Eruptive melanocytic nevi in a patient with amelanotic melanoma: a paraneoplastic phenomenon?

Eruptive melanocytic nevi (EMN) describes the sudden onset of cutaneous nevi over weeks or months. Such a clinical event is generally seen in young adult patients and may be related to several possible causes. We report here a case of EMN in an old male patient followed up for a thick amelanotic cutaneous melanoma. A few months after the eruption, multiple hepatic masses, diagnosed as melanoma metastasis, were detected. The presented case may suggest that EMN may be a paraneoplastic phenomenon of alert in patients being followed for melanoma or other malignancies.

Clinical and dermoscopic changes of acquired melanocytic nevi of patients treated with afamelanotide.

BACKGROUND: Afamelanotide (AFA) is a synthetic analogue of α-melanocyte-stimulating hormone that is approved for the treatment of patients affected by erythropoietic protoporphyria (EPP). AFA induces a "sun free" tanning and changes of acquired melanocytic nevi (AMN) that are generically described as "darkening". OBJECTIVES: To assess clinical and dermoscopic AMN changes during AFA treatment. METHODS: Adult EPP patients treated with two AFA implants 50 days apart were enrolled. They underwent a clinical and dermoscopic examination of all AMN at baseline (T0), and after 5 (T1) and 12 (T2) months from the first AFA implant. The general pattern, symmetry, number, and size of pigmented globules, morphology of the pigment network, and dermoscopic melanoma features were assessed. RESULTS: Fifteen patients were enrolled with 103 AMN. At T1 all reticular and 2-component AMN showed a focal network thickening that returned to baseline by T2. The increase of globules' number was observed at T1 but not at T2. The difference in number was not influenced by patients' age or phototype. Dermoscopic changes suggestive of malignancy were never seen. The development of new AMN was never registered. CONCLUSIONS: AFA treatment induces reversible changes of AMN dermoscopic morphology without findings suggestive of malignant transformation and it does not stimulate the development of new AMN.

Indoor tanning exposure in association with multiple primary melanoma.

BACKGROUND: Patients with primary cutaneous melanoma are at increased risk for subsequent new primary melanomas. Indoor tanning is a recognized risk factor for melanoma. This study was aimed at determining the association between indoor tanning and the occurrence of multiple primary melanoma. METHODS: This was a retrospective case-control study of cases with multiple primary melanoma and sex-matched controls with single primary melanoma retrieved at a 1:2 ratio from the Biological Sample and Nevus Bank of the Melanoma Center of the University of Pittsburgh Cancer Institute. Logistic regression models were used to examine the association between multiple primary melanoma and risk factors. RESULTS: In total, 330 patients (39.1% men) with a median age of 51 years were enrolled. Compared with patients who had a single primary melanoma, patients with multiple melanomas were younger at the diagnosis of their first primary melanoma and were more likely to be discovered at stage 0 or I and to have had indoor tanning exposure, a family history of melanoma, atypical moles, dysplastic nevi, and a Breslow thickness less than 1 mm. Compared with patients' first melanomas, subsequent melanomas were more likely to be thinner or in situ. The estimated probability of the locus for the second primary being the same as that for the first primary melanoma was 34%. In a multivariate analysis after adjustments for age, a family history of melanoma, the presence of atypical and dysplastic nevi, and recreational sun exposure, indoor tanning remained significantly associated with the occurrence of multiple primary melanoma (odds ratio, 2.75; 95% confidence interval, 1.07-7.08; P = .0356). CONCLUSIONS: Indoor tanning is associated with an increased risk of second primary melanoma. Subsequent melanomas are more likely to be thin or in situ and to occur in different anatomic locations.

Optic disc melanocytoma with normal tension glaucoma and angle closure glaucoma: Two case reports.

