Imiquimod:A potential option for inhibition of repigmentation of congenital melanocytic nevus after laser ablation

Congenital melanocytic nevi(CMN) are common skin tumors. Large and specially located nevi cannot be completely removed by surgery, posing the risks of both cosmetic deformities and potential malignancy.Nonsurgical treatments, such as laser therapy and physical dermabrasion, can overcome the limitations of surgery;however, the high rate of repigmentation remains an unresolved global challenge. We conducted a self-controlled observational study of a patient with a nevus on the chest. Two areas of the lesion were treated with an Er:YAG laser and 5% imiquimod cream was applied to one of these areas. After nearly 7-months of follow-up, we observed a significant difference in color between the two areas, suggesting that topical imiquimod may inhibit repigmentation and significantly enhance the effectiveness of laser treatment.

Malignant Melanocytic Matricoma and Criteria for Malignancy

Melanocytic matricoma is a very rare adnexal tumor that recapitulates the anagen hair follicle bulb. Few cases of malignant melanocytic matricoma have been reported, thus criteria for malignant potential have not been previously reviewed. We report a case of an 81 year old male that was originally diagnosed as atypical melanocytic matricoma. The site was re-excised with a small focus of residual tumor, but all margins were negative. The re-excision site healed without complication. However, two years after the original biopsy, a new 8 mm firm nodule appeared at the re-excision site, which was subsequently diagnosed as malignant melanocytic matricoma (MMM). In the following paper we will report a new case of MMM and review potential criteria that could be used in the future to establish malignant potential.

Intracranial Intermediate-Grade Melanocytic Neoplasm: Case Report Associated with Nevus of Ota

Melanocytic lesions of the CNS are rare tumours originating from melanocytes that are present in the leptomeninges. They consist of a spectrum of pigmented tumours ranging from melanocytoma to melanoma. A small group of these tumours have histopathological features between those of a benign melanocytoma and a malignant melanoma;these present as intermediate grade melanocytic neoplasms. Naevus of Ota is a blue hyperpigmented dermal lesion characterized by increased number of melanocytes in the distribution of ophthalmic and maxillary divisions of the trigeminal nerve. The association of an intracranial intermediate-grade melanocytic neoplasm with a nevus of Ota is extremely rare, with only 2 cases reported in the literature to date. As a result, their behavior and progression are still poorly understood. We present the first case of a familial naevus of Ota associated with intermediate-grade melanocytic neoplasm.

A Case of Coexistence of Aplasia Cutis Congenita and Giant Congenital Melanocytic Nevus:Coexistence of Two Rare Skin Diseases

Aplasia cutis congenita(ACC)is a rare disease that is characterized by complete or partial absence of skin at birth,either in a localized or widespread region.Melanocytic nevi refers to tumor-like malformations of the skin or mucous membrane caused by benign proliferation of melanocytes.It is classified as a giant congenital melanocytic nevus(GCMN)when the diameter of the largest nevus exceeds 20 cm.The co-occurrence of ACC and GCMN is extremely rare,to the best of our knowledge.We report a case of coexistence of ACC and GCMN of infancy in a 2-month-old male infant.The lesions consisted of a large hyperpigmented plaque occupying most of the trunk and pelvic region,and smaller hyperpigmented plaques on the trunk,head,and extremities.Additionally,there were large,sharply marginated,triangular,depressed atrophic plaques covered by thin,translucent,glistening epithelial membranes in the center of the GCMN on the back.The presumptive diagnosis was coexistence of GCMN and ACC.This could be a manifestation of SCALP syndrome,a rare neuro-cutaneous condition characterized by the presence of Sebaceous nevus,Central nervous system(CNS)malformations,Aplasia cutis congenita,Limbal dermoid and Pigmented(giant melanocytic)nevus.

