Agminated Flexural Melanocytic Nevi: A Late Sequela of Langerhans Cell Histiocytosis?

Abstract

Agminated flexural melanocytic nevi in children with a history of Langerhans cell histiocytosis (LCH) are rare and thought to be coincidental or related to systemic chemotherapy. We report on an 11-year-old boy in remission from LCH, treated with only topical steroids, who presented years later with an eruption of melanocytic nevi in the bilateral inguinal and axillary regions. Rather than coincidence, we hypothesize that agminated flexural melanocytic nevi are a late sequela of LCH, possibly resulting from immune tolerance or a reaction to local inflammation.

Agminated Spitzoid Naevi after Remission of Langerhans Cell Histiocytosis: First Italian Case and Literature Review

“…LCH skin involvement was described in 4 of 5 patients; however, all patients presented pigmented lesions in the folds, especially the groin and axillae. None of the patients developed naevi on the scalp, the area mostly involved in LCH (3)(4)(5).…”

“…One patient received only vinblastine (3). The case described by Feldstein et al (5) was treated with topical corticosteroids only. Our case received vinblastine, prednisone and methotrexate treatment (Table SI 1 ).…”

“…Despite the appearance of melanocytic naevi on areas previously affected by LCH, Berk & Lane (3) postulated that this manifestation was coincidental. Later, Surinach et al (4) and then Feldstein et al (5) suggested an immune-mediated mechanism with local immune dysregulation and inflammation. They also considered LCH to be an additional cause of eruptive melanocytic naevi, characterized by a specific distribution tracing some of the previous LCH cutaneous lesions.…”

“…They also considered LCH to be an additional cause of eruptive melanocytic naevi, characterized by a specific distribution tracing some of the previous LCH cutaneous lesions. This could be justified by the immune tolerance induced in LCH lesions by high levels of regulatory T cells (CD4 CD25 FoxP3 T-regs) (5,12). Another explanation could be that the proinflammatory cytokine cascade secreted in LCH lesions, especially IL-1, known to upregulate melanocortin-1 receptor (MC1R), may play a role in naevogenesis, stimulating melanocytic lesion development (5,12).…”

“…This could be justified by the immune tolerance induced in LCH lesions by high levels of regulatory T cells (CD4 CD25 FoxP3 T-regs) (5,12). Another explanation could be that the proinflammatory cytokine cascade secreted in LCH lesions, especially IL-1, known to upregulate melanocortin-1 receptor (MC1R), may play a role in naevogenesis, stimulating melanocytic lesion development (5,12). However, the timing of the naevi eruption and whether these naevi are developed de novo or by subclinical naevus nests is still unknown.…”