RATIONALE: Optic disc melanocytoma is an ophthalmic tumor that arises from melanocytes, and is a variant of the melanocytic nevus. Here we report 2 cases of optic disc melanocytoma in Asian patient: one associated with normal tension glaucoma (NTG), and the other associated with angle closure glaucoma (ACG). PATIENT CONCERNS: Case 1 is a 57-year-old Asian female presented to our department for a general ophthalmic examination. Incidentally, brownish pigmented lesion was found on dilated fundus examination of her right eye. The fundus examination and optical coherence tomography (OCT) examination revealed a mass within optic disc, and superotemporal retinal nerve fiber layer (RNFL) thinning. The Humphrey visual field test showed corresponding visual field defect. Fluorescein angiography showed no leakage around the lesion. Case 2 is a 78-year-old Asian woman presented with complaints of acute bilateral ocular pain. The initial examination revealed shallow anterior chamber. Under the impression of intermittent angle closure attack, prophylactic laser peripheral iridotomy were performed. On dilated fundus examination, black pigmented lesion was found at superior sector of optic disc. Further examination revealed bilateral superotemporal, inferotemporal RNFL thinning on OCT, and spatially corresponding visual field defects. DIAGNOSES: Clinical diagnosis of NTG was made for case 1 patient. Although it was a little distant from typical glaucomatous changes, nevertheless she had RNFL defect compatible with visual field defects. Considering her normal IOP and angle structures, we believe NTG was a probable diagnosis for the patient. In case 2, we made diagnosis of ACG presenting as intermittent angle closure attack because of her presenting symptoms, narrowing of anterior chamber and angle structures found on gonioscopic and slit lamp examinations. INTERVENTIONS: In Case 1, we prescribe 0.005% latanoprost ophthalmic solution. In Case 2, at first prophylactic laser peripheral iridotomy was performed. Then, topical eyedrops administration was started, and the patient was examined periodically. OUTCOMES: In Case 1, at 6 months' follow-up, OCT and visual field test showed no progression. In Case 2, to this date, the optic disc melanocytoma remains stable for over a 6-year-follow-up period. LESSONS: The fact that NTG and ACG can coexist in patients with melanocytoma of optic disc should be recognized, and the possibility of such should appropriately be evaluated.

Increased melanocytic nevi and lentigines in two patients with harlequin ichthyosis.

An increased number of melanocytic nevi and lentigines have been reported in patients with two types of autosomal recessive congenital ichthyosis (ARCI): lamellar ichthyosis and nonbullous congenital ichthyosiform erythroderma. These melanocytic lesions may have clinical and dermoscopic features of atypia, necessitating close surveillance. Here, we report two interesting cases of pediatric patients with harlequin ichthyosis (HI) who developed increased melanocytic nevi and lentigines. These cases are unique in that the patients presented at a younger age and one patient had a darker skin phototype than previously described in the literature.

Difference in distribution of malignant melanoma and melanocytic nevus in the palm and finger.

We conducted a study to try to plot the lesions of melanocytic nevus and malignant melanoma on the palm and fingers, and compared them to identify the different distribution pattern of both lesions. Data on 8 patients with melanomas (4 male and 4 female) and 26 patients with melanocytic nevus (6 male and 20 female) of palm and finger pulp who visited Wakayama Medical University Hospital between 1986 and 2018 was retrospectively collected. We found that all of the 8 lesions of melanoma were located on the finger pulps and distal to the 'distal transverse crease' of the palm, and that melanomas were not present proximal to the transverse crease. On the other hand, melanocytic nevus was present in the proximal area to the distal transverse crease of the palm more frequently than melanomas (50.0% vs. 0%), and there was statistically significant difference (p = 0.011 by Fisher's exact probability test). From these observations, our findings may reveal the contribution of mechanical stress to the cause of palmar melanoma, and may facilitate clinical differentiation between malignant melanoma and melanocytic nevus by the localization. Further studies with increased number of patients are needed to validate the finding.

Eruptive Nevi on the Palms and Soles with no Association with an Underlying Disease or Medications.

Eruptive melanocytic nevi are an unusual phenomenon characterized by sudden onset of multiple melanocytic nevi on previously unaffected skin. The majority of case reports have linked this condition with blistering skin disease or immunosuppression. There are only three reports of eruptive nevi developing on the palms and /or soles in healthy individuals. Herein we present the clinical and dermoscopic features of two cases of eruptive acral nevi that developed in healthy individuals in the absence of any recognizable underlying disease and review the current literature of eruptive nevi.

Eruptive Melanocytic Nevi: A Review.

Eruptive melanocytic nevi (EMN) is a phenomenon characterized by the sudden onset of nevi. Our objective was to compile all published reports of EMN to identify possible precipitating factors and to evaluate the clinical appearance and course. We conducted a systematic bibliographic search and selected 93 articles, representing 179 patients with EMN. The suspected causes were skin and other diseases (50%); immunosuppressive agents, chemotherapy or melanotan (41%); and miscellaneous, including idiopathic (9%). The clinical manifestations could largely be divided into two categories: EMN associated with skin diseases were frequently few in number (fewer than ten nevi), large, and localized to the site of previous skin disease, whereas those due to other causes presented most often with multiple small widespread nevi. In general, EMN seem to persist unchanged after their appearance, but development over several years or fading has also been reported. Overall, 16% of the cases had at least one histologically confirmed dysplastic nevus. Five cases of associated melanoma were reported. We conclude that the clinical appearance of EMN may differ according to the suggested triggering factor. Based on the clinical distinction, we propose a new subclassification of EMN: (1) widespread eruptive nevi (WEN), with numerous small nevi, triggered by, for example, drugs and internal diseases, and (2) Köbner-like eruptive nevi, often with big and few nevi, associated with skin diseases and most often localized at the site of previous skin disease/trauma. The nature of the data precluded assessment of risk of malignant transformation.