Paraneoplastic retinopathies: an update on pathogenesis, diagnosis and management

The paraneoplastic retinopathies are a heterogeneous group of disorders with significant visual consequences occuring in the setting of a systemic malignancy.These conditions may be characterized by the presence of antiretinal antibodies and may predate or follow the diagnosis of an underlying malignancy.Herein I review the clinical findings,pathophysiology,laboratory testing and management of the paraneoplastic retinopathies:cancer-associated retinopathy(CAR),melanoma-associated retinopathy(MAR),bilateral diffuse uveal melanocytic proliferation(BDUMP)and paraneoplastic vitelliform maculopathy(PVM).The pathophysiology of the paraneoplastic retinopathies varies from molecular mimicry resulting in anti-retinal antibody production(CAR,MAR)to relases of soluble factors either by the primary tumor(BDUMP)and/or immune system in response to the primary tumor(PVM)which result in retinal and/or retinal pigment epithelium dysfunction.For each condition,structural and functional multimodal retinal testing can be helpful in establishing the diagnosis.Treatment for the paraneoplastic retinopathies involves a combination of treating the underlying malignancy plus additional local and/or systemic immunosuppressive agents though no systemic therapeutic protocols exist.Despite these interventions,the retinopathy may be progressive or the retinopathy may be a harbinger of poor survival.Nevertheless,prompt diagnosis may help identify an underlying malignancy earlier and may thus improve cancer-related survival.

Decoding the Molecular Mechanisms of BRAFV600E-Induced Nevi Formation

Melanocytes derived from neural crest cells harbor the BRAFV600E mutation,which is the predominant driver of nevus formation in humans.This mutation leads to malignant cell proliferation and subsequent cell cycle arrest,culminating in oncogene-induced senescence and nevus development.Nevertheless,emerging evidence has highlighted the heterogeneity of cellular senescence markers in BRAFV600E-induced senescent melanocytes.Moreover,the capacity of melanocytes within nevi to regain their proliferative ability raises questions about the molecular mechanisms by which BRAFV600E,via the mitogen-activated protein kinase signaling pathway,triggers nevus formation.This study provides an overview and discussion of the molecular mechanisms underpinning BRAFV600E-induced melanocyte nevus formation and the relevant animal models employed for their elucidation.It also highlights the significance of elucidating dynamic changes in cytoplasmic and nuclear substrates that interact with phosphorylated extracellular signal-regulated protein kinases 1 and 2 and underscores the value of using targeted BRAFV600E animal models created through gene editing technologies.

MicroRNA-370-5p inhibits pigmentation and cell proliferation by downregulating mitogen-activated protein kinase kinase kinase 8 expression in sheep melanocytes

In mammals,microRNAs(miRNAs)play key roles in multiple biological processes by regulating the expression of target genes.Studies have found that the levels of miR-370-5p expression differ significantly in the skins of sheep with different hair colors;however,its function remains unclear.In this study,we investigated the roles of miR-370-5p in sheep melanocytes and found that the overexpression of miR-370-5p significantly inhibited cell proliferation(P<0.01),tyrosinase activity(P=0.001)and significantly reduced(P<0.001)melanin production.Functional prediction revealed that the 3′-untranslated region(UTR)of MAP3K8 has a putative miR-370-5p binding site,and the interaction between these two molecules was confirmed using luciferase reporter assays.In situ hybridization assays revealed that MAP3K8 is expressed in the cytoplasm of melanocytes.The results of quantitative RT-PCR and Western blotting analyses revealed that overexpression of miR-370-5p in melanocytes significantly inhibits(P<0.01)MAP3K8 expression via direct targeting of its 3′UTR.Inhibition of MAP3K8 expression by siRNA-MAP3K8 transfection induced a significant inhibition(P<0.01)of melanocyte proliferation and significant reduction(P<0.001)in melanin production,which is consistent with our observations for miR-370-5p.Target gene rescue experiments indicated that the expression of MAP3K8 in melanocytes co-transfected with miR-370-5p and MAP3K8-cDNA(containing sites for the targeted binding to miR-370-5p)was significantly rescued(P≤0.001),which subsequently promoted significant increases in cell proliferation(P<0.001)and melanin production(P<0.01).Collectively,these findings indicate that miR-370-5p plays a functional role in inhibiting sheep melanocyte proliferation and melanogenesis by downregulating the expression of MAP3K8.

