante possuem maior risco de desenvolver melanoma. Após o primeiro diagnóstico de melanoma, há também uma maior incidência de melanomas subsequentes em um mesmo paciente. No entanto, a terapêutica ideal para esta forma de nevo ainda é controversa. É relatado o caso de um paciente com nevo congênito gigante associado a melanoma múltiplo sincrônico e o tratamento proposto.

Patients with giant congenital melanocytic nevus are at higher risk of developing melanoma. After the first diagnosis of melanoma, there is also a higher incidence of subsequent melanomas in the same patient. However, the ideal therapy for this type of nevus is still controversial. We report the case of a patient with giant congenital nevus associated with multiple synchronous melanomas and the proposed treatment

Eruptive disseminated Spitz nevi - Case report

Abstract Spitz nevus is a benign melanocytic lesion, which presents in several ways: solitary, agminated, or disseminated. The disseminated variant is uncommon; it may have a rapid evolution (the eruptive form) and be difficult to manage. This report presents the case of a 24-year-old patient with multiple papules on his limbs, which had appeared four years previously. On physical examination, 120 pink and skin-colored papules were seen, which under dermoscopy were observed to be homogeneous, pink vascular lesions. Histopathologic study revealed epithelioid cells arranged in groups or singly in the dermis and dermo-epidermal junction. They were HMB-45 positive in the superficial dermis, and Ki-67 < 1%. Given these findings, a diagnosis of eruptive disseminated Spitz nevi was made.

Effect of nucleolar protein 14 on angiogenesis in melanoma and its mechanism / 中华皮肤科杂志

Objective To evaluate the effect of nucleolar protein 14 (NOP14) on angiogenesis in melanoma.Methods Melanoma tissues were collected from 40 patients with pathologically diagnosed melanoma in Guangzhou First People's Hospital from January 2016 to December 2018,and immunohistochemical study was conducted to determine the expression of NOP14 and CD31 (expressed as microvessel density [MVD]).Melanoma cell lines A375 and SK-MEL-1 were both divided into 4 groups:empty vector group transfected with the empty vector,NOPI4 group transfected with a NOP14-overexpressing vector,siNOP14 group transfected with the siRNA targeting NOP14,and siNC group transfected with a negative control siRNA.Fluorescence-based quantitative PCR and Western blot analysis were performed to determine the mRNA and protein expression of NOP14 respectively,and Western blot analysis and enzyme-linked immunosorbent assay (ELISA) to measure the expression of vascular endothelial growth factor (VEGF) and VEGF receptor (VEGFR) in cells and their culture media.Coculture models of human umbilical vein endothelial cells (HUVECs) and A375/SK-MEL-1 cells in the above groups were established in Transwell chambers,and cell counting kit-8 (CCK8) assay,Transwell migration and invasion assays and Matrigel-based vasculogenic mimicry assay were performed to evaluate the cellular proliferative,migratory,invasive activity and tube formation capacity respectively.A linear regression model was used to analyze the relationship between NOP14 expression and MVD in melanoma tissues,multi-way analysis of variance to analyze the difference in cellular proliferative activity,and independent-sample t test to compare other experimental indices between 2 groups.Results The expression of CD31 (MVD) was 44 ± 13 in the group with high NOP14 expression (n =20),58 ± 16 in that with moderate NOP14 expression (n =17),and 62 ± 11 in that with low NOP14 expression (n =3).The NOP14 expression was negatively correlated with MVD (r =-0.525,P =0.017).Compared with the empty vector group,the expression of VEGF and VEGFR in A375 and SK-MEL-1 cells and their culture media significantly decreased in the NOP14 group (all P ＜ 0.05).Compared with the siNC group,the expression of VEGF and VEGFR in the A375 and SK-MEL-1 cells and their culture media significantly increased in the siNOP14 group(all P ＜ 0.05).In the co-culture models of A375 cells and HUVECs,the NOP14 group showed significantly decreased proliferative activity of HUVECs (F =131.85,P ＜ 0.05),and numbers of migratory cells (22 ± 5 vs.63 ± 8,t =7.07,P =0.002),invasive cells (14 ± 5 vs.45 ± 10,t =4.94,P =0.008) and branch points (8 ± 2 vs.14 ± 3,t =5.06,P ＜ 0.001) compared with the empty vector group;compared with the siNC group,the siNOP14 group showed significantly increased proliferative activity of HUVECs (F =79.92,P ＜ 0.01),and numbers of migratory cells (152 ± 30 vs.59 ± 4,t =5.36,P =0.006),invasive cells (134 ± 21 vs.50 ± 8,t =6.40,P ＜ 0.001) and branch points (27 ± 3 vs.15 ± 4,t =6.10,P ＜ 0.001).In the co-culture models of SK-MEL-1 cells and HUVECs,the 4 groups showed the same trend of changes in the cellular proliferative,migratory,invasive activity and tube formation capacity of HUVECs as the above groups in the co-culture models of A375 cells and HUVECs.Conclusion The NOP14 expression is negatively correlated with MVD in melanoma tissues,and NOP14 can inhibit angiogenesis in melanoma.

