Dermal Melanocytes Research Articles

GD2 in Breast Cancer: A Potential Biomarker and Therapeutic Target.

Expression of disialoganglioside GD2 in normal tissues is primarily limited to the central nervous system, peripheral sensory nerve fibers, dermal melanocytes, lymphocytes, and mesenchymal stem cells. Its widespread overexpression in various cancer types allows it to be classified as a tumor-associated antigen with potential diagnostic and therapeutic implications. This article reviews the synthesis pathways of GD2 and its role in cancer cell adhesion, proliferation, and metastasis with a focus on breast cancer. GD2 appears to be overexpressed on the outer membrane of most breast cancer cells and breast cancer stem cells (BCSCs) and is closely linked to epithelial-mesenchymal transition (EMT). GD3 synthase (GD3S) is considered to be the rate-determining step in GD2 synthesis. Clinical studies indicate that GD2 expression is increased in 35-70% of breast cancer samples, with higher levels in triple-negative breast cancer (TNBC). This overexpression correlates with more aggressive tumor features and worse prognosis. Therapeutic targeting of GD2 with monoclonal antibodies (moABs) like dinutuximab and naxitamab has demonstrated anti-cancer activity in preclinical cancer models and human clinical trials against high-risk neuroblastoma reducing tumor growth and enhancing survival. GD2-specific chimeric antigen receptor (CAR) T-cell therapy and GD3S inhibition present other promising therapeutic strategies to improve clinical outcomes. Furthermore, GD2-targeted vaccines are currently being investigated in cancer therapy. This narrative review article underscores the critical role of GD2 in breast cancer pathogenesis and highlights the promising therapeutic opportunities it offers. It advocates for the initiation of clinical trials to further explore the potential of GD2-targeted treatment in combination with standard breast cancer therapies.

A Review of Dermal Melanocytosis

Abstract Dermal melanocytosis is a histological term used to describe a clinical spectrum of cutaneous diseases which present as bluish-gray pigmentation of the skin. The most common forms include the Mongolian spot (MS), nevus of Ota, nevus of Ito, and dermal melanocyte hamartoma sharing similar etiologies and histologic findings but different associations and prognosis. Although these lesions usually resolve by 1 to 2 years of age, widespread aberrant MSs, nevus of Ota, and nevus of Ito can persist into adulthood and can become a great concern for the patients regarding the pigmentation and health risk associated with the same. An extensive literature search was done; all clinical trials, randomized double-blind or single-blind controlled trials, open-label studies, retrospective studies, reviews, case series, and case reports concerned with dermal melanocytosis were screened. The selected articles were retrieved; the final manuscript was prepared, analyzed, and presented in a narrative fashion.

Signalling by senescent melanocytes hyperactivates hair growth

Niche signals maintain stem cells in a prolonged quiescence or transiently activate them for proper regeneration1. Altering balanced niche signalling can lead to regenerative disorders. Melanocytic skin nevi in human often display excessive hair growth, suggesting hair stem cell hyperactivity. Here, using genetic mouse models of nevi2,3, we show that dermal clusters of senescent melanocytes drive epithelial hair stem cells to exit quiescence and change their transcriptome and composition, potently enhancing hair renewal. Nevus melanocytes activate a distinct secretome, enriched for signalling factors. Osteopontin, the leading nevus signalling factor, is both necessary and sufficient to induce hair growth. Injection of osteopontin or its genetic overexpression is sufficient to induce robust hair growth in mice, whereas germline and conditional deletions of either osteopontin or CD44, its cognate receptor on epithelial hair cells, rescue enhanced hair growth induced by dermal nevus melanocytes. Osteopontin is overexpressed in human hairy nevi, and it stimulates new growth of human hair follicles. Although broad accumulation of senescent cells, such as upon ageing or genotoxic stress, is detrimental for the regenerative capacity of tissue4, we show that signalling by senescent cell clusters can potently enhance the activity of adjacent intact stem cells and stimulate tissue renewal. This finding identifies senescent cells and their secretome as an attractive therapeutic target in regenerative disorders.