Not Follicular but Dermal Melanocyte Precursors Are Histopathologically Retained in Vitiligo

Although perifollicular repigmentation in the vitiligo lesions is owing to activation of follicular melanocyte stem cells and/or precursor cells followed by supplying matured melanocytes, the underlying mechanism of diffuse repigmentation on the whole vitiligo surface remains still unknown. In addition to the presence of remaining melanocytes, it is conceivable that dermal melanocyte precursor cells contribute to induce diffuse repigmentation after treatment. Therefore, we investigated here whether dermal and follicular melanocyte precursor cells were reduced or not in vitiligo lesions. We performed an immunostaining for Nestin and p75NGFR as dermal melanocyte precursor cells and MITF/Fzd4 as follicular melanocyte precursor cells and compared the positive cells number between lesions and non-lesions (n = 11). Although MITF+/Fzd4+ cells in the hair follicle were significantly decreased in number in the lesions, Nestin+ and p75NGFR+ cells were not. This result indicates that dermal precursor cells could be retained in the vitiligo lesions but be disturbed to differentiate into matured melanocytes.

A retrospective study of 2228 cases with eyelid tumors

AIM： To describe the histopathologic and clinical features of eyelid tumor cases from Tianjin Eye Hospital during 2002 to 2015. METHODS： In this retrospective study, a total of 2228 cases of eyelid tumors with pathologic diagnoses were enrolled. The eyelid tumors were classified into three groups according to tumor origin： epidermal, adnexal and miscellaneous, including melanocytic, neural and vascular lesions. Inflammatory tumor-like lesions were excluded. The clinical characteristics of the eyelid tumors were analyzed, including age, gender and lesion location. RESULTS： Most eyelid tumors were epidermal in origin（1080, 48.5%）, followed by miscellaneous（885, 39.7%） and adnexal tumors（263, 11.8%）. Among all the tumors, 292（13.1%） were malignant lesions, 1910（85.7%） benign and 26（1.1%） premalignant lesions. Most malignant tumors originated from epidermal cells（60.0%）, followed by adnexal cells（34.6%）. The most common malignant tumors were basal cell carcinomas（56.5%） followed by sebaceous carcinoma（34.6%）, squamous cell carcinomas（3.8%） and lymphoma/plasmocytoma（1.7%）. The benign and premalignant eyelid lesions mostly originated from epidermal cells（46.4%） followed by miscellaneous cell sources（45.2%）, including melanocytic nevus（33.8%）, seborrheic keratosis（13.7%）, squamous cell papilloma（13.0%） and epidermal cysts（11.5%）. CONCLUSION： Eyelid tumors are mostly epithelial in origin. Benign tumors are significantly more common than malignant tumors with an obvious female predominance, and the most frequent malignant tumor are basal cell carcinoma, sebaceous carcinoma and squamous cell carcinomas. The tumor clinical features varied among the different subtypes.

APPLICATION OF HMB－45 MONOCLONAL ANTIBODY AND S100 PROTEIN IN THE IMMUNOHISTOCHEMICAL DIAGNOSIS OF MELANOMA

We tested a variety of fixed embedded sections of malignant tumors with HMB-45 MoAband S-100 polyclonal antibody.The results showed that RMB-45 was a highly sensitive and specificantibody for recongnizing melanoma on fixed paraffin-embedded tissue sections, it reacted with 96.6percent of melanomas tested(all primary and 6 of 7 metastatic lesions)Both pigmented and nonpigmeated melanomas were recongnized.Malignant tumors of epithelial,lymphoid and mesenchymal origin were all negative.Although antibody to S-100 protien quite sensitive,it was not melanome-specific and it reached with all melanomas including the one metastatic melanoma that did not react withHMB-45,it we also positive in one of five lymphomas and one of three sarcomas.AdditionallyHMB-45 reacted with junctional nevi and componentes of compound neai and not with intradermalnevi and the dermal components of compound nevi.

