Aberrant expression of HMB45 and negative PRAME expression in halo nevi.

BACKGROUND: Traditionally, most cutaneous nevi show a gradient of HMB45 (human melanoma black 45) and negative PRAME (preferentially expressed antigen in melanoma) immunostaining, while melanomas often show irregularly positive, diffusely positive or completely negative HMB45 expression, and PRAME immunopositivity. However, we have occasionally observed benign halo nevi with loss of HMB45 gradient, raising diagnostic consideration for melanoma. The purpose of this study was to elucidate the expression pattern of HMB45 and PRAME in nevi with the halo phenomenon (NHP). METHODS: PRAME and HMB45 staining patterns in 20 cases of NHP and 16 cases of conventional nevi were evaluated using light microscopy. An HMB45 gradient was defined as immunopositivity in only superficial melanocytes. HMB45 aberrant expression consisted of superficial and deep immunopositivity. RESULTS: Aberrant HMB45 expression was observed in 10 of 20 NHP (50%). A gradient of HMB45 staining was seen in most conventional nevi, with only one showing focal weak expression in the deep dermis (6.3%). All cases of NHP and conventional nevi showed essentially negative immunostaining by PRAME. CONCLUSION: Aberrant HMB45 expression in NHP is not uncommon and may be a diagnostic pitfall. Negative PRAME immunostaining may be a reassuring finding to help differentiate halo nevus from malignant melanoma.

Comparison of the Inflammatory Infiltrates in Tumoral Melanosis, Regressing Nevi, and Regressing Melanoma.

BACKGROUND: Tumoral melanosis (TM) is a histologic diagnosis characterized by abundant pigment-laden macrophages in the dermis. It is generally thought to represent a regressed melanoma, although it has also been reported after benign pigmented lesions as well. Determining the antecedent lesion in cases of TM is of clinical importance to accurately guide therapy and prognostication. Comparing the histopathologic and immunohistochemical (IHC) characteristics of TM, halo nevi (HN), and regressing melanoma (RM) may help predict the antecedent lesion in cases of TM. METHODS: Cases of TM, HN, and RM were selected and assessed for histopathologic (preservation of junctional melanocytic component, depth and width, solar elastosis, fibrosis, and preservation of rete ridge architecture) and IHC (SOX-10, CD138, and PD-1) parameters. PD-L1 immunostaining was also evaluated in cases of HN and RM. RESULTS: Severe solar elastosis, fibrosis, and marked rete ridge effacement were more frequent in RM than in HN. By contrast, numerous plasma cells, clusters of lymphocytes expressing PD-1, and >50% PD-L1 expression in melanocytes were more common in HN than in RM. However, the association of these variables did not reach statistical significance. DISCUSSION: Although studies with higher statistical power are needed, this study serves as an initial investigation to characterize the histopathologic and IHC characteristics, which may help better understand TM and its precursor lesions.

The color of skin: white diseases of the skin, nails, and mucosa.

White diseases are a heterogenous group characterized by hypopigmentation or depigmentation. Skin and eye color are determined by the number and size of melanosomes present. Melanin is produced by melanosomes in the melanocytes present within the epidermis of the skin, uvea, and retinal pigmented epithelium (RPE). Conditions altering the number of melanocytes or concentration of melanin result in a lack of pigmentation, appearing as "white diseases" ranging from the well-known albinism and vitiligo to more esoteric white hand syndrome and Degos disease.

Factors Associated with Development of Vitiligo in Patients with Halo Nevus.

BACKGROUND: Halo nevus (HN) has been shown to be associated with vitiligo, but no standard signs are currently available to identify HN patients at risk of vitiligo, and the relevant data obtained in previous studies are somewhat conflicting. This study aimed to identify factors affecting the presence of vitiligo in HN patients. METHODS: We performed a retrospective study on consecutive patients with HN at the First Affiliated Hospital of Sun Yat-sen University between January 2011 and December 2016. Detailed demographic and clinical data were collected to identify the factors associated with the presence of vitiligo in this cohort of patients using uni- and multi-variate logistic regression analyses. RESULTS: A total of 212 HN patients were included, 101 of whom had vitiligo-associated HN (HNV). Univariate analysis indicated that a personal history of thyroid diseases was positively associated with HNV (odds ratio [OR] = 10.761, P = 0.025), while the onset age of HN was negatively associated with HNV (OR = 0.537, P = 0.026). Multivariate analysis demonstrated that the Koebner phenomenon (KP; OR = 10.632, P < 0.0001), multiple HN (OR = 3.918, P < 0.0001), and a familial history of vitiligo (OR = 3.222, P = 0.014) were independent factors associated with HNV. CONCLUSIONS: HN without vitiligo has clinical features distinct from HN associated with vitiligo. HN patients with KP, multiple lesions, or familial history of vitiligo are more likely to develop vitiligo and therefore should be monitored for clinical signs of such accompanied conditions.

Differences in the melanosome distribution within the epidermal melanin units and its association with the impairing background of leukoderma in vitiligo and halo nevi: a retrospective study.