Bilateral nevus of Ota – A rare clinical presentation

Nevus of Ota is a rare congenital hamartoma of the dermal melanocytes causing a blue-grey hyperpigmentation of the eye and adnexa. The condition is usually unilateral but rarely it can be bilateral. A 28-year-old lady from West Bengal, India, visited the Ophthalmology outpatient department with the complaints of blackish discoloration of left side of the face and periorbital region. On examination, a large (5x6 cm) lesion was noted on the skin of the left side of face, forehead, sclera, lower palpebral conjunctiva, ala of nose, hard palate along with sclera and iris of the right eye. Cutaneous examination revealed that the lesion is unilateral diffuse, homogenous, blue-gray colored macular pigmentation with ill-defined borders. The lesions do not undergo spontaneous regression, but the intensity of the blue-black discolored lesions may vary during menstruation, fatigue or change in weather. The patient needs to be followed up annually, checking at each visit for visual acuity, biomicroscopy, intraocular pressure, gonioscopy and fundus examination. A thorough knowledge of the disease process, possible complications and screening protocol can help the ophthalmologist to pick up sight threatening complications early, initiate prompt treatment which may avert possible visual loss.

Canine melanocytes: Immunohistochemical expression of melanocytic markers in different somatic areas.

Melanoblasts originate in the neural crest from where they migrate to peripheral tissues and differentiate into melanocytes. Alteration during melanocyte development and life can cause different diseases, ranging from pigmentary disorders and decreased visual and auditory functions, to tumours such as melanoma. Location and phenotypical features of melanocytes have been characterised in different species, yet data on dogs are lacking. This study investigates the expression of melanocytic markers Melan A, PNL2, TRP1, TRP2, SOX-10 and MITF in melanocytes of selected cutaneous and mucosal surfaces of dogs. At necropsy, samples from five dogs were harvested from oral mucosa, mucocutaneous junction, eyelid, nose and haired skin (abdomen, back, pinna, head). Immunohistochemical and immunofluorescence analyses were performed to assess marker expression. Results showed variable expression of melanocytic markers in different anatomical sites, particularly within epidermis of haired skin and dermal melanocytes. Melan A and SOX-10 were the most specific and sensitive melanocytic markers. PNL2 was less sensitive, while TRP1 and TRP2 were seldomly expressed by intraepidermal melanocytes in haired skin. MITF had a good sensitivity, yet the expression often was weak. Our results indicate a variable expression of melanocytic markers in different sites, suggesting the presence of subpopulations of melanocytes. These preliminary results pave the way to understanding the pathogenetic mechanisms involved in degenerative melanocytic disorders and melanoma. Furthermore, the possible different expression of melanocyte markers in different anatomical sites could influence their sensitivity and specificity when used for diagnostic purposes.

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 Case Series With Acquired Dermal Melanocytosis: A Retrospective Study From 2001 to 2018.

Acquired dermal melanocytosis (ADM) is a pigmented lesion caused by melanocytes in the dermis, and it is most often observed on the face of young and middle-aged Asian women. ADM development may be associated with melanin synthesis alterations, but little evidence of its molecular and histological alteration has yet been reported. This study aimed to evaluate ADM in different body locations using different immunohistochemical and chemical staining techniques. This retrospective case series includes consecutive patients confirmed as ADM by biopsy between 2001 and 2018. Patient data and archival images were used to determine the pattern and duration of skin lesions, as confirmed by data analysis of immunohistopathological staining of skin biopsy specimens. A total of 22 ADM patients were included with mean age at diagnosis of 47 years, and 63.6% were female. The most common site was limbs (36.4%), followed by face (27.3%), trunk (22.7%), and scalp (13.6%). Melanin levels were highest in the face and upper extremities and lowest in the trunk. All participants had perivascular distribution of dermal melanocytes, particularly on the face and limbs. The perineural distribution of dermal melanocytes was observed in the lower limbs, with prominent inflammation and fibrosis on the scalp. Dermal melanocytes expressed most markers recognizing melanocytes except for CD117. Analysis of this ADM case series has confirmed that melanin is activated by dermal melanocytes that may aggregate along blood vessels. CD117 may be a useful biomarker by which to identify the migration of epidermal melanocytes.

