Benign Melanocytic Nevi Research Articles

AB0519 “Skin lesions induced by biological therapies in patients with inflammatory rheumatic diseases: are there any differences between rheumatoid arthritis and spondyloarthropathies?”

BackgroundBiological therapy (BT) has been a major advance in the treatment of inflammatory arthritis; however, they have also been associated with many side effects. Recently, a broad spectrum of skin...

Genome‐wide promoter methylation analysis identifies epigenetic silencing of MAPK13 in primary cutaneous melanoma

The involvement of epigenetic alterations in the pathogenesis of melanoma is increasingly recognized. Here, we performed genome-wide DNA methylation analysis of primary cutaneous melanoma and benign melanocytic nevus interrogating 14495 genes using BeadChip technology. This genome-wide view of promoter methylation in primary cutaneous melanoma revealed an array of recurrent DNA methylation alterations with potential diagnostic applications. Among 106 frequently hypermethylated genes, there were many novel methylation targets and tumor suppressor genes. Highly recurrent methylation of the HOXA9, MAPK13, CDH11, PLEKHG6, PPP1R3C, and CLDN11 genes was established. Promoter methylation of MAPK13, encoding p38δ, was present in 67% of primary and 85% of metastatic melanomas. Restoration of MAPK13 expression in melanoma cells exhibiting epigenetic silencing of this gene reduced proliferation, indicative of tumor suppressive functions. This study demonstrates that DNA methylation alterations are widespread in melanoma and suggests that epigenetic silencing of MAPK13 contributes to melanoma progression.

Abstract 1116: Sleeping Beauty mutagenesis identifies genes and pathways that cooperate with BrafV600E in melanoma initiation and progression.

Abstract Malignant melanoma is a devastating disease the prevalence of which is on the rise. In humans, somatic mutation of BRAF, to encode the BRAFV600E oncoprotein, is an early predisposing event in melanoma initiation, but is insufficient to drive malignant melanomagenesis in the absence of additional cooperating events. We describe a genome-wide, forward genetic screen in mice restricted to pigment producing melanocytes as an unbiased approach to identify new candidate melanoma progression genes. By combining Sleeping Beauty (SB) with a Cre-activated BRafCA allele we observed frank melanomas with average latency of 36 weeks. By contrast, melanocyte specific expression of BRAFV600E elicited benign melanocytic nevi that failed to progress to malignant melanoma by one year of age. These findings confirm that SB mobilization altered genes that cooperate with BRAFV600E to promote melanoma progression. A discovery set of 1,200 statistically-defined candidate melanoma genes was identified from 70 SB|BRAFV600E tumors. Importantly, our screen identified seven SB mutated genes with human orthologs that are well established human melanoma drivers including: Cdkn2a, Pten, Gnaq, Mitf, Nf1, Rac1 and Ppp6c. Many biological signaling pathways and cellular processes were enriched for candidate melanoma genes altered in SB|BRAFV600E melanomas, including Wnt/Beta-catenin, TGFβ, PI3’-kinase and MAPK signaling pathways and biological processes regulating ubiquitin mediated proteolysis, tight junctions, cell cycle and axonal guidance. Integrated comparative oncogenomic analysis with human melanoma data sets provided a data-driven method to filter and prioritize candidate melanoma genes. The genes identified using the SB|BRAFV600E model may represent new human melanoma candidate cancer genes with potential clinical relevance to the progression and maintenance of human BRAF mutated melanoma. Citation Format: Michael B. Mann, Michael A. Black, Jerrold M. Ward, Marcus W. Bosenberg, Martin McMahon, Cristin G. Print, David J. Adams, Neal G. Copeland, Nancy A. Jenkins. Sleeping Beauty mutagenesis identifies genes and pathways that cooperate with BrafV600E in melanoma initiation and progression. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1116. doi:10.1158/1538-7445.AM2013-1116

Atypical melanocytic lesions of the thigh with spitzoid and dysplastic features: a clinicopathologic study of 29 cases

