Beyond Coincidence in Neurofibromatosis Type 1: Becker Nevus Adjacent to Plexiform Neurofibroma with Brachial Plexus Involvement and Integrated Mechanistic Illustration
Year: 2026
Type: article
Study design: Case Report
Abstract: Madam, Neurofibromatosis type 1 (NF1) is an autosomal dominant genodermatosis characterized by pigmented lesions, such as café-au-lait macules (CALMs), axillary freckling, and benign peripheral nerve sheath tumors.[1] Becker nevus (BN), a benign cutaneous hamartoma typically presenting as a hyperpigmented, hypertrichotic patch, is rarely associated with NF1.[1,2] Herein, we describe a pediatric case of genetically confirmed NF1 with a histologically and dermoscopically validated BN colocalized with a plexiform neurofibroma (PN) involving the brachial plexus. A 12-year-old girl presented with a darkly pigmented lesion on her left neck and upper extremity that had enlarged during puberty. Examination revealed bilateral axillary freckling, multiple CALMs, and Lisch nodules. Genetic testing confirmed a mutation in intron 48 of the NF1 gene, confirming a diagnosis of NF1. On palpation, the lesion was soft and exhibited a “worm-like” consistency. A 4 mm punch biopsy revealed a well-defined dermal spindle cell proliferation that tested positive for SOX-10 and S-100. A magnetic resonance imaging showed a C7–T1 posterior mediastinal mass with a hyperintense extension along the left brachial plexus, leading to a diagnosis of PN with brachial plexus involvement. The lesion was surrounded by a hyperpigmented, patchy area characterized by dense hair growth at the edges and satellite lesions extending from the area behind the left ear to the deltoid region [Figure 1a and b]. Its dermoscopic examination revealed perifollicular and focal hypopigmented areas, thickening of skin lines, focal thickening of pigment networks, and brown spots, leading to a diagnosis of PN with BN [Figure 1c and d]. Pigmented PN was excluded based on diffuse pubertal onset, irregular borders, terminal hair proliferation, satellite lesions, and absence of hallmark dermoscopic features such as a brown halo or fingerprint structures.[2]Figure 1: The view of the current lesion from different angles and dermoscopic findings. (a) Close-up view. (b) The rear view. (c) Thickening of skin lines (yellow arrows), perifollicular hypopigmentation (blue arrows), presence of brown spots (black circle, ×70). (d) Pigment network (red arrows), focal thickening of the pigment network (black circle), perifollicular/focal hypopigmentation (blue arrows, ×20)Although a few cases BN associated with NF have been reported in the literature, cases of BN adjacent to PN are extremely rare. In addition, our case stands out due to brachial plexus involvement.[2] There remains uncertainty regarding whether this association is coincidental or a variation of a common developmental process. Several hypotheses have been proposed to explain the link between BN and NF.[1-4] This rare association is linked to hamartomatous processes associated with abnormal development of neural crest cells in NF1, as these cells are the source of melanocytes, glia, and Schwann cells.[1] Somatic “second-hit” NF1 mutations cause localized neurofibromin loss, and when combined with the somatic mosaic events that generate BN, explain why only some NF1 patients develop such nevi.[3] Neurofibromin deficiency caused by NF1 mutation increases melanin production in melanocytes by activating the mitogen-activated protein kinase and phosphoinositide 3-kinase/mammalian target of rapamycin pathways through Ras hyperactivation.[4] Fibroblast-derived cytokines and mast cell-released pro-opiomelanocortin may also contribute to pigmentation in the PN region[1,2] [Figure 2]. Increased melanocyte hyperactivation resulting from these mechanisms emerges as a primary pathogenic process that can explain the association of NF1 with CALMs, BN, and other hyperpigmented lesions.Figure 2: Schematic illustration synthesizing proposed mechanisms of melanocyte hyperactivation and pigmentary mosaicism in neurofibromatosis type 1 (NF1). Neural crest-derived melanocytes may be influenced by local somatic NF1 “second-hit” mutations and the tumor microenvironment. Loss of neurofibromin leads to Ras pathway activation, driving melanin synthesis and melanocyte proliferation through mitogen-activated protein kinase and phosphoinositide 3-kinase/mammalian target of rapamycin cascades. Fibroblast-secreted growth factors (nerve growth factor, hepatocyte growth factor, and stem cell factor) and mast cell-derived alpha-melanocyte-stimulating hormone further contribute to localized melanocyte stimulation in lesions such as café-au-lait macules and Becker nevus. NF1: Neurofibromatosis type 1, NGF: Nerve growth factor, HGF: Hepatocyte growth factor, SCF: Stem cell factor, POMC: Pro-opiomelanocortin, α-MSH: Alpha-melanocyte-stimulating hormone, MAPK: Mitogen-activated protein kinase, PI3K: Phosphoinositide 3-kinase, mTOR: Mammalian target of rapamycin.In our case, the presence of PN surrounding BN provides important clues for understanding the cellular and molecular dynamics involved in these lesions and may guide future studies. Declaration of consent The authors certify that they have obtained all appropriate consent forms, duly signed by the parent(s)/guardian(s) of the patient. In the form, the parent(s)/guardian(s) has/have given his/her/their consent for the images and other clinical information of their child to be reported in the journal. The parents understand that the names and initials of their child/children will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.
Authors: Niyazi Cetin, Ahmet Ugur Atilan, Ahmet Metin
Institution: Pamukkale University
Language: English
Subfield: Clinical Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W7141664069