The Assessment of Meloxicam Phototoxicity in Human Normal Skin Cells: In Vitro Studies on Dermal Fibroblasts and Epidermal Melanocytes.

Meloxicam (MLX), which belongs to the oxicam nonsteroidal anti-inflammatory drug derivatives, is an inhibitor of the cyclooxygenase-2 (COX-2) enzyme. Cutaneous adverse effects caused by interaction between UVA radiation and exogenous factors can manifest as phototoxic reactions. Phototoxicity may be a reason for the accumulation of genetic and molecular changes in long-lived cells with low proliferation potential, leading to tumor development. There are several potentially phototoxic drugs, the active component of which is meloxicam. The research aimed to evaluate the influence of MLX and UVAR on skin cells—fibroblasts and melanocytes homeostasis. The obtained results indicated that co-treatment with MLX and UVAR inhibited skin cell proliferation, proportionally to the drug concentration. The observation was confirmed by cytometric analysis of the cell number and viability. The phototoxic effect of MLX was revealed in morphological changes. It was stated that MLX with UVAR lowered the mitochondrial transmembrane potential and changed the cell cycle profile. Additionally, MLX and UVAR caused the disruption of redox homeostasis by lowering the intracellular level of reduced thiols. The presented study revealed that the phototoxic activity of MLX is associated with oxidative stress induction and disruptions in cell homeostasis. The differences in the phototoxic effects of MLX at the cellular level may be related to the different content of melanin pigments.

Pharmacological Modulation of Melanocortin 1 Receptor Signaling by Mrap Proteins in Xenopus tropicalis.

The melanocortin system consists of five G protein–coupled receptors (MC1R-MC5R), the bidirectional endogenous ligands (MSH and Agouti families), and accessory proteins (MRAP1 and MRAP2). Accumulative studies of vertebrate species find high expression level of melanocortin 1 receptor (MC1R) in the dermal melanocyte and elucidate the essential roles in the skin and fur pigmentation, morphological background adaptation, and stress response. The diploid amphibian Xenopus tropicalis (xt) has been utilized as a fantastic animal model for embryonic development and studies of physiological cryptic colouring and environmental adaptiveness. However, the interaction of xtMc1r signaling with xtMrap proteins has not been assessed yet. In this study, we carried out in silico evolutionary analysis of protein alignment and genetic phylogenetic and genomic synteny of mc1r among various vertebrates. Ubiquitous expression of mrap1 and mrap2 and the co-expression with mc1r transcripts in the skin were clearly observed. Co-immunoprecipitation (ip) and fluorescent complementary approach validated the direct functional interaction of xtMc1r with xtMrap1 or xtMrap2 proteins on the plasma membrane. Pharmacological assay showed the improvement of the constitutive activity and alpha melanocyte-stimulating hormone (α-MSH) stimulated plateau without dramatic alteration of the cell surface translocation of xtMc1r in the presence of xtMrap proteins. Overall, the pharmacological modulation of xtMc1r by dual xtMrap2 proteins elucidated the potential role of this protein complex in the regulation of proper dermal function in amphibian species.

