Pigmented Nevi Research Articles

Mechanism of miR-137 regulating migration and invasion of melanoma cells by targeting PIK3R3 gene.

To investigate the effect of microRNA-137 (miR-137) on the migration and invasion of melanoma cells and its mechanism. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression of miR-137 in melanoma tissues and cells. miR-137 mimics, phosphoinositide-3-kinase regulatory subunit 3 (PIK3R3) small interfering RNA and corresponding controls were transfected into A375 and WM451 cells by lipofection. The expression of PIK3R3 was examined by qRT-PCR and Western blot analysis. The Trans-well assay was conducted to measure cell migration and invasion. Dual luciferase reporter assay was used to detect the interaction between miR-137 and PIK3R3. Compared with normal pigmented nevus tissue, miR-137 expression was significantly reduced in melanoma tissues. Compared with keratinous HaCaT cells, the level of miR-137 was significantly decreased in melanoma SK-MEL-1, A375, and WM451 cells. Knockdown of miR-137 significantly reduced the migrated and invasive abilities of melanoma A375 and WM451 cells. Moreover, inhibition of PIK3R3 obviously suppressed the migration and invasion abilities of melanoma A375 and WM451 cells. Luciferase activity assay showed that PIK3R3 was a direct target of miR-137. In addition, overexpression of miR-137-inhibited PIK3R3 expression, while knockdown of miR-137-enhanced PIK3R3 abundance. Restoration of PIK3R3 reversed the regulatory effect of miR-137 on cell migration and invasive in melanoma A375 and WM451 cells. miR-137 inhibited melanoma cell migration and invasion by targeting PIK3R3 gene.

MiR-122-5p inhibits the proliferation of melanoma cells by targeting NOP14

To investigate the expression profile of miR-122-5p in melanoma tissues and the effect of miR-122-5p on the proliferation, cell cycle and apoptosis of human melanoma cell lines SK-MEL-110 and A375. The expression profiles of miR-122-5p in melanoma and pigmented nevus tissues were detected using real-time fluorescence quantitative PCR (qRT-PCR). SK-MEL-110 and A375 cells transfected with miR-122-5p inhibitor or negative control inhibitor (NC) I were examined for miR-122- 5p expression using qRT-PCR and changes in cell proliferation, cell cycle and apoptosis using MTT assay or flow cytometry. NOP14 mRNA and protein expressions in the cells were detected using qRT- PCR and Western blotting, respectively. Luciferase reporter assay was used to confirm the identity of NOP14 as the direct target of miR-122-5p. The relative expression of miR-122-5p in human pigmented nevus tissues and melanoma tissues was 1.23±0.270 and 7.65 ± 1.37, respectively. The relative expression of miR-122-5p in SK-MEL-110 and A375 cells transfected with miR-122-5p inhibitor was 0.21 ± 0.08 and 0.17 ± 0.05, respectively. miR-122-5p inhibitor obviously inhibited the cell proliferation and increased the percentage of cells in G1 stage in both SK-MEL-110 and A-375 cells, but did not cause obvious changes in the apoptosis of the two cells. miR-122-5p inhibitor did not significantly affect the expression level of NOP14 mRNA, but obviously increased the expression level of NOP14 protein. Luciferase reporter assay revealed a significantly lower luciferase activity in cells co-transfected with miR-122-5p mimics and wild-type psi-CHECK2-3'UTR plasmid than in the cells cotransfected with NC and wild-type psi-CHECK2-3'UTR plasmid (0.21 ± 0.14 vs 0.56 ± 0.1, P < 0.01). miR-122-5p expression is upregulated in melanoma tissues, indicating its involvement in the development of melanoma. miR-122-5p inhibits the proliferation of SK-MEL-110 and A-375 cells possibly by affecting the cycle through NOP14.