Inhibitory effect of fenretinide-loaded liposomes on subcutaneous transplanted tumors in nude mice inoculated with A375 melanoma cells: a preliminary study / 中华皮肤科杂志

Objective To evaluate the inhibitory effect of fenretinide-loaded liposomes(4-HPR-L) on subcutaneous transplanted malignant melanomas in nude mice.Methods A film-ultrasonic dispersion method was used to prepare 4-HPR-L.BALB/c nude mice were subcutaneously inoculated with A375 melanoma cells in the right axillary fossae to establish malignant melanoma-bearing nude mouse models.Ten nude mouse models were randomly and equally divided into 2 groups to be injected with near-infrared fluorescent cell membrane label (DiR) solution or DiR liposomes (DiR-L)at the same concentration in the caudal vein,and a live imaging system was used to observe the distribution of DiR or DiR-L in nude mice at 6,12,24 hours after the injection.Another 30 nude mice were randomly and equally divided into 3 groups to be injected with 5％ (mass fraction) glucose solution at a single-dose of 0.2 ml (control group),25 mg/kg 4-HPR solution (4-HPR group)and 25 mg/kg 4-HPR-L solution (4-HPR-L group) respectively on days 8,10,12,14,16,18,20 and 22 after the inoculation with A375 cells.The mouse body weight and tumor volume were dynamically monitored in the above groups after the injection,and the survival situation was observed.The nude mice were sacrificed on day 2 after the final injection,and the heart,liver,spleen,lung,kidney and tumor tissues were resected.These tissues were subjected to hematoxylin-eosin staining and immunohistochemical staining to observe the metastasis of melanoma in mice,and terminal deoxyribonucleotidyl transferase-mediated nick end labelling was performed to detect the apoptosis in tumor cells.One-way analysis of variance and independent-sample t test were used to analyze measurement data.Results The live imaging system showed that DiR-L could be retained in melanoma for a long time,and strong fluorescence of DiR-L could be still observed in the tumors at 24 hours after injections.Quantitative fluorescence analysis revealed that the fluorescence intensity of DiR-L (22.85 ± 1.66) was significantly higher than that of DiR in tumor tissues (8.45 ± 0.97,t =12.957,P ＜ 0.01).Compared with the control group and 4-HPR group,the resected tumor weight on day 2 after the final injection was significantly decreased in the 4-HPR-L group (F =27.055,t =4.768,6.640,respectively,both P ＜ 0.05).Hematoxylineosin staining showed that liver metastasis occurred in 2 nude mice in the 4-HPR-L group,but in all the nude mice in the control group and 4-HPR group.All the nude mice in the 4-HPR-L group died within 76 days after inoculation,and the mice in the control group and 4-HPR group all died within 56 and 59 days respectively after inoculation.There were significant differences in the apoptotic index among the control group (12.14‰ ± 1.33‰),4-HPR group (67.17‰± 15.18‰) and 4-HPR-L group (152.73‰ ± 11.27‰;F =167.588,P ＜ 0.05),and the apoptotic index was significantly higher in the 4-HPR-L group than in the control group and 4-HPR group (t =18.162,11.075 respectively,both P ＜ 0.05).Conclusion 4-HPR-L can effectively inhibit the growth of subcutaneous melanoma in nude mice and metastasis of melanoma cells,and prolong the survival duration of nude mice.

