Eruptive Junctional Nevi Appearing During Langerhans Cell Histiocytosis Treatment

Abstract

Langerhans cell histiocytosis (LCH) is a multisystemic disorder that results from the clonal proliferation of immunophenotypically and functionally immature Langerhans cells (LC). The detection of the V600E mutation in the BRAF oncogene in LCH biopsy specimens supports previous evidence that LCH is a neoplastic disorder. This mutation is present in other cutaneous lesions including malignant melanoma and benign nevi. Single case reports of a correlation between LCH and the appearance of eruptive nevi limited to the inguinal folds after chemotherapy have previously been described in the literature. This suggested that LCH could be an additional cause of eruptive melanocytic nevi, with a specific distribution mimicking that of LCH cutaneous lesions. We present the case of a 6-year-old boy, previously treated with chemotherapy for Langerhans cell histiocytosis, with disseminated junctional nevi. Although this co-occurrence may be coincidental, the skin involvement is distinct from other previously reported clinical cases. It would be interesting to evaluate whether the BRAF mutation described in LCH cells might in fact support a genetic background for the development of nevi in these patients. LEARNING POINTS Langerhans cell histiocytosis (LCH) is a clonal neoplastic proliferation of immature Langerhans cells, with the V600E mutation in the BRAF oncogene present in approximately 60% of cases. The V600E mutation in the BRAF oncogene is also documented in other cutaneous lesions, namely malignant melanoma and benign nevi. There are case reports of a correlation between LCH and the appearance of eruptive nevi after chemotherapy, but it is not known whether the BRAF mutation described in LCH cells supports a genetic background for the development of nevi in these patients.

Eruptive agminated nevi in a successfully treated Langerhans cell histiocytosis patient

“…8 Another hypothesis is that nevi formed in response to increased regulatory T cells and pro-inflammatory cytokines associated with LCH. 7,9 With recent understanding of common genetic mechanisms that contribute to both LCH and nevogenesis, our case supports the hypothesis proposed by Carreno-Gayosso et al 5 Their hypothesis suggests that over-expression of the MAPK pathway explains the development of agminated nevi in patients with prior diagnosis of LCH. However, our findings are in contrast to Rotunno et al whose patient had positive cytoplasmic expression of BRAF V600E by immunochemistry in the original Langerhans cells, but not in the later noted nevi.…”

“…later development of numerous (>100) agminated nevi has been described previously in six pediatric patients ranging in age from 2 to 11 years, with a predominance of inguinal and flexural lesions where LCH of the skin tends to predominate. [5][6][7][8][9] Our case represents an unusually wide distribution of nevi. In our patient, we did not have sufficient photo documentation from the patient's diagnosis in 2011 to allow comparison of possible cutaneous LCH with sites of agminated nevi; however, the distribution of nevi appears mostly flexural (which is not consistent with descriptions of the original eruption).…”

“…Review of the literature identified another recent case report with a similarly wide distribution of nevi, but in that case, the nevi erupted while the patient was still undergoing treatment and there was no mention of correlation to LCH disease location. 7 Previously, it has been hypothesized that chemotherapy may have triggered the nevi development, but more recently, a case has been described in a child whose LCH treatment did not include chemotherapy. 8 Another hypothesis is that nevi formed in response to increased regulatory T cells and pro-inflammatory cytokines associated with LCH.…”

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

“…Lesions are clinically stable over time in terms of number and color after their first appearance [1,3]. Reported causes for EMN include immunosuppression, drugs, immunosuppressive agents, bullous skin diseases, neoplastic diseases, toxin exposure, concurrent medical conditions and idiopathic factors [1,[4][5][6][7].…”