To analyze a rare case with multiple spinal neurofibromas with KRAS mutation and no reportable NF1 variations.

Multiple neurofibromas are tumors growing from nerve cells that are usually associated with Neurofibromatosis type 1 (NF1), a condition with germline mutation in the NF1 tumor suppressor gene. These benign nerve sheath tumors arise as bulging and deforming masses and can cause significant neurological morbidity. We present a unique case of a patient with segmental neurofibromas that can be seen in mosaic NF1 without other NF1 clinical features. Genetic testing unexpectedly revealed a KRAS missense variation in exon 2, while no reportable NF1 variations were identified in the tumor tissues.

We performed a comprehensive review of patient’s medical history for NF1 stigmata, investigated further molecular genetic testing of tumor tissues, and also performed a literature search for other similar cases.

This patient presented with 1 cutaneous neurofibroma and multiple large spinal neurofibromas involving the cervical and upper thoracic spine but otherwise minimal manifestations of other NF1 clinical features such as café au lait macules. Further molecular testing through next generation sequencing and subsequent Sanger sequencing of 2 different tumor tissues confirmed a pathogenic KRAS variant with no reportable NF1 variations. Patient is now characterized to have a RASopathy.

The molecular targeted therapies available for treating NF1 differ from those for KRAS alterations. This case study underscores the importance of conducting further molecular investigations in atypical NF1 cases and finding new methods to differentiate NF1 from genetic alterations that may resemble it.