Melanocyte Counts Research Articles

Subungual melanoma: molecular analysis of 31 cases from early stage to invasive melanoma.

The distinction between the benign subungual melanocytic lesions and an early lesion of subungual melanoma (SUM) remains a diagnostic challenge. We evaluated the routine diagnostic utility of array Comparative Genomic Hybridization (aCGH) to detect whole-genome copy number variations (CNV) as well as targeted next-generation sequencing (NGS) in SUM. This retrospective study included 20 cases of in situ SUM and 11 cases of invasive SUM. Analysis by aCGH detected common oncogene amplifications in all but one case of invasive SUM (n = 10) and in all cases of in situ SUM with a melanocyte count (MC) >45/mm (n = 4 true positive) and the average number of CNV was 8.5. Thirteen remaining cases of in situ SUM gave false negative results (n = 13), owing to a lack of sufficient melanocytes to analyse (median MC of 35.35; range: 10.16-39.5). Molecular analysis failed in four cases (three in situ SUM and one invasive SUM) due to insufficient amounts of DNA. Across the whole cohort, the sensitivity of aCGH was 52%, but when adjusting the cutoff to MC >45/mm, the sensitivity was 93%. Targeted NGS was less informative than aCGH analyses in our series of SUM. To distinguish malignant from benign lesions, especially in situ SUM versus atypical lentiginous melanocytic proliferations, aCGH analysis should be performed when the MC is above 45 melanocytes per linear millimetre. This pangenomic method can detect oncogene amplifications, as well as a number of CNV >3, which strongly support the diagnosis of malignancy.

Changes in human skin composition due to intrinsic aging: a histologic and morphometric study

Skin represents the main barrier against the external environment, but also plays a role in human relations, as one of the prime determinants of beauty, resulting in a high consumer demand for skincare-related pharmaceutical products. Given the importance of skin aging in both medical and social spheres, the present research aims to characterize microscopic changes in human skin composition due to intrinsic aging (as opposed to aging influenced by external factors) via histological analysis of a photoprotected body region. Samples from 25 autopsies were taken from the periumbilical area and classified into four age groups: group 1 (0–12 years), group 2 (13–25 years), group 3 (26–54 years), and group 4 (≥ 55 years). Different traditional histological (hematoxylin–eosin, Masson’s trichrome, orcein, toluidine, Alcian blue, and Feulgen reaction) and immunohistochemical (CK20, CD1a, Ki67, and CD31) stains were performed. A total of 1879 images photographed with a Leica DM3000 optical microscope were morphometrically analyzed using Image ProPlus 7.0 for further statistical analysis with GraphPad 9.0. Our results showed a reduction in epidermis thickness, interdigitation and mitotic indexes, while melanocyte count was raised. Papillary but not reticular dermis showed increased thickness with aging. Specifically, in the papillary layer mast cells and glycosaminoglycans were expanded, whereas the reticular dermis displayed a diminution in glycosaminoglycans and elastic fibers. Moreover, total cellularity and vascularization of both dermises were diminished with aging. This morphometric analysis of photoprotected areas reveals that intrinsic aging significantly influences human skin composition. This study paves the way for further research into the molecular basis underpinning these alterations, and into potential antiaging strategies.

The Treatment of Refractory Vitiligo With Autologous Cultured Epithelium Grafting: A Real-World Retrospective Cohort Study.

Surgical intervention is the main therapy for refractory vitiligo. We developed a modified autologous cultured epithelial grafting (ACEG) technique for vitiligo treatment. Between January 2015 and June 2019, a total of 726 patients with vitiligo underwent ACEG in China, with patient characteristics and clinical factors being meticulously documented. Using a generalized linear mixed model, we were able to assess the association between these characteristics and the repigmentation rate. ACEG demonstrated a total efficacy rate of 82.81% (1754/2118) in treating 726 patients, with a higher repigmentation rate of 64.87% compared to conventional surgery at 52.69%. Notably, ACEG showed a better response in treating segmental vitiligo, lesions on lower limbs, age ≤ 18, and stable period > 3 years. A keratinocyte:melanocyte ratio below 25 was found to be advantageous too. Single-cell RNA sequencing analysis revealed an increase in melanocyte count and 2 subclusters of keratinocytes after ACEG, which remained higher in repigmented sites even after 1 year. ACEG is a promising therapy for refractory vitiligo. Patient age, clinical type, lesion site, and stability before surgery influence repigmentation in ACEG. The mechanism of repigmentation after ACEG treatment is likely not confined to the restoration of melanocyte populations. It may also involve an increase in the number of keratinocytes that support melanocyte function within the affected area. These keratinocytes may aid the post-transplant survival and function of melanocytes by secreting cytokines and extracellular matrix components. registered with Chictr.org.cn (ChiCTR2100051405).

