Unmasking the genetic simulator: Late diagnosis of neurofibromatosis type 1 after the discovery of a renal neurofibroma

ABSTRACT Background Neurofibromatosis type 1 (NF1) predisposes patients to various tumors. However, the sequential occurrence of rare visceral neoplasms of different histological origins in a single patient is exceptional. Case Presentation A two-year-old male was diagnosed with an embryonal bladder rhabdomyosarcoma (RMS). A decade later, at age 12, he presented with lumbar pain; subsequent imaging revealed a suspicious renal mass, prompting a nephrectomy. Histopathological and immunohistochemical analyses confirmed a plexiform renal neurofibroma (RNF). This unexpected RNF discovery prompted a comprehensive clinical evaluation, revealing skeletal dysplasia and café-au-lait macules; molecular genetic testing subsequently identified a de novo pathogenic NF1 variant, establishing the delayed diagnosis. Conclusion This constitutes, to our knowledge, one of the first documented cases of an RNF associated with NF1. It underscores that any visceral neurofibroma mandates ruling out underlying syndromic conditions. Crucially, it underscores the rare occurrence of a renal neurofibroma as a second, histologically distinct neoplasm in a pediatric NF1 patient who is a long-term survivor of bladder RMS, and highlights the value of extended oncologic surveillance, bearing in mind that the cardinal cutaneous, neural, and skeletal stigmata of NF1 emerge at different ages and need not all be present in early childhood.