Malignant transformation in three cases of congenital pigmented nevi

Malignant transformation in three cases of congenital pigmented nevi

Becker's Nevus Syndrome

The simultaneous occurrence of a patch of light or dark brown hyperpigmentation with hypertrichosis (Becker's nevus) together with (usually ipsilateral) soft tissues hypoplasia (especially breast, in women) and underlying skeletal anomalies (i.e., vertebral hypoplasia, scoliosis, pectus carinatum or excavatum) represents the Becker's nevus syndrome (BNS) phenotype. It was first described (as a single cutaneous lesion) by Becker in 1949 and then associated with the surrounding musculoskeletal disorders. The syndrome has also been reported as pigmentary hairy epidermal nevus syndrome. Less than 100 cases have been reported in the literature, with a slightly higher incidence in females and only few familiar cases: paradominant postzygotic mutations and/or an androgen-dependent hyperactivation have been reported as the causes of the diseases.The extracutaneous lesions are congenital and nonprogressive, and the natural history of the Becker's nevus is the same as that of isolated nevi: in prepubertal boys, the pigmentation may be less intense and the hairiness may be absent or mild, as occurs in women, whereas in men, there is an increase of hairiness after puberty. The treatment is essentially cosmetic, and potential therapeutic options include electrolysis, waxing, makeup, or laser.

Phacomatosis Pigmentovascularis

AbstractThe coexistence of a widespread vascular nevus and an extensive pigmentary nevus is defined as “phacomatosis pigmentovascularis” (PPV). More than 250 (sporadic) cases of PPV have been so far reported, mainly in Asian or Asian-related populations: mutations in genes related to angiogenic pathways (RAS, MAPK, mTOR, PI3K/AKT, and GNAQ) have been recently identified as the causes of this complex phenotype. In many cases, mutations in two different genes may coexist, representing the classical example of “twin spotting” phenomenon. PPV is usually associated with several extracutaneous anomalies including ocular manifestations (melanosis bulbi, glaucoma, iris mammillations, megalocornea, buphthalmos, strabismus, and hyperpigmentation of the conjunctiva, sclera, episclera, iris, trabecular meshwork, and choroid) and musculoskeletal alterations (limb hypertrophy, Klippel–Trenaunay type abnormalities, hemifacial hypertrophy, hemicorporal hypertrophy, macrocephaly, microcephaly, and scoliosis). Central nervous system anomalies have been reported in most of the patients and include seizure, cognitive delay, cerebral atrophy, hydrocephalus, sensorineural deafness, and intracranial hypertension, as well as migraine, pseudotumor cerebri, and intracerebral vascular malformations. More rarely, PPV has been associated with structural and/or vascular renal anomalies, hepatosplenomegaly, pyogenic granuloma, cavernous hemangioma, portal hypertension, umbilical hernia, hypoplasia of leg veins, and hypo- or hyperactivity of the immune system.

Genomic Fusions in Pigmented Spindle Cell Nevus of Reed.

Recent molecular studies of spitzoid neoplasms have identified mutually exclusive kinase fusions involving ROS1, ALK, RET, BRAF, NTRK1, MET, and NTRK3 as early initiating genomic events. Pigmented spindle cell nevus (PSCN) of Reed is a morphologic variant of Spitz and may be very diagnostically challenging, having histologic features concerning for melanoma. Their occurrence in younger patients, lack of association to sun exposure, and rapid early growth phase similar to Spitz nevi suggest fusions may also play a significant role in these lesions. However, to date, there is little data in the literature focused on the molecular characterization of PSCN of Reed with next-generation sequencing. We analyzed a total of 129 melanocytic neoplasms with RNA sequencing including 67 spitzoid neoplasms (10 Spitz nevi, 44 atypical Spitz tumors, 13 spitzoid melanomas) and 23 PSCN of Reed. Although only 2 of 67 (3.0%) of spitzoid lesions had NTRK3 fusions, 13 of 23 (57%) of PSCN of Reed harbored NTRK3 fusions with 5' partners ETV6 (12p13) in 2 cases and MYO5A (15q21) in 11 cases. NTRK3 fusions were confirmed with a fluorescent in situ hybridization break-apart probe. The presence of a NTRK3 fusion correlated with younger age (P=0.021) and adnexal extension (P=0.001). Other minor fusions identified in PSCN of Reed included MYO5A-MERTK (2), MYO5A-ROS1, MYO5A-RET, and ETV6-PITX3 leading to a total of 78% with fusions. Our study suggests that the majority of PSCN of Reed are the result of genomic fusions, and the most frequent and characteristic genomic aberration is an NTRK3 fusion.

