Atypical Neurofibromatous Neoplasms of Uncertain Biological Potential in Children with Neurofibromatosis Type 1: Report of Two Patients and Review

Atypical neurofibromatous neoplasm of uncertain biological potential (ANNUBP) lies between plexiform neurofibroma and malignant peripheral nerve sheath tumor (MPNST) in neurofibromatosis type 1 (NF1). Pediatric data are limited. We report two children with NF1 and rapidly enlarging peripheral nodules. Patient 1: a 13-year-old boy developed a lumbogluteal nodule despite prior selumetinib. Ultrasound showed a hypoechoic lesion with vascularity; magnetic resonance imaging confirmed interval growth. Excision revealed hypercellularity, architectural loss, cytologic atypia, and up to 2 mitotic figures/10 high-power fields. Immunohistochemistry showed S100/SOX10 positivity, focal CD34 loss, p16 loss, p53 wild-type pattern, and Ki-67 ≈1% overall, consistent with ANNUBP. Patient 2: a 15-year-old girl had a painful mass on the volar forearm. Resection disclosed a tumor embedded with a median-nerve fascicle. Histology showed hypercellularity, architectural loss, and 1 mitotic figure/10 high-power fields without necrosis; Immunohistochemistry showed S100, focal CD34/p16 reduction, and Ki-67 < 1%. Both patients remain recurrence-free under risk-adapted surveillance. ANNUBP is defined by ≥2 of atypia, hypercellularity, architectural loss, and low-level mitotic figures. Frameworks integrate morphology with CDKN2A/B and emphasize retained H3K27me3 to distinguish ANNUBP from MPNST. In children, ultrasound, magnetic resonance imaging, and positron emission tomograph support triage and biopsy. When feasible, complete excision is preferred; unresectable lesions need closer imaging. Early recognition widens cure opportunities and may refine risk stratification.