Melanocytic nevi in certain anatomic locations can display unusual histopathologic features potentially creating diagnostic uncertainty. Benign melanocytic nevi in sites such as acral, genital, and flexural areas may show unusual architecture and cytologic atypia, which can mimic dysplastic nevi and, sometimes, melanoma. Twenty-nine benign melanocytic skin lesions were identified in the thigh of 26 women and 3 men who showed atypical histologic features, including both dysplastic and spitzoid features. All lesions measured less than 1 cm in diameter. Eighteen cases showed features of compound nevi, and 11 were junctional. In all cases, the lesions displayed spitzoid features including large epithelioid and/or spindle cells, some melanocytes with ganglion-like cytomorphology, and focal suprabasilar upward migration. All cases showed dysplastic features. Clinical follow-up was available in 26 patients; no recurrences or metastases were observed. The demographic features and the anatomical sites of these melanocytic nevi appear to be reproducible, and in the assessment of histologically difficult cases, these data are helpful. It is our opinion that the malignant potential of these lesions with hybrid patterns (spitzoid/dysplastic) has yet to be determined, and although we favor these lesions to be benign, longer follow-up may yield a more complete understanding of their biologic potential.

CD10 Expression in Cutaneous Squamous Cell Carcinoma and Its Precursor Lesions: Evaluation Using Tissue Microarray

CD10 Expression in Cutaneous Squamous Cell Carcinoma and Its Precursor Lesions: Evaluation Using Tissue Microarray

Polarization speckle imaging as a potential technique forin vivoskin cancer detection

Skin cancer is the most common cancer in the Western world. In order to accurately detect the disease, especially malignant melanoma-the most fatal form of skin cancer-at an early stage when the prognosis is excellent, there is an urgent need to develop noninvasive early detection methods. We believe that polarization speckle patterns, defined as a spatial distribution of depolarization ratio of traditional speckle patterns, can be an important tool for skin cancer detection. To demonstrate our technique, we conduct a large in vivo clinical study of 214 skin lesions, and show that statistical moments of the polarization speckle pattern could differentiate different types of skin lesions, including three common types of skin cancers, malignant melanoma, squamous cell carcinoma, basal cell carcinoma, and two benign lesions, melanocytic nevus and seborrheic keratoses. In particular, the fourth order moment achieves better or similar sensitivity and specificity than many well-known and accepted optical techniques used to differentiate melanoma and seborrheic keratosis.

Comparative microarray analysis of microRNA expression profiles in primary cutaneous malignant melanoma, cutaneous malignant melanoma metastases, and benign melanocytic nevi

Perturbations in microRNA (miRNA) expression profiles have been reported for cutaneous malignant melanoma (CMM) predominantly when examined in cell lines. Despite the rapidly growing number of newly discovered human miRNA sequences, the availability of up-to-date miRNA expression profiles for clinical samples of primary cutaneous malignant melanoma (PCMM), cutaneous malignant melanoma metastases (CMMM), and benign melanocytic nevi (BMN) is limited. Specimens excised from the center of tumors (lesional) from patients with PCMM (n=9), CMMM (n=4), or BMN (n=8) were obtained during surgery. An exploratory microarray analysis was performed by miRNA expression profiling based on Agilent platform screening for 1205 human miRNAs. The results from the microarray analysis were validated by TaqMan quantitative real-time polymerase chain reaction. In addition to several miRNAs previously known to be associated with CMM, 19 unidentified miRNA candidates were found to be dysregulated in CMM patient samples. Among the 19 novel miRNA candidates, the genes hsa-miR-22, hsa-miR-130b, hsa-miR-146b-5p, hsa-miR-223, hsa-miR-301a, hsa-miR-484, hsa-miR-663, hsa-miR-720, hsa-miR-1260, hsa-miR-1274a, hsa-miR-1274b, hsa-miR-3663-3p, hsa-miR-4281, and hsa-miR-4286 were upregulated, and the genes hsa-miR-24-1*, hsa-miR-26a, hsa-miR-4291, hsa-miR-4317, and hsa-miR-4324 were downregulated. The results of this study partially confirm previous CMM miRNA profiling studies identifying miRNAs that are dysregulated in CMM. However, we report several novel miRNA candidates in CMM tumors; these miRNA sequences require further validation and functional analysis to evaluate whether they play a role in the pathogenesis of CMM.

