Acquired Melanocytic Nevi Mimicking Acral Lentiginous Melanoma in a Patient Taking a BRAF Inhibitor.

This case report describes a patient in their 60s with metastatic colon cancer who developed multiple new dark nevi within 2 months of initiating encorafenib and panitumumab therapy.

Ponatinib-induced eruptive nevi and melanocytic proliferation.

Ponatinib, an oral third-generation tyrosine kinase inhibitor, is indicated for the treatment of imatinib-resistant leukemia. We experienced a case of ponatinib-induced eruptive nevi, and the biologic effects of ponatinib on melanocytes were investigated. Treatment with ponatinib significantly increased the proliferation of normal human melanocyte or melanoma cells through the upregulation of the extracellular signal-regulated kinase and protein kinase B signaling pathways. The downstream molecules of cyclin B1 and D1 were significantly increased in ponatinib-treated melanocytes. These results demonstrate the capacity of ponatinib to induce the proliferation and tumorigenesis of melanocytes.

Regulatory T Cells Play an Important Role in the Prevention of Murine Melanocytic Nevi and Melanomas.

Melanocytic nevi are benign proliferations of pigment cells that can occasionally develop into melanomas. There is a significant correlation between increased nevus numbers and melanoma development. Our previous reports revealed that 7,12-dimethylbenz(a)anthracene (DMBA) and 12-O-tetradecanoyl-phorbol-13-acetate (TPA) induced dysplastic nevi in C3H/HeN mice, with a potential to transform into melanomas. To understand the immune mechanisms behind this transformation, we applied increasing DMBA doses followed by TPA to the skin of C3H/HeN mice. We observed that increased doses of DMBA correlated well with increased numbers of nevi. The increased DMBA dose induced diminished immune responses and promoted the expansion of regulatory T cells (Treg) that resulted in increased IL10 and reduced IFNγ levels. Mice with increased nevus numbers had loss of p16 expression. These mice had increased migration of melanocytic cells to lymph nodes (LN) and a greater percent of LNs produced immortalized melanocytic cell lines. DMBA-induced immunosuppression was lost in CD4-knockout (KO) mice. Lymphocytes in the CD4KO mice produced less IL10 than CD8KO mice. Furthermore, CD4KO mice had significantly reduced nevus numbers and size compared with wild-type and CD8KO mice. These results suggest that Tregs play a vital role in the incidence of nevi and their progression to melanoma.Prevention Relevance: There has been little progress in developing novel strategies for preventing premalignant dysplastic nevi from becoming melanomas. In this study in mice, regulatory-T cells enhanced progression of benign nevi to malignant melanomas; and by inhibiting their activity, melanomas could be retarded. The findings identify new possibilities for melanoma prevention in high risk individuals.

Eruptive melanocytic nevi during etanercept treatment in an ankylosing spondylitis patient: Case report.

Eruptive melanocytic nevi (EMN) are rare multiple melanocytic lesions that rare and associated with dermatological and systemic diseases. Drug induced EMN is also reported with the use of biological or nonbiological chemotherapeutics, immunosuppressive agents, and melanocyte stimulators. In recent years, the increasing use of biological drugs resulted in an increased reports of EMN induced by these drugs. The objective of this abstract is reporting EMN in a patient receiving etanercept treatment. In addition, we also present a literature review of the previously cases with anti-tumor necrosis factor-α biological agents.

Eruptive Melanocytic Nevi Secondary to Encorafenib for BRAF Mutant Metastatic Colorectal Cancer.

A 59-year-old woman, undergoing treatment with encorafenib for metastatic BRAF mutated colorectal cancer, developed during the first two months of therapy multiple eruptive nevi and changes in pre-existing nevi. Development of eruptive nevi has increasingly been reported in association with medications, most frequently conventional immunosuppressants and biologics. Some drugs are associated with eruptive nevi through an indirect effect of their mechanism of action, whereas other drugs are directly implicated in melanocyte proliferation. In this regard, BRAF inhibitors have been demonstrated to activate the MAPK pathway, and to promote cellular proliferation and survival, therefore leading to the development of new melanocytic nevi and to an increase in the size and hyperpigmentation of pre-existing nevi. A dermatological assessment and follow-up should be recommended in all patients presenting with eruptive nevi, regardless of the pathogenesis, because a high number of acquired melanocytic nevi may represent an adjunctive risk factor for melanoma.

[Anti-TNF alpha-induced eruptive nevi: Three cases]. / Nævus éruptifs sous anti-TNF alpha. Trois observations.