Steroidogenic Factor-1 Lineage Origin of Skin Lesions in Carney Complex Syndrome

Carney complex is a rare familial multineoplastic syndrome predisposing to endocrine and nonendocrine tumors due to inactivating mutations of PRKAR1A, leading to perturbations of the cAMP‒protein kinase A signaling pathway. Skin lesions are the most common manifestation of Carney complex, including lentigines, blue nevi, and cutaneous myxomas in unusual locations such as oral and genital mucosa. Unlike endocrine disorders, the pathogenesis of skin lesions remains unexplained. In this study, we show that embryonic invalidation of the Prkar1a gene in steroidogenic factor-1‒expressing cells leads to the development of familial skin pigmentation alterations, reminiscent of those in patients with Carney complex. Immunohistological and molecular analyses, coupled with genetic monitoring of recombinant cell lineages in mouse skin, suggest that familial lentiginosis and myxomas occur in skin areas specifically enriched in dermal melanocytes. In lentigines- and blue nevi‒prone areas from mutant mice and patients, Prkar1a/PRKAR1A invalidation occurs in a subset of dermal fibroblasts capable of inducing, under the influence of protein kinase A signaling, the production of promelanogenic EDN3 and hepatocyte GF signals. Our model strongly suggests that the origin of the typical Carney complex cutaneous lesions is the result of noncell-autonomous promelanogenic activity of a dermal fibroblast population sharing a community of origin with steroidogenic factor-1 lineage.

Toxicité oculaire des thérapies ciblées anti-MEK et anti-BRAF dans le traitement des mélanomes cutanés métastatiques

Cutaneous melanoma is a malignant tumor, which develops from dermal melanocytes. Targeted therapies have changed the therapeutic management of metastatic melanoma and improved the survival rate. Among the various targeted therapies, MEK inhibitors and BRAF inhibitors have demonstrated efficacy, but they may lead to ocular toxicity. The goal of this study was to assess the incidence of ocular complications caused by the use of MEK inhibitors and BRAF inhibitors and to report their clinical features and therapeutic management. This retrospective, observational, descriptive, single center study was conducted between May 2015 and December 2019 and included all patients with metastatic cutaneous melanomas treated with MEK inhibitors and BRAF inhibitors in whom ophthalmic toxicity was suspected. The data collected were demographic data (age, sex), the type of MEK inhibitors and BRAF inhibitors used, the length of time from melanoma diagnosis, mean duration of ophthalmological follow-up, time differential between starting therapy and the emergence of ocular complications, initial and final logMAR visual acuity, biomicroscopic examination of the anterior segment, dilatated fundus examination, and treatment administered. Fifty-four eyes of 27 patients with a mean age of 61.3±14.3 were included. The mean time delay between melanoma diagnosis and initiation of treatment was 23.2±8 months. Twenty patients (74%) were treated with a combination of MEK inhibitors and BRAF inhibitors (trametinib/dabrafenib), 5 patients (19%) were treated with MEK inhibitor monotherapy (cobimetinib), and 2 patients (7%) were treated with BRAF inhibitor monotherapy (vemurafenib). The mean duration of ophthalmological follow-up was 77.8±29 days, and the delay between the start of therapy and the emergence of symptoms was 87.2±78 days. The mean initial visual acuity was 0.075±0.13 logMAR, and the final visual acuity was 0.01±0.03 logMAR. Twelve patients (44%) developed ocular complications due to the targeted therapy. In the patients who received combination trametinib/dabrafenib, 5 patients (18.5%) developed clinical signs of uveitis, from acute anterior uveietis to panuveitis, and 2 patients (7.4%) developed bilateral central serous chorioretinopathy; in the patients who received cobimetinib, 4 patients (14.8%) developed bilateral central serous chorioretinopathy; and one patient (3.7%) who received vemurafenib developed acute anterior uveitis. For these 12 patients with ophthalmic side effects, temporary discontinuation of therapy was chosen for six patients (22.2%), three patients (11.1%) received half the initial dose, and for three patients (11.1%), normal dosing was continued. The two main side effects of targeted therapies are uveitis for BRAF inhibitors and central serous chorioretinopathy for MEK inhibitors. A multidisciplinary approach including ophthalmologists, dermatologists and oncologists is essential in order to adapt treatment in the advent of these ocular complications.

Subungual melanoma with blue naevus-like morphological features: a clinicopathological retrospective analysis of nine cases

Melanocytic lesions in the nail apparatus are often challenging. Both subungual melanomas (SUM) and blue naevus of the nail are very rare. Occasionally, melanomas may mimic blue naevus histologically. Benign and malignant blue melanocytic lesions are commonly associated with G protein mutations, a distinct abnormality not associated with conventional subungual melanomas. We describe the clinical, histological and immunohistochemical features of nine cases of SUM with blue naevus-like morphological features. Mutations in exon 4 and 5 of GNAQ and GNA11 were investigated in two cases, which showed no mutations. RNA-seq of one case revealed unknown mutations along with mutations in ATM, METK and ARID1A. Our study delineates a variant of SUM that mimics blue naevus. Awareness of this pitfall is important when evaluating heavily pigmented lesions around the nail in order to avoid misdiagnosis. Appropriate sampling of subungual lesions and clinicopathological correlation are paramount to reach the correct diagnosis.