Exploring the mechanism of Liuwei Dihuang formula for promoting melanin synthesis in juvenile zebrafish based on network pharmacology and molecular docking

BackgroundVitiligo stands as a challenging skin disorder with limited treatment options available. LiuWei DiHuang formula (LDF), a renowned Traditional Chinese medicine, has exhibited promising results in treating vitiligo over an extended period. However, the precise underlying mechanism of its action remains elusive. MethodsEmploying a comprehensive network pharmacology approach, this study identified active compounds and their corresponding targets within LDF, while also pinpointing vitiligo-associated targets sourced from the TCMSP database, OMIM, DisGenNET, and Genecards. A network was established to illustrate the connections between active compounds and targets, alongside a protein-protein interaction network. Further analyses, encompassing Gene Ontology (GO) function and KEGG pathway enrichment, were conducted using the DAVID platform. Molecular docking simulations were performed utilizing AutoDockTools and AutoDockVina software. To validate the outcomes of the systematic pharmacological investigation, experiments were conducted using juvenile zebrafish. ResultsThe collective effort of the network pharmacology approach yielded a compilation of 41 compounds and 192 targets. Molecular docking simulations notably revealed the lowest binding energies for CAT-quercetin and CAT-Kaempferol interactions. The utilization of juvenile zebrafish experiments highlighted a significant increase in melanocyte count following methoxsalen and LDF treatment. Notably, LDF prominently augmented the expression levels of proteins related to melanogenesis. Additionally, LDF showcased the capacity to enhance CAT and SOD levels while concurrently reducing ROS and MDA activity. In contrast to the model group, substantial increases in protein and mRNA levels of Nrf2 and HO-1 were observed in response to LDF treatment (P < 0.05). ConclusionThrough a meticulous network pharmacology approach, this study successfully predicted active components and potential targets associated with LDF's application in vitiligo treatment. The therapeutic effectiveness of LDF against vitiligo is postulated to stem from its regulation of oxidative stress factors and the Nrf2/HO-1 pathway.

Clinicopathological and prognostic features of subungual melanoma in situ

Objective: To investigate the clinicopathological characteristics, immunohistochemical profiles, molecular features, and prognosis of subungual melanoma in situ (SMIS). Methods: Thirty cases of SMIS were collected in Fudan University Shanghai Cancer Center, Shanghai, China from 2018 to 2022. The clinicopathological characteristics and follow-up data were retrospectively analyzed. Histopathologic evaluation and immunohistochemical studies were carried out. By using Vysis melanoma fluorescence in situ hybridization (FISH) probe kit, combined with 9p21(CDKN2A) and 8q24(MYC) assays were performed. Results: There were 8 males and 22 females. The patients' ages ranged from 22 to 65 years (median 48 years). All patients presented with longitudinal melanonychia involving a single digit. Thumb was the most commonly affected digit (16/30, 53.3%). 56.7% (17/30) of the cases presented with Hutchinson's sign. Microscopically, melanocytes proliferated along the dermo-epithelial junction. Hyperchromatism and nuclear pleomorphism were two of the most common histological features. The melanocyte count ranged from 30 to 185. Most cases showed small to medium nuclear enlargement (29/30, 96.7%). Pagetoid spread was seen in all cases. Intra-epithelial mitoses were identified in 56.7% (17/30) of the cases. Involvement of nailfold was found in 19 cases, 4 of which were accompanied by cutaneous adnexal extension. The positive rates of SOX10, PNL2, Melan A, HMB45, S-100, and PRAME were 100.0%, 100.0%, 96.0%, 95.0%, 76.9%, and 83.3%, respectively. FISH analysis was positive in 6/9 of the cases. Follow-up data were available in 28 patients, and all of them were alive without disease. Conclusions: SMIS mainly shows small to medium-sized cells. High melanocyte count, hyperchromatism, nuclear pleomorphism, Pagetoid spreading, intra-epithelial mitosis, nailfold involvement, and cutaneous adnexal extension are important diagnostic hallmarks. Immunohistochemistry including SOX10 and PRAME, combined with FISH analysis, is valuable for the diagnosis of SMIS.