Dermoscopic features of melanocytic lesions on volar skin: 178 case reports

Objective To investigate the dermoscopic features of palmoplantar melanocytic lesions.Methods The dermoscopic images of palmoplantar melanocytic lesions that underwent examination in the Department of Dermatology in Peking University First Hospital from September 2009 to October 2011,were retrospectively analyzed.Results Totally,155 benign acral melanocytic lesions in 121 patients and 23 acral melanomas in 22 patients were analysed in this study.Among the benign acral melanocytic lesions,the parallel furrow pattern and its variations (34.2％) were the most common,followed by the fibrillar pattern (22.6％).Two benign lesions (1.3％) showed a parallel ridge pattern.Of 23 melanoma lesions,12 (52.2％) exhibited parallel ridge pattern,and 14 (60.9％) showed irregular diffuse pigmentation that was present in all of the invasive melanoma lesions.The fibrillar pattern,as a common benign acral dermoscopic pattern,was also present in 39.1％ of melanoma specimens.Conclusions Dermoscopy is valuable to some extent in the differential diagnosis of benign melanocytic nevi and malignant melanoma in palmoplantar region,and may facilitate the secreening for early melanoma.

Differentiation of Malignant Melanoma From Benign Nevus Using a Novel Genomic Microarray With Low Specimen Requirements

Histologic examination of clinically suspicious melanocytic lesions is very sensitive and specific for the detection of malignant melanoma. Yet, the malignant potential of a small percentage of melanocytic lesions remains histologically uncertain. Molecular testing offers the potential to detect the genetic alterations that lead to malignant behavior without overt histologic evidence of malignancy. To differentiate benign melanocytic nevi from malignant melanoma and to predict the clinical course of melanocytic lesions with ambiguous histology using a novel genomic microarray. We applied a newly developed single-nucleotide polymorphism genomic microarray to formalin-fixed, paraffin-embedded melanocytic lesions to differentiate benign nevi (n = 23) from malignant melanoma (n = 30) and to predict the clinical course of a set of histologically ambiguous melanocytic lesions (n = 11). For cases with unambiguous histology, there was excellent sensitivity and specificity for identifying malignant melanoma with this genomic microarray (89% sensitivity, 100% specificity). For cases with ambiguous histology, the performance of this genomic microarray was less impressive. Without microdissection and with quantities of DNA one-tenth what is required for more commonly used microarrays, this microarray can differentiate between malignant melanoma and benign melanocytic nevi. For histologically ambiguous lesions, longer clinical follow-up is needed to confidently determine the sensitivity and specificity of this microarray. Some of the previous technical hurdles to the clinical application of genomic microarray technology are being overcome, and the advantages over targeted fluorescence in situ hybridization assays currently in clinical use are becoming apparent.

Out-of-plane Stokes imaging polarimeter for early skin cancer diagnosis

Optimal treatment of skin cancer before it metastasizes critically depends on early diagnosis and treatment. Imaging spectroscopy and polarized remittance have been utilized in the past for diagnostic purposes, but valuable information can be also obtained from the analysis of skin roughness. For this purpose, we have developed an out-of-plane hemispherical Stokes imaging polarimeter designed to monitor potential skin neoplasia based on a roughness assessment of the epidermis. The system was utilized to study the rough surface scattering for wax samples and human skin. The scattering by rough skin-simulating phantoms showed behavior that is reasonably described by a facet scattering model. Clinical tests were conducted on patients grouped as follows: benign nevi, melanocytic nevus, melanoma, and normal skin. Images were captured and analyzed, and polarization properties are presented in terms of the principal angle of the polarization ellipse and the degree of polarization. In the former case, there is separation between different groups of patients for some incidence azimuth angles. In the latter, separation between different skin samples for various incidence azimuth angles is observed.

Dysplastic Nevi

Dysplastic nevi have been a subject of much debate since their original description in 1978. Although some question the biological potential of dysplastic nevi themselves, several studies have shown that their presence confers substantial risk for melanoma. In addition to predisposing patients to melanoma, dysplastic nevi have been shown to harbor genetic mutations, indicating their position on a continuum between banal nevi and melanomas. Dysplastic nevi are also clinically relevant as mimickers of melanoma, and can be challenging diagnostically. This article reviews the history, epidemiology, biology and genetics, clinical features, histopathologic features, and management guidelines for patients with these lesions.

Blue nevus with satellitosis mimicking melanoma. Contribution of dermoscopy and reflectance confocal microscopy.