Agminated blue nevi: a case series and updated dermoscopic review.

Blue nevi, usually presenting as solitary, bluish, asymptomatic macules or nodules, are formed by collections of dermal melanocytes that failed to complete their migration from the neural crest to the dermo-epidermal junction. The term "agminated blue nevi" refers to multiple lesions grouped, linear, or arranged in a blashkoid distribution. It is a relatively rare phenomenon with less than 35 cases reported in the literature, but only 14 cases with dermoscopic features. We report another 4 cases along with an updated dermoscopic review.

SFRP4 Expression Is Linked to Immune-Driven Fibrotic Conditions, Correlates with Skin and Lung Fibrosis in SSc and a Potential EMT Biomarker.

Secreted Frizzled Receptor Protein 4 (SFRP4) has been shown to be increased in Scleroderma (SSc). To determine its role in immune-driven fibrosis, we analysed SSc and sclerotic Chronic Graft Versus Host Disease (sclGVHD) biosamples; skin biopsies (n = 24) from chronic GVHD patients (8 with and 5 without sclGVHD), 8 from SSc and 3 healthy controls (HC) were analysed by immunofluorescence (IF) and SSc patient sera (n = 77) assessed by ELISA. Epithelial cell lines used for in vitro Epithelial-Mesenchymal-Transition (EMT) assays and analysed by Western Blot, RT-PCR and immunofluorescence. SclGVHD skin biopsies resembled pathologic features of SSc. IF of fibrotic skin biopsies indicated the major source of SFRP4 expression were dermal fibroblasts, melanocytes and vimentin positive/caveolin-1 negative cells in the basal layer of the epidermis. In vitro studies showed increased vimentin and SFRP4 expression accompanied with decreased caveolin-1 expression during TGFβ-induced EMT. Additionally, SFRP4 serum concentration correlated with severity of lung and skin fibrosis in SSc. In conclusion, SFRP4 expression is increased during skin fibrosis in two different immune-driven conditions, and during an in vitro EMT model. Its serum levels correlate with skin and lung fibrosis in SSc and may function as biomarker of EMT. Further studies are warranted to elucidate the role of SFRP4 in EMT within the pathogenesis of tissue fibrosis.

The Rise of Induced Pluripotent Stem Cell Approach to Hair Restoration.

The advent of pluripotent stem cells following the discovery of Shinya Yamanaka (2012 Nobel prize in Medicine) brought about a regenerative medicine approach to virtually every human condition including hair loss. It is now possible to reprogram somatic cells (eg, blood or skin cells) from a person experiencing hair loss to generate autologous induced pluripotent stem cells (iPSCs), which could be amplified and cryopreserved. Subsequently, these iPSCs could be differentiated into various cell types such as dermal papilla cells, epithelial cells, melanocytes, and other cell types constituting functional hair follicle. Transplantation of human iPSC-derived folliculogenic cells into the nude mice has successfully generated xenografts with hair outgrowth. Because iPSCs provide a virtually unlimited source of folliculogenic cells for de novo formation of hair follicles, this approach has major advantages over current surgical hair restoration procedures, which merely redistribute existing hair follicles from one part of the sculp to another. Combined with robotics and automation of the transplantation process, this novel regenerative medicine approach is well poised to make hair restoration a routine procedure affordable for everybody who can benefit from it.

Diffuse PRAME Expression Is Highly Specific for Thin Melanomas in the Distinction from Severely Dysplastic Nevi but Does Not Distinguish Metastasizing from Non-Metastasizing Thin Melanomas.