Comparison of diagnostic performance of dermatologists versus deep convolutional neural network for dermoscopic images of pigmented nevus and seborrheic keratosis

Objective To compare the diagnostic accuracies of deep convolutional neural network (CNN) and dermatologists for pigmented nevus and seborrheic keratosis. Methods CNN network ResNet-50 was trained with 5 094 dermoscopic images of pigmented nevus and seborrheic keratosis using transfer learning, so as to establish a CNN two-classification model. Then, this model was applied to the automatic classification of 30 dermoscopic images of pigmented nevus and 30 dermoscopic images of seborrheic keratosis. Meanwhile, in combination with clinical photos of skin lesions, 95 experienced dermatologists who had received dermoscopy training gave their diagnosis for the above 60 dermoscopic images. The diagnostic accuracies were compared between the two methods, and misclassified images were further analyzed. Results The CNN automatic classification model had the diagnostic accuracies of 100% (30/30) and 76.67% (23/30) for pigmented nevus and seborrheic keratosis respectively, and the total accuracy was 88.33% (53/60) . The average diagnostic accuracies of 95 dermatologists were 82.98% (25.8/30) and 85.96% (24.9/30) for pigmented nevus and seborrheic keratosis respectively, and the total accuracy was 84.47% (50.7/60) . There were no significant differences in the diagnostic accuracies for pigmented nevus or seborrheic keratosis between the CNN automatic classification model and 95 dermatologists (χ2 = 0.38, P > 0.05) . The dermoscopic images misclassified by CNN were divided into 3 categories: special - type lesions with high pigment content and marked keratosis, typical skin lesions with interference factors, and typical skin lesions without definite reasons for misclassification. Conclusions The performance of CNN automatic classification model is similar to that of experienced dermatologists in the two classification of pigmented nevus and seborrheic keratosis. The reasons for misclassification by CNN still need to be explored by dermatologists and professionals in artificial intelligence. Key words: Nevus, pigmented; Keratosis, seborrheic; Dermoscopy; Neural networks (computer); Artificial intelligence; Convolutional neural network

290 Histological subtype and anatomical location in pediatric malignant melanoma (MM): A population-based study from the surveillance, epidemiology, and end results (SEER) program

Pediatric malignant melanoma (MM) is rare, thus information on its characteristics are not thoroughly reported. This study aimed to report frequencies of MM histological subtype and anatomical location, stratified by age groups and gender. The SEER database (2000-2014) was searched for patients aged 0-19 years, diagnosed with MM. A total of 1,796 patients with MM (218 children, age 0-9 years; 1,578 adolescents, age 10-19) were detected. There were 769 (92 aged 0-9, 677 aged 10-19) males (M) and 1,027 (126 aged 0-9, 901 aged 10-19) females (F). MM NOS (Not Otherwise Specified) was the most common subtype in both groups (138, 63.3%; 848, 53.7%, respectively). Nodular MM, MM in giant pigmented nevus, and mixed epithelioid as well as spindle cell MM were more common in children (19, 8.7%; 11, 5%; 21, 9.6%) than in adolescents (89, 5.6%; 29, 1.8%; 28, 1.8%), respectively. Superficial spreading MM (SSMM) was more common in adolescents (509, 32.3%) than children (19, 8.7%). MM in giant pigmented nevus, as well as mixed epithelioid and spindle cell MM, had higher frequencies in M for both age groups (6.5%; 2.5%, respectively and 9.8%; 2.4%, respectively) compared to F (4.0%; 1.3%, respectively; and 9.5%; 1.3%, respectively). SSMM was more frequent in F for both age groups (9.5%, 35%, respectively) than M (7.6%, 28.7%, respectively). The most common site for M and F adolescents was the trunk (38.6%, 38.5%, respectively), and for children was the lower limb and hip (24.1%, 33.9%, respectively).Findings from this nationwide database show that frequency of some melanoma subtype as well as body site is different when comparing both age groups and both genders, suggesting that possible environmental and biological mechanisms, relevant to age and/or gender, may influence the development of melanoma.