Characterising the Effect of Wnt/β-Catenin Signalling on Melanocyte Development and Patterning: Insights from Zebrafish (Danio rerio).

Zebrafish (Danio rerio) is a well-established model organism for studying melanocyte biology due to its remarkable similarity to humans. The Wnt signalling pathway is a conserved signal transduction pathway that plays a crucial role in embryonic development and regulates many aspects of the melanocyte lineage. Our study was designed to investigate the effect of Wnt signalling activity on zebrafish melanocyte development and patterning. Stereo-microscopic examinations were used to screen for changes in melanocyte count, specific phenotypic differences, and distribution in zebrafish, while microscopic software tools were used to analyse the differences in pigment dispersion of melanocytes exposed to LiCl (Wnt enhancer) and W-C59 (Wnt inhibitor). Samples exposed to W-C59 showed low melanocyte densities and defects in melanocyte phenotype and patterning, whereas LiCl exposure demonstrated a stimulatory effect on most aspects of melanocyte development. Our study demonstrates the crucial role of Wnt signalling in melanocyte lineage and emphasises the importance of a balanced Wnt signalling level for proper melanocyte development and patterning.

PRAME immunohistochemistry can distinguish melanocytic pseudonests of lichenoid reactions from melanoma in situ.

Distinguishing melanocytic pseudonests encountered in lichenoid dermatoses or lichenoid keratoses from melanoma in situ (MIS) with brisk lichenoid inflammation can prove challenging. We designed a case-control study to evaluate the accuracy metrics of PRAME immunohistochemistry to distinguish melanocytic pseudonests in lichenoid dermatoses or keratoses from inflamed MIS. Immunostaining for PRAME was performed on paraffin-embedded formalin-fixed diagnostic tissue using a rabbit monoclonal antibody to PRAME (Abcam), with a 1:3200 dilution on a Leica Bond detection system. Our search identified 21 cases of melanocytic pseudonests (n=21, 46%) encountered in lichenoid dermatoses and 24 cases of inflamed MIS (n=24, 53%). Each method of evaluating PRAME immunohistochemistry (PRAME+ clusters, PRAME % of melanocytes by four categories and PRAME+ melanocyte counts per linear mm of epidermal basal layer) showed statistically significant differences between the MIS and the pseudonest cohorts (respectively, p < 0.001; p < 0.001; and p < 0.001). Receiver operating characteristics analysis for PRAME+ melanocyte counts per linear mm of epidermal basal layer revealed an area under the curve of 0.9 ± 0.05 (95% confidence interval 0.9-1.0). When determining an optimal cut-off point for the best Youden index [sensitivity (%) + specificity (%) - 100], the cut-off of 1.0 PRAME+ melanocytes per linear mm showed a sensitivity of 79.2% and specificity of 85.7% (Youden index 0.65) to distinguish MIS from pseudonests. PRAME immunohistochemistry may constitute an additional tool for this challenging differential diagnosis.

Evaluation of clinical efficacy and laboratory indicators of non-cultured epidermal cell suspension and hair follicle cell suspension in surgical management of stable vitiligo: A randomized comparative trial.

Non-cultured epidermal cell suspension (ECS) and hair follicle cell suspension (HFCS) are well-established methods of surgical treatment of stable vitiligo. The aim of the present study was to compare the laboratory indicators and clinical efficacy of ECS and HFCS in the treatment of stable vitiligo. This was a single centre, open-labeled randomized trial. Vitiligo patches from 74 patients were randomized to receive either ECS or HFCS. Both cell suspensions were analyzed for total cell count, cell viability and melanocyte count. Percentage re-pigmentation was assessed at regular intervals for 36 weeks. The percentage re-pigmentation with ECS was significantly higher than HFCS at week 4 (p=.01) and week 16 (p=.03) however, no difference was observed at weeks 24 (p=.38) and 36 (p=.05). Forty-seven patients completed the study follow-up duration and excellent re-pigmentation (>90%) was achieved in 61.7% and 53.2% and complete re-pigmentation (100%) was observed in 6.4% and 12.8% of participants using ECS and HFCS, respectively. Significantly higher cell yield (p < .01) and percentage of HMB45+ melanocytes (p=.01) were obtained using ECS. No difference was noted in the percentage of viable cells or S100 + melanocytes. The median cell yield was eight times higher in ECS than in HFCS with a significantly higher percentage of HMB45+ melanocytes in the former group. The median percentage of re-pigmentation in both groups was 90% at the end of 36 weeks. ECS provides faster re-pigmentation; however, both ECS and HFCS have comparable safety and efficacy over a longer duration of follow-up.