Analysis of clinical and pathological diagnoses of 29 987 skin biopsy samples in Peking Union Medical College Hospital / 中华皮肤科杂志

Objective To analyze the disease constitution,accuracy of clinical and pathological diagnoses of skin biopsy samples in Peking Union Medical College Hospital.Methods A total of 29987 patients subjected to skin biopsy were collected from Department of Dermatology,Peking Union Medical College Hospital from June 2010 to November 2018,and clinical and histopathological diagnoses of these skin biopsy samples were analyzed retrospectively.Results According to the results of histopathological diagnosis,confirmed diagnoses of these patients could be classified into 33 categories and 242 kinds.Common disease categories included epidermal tumors (2931 cases,9.77％),connective tissue diseases (2809 cases,9.37％),melanocytic tumors (2078 cases,6.93％),erythematous scaly pustular dermatoses (1376 cases,4.59％),lichenoid dermatoses (1291cases,4.31％),allergic or eczematous skin diseases (1282 cases,4.28％)and infectious skin diseases (1156 cases,3.86％).Common skin diseases included scleroderma (1887 cases,6.29％),pigmented nevus (1755 cases,5.85％),seborrheic keratosis (1136 cases,3.79％),eczema (1089 cases,3.63％),psoriasis (881 cases,2.94％),lichen planus (867 cases,2.89％),lupus erythematosus (638 cases,2.13％),pemphigus (549 cases,1.83％),and basal cell carcinoma (501 cases,1.67％).Poor consistency was observed between clinical diagnosis and histopathological diagnosis of lichen planus,bullous pemphigoid,granuloma annulare and hypereosinophilic dermatitis.Conclusions Common disease categories of the skin biopsy samples in Peking Union Medical College Hospital were epidermal tumors,connective tissue diseases,melanocytic tumors,erythematous scaly pustular dermatoses,lichenoid dermatoses,and allergic or eczematous skin diseases.Poor consistency was observed between clinical and pathological diagnosis in some skin diseases,and understanding of these diseases should be improved.

Nevos melanocíticos congénitos / Congenital melanocytic nevus / Nevos melanocíticos congênitos

Resumen: Los nevos melanocíticos congénitos son una proliferación melanocítica benigna presente al nacimiento o que surgen en los primeros 2 o 3 años de vida. Habitualmente se clasifican, según su tamaño, en pequeños, medianos y grandes. Su importancia radica en el potencial riesgo de desarrollar melanoma, en la repercusión que tienen en la calidad de vida de quien los padece y en la asociación con disrafismo y tumores del sistema nervioso central. A mayor tamaño, mayor riesgo de desarrollar melanoma en el nevo o fuera de él. Describiremos las características epidemiológicas, clínicas dermatoscópicas y revisaremos el manejo y seguimiento de los nevos congénitos.

Summary: Congenital melanocytic nevi are a benign melanocytic proliferation present either from birth or during the first 2 or 3 years of life. They are usually classified according to size as: small, medium and large. Their importance lies on the potential risk of developing melanoma, on the impact they have on the patient's quality of life and on its association with dysraphism and tumors of the central nervous system. The larger the size of the nevi, the higher the risk of developing melanoma inside or outside the nevus. We will describe the epidemiological and dermatoscopic clinical characteristics and review the management and follow-up of congenital nevi.

Resumo: Os nevos melanocíticos congênitos são uma proliferação melanocítica benigna presente desde o nascimento ou durante os primeiros 2 ou 3 anos de vida. Eles são geralmente classificados de acordo com o seu tamanho como: pequenos, médios ou grandes. Sua importância está no risco potencial de desenvolver melanoma, no impacto que eles têm na qualidade de vida do paciente e na sua associação com disrafismo e tumores do sistema nervoso central. Quanto maior o tamanho dos nevos, maior o risco de desenvolver melanoma dentro ou fora do nevo. Descreveremos as características clínicas epidemiológicas e dermatoscópicas dos nevos congênitos e revisaremos o seu gerenciamento e acompanhamento.