5-羟甲基胞嘧啶表达与黑素瘤侵袭、转移、预后的相关性分析

Objective To detect the level of 5-hydroxymethyl-cytosine (5-hmc) in melanoma tissues, and to analyze the correlation between 5-hmc and the invasion, metastasis and prognosis of melanoma. Methods A streptavidin-peroxidase immunohistochemical method was used to detect the level of 5-hmc in 67 melanoma tissues and 20 pigmented nevi tissues. Univariate and multivariate analyses were performed with the Cox′s proportional hazards regression model to analyze the correlation between the expression of 5-hmc and the prognosis of melanoma. Results The expression rate of 5-hmc was significantly lower in melanoma tissues than in pigmented nevus tissues (40.30%[27/67] vs. 75%[15/20], χ2 = 7.428, P = 0.006) . According to American Joint Committee on Cancer (AJCC) TNM staging system, the expression level of 5-hmc was significantly lower in the stage Ⅳmelanoma tissues than in the stage Ⅱ and stage Ⅲ melanoma tissues (χ2 = 4.416, P = 0.036) . Patients with lymph node metastasis showed significantly lower expression of 5-hmc compared with those without lymph node metastasis (χ2 = 5.902, P = 0.015) , and the level of 5-hmc expression significantly decreased along with the increase of Clark grade (χ2 = 4.828, P = 0.028) . There were no significant differences in the level of 5-hmc expression between patients of different ages, genders or nationalities (P > 0.05) . Multivariate Cox regression analysis showed that distant lymph node metastasis (HR: 2.67, 95% CI: 1.22-5.84) , not receiving surgical resection (HR: 0.41, 95% CI: 0.18-0.95) , and low expression of 5-hmc (HR: 3.54, 95% CI: 1.09-11.43) were independent risk factors for poor prognosis of melanoma. Conclusion 5-Hmc may participate in the invasion and metastasis of melanoma, and be associated with the prognosis of melanoma. Key words: 5-Methylcytosine; Nevi and melanomas; Biological marker; Prognosis; Neoplasm metastasis

Effects of tumor suppressor gene Dickkopf-3 on proliferation and apoptosis of cutaneous malignant melanoma cells