Evaluation of needling/microneedling as an adjunct to phototherapy in the treatment of stable acral vitiligo: a comparative clinical and immunohistochemical study

Objectives To evaluate the efficacy and tolerability of needling/microneedling as an adjunct to NB-UVB phototherapy in the treatment of stable refractory patches of acral vitiligo, based upon clinical and immunohistochemical assessment of melanocyte count and distribution in response to needling/microneedling. Materials and methods Twenty patients with stable acral vitiligo (≥2 patches) were enrolled. One of the two index patches was randomized to receive needling or microneedling in conjunction with NB-UVB. Patients received phototherapy sessions 3 times weekly, while needling was carried out on biweekly basis for 6 months. Assessment was done clinically using point counting method, VESTA, and global patients’ satisfaction, and immunohistochemically by quantitative assessment of melanocyte count by Melan-A. Results No statistically significant difference was observed between NB-UVB monotherapy and either of the combined therapy regimens as regards the mean percentage change in vitiligo surface area (p = .451), mean change in absolute melanocyte count from baseline (p = .589), and mean VESTA (p = .916). Patches subjected to adjuvant microneedling/needling were afflicted by koebnerization in 50% and 20% of cases, respectively. Conclusion Neither microneedling nor needling appear to confer an added therapeutic value to NB-UVB phototherapy in the treatment of stable acral vitiligo. Moreover, both carry the risk of koebnerization.

Thioredoxin Reductase 1 Modulates Pigmentation and Photobiology of Murine Melanocytes in vivo

Pigment-producing melanocytes overcome frequent oxidative stress in their physiological role of protecting the skin against the deleterious effects of solar UV irradiation. This is accomplished by the activity of several endogenous antioxidant systems, including the thioredoxin antioxidant system, in which thioredoxin reductase 1 (TR1) plays an important part. To determine whether TR1 contributes to the redox regulation of melanocyte homeostasis, we have generated a selective melanocytic Txnrd1-knockout mouse model (Txnrd1mel‒/‒), which exhibits a depigmentation phenotype consisting of variable amelanotic ventral spotting and reduced pigmentation on the extremities (tail tip, ears, and paws). The antioxidant role of TR1 was further probed in the presence of acute neonatal UVB irradiation, which stimulates melanocyte activation and introduces a spike in oxidative stress in the skin microenvironment. Interestingly, we observed a significant reduction in overall melanocyte count and proliferation in the absence of TR1. Furthermore, melanocytes exhibited an elevated level of UV-induced DNA damage in the form of 8-oxo-2'-deoxyguanosine after acute UVB treatment. We also saw an engagement of compensatory antioxidant mechanisms through increased nuclear localization of transcription factor NRF2. Altogether, these data indicate that melanocytic TR1 positively regulates melanocyte homeostasis and pigmentation during development and protects against UVB-induced DNA damage and oxidative stress.

Identification of the fate and regenerative mechanism of zebrafish melanocyte progenitor cells and melanocytes after laser-induced pigment ablation.