Blue nevus is an acquired benign melanocytic nevus that can undergo malignant transformation. We report a 70-year-old man who presented with a recently enlarged long-term blue nodule on his scalp. He reported onset of new satellitosis around the lesion. Although clinically thought to be a malignant melanoma, histopathological, dermoscopic and reflectance confocal-microscopy examinations did not confirm this diagnosis.

The miRNA machinery in primary cutaneous malignant melanoma, cutaneous malignant melanoma metastases and benign melanocytic nevi

Although several studies have shown a dysregulation of microRNA (miRNA) expression profiles in cutaneous melanoma, there has been little research on the miRNA machinery itself. In this study, we investigated the mRNA expression profiles of different miRNA machinery components in primary cutaneous malignant melanoma (PCMM), cutaneous malignant melanoma metastases (CMMM) and benign melanocytic nevi (BMN). Patients with PCMM (n = 7), CMMM (n = 6) and BMN (n = 7) were included in the study. Punch biopsies were harvested from the centers of tumors (lesional) and from BMN (control). In contrast to previous reports exploring specific clusters of miRNAs in PCMM, the present study investigates mRNA expression levels of Dicer, Drosha, Exp5, DGCR8 and the RISC components PACT, argonaute-1, argonaute-2, TARBP1, TARBP2, MTDH and SND1, which were detected by TaqMan real-time reverse transcription polymerase chain reaction (RT-PCR). Argonaute-1, TARBP2 and SND1 expression levels were significantly higher in BMN compared to PCMM (p < 0.05). TARBP2 expression levels were significantly higher in CMMM compared to PCMM (p < 0.05). SND1 expression levels were significantly higher in CMMM compared to PCMM and BMN (p < 0.05). Dicer, Drosha, DGCR8, Exp5, argonaute-2, PACT, TARBP1 and MTDH expression levels showed no significant differences within groups (p > 0.05). The results of this study show that the miRNA machinery components argonaute-1, TARBP2 and SND1 are dysregulated in PCMM and CMMM compared to BMN and may play a role in the process of malignant transformation.

Abstract LB-254: PRMT5 is upregulated in malignant and metastatic melanoma, and regulates expression of the MITF transcription factor

Abstract Protein arginine methyltransferase 5 (PRMT5) is an enzyme which catalyzes the covalent attachment of methyl groups to arginine residues of various proteins. PRMT5 binds and/or methylates both nuclear (e.g. histones) and cytoplasmic (e.g. p53, CRAF) proteins to regulate cellular functions including gene expression, cell cycle, and apoptosis among others. PRMT5 has been characterized in leukemia, lymphoma, glioma, and breast cancer; however little is known regarding its role in malignant melanoma. We hypothesized that PRMT5 plays a unique role in regulating melanoma cell biology. PRMT5 expression was measured by IHC analysis of formalin-fixed samples from patients with melanoma (n=133 primary; n=66 metastases), benign nevi (n=24), and normal adjacent epidermis (n=21). PRMT5 expression was significantly elevated in melanoma samples compared to normal adjacent epidermis (p&amp;lt;0.001, Fisher's exact test). The nuclear and cytoplasmic localization of PRMT5 was heterogeneous within individual melanoma specimens. PRMT5 was significantly higher in the nucleus, but not the cytoplasm, of malignant tissue compared to metastatic tissue (p=0.0004 vs p=0.6, Wilcoxon rank sum). PRMT5 protein was also significantly elevated in benign melanocytic nevi (compound, junctional, and intradermal) compared to normal adjacent epidermis (p&amp;lt;0.0001), suggesting that elevated PRMT5 may represent an early event in tumorigenesis. Analysis of human melanoma cell lines revealed that PRMT5 expression was predominantly cytoplasmic and its expression did not differ based on B-Raf or N-Ras mutational status. Co-immunoprecipitation experiments revealed PRMT5 associated with its enzymatic co-factor MEP-50, but not cyclin D1 or STAT3, in both bulk cultured or synchronized cells, as has been reported in other cell types. Depletion of PRMT5 with siRNA led to decreased transcript and protein level of MITF-M (microphthalmia-associated transcription factor) in human melanoma cell lines with V600E-mutated B-Raf (A375, Hs294T, 1106 MEL, FO1), or wild-type B-Raf (CHL-1, Wm1366). Furthermore, depletion of PRMT5 led to a significant growth inhibition in 1106 MEL, Wm1366, and FO1 cells at 48 and 72 hours post-transfection. These data uncover important differences between the biology of PRMT5 in melanoma cells as compared to other tumor types, and are the first to demonstrate that PRMT5 is a regulator of MITF expression, a key transcription factor regulating melanoma cell biology and cell proliferation. The upregulation of PRMT5 in human melanoma specimens and cell lines further suggests that PRMT5 inhibition deserves exploration as a novel therapeutic strategy for melanoma. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-254. doi:1538-7445.AM2012-LB-254