Skin color is determined by the number of melanin granules produced by melanocytes that are transferred to keratinocytes. Melanin synthesis and the distribution of melanosomes to keratinocytes within the epidermal melanin unit (EMU) within the skin of vitiligo patients have been poorly studied. The ultrastructure and distribution of melanosomes in melanocytes and surrounding keratinocytes in perilesional vitiligo and normal skin were investigated using transmission electron microscopy (TEM). Furthermore, we performed a quantitative analysis of melanosome distribution within the EMUs with scatter plot. Melanosome count within keratinocytes increased significantly compared with melanocytes in perilesional stable vitiligo (P < 0.001), perilesional halo nevi (P < 0.01) and the controls (P < 0.01), but not in perilesional active vitiligo. Furthermore, melanosome counts within melanocytes and their surrounding keratinocytes in perilesional active vitiligo skin decreased significantly compared with the other groups. In addition, taking the means-standard error of melanosome count within melanocytes and keratinocytes in healthy controls as a normal lower limit, EMUs were graded into 3 stages (I-III). Perilesional active vitiligo presented a significantly different constitution in stages compared to other groups (P < 0.001). The distribution and constitution of melanosomes were normal in halo nevi. Impaired melanin synthesis and melanosome transfer are involved in the pathogenesis of vitiligo. Active vitiligo varies in stages and in stage II, EMUs are slightly impaired, but can be resuscitated, providing a golden opportunity with the potential to achieve desired repigmentation with an appropriate therapeutic choice. Adverse milieu may also contribute to the low melanosome count in keratinocytes.

Cutaneous Metastatic Melanoma Resembling a Halo Nevus, in the Setting of PD-1 Inhibition.

Malignant melanoma is a common source of cutaneous metastases and can occasionally adopt a histological appearance which mimics a primary melanocytic lesion, either benign or malignant. The authors describe a case of new cutaneous deposits of metastatic melanoma in a 70-year-old woman with a prominent admixed lymphocytic infiltrate, imparting a striking resemblance to a halo nevus. The authors believe this appearance was a direct reflection of treatment with pembrolizumab, a humanized antibody against the immune checkpoint inhibitor programmed death-1. With increasing use of immune-modulating drugs, this potential histological mimic may be seen more frequently in the future.

Association analysis of class II cytokine and receptor genes in vitiligo patients.

The loss of melanocytes in vitiligo is mainly attributed to defective autoimmune mechanisms and lately autoinflammatory mediators have become more emphasized. Among these, a number of class II cytokines and their receptors have displayed altered expression patterns in vitiligo. Thus, we selected 30 SNPs from the regions of respective genes to be genotyped in Estonian case-control sample (109 and 328 individuals, respectively). For more precise analyses, patients were divided into subgroups based on vitiligo progression activity, age of onset, sex, occurrence of vitiligo among relatives, extent of depigmented areas, appearance of Köbner's phenomenon, existence of halo nevi, occurrence of spontaneous repigmentation, and amount of thyroid peroxidase antibodies. No associations appeared in whole vitiligo group. In subgroups, several allelic and haplotype associations were found. The strongest involved SNPs rs12301088 (near IL26 gene), that was associated with familial vitiligo and existence of halo nevi, and rs2257167 (IFNAR1 gene), that was associated with female vitiligo. Additionally, haplotypes consisting of rs12301088 and rs12321603 alleles (IL26-IL22 genes), that were associated with familial vitiligo and existence of halo nevi. In conclusion, several genetic associations with vitiligo subphenotypes were revealed and functional explanations to these remain to be determined in respective studies.

Resolution of vitiligo following excision of halo congenital melanocytic nevus: a rare case report.

Halo congenital melanocytic nevus (CMN) associated with vitiligo is rare, especially with regard to CMN excision. Only two reports of excision of halo CMN following repigmentation of vitiligo are found in the literature. We present a case of a girl with halo CMN and periorbital vitiligo. The halo CMN was excised and followed by spontaneous improvement of vitiligo. The result suggests excision of the inciting lesion may be a promising way to control vitiligo.

Hemangioma hemosiderótico en diana / Targetoid hemosiderotic hemangioma

No disponible

Study of the immunophenotype of the inflammatory cells in melanomas with regression and halo nevi.

The pathogenesis and prognostic implications of regression in melanoma are not well understood. It has traditionally been considered an immunologically mediated phenomenon. Improvement in the knowledge of the mechanisms that lead to regression may prove to be of great value in an era in which treatments oriented to the augmentation of the host's immunity against melanoma have demonstrated excellent clinical results. This study was designed to improve the understanding of the mechanisms underlying melanoma regression and the differences between similar situations in benign melanocytic nevus. The study sample consisted of 77 lesions: 62 melanomas and 15 halo nevi. The following markers were included in the study: CD4, CD8, FoxP3, PD1, CD123, granzyme, and TIA-1. Staining was evaluated in 5 categories, according to the percentage of labeled cells. Granzyme, PD1, and TIA-1 stained significantly more cells in halo nevi than in melanomas with regression (P < 0.01). The ratio CD123/TIA-1 was higher in melanomas than in halo nevi (1 vs. 0.67, P < 0.05). Regression in the 62 melanomas was categorized as early in 14 cases and late in 48 cases. Early regression was associated with a higher percentage of CD123, CD4, and TIA-1 staining than late regression. The inflammatory infiltrate found in halo nevi is characterized by a higher number of active cytotoxic T cells and regulatory PD1-positive T cells than the infiltrate found in melanoma with regression. CD123 staining was higher in early regression than in late regression, suggesting the presence of a tolerogenic mechanism in this phenomenon's initiation phase.