Objective To investigate the expression of Dickkopf-3 (DKK3) in human malignant melanoma cell lines and tissues, and to evaluate effects of DKK3 on the proliferation and apoptosis of malignant melanoma cell line A375. Methods Reverse transcription PCR (RT-PCR) and real-time fluores-cence-based quantitative PCR (qRT-PCR) were performed to measure the mRNA expression of DKK3 in human malignant melanoma cell lines HM, A375, WM451, WM35, SK-MEL-1, Hs-695T and MDA-MB-435s, as well as in 38 primary melanoma tissues, 4 metastatic melanoma tissues and 20 pigmented nevus tissues. Cultured malignant melanoma A375 cells were divided into 2 groups to be transfected with pcDNA3.1 (+) -Flag-DKK3 (experiment group) and pcDNA3.1 (+) -Flag-Vector (control group) respectively. The overexpression of DKK3 was verified by RT-PCR. Cell counting kit-8 (CCK8) assay and plate colony formation assay were performed to evaluate the proliferative activity of A375 cells, flow cytometry was conducted to detect apoptosis of A375 cells, and Western blot analysis was performed to determine the expression of cell cycle- and cell apoptosis-related proteins. Results The mRNA expression of DKK3 was downregulated in WM35 cells, absent in HM cells, A375 cells, WM451 cells, SK-MEL-1 cells and Hs-695T cells, but upregulated in MDA-MB-435s cells. Compared with pigmented nevus tissues, the mRNA expression of DKK3 was significantly decreased in malignant melanoma tissues (P < 0.001) . Compared with the control group (100%) , cell colony formation was markedly suppressed in the experiment group (23.22% ± 3.55%) , and the proliferative activity of A375 cells was also significantly inhibited in the experiment group 24, 48, 72 hours after the transfection (all P < 0.05) . Flow cytometry showed that compared with the control group, A375 cells were significantly arrested in G1 phase (48.68% ± 3.92% vs. 25.38% ± 2.92%, P < 0.001) , and the apoptosis rate of A375 cells was significantly increased in the experiment group (P < 0.001) . Compared with the control group, the experiment group showed significantly higher expression of p21, Bax, cleaved-parp and cleaved-casp3, but significantly lower expression of cyclin D1 and Bcl2 (all P < 0.001) . Conclusion DKK3 expression is downregulated in human malignant melanoma tissues, so it may serve as a potential tumor suppressor gene involved in the development of cutaneous malignant melanoma. Key words: Melanoma; Cell proliferation; Apoptosis; DKK3; Tumor suppressor genes

Proteus Syndrome-A Rare Disease

The Proteus syndrome is an extremely rare disease about cases have been described worldwide with about alive Is characterized by pigmented verrucous nevus and skin thickening lipomas hemangiomas hemihypertrophy gigantism of the extremities free hands visceral abnormalities and accelerated patient rhythm in the first years of life Most patients have normal neuropsychomotor development with life expectancy between months and years according to the severity and location of the abnormalities Partial gigantism of the hands and or feet is the most important manifestation of Proteus syndrome which may be of the fingers and are not always located on the same side of hemihipertrophy Treatment includes emptying and liposuction but the results are unsatisfactory by tumor recurrence and local hypertrophic scar formation

Giant Congenital Melanocytic Nevus (GCMN) - A New Hope for Targeted Therapy?

We present a 6-month-old male patient, who was consulted with dermatologist by his parents, because of a pigmented lesion, present since birth, covering almost the all skin of the back and buttocks. A sharply bordered, unequally coloured congenital pigmented nevus, measuring approximately 21 cm in diameter was observed in the whole body skin examination. The lesion was affecting the lower 2/3 of the skin of the back and the top half of the gluteus area, extending to the lateral part of the tors, forward the abdomen and the upper lateral part of the hips, composed by multiple darker-pigmented nests and several lighter areas, with single depigmented zones, hairy surface, irregularly infiltrated on palpation. Congenital melanocytic nevi are presented in approximately 1% of newborns, while giant congenital melanocytic nevi (GCMN) are the most uncommon subtype of them; with occurrence rate 1 in 50,000 births. They affect 2% of a total body surface or presenting in a diameter larger than 20 cm in older children. Although not common, the possible malignant transformation remains one of the most important considerations related to them, as the related lifetime risk of melanoma is 4% to 10%. Treatment recommendations include non-surgical methods as dermabrasion only within the first two weeks of life, for prevention the possible melanocytic deeper migration, while serial surgical excisions or tissue expanders could be useful treatment tool even in later stages. Nevertheless, cosmetic result is not always satisfactory, and the risk of malignant changes remains, in cases of previous melanocytic migration in deeper layer. Recent article suggests the potential role in the treatment of GCMN with NRAS inhibitor trametinib, approved for treatment of advanced melanoma, associated with underlying NRAS mutations. Although promising, the drug could be useful in paediatric patients, only with associated NRAS gene mutation. It is still unclear whether it could be helpful, independent of the NRAS status.