Aberrant expression of HMB-45 in traumatized melanocytic nevi

Assessment of histologic and immunohistochemical maturation (with HMB-45 and anti-Ki-67) may be helpful in differentiating benign melanocytic nevi (BMN) from malignant melanoma. Recently, we reported loss of maturation and aberrant immunohistochemical findings in melanocytic nevi after liquid nitrogen cryotherapy (Adeniran etal, J Am Acad Dermatol 2009;61:341-5). Herein we report a similar phenomenon identified in traumatized melanocytic nevi (TMN). We sought to evaluate the histologic and immunohistochemical findings in early and late stages of traumatized nevi. Twenty-four cases of TMN were retrieved from the pathology archives. These were then assessed by two pathologists (T.L. and A.H.D.) using HMB-45 and MIB-1 (for Ki-67) antibodies. TMN showed some of the following findings: epidermal changes (parakeratosis, ulceration, serum crust, flattening of the epidermis) and dermal changes including fibrosis and the presence of melanophages. In some cases, there was architectural disorder of the overlying melanocytes, with crowding in the basal layer, but without significant pagetoid spread. Occasionally, the dermal scar contained larger, more epithelioid-appearing melanocytes than those beneath the scar. Fifty-four percent of TMN lacked obvious immunohistochemical maturation with HMB-45, since nevus cells within the scar or directly beneath it were strongly labeled. None of the TMN showed appreciable labeling for Ki-67. The exact clinical duration between trauma and biopsy could not be determined. Loss of maturation with HMB-45 in TMN can be a diagnostic pitfall in challenging cases. Concurrent evaluation of MIB-1 expression, along with the characteristic histologic features of trauma, should allow the correct diagnosis to be reached.

Grade of atypia in dysplastic nevi and relationship with dermal fibroplasia

Dysplastic nevus is described as an important factor in increasing the risk of melanoma. Many authors suggested dysplastic nevi should be graded according to architectural and cytological features. Dermal fibroplasia can be in concentric or lamellar fashion. In our study we aim to grade architectural and cytological atypia in dysplastic nevi and to assess the relationship between atypia and dermal fibroplasia. Ninety-three biopsies obtained from 71 patients were included in the study group. Hematoxylin-eosin stained slides were evaluated and graded according to architectural and cytological features. A total score was obtained for both architectural and cytological atypia in each case. Masson Trichrome stained sections were used to assess dermal fibroplasia and evaluated semiquantitatively. Twenty-eight (30.1%) cases had mild, 48 (51.6%) cases moderate, and 17 (18.3%) cases had severe atypia regarding architectural features. Nine (9.7%) cases were scored having mild, 28 (30.1%) cases moderate, and 56 (60.2%) cases having severe atypia regarding cytologic features. There was a significant correlation between the degree of architectural and cytologic atypia. Six (21.4%) cases with mild, 31 (64.6%) cases with moderate,, and 12 cases (70.6%) with severe architectural atypia had dermal fibroplasia. One case (11.1%) with mild, 10 cases (% 35.7) with moderate, and 10 cases (67.9%) with severe cytological atypia had dermal fibroplasia. A significant relationship was found between the presence of fibroplasia and the degree of cytological and architectural atypia. A statistically significant relationship was revealed between the increase of architectural and cytological atypia and dermal fibroplasia. Detection and evaluation of stromal changes by histochemical methods, and scoring of atypia in dysplastic nevi may be helpful to distinguish dysplastic from other banal nevi.