人毛囊无色素性黑素细胞及其治疗白癜风的研究进展

毛囊无色素性黑素细胞可以作为皮肤黑素细胞的储库，给白癜风的治疗提供黑素细胞来源。人黑素细胞（melanocyte，MC）起源于胚胎神经嵴，在胚胎发育2～5周开始向表皮和毛囊移行。向表皮移行的黑素细胞最终定居在基底膜上，形成连续产生黑素的成熟黑素细胞；而向毛囊移行的黑素细胞则分为两种类型：一种是位于生长期毛囊毛母质和漏斗部具有黑素合成活性的黑素细胞；另一种是分布于生长期毛发外毛根鞘（Outer Root Sheath，ORS）中，无黑素合成活性、未活化的无色素性黑素细胞（amelanotic melanocyte，AMMC）。

Differences in MITF gene expression and histology between albino and normal sea cucumbers (Apostichopus japonicus Selenka)

Albino Apostichopus japonicus occur both in the wild and in captivity. The offspring of albino A. japonicus also suffer from albinism. The formation of melanin in the melanocytes is dependant on microphthalmia-associated transcription factor (MITF). To investigate the role of MITF in controlling albinism, we cloned the full-length MITF cDNA from A. japonicus and compared MITF mRNA expression in albino and normal A. japonicus. In addition, we used light and electron microscopy to compare histological samples of normal and albino A. japonicus. The body wall of albino adults was characterized by significantly lower levels of MITF expression and lower numbers of epidermal melanocytes, which also contained less melanin. In albino juvenile offspring, MITF expression levels were significantly lower 32 d after fertilization and there were fewer, and less developed, epidermal melanocytes. Thus, we conclude that albino A. japonicus have fewer melanocytes and a reduced ability to synthesize melanin, likely because of lower expression of MITF.

Distribution and ultrastructure of pigment cells in the skins of normal and albino adult turbot, Scophthalmus Maximus

The distribution and ultrastructure of pigment cells in skins of normal and albino adult turbots were examined with transmission electron microscopy （TEM）. Three types of pigment cells of melanophore, iridophore and xanthophore have been recognized in adult turbot skins. The skin color depends mainly on the amount and distribution of melanophore and iridophore, as xanthophore is quite rare. No pigment cells can be found in the epidermis of the skins. In the pigmented ocular skin of the turbot, melanophore and iridophore are usually co-localized in the dermis. This is quite different from the distribution in larvae skin. In albino and white blind skins of adult turbots, however, only iridophore monolayer still exists, while the melanophore monolayer disappears. This cytological evidence explains why the albino adult turbot, unlike its larvae, could never resume its body color no matter what enviroumental and nutritional conditions were provided. Endocytosis is quite active in the cellular membrane of the iridophore. This might be related to the formation of reflective platelet and stability of the iridophore.

Dorsal root ganglion-derived Schwann cells combined with poly(lactic-co-glycolic acid)/chitosan conduits for the repair of sciatic nerve defects in rats

Schwann cells, nerve regeneration promoters in peripheral nerve tissue engineering, can be used to repair both the peripheral and central nervous systems. However, isolation and puriifcation of Schwann cells are complicated by contamination with ifbroblasts. Current reported measures are mainly limited by either high cost or complicated procedures with low cell yields or purity. In this study, we collected dorsal root ganglia from neonatal rats from which we obtained highly puriifed Schwann cells using serum-free melanocyte culture medium. The purity of Schwann cells （〉95%） using our method was higher than that using standard medium containing fetal bovine serum. The obtained Schwann cells were implanted into poly（lactic-co-glycolic acid）/chi-tosan conduits to repair 10-mm sciatic nerve defects in rats. Results showed that axonal diameter and area were signiifcantly increased and motor functions were obviously improved in the rat sciatic nerve tissue. Experimental ifndings suggest that serum-free melanocyte culture medium is conducive to purify Schwann cells and poly（lactic-co-glycolic acid）/chitosan nerve conduits combined with Schwann cells contribute to restore sciatic nerve defects.

Follicle and melanocyte stem cells, and their application in neuroscience A Web of Science-based literature analysis