Aesthetic repair of medial upper lip defects

Objective To explore the aesthetic results of medial upper lip repair for skin and soft tissue defects using local flap. Methods According to the location and the size of upper lip defect, the modified rhomboid flap of 60 ° above the defect was designed to repair the wound in philtrum; the O-L flap along philtral column to vermilion border was designed to cover the wound close to the peak and lateral to philtral column. Results Twenty-one postoperative patients that underwent pigmented nevus removal (12 female, 9 male; ages 16-33 years) had defects in philtrum for 10 cases and close to the peak and philtral column for 11 cases. The diameter of the defect ranged from 0.5 cm to 1.0 cm. All flaps survived primarily without any complications and follow-up was for 1 to 18 months with excellent outcomes in all cases. All patients were satisfied with contour and functions. No pigmented nevus recurrence occurred. Conclusions The flap designed according to the aesthetic principle could be used to repair medial upper lip defect of medium-sized, which not only obtains functional reconstruction, but also satisfies aesthetic results, with aesthetic subunits saved and scar concealed. Key words: Upper lip defect; Philtrum; Aesthetic repair

Role of testosterone synthesized by skin melanocytes in preventing malignant transformation of nevi.

e21066 Background: Melanocytes are involved into the synthesis and metabolism of steroid hormones in the skin. Cutaneous melanoma in 75% of cases occurs in congenital or acquired pigmented nevi. There are no studies comparing local hormonogenesis in nevi and melanomas. The purpose of the study was a comparative analysis of hormone levels in tissues of dysplastic nevi and cutaneous melanoma (pТ1-2N0M0). Methods: Levels of prolactin (PRL), progesterone (P4), total and free testosterone (T and fT), estrone (E1) and estriol (E3) and sex steroid-binding globulin (SSBG) were studied by ELISA in 17 samples of рТ1-2N0M0 melanoma and in 23 samples of dysplastic nevi. Intact tissues (n = 15) obtained from non-cancer patients during surgical treatment was used as the control. Results: Levels of T in nevi, compared to intact tissues, were 1.4 times higher, fT – 8.7 times higher, while SSBG content was 1.9 times lower; E3 was 1.6 times higher, PRL – 1.4 times lower, and levels of E1 in nevi were similar to the values in intact tissues. рТ1-2N0M0 melanomas, compared to intact tissues, demonstrated local androgen imbalance: T levels were decreased by 1.8 times, while fT exceeded the norm by 1.8 times, and SSBG – by 6 times. E1 content increased by 1.6 times, E3 decreased by 2.8 times. The E1/E3 ratio in nevi was reduced by 1.6 times, while in melanoma it was increased by 4.4 times. The T/E1 ratio in nevi was increased by 1.4 times, and in melanoma it was decreased by 2.8 times. Levels of PRL and P4 in melanomas, nevi and in intact tissues did not differ significantly. Conclusions: Melanoma was characterized by hyperestrogenia due to increased levels of E1 and low E3 concentrations which caused malignant transformation of melanocytes. Most likely, in melanoma spent SVT estrone synthesis, as evidenced by increase in the E1 / E3 and decrease T / E1.Apparently, fT in melanoma is used for estrogen synthesis, as indicated by the E1/E3 increase and decrease in the T/E1 ratio. Increased E1 synthesis can contribute to the realization of estrogen genotoxic effects. These mechanisms are absent in tissues of nevi. Hyperandrogenism in nevi probably prevents malignant transformation due to low aromatase activity.