Onychocytic matricoma

Abstract Onychocytic matricoma is a newly described tumor of the nail matrix. Clinically, it presents with localized thickening of the nail plate and melanonychia. Histologically, it represents a benign acanthoma of onychocytes. There are 8 cases reported in the literature. A 12-year-old girl presented with localized melanonychia and concurrent thickening of the nail plate restricted to the area of pigmentation affecting the right thumb, with no history of trauma or pain. We report a case of this rare tumor occurring in late childhood and provide a comprehensive review of its clinical presentation and differential diagnosis. Both clinicians and dermatopathologists should be aware of the presentation of onychocytic matricoma and include it in their scope of diagnosis of longitudinal nail bands.

Expression of ubiquitin-conjugating enzyme E2S in malignant melanoma and its effect on the biological behavior of melanoma cells / 中华皮肤科杂志

Objective To determine the expression of ubiquitin-conjugating enzyme E2S (UBE2S) in malignant melanoma (MM),and to evaluate its effect on the biological behavior of melanoma cells.Methods Immunohistochemical study was performed to determine the UBE2S expression in 128 primary MM tissue chips,64 metastatic MM tissue chips,16 non-tumor tissue chips (8 paralesional normal skin tissues and 8 normal epidermal tissues).Real-time quantitative RCR was conducted to determine the UBE2S mRNA expression in the melanoma cell lines A375,MUM-2B and MUM-2C.The melanoma cell lines A375 and MUM-2B were divided into 2 groups separately:interference group transfected with a lentiviral vector carrying UBE2S RNA interference sequence,and control group transfected with a lentiviral vector carrying control sequence.After 72 hours,real-time quantitative RCR was performed to determine the UBE2S mRNA expression in the melanoma cell lines A375 and MUM-2B.Caspase-3/7 activity in the groups was assessed by using kits,and cell apoptosis and cell cycle distribution were detected by flow cytometry.The effect of UBE2S knockdown on the migratory and invasive abilities of and N-cadherin expression in A375 cells were evaluated by Transwell assay and Western blot analysis respectively.Statistical analysis was carried out with SPSS 22.0 software by using independent sample t-test for the comparison of normally distributed data between two groups,chi-square test for enumeration data,MannWhitney U test for the comparison of non-normally distributed data,and Spearman's coefficient for assessment of the correlation of UBE2S expression with T staging of melanoma.Results UBE2S was highly expressed in 98 (51.0％) MM tissues,but lowly expressed in 16 non-tumor tissues,and the UBE2Sexpression rate significantly differed between the above two kinds of tissues (x2 =11.905,P ＜ 0.01).UBE2S expression was negatively correlated with T staging of melanoma (ρ =-0.210,P =0.043).The relative mRNA expression of UBE2S significantly differed among the A375,MUM-2B,and MUM-2C cells (F =817.228,P ＜ 0.01).After UBE2S knockdown,the caspase-3/7 activity was significantly up-regulated in the A375 interference group (t =17.572,P ＜ 0.01) and MUM-2B interference group (t =24.552,P ＜0.01) compared with the A375 and MUM-2B control groups respectively.Compared with the control group,the A375 interference group showed significantly increased proportion of A375 cells at G1 phase (t =7.365,P ＜ 0.01),decreased proportion at S phase (t =-9.190,P ＜ 0.01),and no change in the proportion of A375 cells at G2/M phase (t =-0.227,P ＞ 0.05).The MUM-2B interference group showed significantly increased proportions of MUM-2B cells at G1 (t =12.676,P ＜ 0.01) and G2/M phases (t =13.045,P ＜0.01),but significantly decreased proportion at S phase (t =-15.718,P ＜ 0.01) compared with the control group.Transwell assay revealed decreased migratory and invasive abilities of A375 cells in the interference group compared with the control group (t =-35.727,-125.000,P ＜ 0.05,＜ 0.01,respectively).Western blot analysis showed down-regulated expression of N-cadherin protein in A375 cells in the interference group compared with the control group.Conclusions UBE2S is over-expressed in melanoma tissues,whose expression is associated with the T staging of melanoma.Knockdown of UBE2S affects the apoptosis,cell cycle,migration and invasion of melanoma cells,and may promote the metastasis of MM cells by regulating N-cadherin expression.