OBJECTIVE： To identify global research trends of follicle and melanocyte stem cells, and their application in neuroscience. DATA RETRIEVAL： We performed a bibliometric analysis of studies from 2002 to 2011 on follicle and melanocyte stem cells, and their application in neuroscience, which were retrieved from the Web of Science, using the key words follicle stem cell or melanocyte stem cell, and neural, neuro or nerve. SELECTION CRITERIA： Inclusion criteria： （a） peer-reviewed published articles on follicle and melanocyte stem cells, and their application in neuroscience, which were indexed in the Web of Science; （b） original research articles, reviews, meeting abstracts, proceedings papers, book chapters, editorial material, and news items. Exclusion criteria： （a） articles that required manual searching or telephone access; （b） documents that were not published in the public domain; and （c） a number of corrected papers from the total number of articles. MAIN OUTCOME MEASURES： （1） Distribution of publications on follicle and melanocyte stem cells by years, journals, countries, institutions, institutions in China, and most cited papers. （2） Distribution of publications on the application of follicle and melanocyte stem cells in neuroscience by years, journals, countries, institutions, and most cited papers. RESULTS： Of the 348 publications from 2002 to 2011 on follicle and melanocyte stem cells, which were retrieved from the Web of Science, more than half were from American authors and institutes. The most prolific institutions in China for publication of papers on follicle and melanocyte stem cells were the Fourth Military Medical University and Third Military Medical University. The most prolific journals for publication of papers on follicle and melanocyte stem cells were the Journal of Investigative Dermatology, Pigment Cell ＆ Melanoma Research. Of the 63 publications from 2002 to 2011 on the application of follicle and melanocyte stem cells in neuroscience, which were retrieved from the Web of Science, more than half were from American authors and institutes, and no papers were from Chinese authors and institutes. The most prolific journals for publication of papers on the application of follicle and melanocyte stem cells in neuroscience were the Journal of Investigative Dermatology, Pigment Cell ＆ Melanoma Research. CONCLUSION： Based on our analysis of the literature and research trends, we found that follicle stem cells might offer further benefits in neural regenerative medicine.

Effect of Xiaobailing Decoction on Melanocytes in Vitro

To observe the effect of Xiaobailing Decoction （消白灵汤） on murine melanocytes in vitro and to explore the mechanism of Xiaobailing Decoction in the treatment of vitiligo. Methods： B-16F10 murine melanoma cells were cultured in 1640 medium and treated respectively with different concentrations （lmg/ml, 2mg/ml, 3mg/ml） of the Chinese drug Xiaobailing Decoction and its main components, the drugs for replenishing the lddney-yang, and the drugs for nourishing blood and activating blood circulation, etc. for 7 days. MMT assay was used to determine the proliferation of B-16F10 murine melanoma cells. NaOH cleavage assay was adopted to measure the melanogenesis of melanocytes. Results：Xiaobailing Decoction, the drugs for replenishing the kidney-yang and the drugs for nourishing blood and activating blood circulation at different concentrations significantly improved the proliferation of B-16F10 murine melanoma cells from the 3rd day to the 5th day （P〈0.05）, with Xiaobailing Decoction at the concentrations of lmg/ml having the most distinct action on promoting the proliferation of melanocytes on the 3rd day （P〈0.001）; And the drugs for replenishing the lodney-yang at the concentrations of 2mg/ml and 3mg/ml and the drugs for nourishing blood and activating blood circulation at 3mg/ml significantly increased melanogenesis of melanocytes （P〈0.05）. Conclusion： Xiaobailing Decoction can promote melanocytic proliferation and melanogenesis in vitro, and it is indicated that the drugs for replenishing the kidney-yang and the drugs for nourishing blood and activating blood circulation play an important role in treating vitiligo.

Direct Transplant of Melanocytes from Normal Donor Area into Vitiligenous Recipient Area by Intralesional Injection of Melanocytes Using Spade Like Needle Technique