[miR-122-5p inhibits the proliferation of melanoma cells by targeting NOP14].

OBJECTIVE: To investigate the expression profile of miR-122-5p in melanoma tissues and the effect of miR-122-5p on the proliferation, cell cycle and apoptosis of human melanoma cell lines SK-MEL-110 and A375. METHODS: The expression profiles of miR-122-5p in melanoma and pigmented nevus tissues were detected using real-time fluorescence quantitative PCR (qRT-PCR). SK-MEL-110 and A375 cells transfected with miR-122-5p inhibitor or negative control inhibitor (NC) I were examined for miR-122- 5p expression using qRT-PCR and changes in cell proliferation, cell cycle and apoptosis using MTT assay or flow cytometry. NOP14 mRNA and protein expressions in the cells were detected using qRT- PCR and Western blotting, respectively. Luciferase reporter assay was used to confirm the identity of NOP14 as the direct target of miR-122-5p. RESULTS: The relative expression of miR-122-5p in human pigmented nevus tissues and melanoma tissues was 1.23±0.270 and 7.65 ± 1.37, respectively. The relative expression of miR-122-5p in SK-MEL-110 and A375 cells transfected with miR-122-5p inhibitor was 0.21 ± 0.08 and 0.17 ± 0.05, respectively. miR-122-5p inhibitor obviously inhibited the cell proliferation and increased the percentage of cells in G1 stage in both SK-MEL-110 and A-375 cells, but did not cause obvious changes in the apoptosis of the two cells. miR-122-5p inhibitor did not significantly affect the expression level of NOP14 mRNA, but obviously increased the expression level of NOP14 protein. Luciferase reporter assay revealed a significantly lower luciferase activity in cells co-transfected with miR-122-5p mimics and wild-type psi-CHECK2-3'UTR plasmid than in the cells cotransfected with NC and wild-type psi-CHECK2-3'UTR plasmid (0.21 ± 0.14 vs 0.56 ± 0.1, P < 0.01). CONCLUSIONS: miR-122-5p expression is upregulated in melanoma tissues, indicating its involvement in the development of melanoma. miR-122-5p inhibits the proliferation of SK-MEL-110 and A-375 cells possibly by affecting the cycle through NOP14.

Importancia del seguimiento de lesiones melanocíticas con dermatoscopia digital para el diagnóstico temprano de melanoma / Importance of monitoring melanocytic lesions with digital dermatoscopy for diagnosis early melanoma

La dermatoscopia digital es una herramienta que permite el diagnóstico de melanomas en estadios tempranos, por medio del seguimiento de las lesiones pigmentarias a largo plazo. Se comunican tres casos de pacientes con alto riesgo de melanoma, en los cuales ‒a través del seguimiento con dermatoscopia digital‒ se realizó el diagnóstico de la enfermedad mediante la detección de cambios morfológicos, arquitecturales y de pigmentación de las lesiones estudiadas. (AU)

Digital dermoscopy is a tool that allows the early diagnosis of melanomas, through the long-term follow up of pigmentary skin lesions. We report three cases of patients with high-risk of melanoma, in which the diagnosis had been made by morphological, arquitectural and pigmentary changes observed by the digital dermoscopy follow-up. (AU)

Eruptive melanocytic nevi in HIV infected patients: report of three cases.

The abrupt development of multiple melanocytic nevi has been described in association with many conditions, including human immunodeficiency virus infection. We report three cases of eruptive nevi in men with human immunodeficiency virus type 1 infection. One patient developed this phenomenon during the stage of acquired immunodeficiency syndrome. The other two patients had human immunodeficiency virus infection recently diagnosed and presented to our clinic reporting the development of multiple melanocytic nevi after starting highly active antiretroviral treatment, with improvement of their immunity. To our knowledge, this is the first report of eruptive melanocytic nevi as a possible consequence of the immune reconstitution inflammatory syndrome.

Phototherapy-induced blistering reaction and eruptive melanocytic nevi in a child with transient neonatal porphyrinemia.

Neonatal blue-light phototherapy induced a blistering reaction followed by eruption of melanocytic nevi on the exposed skin surface of a child with transient neonatal porphyrinemia. New nevi are still developing 4 years after the triggering event. The role of phototoxicity-induced epidermal injury, that of porphyrins and the influence of neonatal blue-light therapy, in this unique phenomenon are discussed.