Simple SummaryHistological diagnoses within the spectrum from moderately dysplastic nevi to thin melanomas are neither accurate nor reproducible, emphasizing the need for more objective supplemental immunohistochemical markers. PRAME immunohistochemistry aids in differentiating unequivocal melanomas from unequivocal nevi. The aim of our study was to determine whether PRAME IHC also allows differentiation of severely dysplastic nevi from thin melanomas and whether PRAME is of prognostic significance in thin melanomas. We studied 70 thin melanomas, of which 35 metastasized and 35 did not metastasize and 35 severely dysplastic nevi. We found that diffuse PRAME expression was highly specific but only moderately sensitive for thin melanomas. Melanomas and severely dysplastic nevi with PRAME immunoreactivity had different staining patterns. Most Melanomas demonstrated diffuse PRAME staining of intraepidermal and dermal melanocytes while most severely dysplastic nevi showed a decreasing gradient with depth. PRAME did not allow for the differentiation of metastasizing and non-metastasizing melanomas.Background: PReferentially expressed Antigen in MElanoma (PRAME) immunohistochemistry is increasingly used as diagnostic adjunct in the evaluation of melanocytic tumors. The expression and prognostic significance of PRAME in melanomas ≤1.0 mm and its diagnostic utility in the distinction from severely dysplastic compound nevi (SDN) have not been studied. Methods: We investigated and compared the immunohistochemical PRAME expression in 70 matched thin metastasizing and non-metastasizing melanomas and 45 nevi from patients with long-term follow-up (35 SDN and 10 unequivocally benign compound nevi). Results: Diffuse PRAME staining in >75% of lesional epidermal and dermal melanocytes identified 58.6% of thin melanomas but did not distinguish metastasizing from non-metastasizing melanomas (p = 0.81). A superficial atypical melanocytic proliferation of uncertain significance, in which the final diagnostic interpretation favored a SDN was the only nevus with diffuse PRAME expression (1/45). Melanomas and SDN with PRAME immunoreactivity exhibited different staining patterns. Most melanomas (67.6%) showed uniform PRAME expression in the in situ and invasive component, whereas most SDN (81.0%) showed a decreasing gradient with depth. Conclusion: Diffuse intraepidermal and dermal PRAME staining is highly specific for melanomas in the distinction from SDN. PRAME expression is not a prognostic biomarker in melanomas ≤1.0 mm.

Dermal papilla cells and melanocytes response to physiological oxygen levels depends on their interactions.

BackgroundHuman dermal papilla (DP) cells and melanocytes (hMel) are central players in hair growth and pigmentation, respectively. In hair follicles (HFs), oxygen (O2) levels average 5%, being coupled with the production of reactive oxygen species (ROS), necessary to promote hair growth.Materials and MethodsDP cell and hMel proliferation and phenotype were studied under physiological (5%O2, physoxia) or atmospheric (21%O2, normoxia) oxygen levels. hMel‐DP cells interactions were studied in indirect co‐culture or by directly co‐culturing hMel with DP spheroids, to test whether their interaction affected the response to physoxia.ResultsPhysoxia decreased DP cell senescence and improved their secretome and phenotype, as well as hMel proliferation, migration, and tyrosinase activity. In indirect co‐cultures, physoxia affected DP cells’ alkaline phosphatase (ALP) activity but their signalling did not influence hMel proliferation or tyrosinase activity. Additionally, ROS production was higher than in monocultures but a direct correlation between ROS generation and ALP activity in DP cells was not observed. In the 3D aggregates, where hMel are organized around the DP, both hMel tyrosinase and DP cells ALP activities, their main functional indicators, plus ROS production were higher in physoxia than normoxia.ConclusionsOverall, we showed that the response to physoxia differs according to hMel‐DP cells interactions and that the microenvironment recreated when in direct contact favours their functions, which can be relevant for hair regeneration purposes.