Lasers are known to be the most effective treatment modality for pigmentary skin diseases. However, melanocytes and melanin pigment often recur or leave post-inflammatory hyperpigmentation after the laser procedure. Studies have reported on the role of progenitor cells in pigment cell regeneration, which can be constantly replenished through mitosis. However, the response of unpigmented melanocyte progenitor cells to laser treatment is poorly understood. In this study, we used adult zebrafish skin as the melanocyte regenerative system and examined the response of melanocyte progenitor cells to laser photothermolysis. The two groups of adult zebrafish were irradiated with 1064 nm wavelength laser system of Q-switched neodymium:yttrium-aluminum-garnet (Nd:YAG) laser with 0.3 or 0.7 J·cm-2 . We compared the regeneration of pigment at different energy levels by measuring new melanocyte counts and pigment area. We traced and quantitatively compared the melanocyte lineage cells by immunohistochemical staining using specific markers such as sox10, mitfa, and dct during the regeneration process. Three repetitive laser ablations were also held to test the postinflammatory hyperpigmentation. After the laser ablation of melanocytes, most of the new melanocytes appeared between Days 5 and 10. In high-energy irradiation of 0.7 J·cm-2 , the unpigmented mitfa-expressing cells showed significant decrease (p < 0.05) and showed delay in the differentiation process of melanocyte lineage cells. After repeated laser irradiation, hyperpigmentation did not appear and the final recovery ratio of the pigmented area was 87.5% and 75.3% at the 0.3 and 0.7 J·cm-2 energy levels, respectively. We suggest that laser treatment overcoming the recurrence should be planned based on the adequate energy level targeting the melanocyte progenitor cells. High-energy irradiation may induce apoptosis of progenitor cells and delay their process of differentiation. Short-term repetitive sessions of laser therapy can reduce the pigmentation in the long-term observation.

Clinicopathological, immunohistochemical and fluorescence in-situ hybridisation features of early subungual melanoma: an analysis of 65 cases.

Very limited data are available concerning the clinicopathological and molecular features of early subungual melanoma (SM), especially with regard to the Asian population. The aim of this study was to investigate the clinical, histological, immunohistochemical and chromosomal features of early SM. Fifty-two in-situ and 13 thin (Breslow thickness ≤1.0mm) SM cases were retrospectively reviewed. All patients presented with longitudinal melanonychia involving a single digit, and the thumb was the most affected digit (35 of 65, 53.8%). Microscopically, most cases showed small to medium nuclear enlargement (58 of 65) and mild to moderate nuclear atypia (57 of 65). Hyperchromatism and irregular contours of nuclei were persistent features in all cases. The variation of melanocyte count (the number of melanocytes per mm dermal-epithelial junction) ranged from 31 to 255. Intra-epithelial mitoses were identified in 34 cases (52.3%). Statistically, features of in-situ lesions including higher melanocyte count (>70), presence of multinucleated melanocytes, inflammatory infiltrate and cutaneous adnexal extension, were associated with early invasion. Melan-A, human melanoma B (HMB)45, mouse monoclonal melanoma antibody (PNL2) and SOX10 antibodies (>95.0%) showed superior diagnostic sensitivity to S-100 protein (83.1%). Fluorescence in-situ hybridisation (FISH) results were positive in 15 of 23 successfully analysed cases. To the best of our knowledge, this is the largest single-institution study of early SM in an Asian population, and the largest cohort tested by FISH. Early SM mainly showed small to medium nuclear enlargement and mild to moderate nuclear atypia. High melanocyte count, hyperchromatism and irregular contours of nuclei and intra-epithelial mitoses are crucial diagnostic parameters. Immunohistochemistry, especially SOX10 staining, and FISH analysis are valuable in the diagnosis of SM.

Outcome of Repeated Use of Donor Site for Noncultured Epidermal Cellular Grafting in Stable Vitiligo: A Retrospective Study.

Background Noncultured epidermal suspension (NCES) is a surgical technique which employs cellular grafting onto depigmented lesions. However, scarring and dyschromia at the donor site often occurs. Objective To assess the outcome of reusing the same donor site in subsequent sessions of NCES procedures. Methods Electronic records of vitiligo patients who had undergone two sessions of NCES procedures were retrospectively reviewed. Information on the first and second NCES was retrieved for analyses. Results A total of 30 patients (female 19 and male 11) were included. The majority of patients had nonsegmental vitiligo (66.7%). The median donor-to-recipient ratios were 1 : 3 (1 : 1–1 : 20) for the first session and 1 : 3 (1 : 1–1 : 13.5) for the second session (p=0.661). The mean melanocyte count was 220.7 ± 65.5 cells/mm2 vs. 242.4 ± 55.3 cells/mm2 on the first and second sessions, respectively (p=0.440). The mean repigmentation rate was 84.2% (±21.1%) and 82.3 (±22.1%) for the first and second NCESs, respectively (p=0.645). The frequency of color mismatch and pigment loss were similar between both sessions (p=0.706 and p=1.000). Conclusions Repeated use of donor sites in subsequent NCES sessions gave comparable repigmentation.