Atypical Nevi in a Patient After Toxic Epidermal Necrolysis.

Dear Editor, There are few literature data about nevi in patients with a history of toxic epidermal necrolysis (TEN) and little recommendations for follow-up and risks of melanoma (MM). Eruptive melanocytic nevi (EMN) is a rare phenomenon that has been associated with bullous disorders, immunosuppression, and immunodeficiency, but in some cases can occur without precipitating factors (1). The etiology is largely unknown, but there is evidence that immunosuppression might play a crucial role in nevogenesis, probably due to the inability of the immune system to inhibit melanocytic (MC) proliferation (2,3). We report the follow-up of a patient with a history of TEN who later developed atypical nevi. A 17-year-old man with a history of severe TEN two years earlier, most probably due to valproic acid and diclofenac, was referred to our Department due to atypical nevi. The patient presented with scars, scattered pigmentation (Fig. 1), and symblepharon as a consequence of TEN (Fig. 2). Most of his nevi developed in following two years after TEN. During the first visit in 2009, clinical and dermoscopic photodocumentation was performed. The patient presented with a moderate number of nevi (Fig. 3), dermoscopically subclassified as globular. One atypical MN was found on the back, with dermoscopic findings of reticular pattern and presence of suspected areas of regression (Fig. 4. a, b), and it was excised to rule out melanoma (Fig. 4, Fig. 5). The patient did not come to regular follow-up from 2009 to 2014, and presented in 2014 which was when comparative photo documentation was made. As this visit another, speckled type of newly-occurred nevus was excised. Both excised nevi were histopathologically characterized as dysplastic. Only a few references are available on nevi development after TEN. Anticonvulsives and NSAIDs, as in our case, are often involved in the etiopathogenesis of TEN (4,5). Survivors may experience a variety of long-term complications; authors reported that 19% of their patients developed new nevi after TEN (6,7). EMN develop several years after TEN as a suddenly arising large number of nevi that may resemble speckled lentiginous nevi (8). Histologically. EMN demonstrate a proliferation of MC at the dermo-epidermal junction and, if compound, in the papillary dermis, arranged mostly in nests. Junctional MC may appear slightly pleomorphic, but no significant cytological atypia or prominent pagetoid spread of MC was reported (9). EMN have been associated with a specific dermoscopic finding of a symmetrical peripheral rim of globules which represent pigmented junctional nests of MC in the periphery and are a specific feature of rapidly enlarging MC nevi (10,11). The pathogenesis of EMN is not known. The microenvironment of epidermal regeneration may have some effects on MC because MC hyperplasia develops after cutaneous trauma (observed in recurrent nevi). The cytokines and growth factors produced and secreted during epidermal regeneration might contribute to the proliferation of residual epidermal MC and subsequent nevus formation (12). Because most of the bullous disorders associated with EMN are transient, the authors believe that changes in local growth factors may also be temporary and MN remain stable without a propensity to malignant degeneration without further stimuli (13). This is corroborated by the fact that no reports of malignant change of EMN in patients with bullous disorders have been described. It is likely that the etiology and natural course of EMN differs between two main populations of patients, with EMN arising after bullous disorders being more likely to remain benign compared with those with ongoing immunosuppression, but this hypothesis has yet to be proven. The actual risk of MM in patients with EMN remains unknown. Since our patient did not have many nevi, he does not fit into the EMN category. Due to the atypical appearance of his nevi, long-term follow-up on 6-month basis is recommended.

Sun-Protection Behavior, Pubertal Development and Menarche: Factors Influencing the Melanocytic Nevi Development-The Results of an Observational Study of 1,512 Children.

Observational studies consistently show that melanocytic nevus prevalence increases with age and that phenotypic traits are significantly associated with nevus count in children. An observational study of 1,512 children and adolescents from 2010 to 2013 was conducted. Study dermatologists counted the full body, arm, and facial nevi of each participant. Children and their parents were asked to complete a survey to gather data on personal characteristics, pubertal development, and early-life sun exposure. The main aim of the study was to establish pediatric nevus prevalence and its relationship with age, phenotype, sex, menarche, early-life sun exposure, and sun-protection behaviors. Females had a significantly lower nevus count compared with males, but this sex-related difference was significantly modified by menarche. Sun exposure and sun-protection habits were all significantly associated with nevus count; in particular, children who used sunscreen with a sun-protection factor > 30 had a lower nevus count compared with sun-protection factor ≤ 30 sunscreen users. This study shows that sex, menarche status, and sun-protection practices significantly influence nevus count in this pediatric population.