BACKGROUND: Eruptive melanocytic nevi (EMN) are a rare phenomenon characterized by simultaneous rapid onset of multiple nevi. The condition has been described in different contexts: immunosuppression, immunosuppressive drugs, targeted therapies, bullous diseases, and chemical melanocytic stimulation. We report 3 cases of EMN following anti-TNF alpha treatment. PATIENTS AND METHODS: Case 1 - A 51-year-old female patient was receiving adalimumab for spondyloarthritis (the first treatment for this patient). A few months after the start of treatment, multiple nevi were noted on the 4 limbs, and in particular on the right palm. The patient confirmed the absence of these lesions before initiation of treatment. A diagnosis was made of adalimumab-induced EMN. Case 2 - A 49-year-old male patient was receiving etanercept for spondyloarthritis (the first biologic in this patient). Multiple small nevi developed on the trunk in the months after the start of treatment. The patient indicated that these lesions had appeared after the start of treatment. A diagnosis was made of etanercept-induced EMN. Case 3 - A 20-year-old woman with hidradenitis suppurativa was treated with infliximab. After 1.5 months, she reported the outbreak of various pigmented lesions 2-3mm in diameter on the trunk and one lesion on her right palm. The clinical diagnosis was EMN. After follow-up of 4 months to 5 years, no transformation to melanoma was noted in any of these 3 patients. CONCLUSION: EMN remains a rare phenomenon in patients on anti-TNF alpha. These cases, associated with the description of a moderate increased risk of developing cutaneous carcinoma under anti-TNF alpha, underscore the need for dermatological follow-up and increased sun protection in patients receiving this treatment.

Regressed melanocytic nevi secondary to pembrolizumab therapy: an emerging melanocytic dermatologic effect from immune checkpoint antibody blockade.

BACKGROUND: Immune checkpoint antibody blockade is an emerging therapeutic option for treating certain cancers including melanoma. This therapy is associated with dermatologic and systemic toxicities, some of which are more severe than others and may require withholding therapy. CASE REPORTS: We report two patients with melanocytic nevi that regressed with pembrolizumab therapy. The first patient had stage IV BRAF K601E/L584F mutant melanoma that developed a regressed melanocytic nevus while being treated with pembrolizumab. The second patient had stage III BRAF V600R mutant melanoma that was treated with pembrolizumab and dabrafenib, and also developed a regressed melanocytic nevus. Both patients had good response to therapy and stable disease at 8 and 12 months of treatment, respectively. RESULTS: Regressed melanocytic nevi were observed in both patients treated with pembrolizumab for advance-stage melanoma. Immunohistochemical analysis of a regressed melanocytic nevus was associated with an inflammatory infiltrate rich in CD8+ T cells and CD163+, CD11c+ histiocytes. CONCLUSION: Regressed melanocytic nevi are an emerging dermatologic effect from pembrolizumab therapy.

Sequential monitoring of pigmented lesions during dabrafenib treatment: a prospective study and a literature overview.

BACKGROUND: Targeted therapies in melanoma have shown clinical benefit in incrementing the overall survival of metastatic patients. However, cutaneous adverse events have been frequently associated with these drugs. METHODS: We report our experience in the management of patients treated with dabrafenib for metastatic melanoma, focusing on the monitoring of pigmented lesions. Dermatologic evaluation was performed during the first visit, at the start of each treatment and subsequently after every four weeks. Global nevi count, videodermoscopy of suspected lesions, and surgical excisions when necessary were performed at the beginning of the treatment and every fourth week. All other cutaneous adverse events (cAEs) were noted and documented. Eleven patients were included. RESULTS: The most important cAEs included palmo-plantar hyperkeratosis, diffuse xerosis and pigmented lesion changes. Regarding the latter, in 6 patients, especially in the first months of treatment, we observed hyperpigmentation and hyperkeratosis of the nevi, of the pigmented mucosae and, in one patient, hyperkeratotic changes on a cutaneous metastasis. Histopathology of the excised lesions showed one ex novo melanoma occurrence and benign changes to pre-existing nevi. CONCLUSIONS: The awareness of the importance of sequential monitoring of pigmented lesions, with particular attention to the lesions of new onset, is crucial for the best management of these complex patients.

FR - Nevus melanocíticos eruptivos asociados a medicamentos / Drug-Induced Eruptive Melanocytic Nevi

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Eruptive Melanocytic Acral Nevi in the Setting of 6-mercaptopurine Therapy.

Eruptive melanocytic nevi (EMN) are a rare clinical finding characterized by sudden-onset nevi that often present in a grouped distribution. They have been associated with chemotherapy, immunosuppression, bullous diseases, and medications including multikinase and BRAF inhibitors. It is important for dermatologists to be able to identify patients with sudden development of new melanocytic nevi secondary to particular medications. Herein, we describe a case of eruptive melanocytic acral nevi secondary to 6-mercaptopurine therapy.

J Drugs Dermatol. 2017;16(5):516-518.