Mitotic Activity Within Dermal Melanocytes of Benign Melanocytic Nevi: A Study of 100 Cases With Clinical Follow-up

Mitotic Activity Within Dermal Melanocytes of Benign Melanocytic Nevi: A Study of 100 Cases With Clinical Follow-up

Prognostic significance of phosphorylated signal transducer and activator of transcription 3 and suppressor of cytokine signaling 3 expression in human cutaneous melanoma

Cutaneous malignant melanoma is one of the most common and aggressive forms of human cancers and has a poor prognosis. Activation of signal transducer and activator of transcription 3 (STAT3) has been found in several human cancers and is thought to correlate aggressive disease and poor response. In this study, we investigated the clinical role of STAT3 and its natural inhibitor, suppressor of cytokine signaling 3 (SOCS3), in human cutaneous melanoma development and progression. Immunohistochemical analysis of pSTAT3, SOCS3, matrix metalloproteinase (MMP)-2, and MMP-9 expression was performed on 90 primary melanomas and 43 common melanocytic nevi specimens. The expression of STAT3 mRNA was further detected by in-situ hybridization in the same cohort of patients. The association of STAT3 mRNA, pSTAT3, and SOCS3 protein expression with clinicopathological parameters and patient survival was analyzed. Altered expression of STAT3 mRNA, pSTAT3, and SOCS3 protein was observed in melanoma specimens, compared with benign melanocytic nevi. High expression of pSTAT3 was correlated to large tumor diameter, depth of tumor invasion, tumor lymph node metastasis, MMP-2 and MMP-9 expression, and poor patient survival. Decreased expression of SOCS3 was correlated to depth of tumor invasion, tumor lymph node metastasis, the expression of MMP-2, MMP-9, and pSTAT3, and poor patient survival. Moreover, the expression of pSTAT3 was conversely correlated to SOCS3 expression in melanoma. Our results indicate that deregulated expression of pSTAT3 and SOCS3 might possess potential roles in the development and progression of human cutaneous melanoma.

The important role of interdisciplinary collaboration in the management of a melanocytic skin lesion.

One of the most confounding characteristics, commonly seen in malignant, but even in benign melanocytic nevi, is represented by the regression phenomenon. The identification of regression, through dermoscopical observation, can be predictive of a tricky histopathological examination. Therefore, this feature should be an alert to a meticulous clinical, dermoscopical and histopathological correlation for correct analysis of melanocytic skin lesions. A 26-year-old man was referred to our department for a pigmented skin lesion localized on his trunk. It was clinically and dermoscopically diagnosed as atypical melanocytic nevus with central regression. After 1 year the lesion underwent considerable changes, leading to a nearly complete regression. The lesion was excised and, on the basis of clinical, dermoscopical and histopathological correlation, was interpreted as a junctional melanocytic nevus with regression. In our case the association of clinical, dermoscopical and histopathological experience, resulted an important and useful method, in order to proper interpret and correctly diagnose an atypical melanocytic skin lesion.

Benign Dermoscopic Parallel Ridge Pattern Variants

T HE PARALLEL RIDGE PATTERN (PRP) IS A VOlar dermoscopic pattern that is characterized by an accentuated pigmentation on the ridges of the skin markings, while the furrows are hypopigmented or unpigmented. It has been demonstrated to be highly specific for acral melanoma, and its presence must be considered a warning sign of melanoma. However, rare cases of benign acral melanocytic nevus can exhibit the PRP, as in the edge of the compound melanocytic nevus shown in Figure1A. The acral blue nevus (Figure 1B) usually shows a bluish, quite homogeneous pigmentation involving the ridges. Ethnic pigmentation clinically presents as pigmented macules with a typical PRP on the palms and soles (Figure2A). The multiplicity, bilateral location, and chronicity of the lesions are suggestive of ethnic-type pigmentation. The presentation is similar in Laugier-Hunziker or Peutz-Jeghers syndrome. Ectasic papillary capillaries of acral angioma present as regular red-blue globules along the ridges (Figure 2B). Repetitive microtrauma can cause extravasation of erythrocytes in the cornified layer, with subsequent misleading globular reddish brown pigmentation on the ridges, as seen in Figure 3A, which shows a posttraumatic purpura due to the friction of the fifth finger caused by regular use of the computer mouse. The PRP was also found in subcorneal hematoma. The lesion appears as well-demarcated roundish macule, with reddish brown pigmentation along the ridges (Figure 3B). Deposit of exogenous pigmentation on the ridges, especially in areas where the stratum corneum is thicker, can also simulate melanoma, as shown in Figure 4, with the use of a self-tanning preparation by a woman with localized palmar hyperkeratosis.