Expression of Notch pathway receptors and ligands in cutaneous malignant melanoma

Objective To determine the expression of Notch pathway receptors (Notch1 and Notch4) and ligands (Jagged1 and Dll4) in cutaneous malignant melanoma (CMM) tissues, and to preliminarily explore the role of the Notch signaling pathway in the pathogenesis of CMM. Methods Immunohistochemical study was performed to determine the expression pattern and intensity of Notch1, Notch4, Jagged1 and Dll4 in 40 paraffin-embedded CMM specimens and 15 paraffin-embedded pigmented nevus specimens. Statistical analysis was carried out by chi-square test and Spearman rank correlation analysis with the SPSS 21.0 software. Results Notch1 was detected in 31 (77.5%) of 40 CMM specimens, as well as in 3 of 15 pigmented nevus specimens, and the positive rates significantly differed between the two groups (χ2= 15.281, P < 0.001) . However, no significant difference in the expression intensity of Notch1 was observed between 18 in situ melanoma tissues and 22 invasive melanoma tissues (χ2= 0.631, P= 0.427) . In addition, the positive rates of Notch4, Jagged1 and Dll4 were also significantly higher in the CMM group than those in the pigmented nevus group (all P < 0.05) , and the expression intensity of Notch4, Jagged1 and Dll4 significantly differed between in situ and invasive melanoma tissues (all P < 0.05) . In CMM tissues, the expression of Notch1 was positively correlated with that of Jagged1 (rs= 0.350, P= 0.027) and Dll4 (rs= 0.562, P < 0.001) , while the expression of Jagged1 was negatively correlated with that of Dll4 (rs=-0.734, P < 0.001) . Conclusion Abnormality of the Notch signaling pathway may be involved in the pathogenesis of melanoma, but further researches are still needed to elucidate the detailed mechanism. Key words: Nevi and melanomas; Receptors, Notch; Immunohistochemistry; Jagged1; Dll4

Pigmented intramucosal nevus of gingiva with a special insight on its pathophysiology: Report of a rare entity

Oral melanotic nevi can be characterized as developmental malformations or melanocytic tumors. Nevi are benign in nature originating from proliferating malfunctioning melanoblasts of the neural crest cells either in the epithelium or in connective tissue. It is an infrequent oral lesion triggering focal pigmentation. Considerable debate exists in the literature with respect to their origin, development, maturation, and their association to oral melanocytes. Nevi present in the mucous membrane have been documented to ensure the risk of malignant transformation. Hence, it is appropriate to cautiously diagnose all pigmented lesions of the oral cavity. Here, we report a case of intramucosal nevus with unusually large size in maxillary anterior gingival mucosa.

NEUROFIBROMATOSIS TYPE 1 OR GIANT MELANOCYTIC NEVUS: PROBLEMS OF DIAGNOSTIC

Neurofibromatosis type 1 (NF-1) is a hereditary disease mainly affecting skin and peripheral nervous system. Individual signs of cutaneous manifestations of NF-1 can imitate or be combined with other neurocutaneous syndromes. At present on the outpatient phase is not always possible to conduct a detailed examination of the patients with NF-1 and to determine the indications for modern diagnostic examination in a specialized hospital. It can be important to verify the diagnosis. The authors presented short review of russian and foreign literature and clinical case of the patient with a specific lesion of the skin against the background of congenital giant melanocytic nevus. Problems of differential diagnosis of NF-1 and congenital giant pigmented nevus were analyzed.

Spitz nevi: diverse clinical, dermatoscopic and histopathological features in childhood.

The characterization of clinical features and biological potential of Spitz nevi has attracted a lot of interest in past decades. The aim of our paper was to describe the clinical, dermatoscopic features as well as the clinical outcome of surgically excised Spitz nevi in three different pediatric age groups. A retrospective study analyzing clinical features, videodermatoscopic images, histopathological diagnosis and patient outcome. The level of pigmentation was evaluated both clinically and histopathologically. 72 spitzoid neoplasms were excised from 71 pediatric patients. Videodermatoscopic images were available for 41 patients. The distribution of pigmentation significantly correlated with patient age: hyperpigmented lesions were rather rare in preschool children, becoming more frequent in patients aged 7 to 12years and older than 13years. The histopathological diagnosis of atypical Spitz nevus was uncommon. None of the patients originally diagnosed with atypical Spitz nevi developed local recurrence or metastases during subsequent follow-up. Pigmented Spitz nevi were more common after 13years of age. The study confirms other reports regarding the distribution of pigmentation patterns, and underlines the low number of atypical Spitz nevi in pediatric patients as well as their low recurrence rate during long-term follow-up.