Drug consumption and melanocytic nevi: correlation between oral contraceptives or hormone replacement therapy and a high melanocytic nevi count

The prolonged use of drugs such as beta-blockers, acetylsalicylic acid, omeprazole, statins, oral contraceptives and hormone replacement therapy might have some role in melanocytic nevi development and be ultimately linked to melanoma risk. Aims of the study were to evaluate a possible association between the above-mentioned drugs and features such as number and atypia of melanocytic nevi in long-term users. We retrospectively looked at pharmacological, clinical and dermoscopic records of 1321 patients that attended our unit for routine mole check between January 2013 and January 2018. Patients were divided into two groups (low or high melanocytic nevi count), and multivariate analysis was performed with regards to the presence and number of melanocytic nevi and drug assumption. A positive association between the use of oral contraceptives or hormone replacement therapy (P = 0.012) and a high melanocytic nevi count was found through multivariate analysis, after adjusting for sex, age and multiple confounding factors, such as freckles, phototype and a reported history of sun exposure and sunburns. Further prospective studies are necessary to establish whether women using oral contraceptives or on hormone replacement therapy should undergo periodic monitoring of pigmented lesions.

Clinical & ultrastructural evaluation of the effect of fractional CO2 laser on facial melasma

ABSTRACTMelasma represents the most obvious and disfiguring change of the face leading to psychological problems especially in females. Ablative lasers have also been used by many professionals to treat melasma, although there is few scientific data supporting this indication. The exact mechanism of action of ablative lasers in melasma is not yet clear enough. We aimed to evaluate the ultrastructural effect of fractional ablative CO2 (FrCo2) laser on facial melasma. Eleven melasma patients evaluated clinically by clinical modified area and severity index (MASI) score, treated by two sessions of fractional CO2 laser one month a part. Two punch biopsies of 2 mm diameter were obtained from all subjects one before and the other 3 months after treatment. All biopsies were analyzed by light and electron microscopy. Clinically, significant improvement of pigmentation and 48% reduction of (MASI) score were observed after two sessions of laser treatments. Light microscopic analysis of specimens revealed significant decrease in melanocyte count after treatment. Electron microscopic analysis of specimens after treatment revealed significant decrease in the number and size of melanocytes and significant decrease or complete absence of melanin granules in the surrounding keratinocytes compared to pre-treatment specimens. No scarring or post inflammatory hyper or hypopigmentation. We concluded that repeated application of Fractional CO2 laser on melasma skin may result in long lasting improvement due to its destructive effect on melanocytes.

Dual role of laminin‑511 in regulating melanocyte migration and differentiation

Laminins are the major basement membrane (BM) components and are heterotrimers composed of an α, a β and a γ chain. In skin, laminins are present in basement membranes surrounding vascular structures, nerves, adipose tissue and in the specialized junctional BM between the epidermis and dermis. The main laminin isoforms in the dermo-epidermal BM are laminin‑332, laminin‑511 and laminin‑211, the latter being restricted to hair follicles (HFs). The laminin γ1 chain is the most abundant γ chain; its global ablation in mice leads to early embryonic lethality at E5.5. To elucidate the cellular function of the γ1 chain in skin, we generated mice with keratinocyte-specific deletion of this chain (Lamc1EKO) by using the keratin (K)14-Cre/loxP system. These mice showed delayed coat pigmentation despite normal melanocyte counts in the skin. However, levels of differentiation-specific melanocyte enzymes TRP‑1, TRP‑2 and tyrosinase were reduced in Lamc1EKO mice, and melanocytes failed to migrate to their differentiation niche in HFs and accumulated in the IFE. These results suggested that the pigmentation defect results from impaired melanocyte migration. The impaired migratory capacity of melanocytes is due to the altered composition of laminins in the BM of Lamc1EKO mice: Loss of keratinocyte-derived pro-migratory laminin‑511 is not compensated by ectopically deposited fibroblast-derived laminin‑211. Furthermore, contact of melanocytes with recombinant laminin‑511, but not with laminin‑211, induces the expression of the chemokine receptor CXCR4 on melanocytes, needed for SDF‑1 (stromal cell‑derived factor‑1)-mediated migration into HFs. We here demonstrate that laminin‑511 controls the differentiation of melanocytes by regulating their migration from the epidermis into HFs and by activating CXCR4 expression on melanocytes required for their recruitment into HFs in an SDF‑1-dependent manner.