Engineered Protein Nanocages for Targeted and Enhanced Dermal Melanocyte Cellular Uptake

Hyperpigmentation is a major cosmetic concern that results from the overproduction of melanin from melanocyte cells in the skin. Current formulations of therapeutic drugs and active molecules that are intended to be delivered to the melanocytes are not targeted, leading to inefficient delivery and undesirable side effects. There is a compelling need for delivery vehicles that target melanocytes to effectively regulate melanin production. Self‐assembling protein nanocages (PNCs) have been shown to offer safe and efficient delivery of active molecules. They are versatile protein nanoparticle platforms that can be engineered to display functional ligands to impart specific biological functions. In this work, E2 PNCs are engineered to display alpha‐melanocyte‐stimulating hormone (AlphaMSH) peptides as ligands for targeting and enhancing uptake by melanocytes. At 500 pM, the AlphaMSH‐modified E2 PNCs show 4‐fold increase in melanocyte cell uptake compared to bare E2 PNCs in 2 hours. This increase was less pronounced in keratinocytes. Competitive inhibition assay proves that the MC1R melanocyte cell surface receptor facilitates the uptake of E2 PNCs by mediating interaction with the displayed AlphaMSH peptides. PNCs can thus be used as targeted delivery vehicles of drugs and active molecules to melanocytes for the management of hyperpigmentation.

Angiotropic melanocytes: Possibly a distinctive finding in extra-facial acquired dermal melanocytosis.

Acquired dermal melanocytosis is a heterogenous group of hyperpigmented lesioins which predominantly involve the face. The aim of this study was to study the clinical presentation and histopathology of cases with extra-facial acquired dermal melanocytosis. Retrospective record analysis was performed between May 2016 to August 2019 to retrieve cases of extra-facial acquired dermal melanocytosis seen at the out-patient department of dermatology at the All India Institute of Medical Sciences, Jodhpur. Consecutive cases with histopathologically proven diagnosis of acquired dermal melanocytosis were included. Documentation of variation in clinical presentation and histopathologic findings was done in light of the existing literature. Overall, four cases of extra-facial acquired dermal melanocyosis (female:male = 1:3) were seen during the study period. The lone case on head and neck involved the ear lobule and peri-auricular area. The other three cases had involvement of the hand. The histopathology confirmed the diagnosis of dermal melanocytosis but revealed peculiar findings of angiotropic melanocytes and dilated capillaries. Small sample size and lack of comparison with perilesional normal skin were the limitations of this study. The findings of angiotropic melanocytes may be unique to extra-facial acquired dermal melanocytosis. This might indicate interaction between dermal melanocytes and capillary endothelial cells. This finding along with dermal capillary ectasia may indicate a possible role for vascular lasers in the management of these disorders.

Histological and Immunohistochemical Changes of Congenital Melanocytic Nevi With Age.

Clinical but not histological changes of congenital melanocytic nevi (CMN) with age are well characterized. Our objective was to analyze histological changes of CMN with age and discuss possible clinical implications of our findings. We investigated serial excisions of 21 patients with CMN and compared histological and immunohistochemical features over time. The median number of serial excisions was 6 [interquartile range (IQR) 5-7], the median age at the first excision was 12 months (IQR 5-98), and the median time between the first and last analyzed excision was 53 months (IQR 45-64). The projected adult size of the excised CMN was "large" or "giant" in 14 of the 21 CMN (67%) and "medium" in the remaining lesions (33%). Nineteen CMN (90%) involved the subcutaneous fat, and 16 of the 21 CMN (76%) reached the lower surgical margin. The histological pattern and depth did not change over time but the cellularity and HMB-45 expression of dermal melanocytes decreased in 16 of the 21 patients (76%) and in 15 of the 21 patients (71%), respectively (both P < 0.001). Patients with decreasing HMB-45 expression were significantly younger at the first excision (median 6 months, IQR 4-28) than patients with unchanged HMB-45 expression (median 176 months, IQR 12-186; P = 0.018). The expression of Ki-67 and p16 did not change significantly with age. Our study demonstrates that (1) the cellularity and pigment production of CMN decreases with age, (2) the histological pattern and extension in depth remain stable, and (3) clear resection margins can rarely be achieved in larger CMN.