Histopathological characteristics of melasma

Objective To investigate histopathological and ultrastructural differences between melasma tissues and normal skin tissues around pigmented nevus. Methods Eight patients with melasma and 16 patients with facial pigmented nevus were included in this study. Two millimeter punch biopsies were taken from melasma lesions and adjacent normal skin of facial pigmented nevus. Biopsy specimens were then subjected to hematoxylin-eosin (HE) staining, Fonton-Masson staining, Verhoeff-van Gieson staining, and immunohistochemical staining with monoclonal antibodies HMB45 and NKI/beteb. Transmission electron microscopy was used to observe the tissue specimens. Semi-quantitative analysis was performed under a light microscope, and quantitative analysis by using a computerized image analysis system. Results Histopathological study revealed increased number of melanin granules mainly in the basal and prickle cell layers, sometimes in the dermis, in melasma tissues compared with normal skin tissues. Melanocytes were only observed in the epidermis of melasma tissues. Compared with normal skin tissues, melasma tissues showed no significant difference in the quantity of melanocytes, but a significant increase in the volume, staining intensity and dendrite number of melanocytes. In all of the 8 patients with melasma, mild to moderate lymphocytic infiltration was observed in the superficial dermis and around capillaries, with moderate telangiectasis in the superficial dermis. Electron microscopy revealed that there were more melanosomes in melanocytes and keratinocytes, and melanocyte dendrites extended into the dermis in melasma tissues. Conclusions Among the 8 patients, there were only two types of melasma, i.e., epidermal melasma and mixed melasma, and no dermal melasma was found. Inflammation and telangiectasis may induce or aggravate melasma. Key words: Chloasma; Pathology; Immunohistochemistry; Microscopy, electron, transmission; Inflammation; Telangiectasis

Expression of CC chemokine ligand 18 in cutaneous malignant melanoma tissues and its relationship with vascular endothelial growth factor and Ki67 antigen expressions

Objective To measure the expression of CC chemokine ligand 18 (CCL18) in cutaneous malignant melanoma (CMM) tissues, and to explore its clinical significance, as well as relationship with vascular endothelial growth factor (VEGF) and Ki67 antigen expressions. Methods Immunohistochemistry was performed to measure CCL18, VEGF and Ki67 expressions in 58 paraffin-embedded CMM tissue specimens, as well as CCL18 expression in 20 paraffin-embedded pigmented nevus specimens, and immunofluorescence assay to confirm the expression of CCL18 in fresh CMM tissue specimens. Correlations of CCL18 expression with CMM clinicopathologic features, VEGF and Ki67 expressions were analyzed. Results CCL18 was detected in 49 (84.48%) of 58 paraffin-embedded CMM specimens, but in none of the 20 paraffin-embedded pigmented nevus specimens, with a significant difference in the positive rate of CCL18 between the CMM group and pigmented nevus group (χ2 = 45.46, P 0.05). In addition, the expression of CCL18 in CMM tissues was positively correlated with that of VEGF (rs = 0.727, P 0.05). Immunofluorescence assay showed CCL18 expression in the cytoplasm of tumor cells in CMM tissues. Conclusion CCL18 is highly expressed in CMM tissues, and may be involved in tumor invasion and metastasis. Key words: Nevi and melanomas; Chemokine CCL18; Pathologic processes; Vascular endothelial growth factors; Ki-67 antigen