Decreased melanocyte counts in topical imiquimod-treated skin

Decreased melanocyte counts in topical imiquimod-treated skin

Melanocytes Pattern in the Normal Nail, With Special Reference to Nail Bed Melanocytes.

Previous studies of the density of melanocytes in the normal nail bed have had conflicting results. This is unfortunate because knowing the normal values might help the difficult distinction between a benign subungual melanotic macule and an early melanoma in situ. Five specimens of normal nail unit were analyzed. On hematoxylin and eosin-stained sections the melanocytes were undetectable. We defined the melanocyte count (MC) as the number of melanocytes per 1-mm stretch of nail epithelium. The mean MC for nail matrix was 6.86 with a range of 4-14. The melanocytes were irregularly scattered in the basal and suprabasilar layer of the matrix epithelium. Abundant and uneven cytoplasmic dendrites were focally observed in the matrix. The MC for the nail bed ranged from 0 to 5 with a mean of 0.43. The melanocytes were restricted to the basal layer with thin cytoplasmic dendrites. Two cases showed a complete absence of melanocytes in the nail bed. In the ventral portion of the proximal nail fold, called the eponychium, the MC ranged between 0 and 5/mm with a mean of 2.27/mm. In conclusion, we discovered foci in normal nail beds, in which the melanocytic density can be relatively high and reach the level seen in the matrix. HMB45 is more sensitive than Microphtalmia-associated transcription factor (MITF) for the evaluation of intraepithelial melanocytic density of the nail unit. If MITF is used alone in the nail bed, its weak sensitivity may result in a false-negative interpretation and may be wrongly reassuring in the evaluation of early melanomas. On hematoxylin and eosin sections, basal and suprabasal nail keratinocytes are sometimes crowded, showing oval or elongated dark-staining nucleus and a clear cytoplasm and mimics a melanocytic proliferation. On HMB45 or Melan A staining, the morphology and the distribution of the dendrites of matrical melanocytes can mimic the dendritic pattern usually described in acral melanoma. Therefore, the interpretation of nail melanocytic atypia must be prudent.

A clinical, histologic, and follow-up study of genital melanosis in men and women

Genital melanosis may clinically mimic melanoma. Little is known about the potential risk for genital and nongenital melanoma in these patients. In this retrospective cohort study, we analyzed clinical and histologic data from patients with genital melanosis to better characterize these lesions and the risk they confer for genital and nongenital melanoma. In all, 41 patients were identified for a retrospective chart review and histologic analysis. Genital melanosis can clinically mimic melanoma but the typical age of onset is younger than for genital melanoma. A majority of lesions were found to stabilize or regress over time. Five patients were found to have a history of melanoma, only 1 of which was in the genital region. Lesions from these patients were more likely to show melanocytes with suprabasal movement (P=.0101) and to have a higher melanocyte count (P<.0462). We present a relatively small cohort of patients with an average follow-up of only 30.5months. Patients with genital melanosis, and in particular those with any level of histologic atypia in the genital melanosis lesion, may require careful total body skin examinations for the possibility of melanoma in any body site.

Pigmented basal cell carcinoma: increased melanin or increased melanocytes?

Studies on the precise cause of increased melanization in pigmented basal cell carcinomas (BCC) are limited. We aimed to determine whether the cause of melanization is from increased number of melanocytes or increased melanin pigment, and if there is a difference in the number of melanocytes on different sun-exposed locations. A retrospective review of 45 skin biopsies from January 2011 to February 2011 was performed; 30 were diagnosed as pigmented BCC and 15 as non-pigmented BCC. Immunohistochemistry for MART-1 (melanoma-associated antigen recognized by T-cell 1)/Melan-A (clone M2-7610 + M2-9E3; Leica Microsystems Inc. Buffalo Grove, IL, USA) from Biocare Medical (Concord, CA, USA) was performed on all biopsies. Associations between histopathologic features, number of melanocytes, location, and specific diagnoses were analyzed by Mann-Whitney U test. The mean melanocyte count per high powered field in pigmented BCCs from sun-exposed skin was 101.9 and from intermittently sun-exposed skin was 122.5, as compared to the controls (nodular non-pigmented BCC) of 27.4 (p = 0.002) and 34.9 (p = 0.002), respectively. Pigmented BCCs have a higher mean melanocyte count as compared to non-pigmented BCCs irrespective of location. Therefore, the pigment is not only due to increased melanin, but also due to increased melanocytes.