Pigment cell‐related manifestations in neurofibromatosis type 1: an overview

Abstract

SummaryNeurofibromatosis type 1 (NF1) is an autosomal dominant neurocutaneous disorder, affecting approximately 1 in 3500 individuals. The most commonly seen tumors in NF1 patients are the (sub)cutaneous neurofibromas. However, individuals with NF1 typically present in childhood with welldefined pigmentary defects, including café -au-lait macules (CALMs), intertriginous freckling and iris Lisch nodules. NF1 is considered a neurocristopathy, primarily affecting tissues derived from the neural crest. Since the pigment producing melanocyte originates in the neural crest, the presence of (hyper)pigmentary lesions in the NF1 phenotype because of changes in melanocyte cell growth and differentiation is to be expected. We want to discuss the pigmentary cutaneous manifestations of NF1 represented by CALMs and intertriginous freckles and the pigmentary non-cutaneous manifestations represented by iris Lisch nodules. Several hypotheses have been suggested in explaining the poorly understood etiopathogenesis of CALMs. Whether other pigmentary manifestations might share similar etiopathogenic mechanisms remains obscure. Additional attention will be drawn to a readily seen phenomenon in NF1: hyperpigmentation overlying (plexiform) neurofibromas, which could suggest common etiopathogenetic-environmental cues or mechanisms underlying CALMs and neurofibromas. Finally, we want to address the relationship between malignant melanoma and NF1.

Mucosal Pigmentation Caused by Imatinib: Report of Three Cases

“…Addison disease represents primary adrenocortical insufficiency, stimulating the expression of ACTH and a-MSH similar to the estrogen-induced pigmentation mentioned previously. The pathophysiologic mechanism of pigmentation in neurofibromatosis remains uncertain [24]. In all these conditions, there is an increase in melanin pigment within the basal cell layer with incontinent melanin and melanophages in the lamina propria to varying degrees, without concomitant deposition of iron unless there has been hemorrhage.…”

“…Diffuse post-inflammatory hyperpigmentation is a macular hypermelanosis associated with damage to the epithelium, such as in lichenoid processes where the basal cell layer is degenerated. Pigmentation associated with systemic disease, such as Albright syndrome, Peutz-Jegher syndrome, Addison disease, and neurofibromatosis, occurs as Cafe´au lait macules or diffuse pigmentation involving mucosa and skin [24]. Gsa gene mutation and cAMPmediated tyrosine kinase activation in melanocytes may play important roles in the formation of pigmented lesions in Albright syndrome [25].…”

Multipotent skin-derived precursors: adult neural crest-related precursors with therapeutic potential

“…NB affects migrating early NC precursors of the sympathoadrenal lineage and results in tumours whose primary sites are the adrenal glands and paraspinal sympathetic ganglia, with metastases to bone, lymph nodes, liver and even skin (Kushner 2004;Henry et al 2005). A second candidate is neurofibromatosis type 1 (NF1; Lakkis & Tennekoon 2000;De Schepper et al 2005). NF1 is a highly prevalent (1 : 3500) autosomal dominant disorder that results from mutations in the gene encoding neurofibromin.…”

Plexiform Neurofibroma on Giant Congenital Melanocytic Nevi - Neurofibromatosis Type 1 Case

“…Yüzeysel yerleşimli olanlar palpe edilebilirler ve palpasyonla elde uyandırdıkları his itibariyle "solucan torbası'' olarak isimlendirilmişlerdir. Üzerlerindeki epidermis diğer alanlara göre daha koyu renkli ve fazlaca tüylenme gösterebilir (9). Çok daha büyük olan pleksiform nörofibromlarda tümör üzerindeki derinin birbiri üzerine katlanmasıyla lokalize bir kutis laksa görünü-mü oluşabilir (10).…”

“…Pleksiform kitlesi, zemine göre daha kızıl-kahverengiydi ve üzerindeki tüyler çevre-sindeki alana göre daha seyrekti ve lezyonda tipik kutis laksa görünümü oluşmaya başlamıştı. Doğumda var olan geniş çaplı, genellikle düzensiz sınırlı hiperpigmentasyonların (melanositik nevüsler, kafeola makülü) ve lokalize hipertrikoz alanlarının, altta yatan bir pleksiform nörofibromun habercisi olabileceği belirtilmiştir (9). Literatürde az sayıda olguda pleksiform nörofibroma eşlik eden, dev pigmente kıllı nevüs (nöronevüs) ve sakral hipertrikoz gibi lokalize hipertrikoz olguları vardır (11).…”