Background: Vitiligo is a common autoimmune inflammatory skin disease, where there are different surgical techniques for treatment of stable patches of vitiligo .Objective: To find non-costly, minimally invasive, simple technique by direct melanocytes transplant by spade needle technique in treatment of vitiligo. Patients and Methods: This interventional, therapeutic, comparative study was done in Department of Dermatology, Baghdad Teaching Hospital, Baghdad, Iraq from April 2014-March 2015. Twenty patients with localized, generalized and segmental vitiligo were included. Full history and examination for each patient was done with 4 (20%) males and 16 (80%) females and their ages ranged from 9 - 40 (23.15 ± 11.44) years. Forty one patches in 20 patients treated by spade grafting technique and the donor and recipient sites were demarcated and anesthesia done by xylocaine 2% with adrenalin 1:100,000. Transplantation was started by using disposable needle gauge 18 (the sharp end of needle was cut by a scissor to make it a spade like) with medical syringe 5 ml supplied with normal saline. The micro-pieces were taken from donor site and transplanted directly, easily and rapidly into dermis of recipient site and followed by pushing normal saline and the procedure was repeated to cover all recipient sites with 5 mm distance between injection points. The surface area of the lesions was calculated and the reduction rate was estimated every month till the end of the 4th month period of the treatment. Results: Including 41 patches in 20 patients with the surface area of the patches ranged from 1.5 - 90 cm2 (13.78 ± 17.57) cm2. The mean ±SD of surface area of lesions was decreased from 13.78 ± 17.57 cm2 at baseline visit to 13.61 ± 17.48 cm2 at the second visit (after 2 weeks ) which was statistically significant (p value ≤ 0.001). The mean surface area continued to be reduced till reaching 12.20 ± 15.68 cm2 at the third visit and 12.01 ± 15.55 cm2 at the fourth visit. All were statistically significant when compared to baseline visit. There was reduction in surface area 1.1% at two weeks, 9.93%, and 12.5% at the 2nd, 4th months respectively. Conclusions: Intradermal injection of melanocytes in patients with vitiligo by spade like needle was very quick and simple non-costly technique, and gave 12.5% reduction which could be repeated at different times until satisfactory re-pigmentation of vitiligenous skin is achieved.

EFFECTS OF BU GU ZHI(PSORALEA CORYLIFOLIA L) AND BAI ZHI(DAHURIAN ANGELICA ROOT) EXTRACTS ON MELANOCYTE ADHESION AND MIGRATION

Objective To find direct effect of Chinese herbs Bu Gu Zhi (Psoralea corylifolia L) and Bai Zhi (Dahurian angelica root) Extracts on melanocyte adhesion and migration in vitro. Methods Ethanol extracts obtained from two kind of Chinese medicinable herbs were tested. Human melanocytes were obtained from neonatal foreskins and 48-well culture dish covered with fibronectin were used to perform melanocyte adhesion assay; Motility was assessed using the micropore filter method. Results: The extracts of Bu Gu Zhi(Psoralea corylifolia L), Bai Zhi(Dahurian angelica root) obviously showed an effect in increasing of human melanocyte adhesion and migration on fibronectin. Conclusion It is suggested that Buguzhi(Fructus Psoraleae) and Baizhi(Radix Angelicae Dahuricae) might induce melanocyte adhesion and/or migration in the treatment of vitiligo.

Difficulties in diagnosing anorectal melanoma: A case report and review of the literature

BACKGROUND Anorectal melanoma is a tumour that is difficult to identify due to its rarity and variability of presentation.Insufficient data published in the literature do not allow for diagnostic and treatment guidelines to be established.Anorectal melanoma has the worst prognosis among mucosal melanomas and is frequently misdiagnosed by standard identification methods.CASE SUMMARY A 66-year-old woman presented with intermittent anal bleeding,pain,and tenesmus in the past month,with no associated weight loss.Colonoscopy revealed a cauliflower-like tumour with a diameter of 1.5 cm,with exulcerated areas and an adherent clot but without obstruction.Biopsy results identified an inflammatory rectal polyp with nonspecific chronic rectitis.Tumour markers CA 19-9 and CEA were within the normal range.After 6 mo,due to the persistence of symptoms,a pelvic magnetic resonance imaging scan was performed.A lesion measuring 2.8 cm×2.7 cm×2.1 cm was identified at the anorectal junction,along with two adjacent lymphadenopathies.No distant metastases were detected.Immunohistochemistry was performed on the second set of biopsies,and a diagnosis of anorectal melanoma was established.Surgical treatment by abdominoperineal resection was performed.Evolution was marked by the appearance of lung metastases at 1 mo postoperatively,detected on a positron emission tomography-computer tomography scan,and perineal recurrence after 5 mo.After molecular testing,the patient was included in an immunotherapy trial.CONCLUSION This case highlights the difficulty of establishing a definitive early diagnosis of anorectal melanoma,the importance of performing histological analysis on a wellrepresented biopsy specimen,and the poor prognosis,even with radical surgery.