All of the three affected patients in the present case series exhibit a distinct clinical entity of SNF, consisting of extensively and apparently symmetrically distributed, histologically proven, neurofibromas involving one segment of the spine and/ or body (i.e. cervical spine and neck in two cases and lumbar spine and buttock in the other). Surgical intervention is indicated when myelopathy and motor losses develop, which are frequently localized to the cervical and lumbar regions.
In our case series, one patient presented in middle age, and one as a teenager. None of them have cognitive or skeletal involvement, and all have very limited cutaneous disease. The patient with lumbar disease has a large plexiform tumor of the buttock. One of the two cervical patients has an extensive tumor burden in the soft tissue of the neck including the sympathetic chain and/ or brachial plexus. In our opinion, bilateral neurofibromas in all roots of a given spinal segment should be regarded as segmental phenotype. Since 2 of the 3 patients presented later in their life, it is reasonable to refer to them as phenotypically segmental/mosaic NF1 which involves bilateral neurofibromas in all the spinal roots of a given segment later involved entire spinal roots bilaterally. Furthermore, the plexiform neurofibroma observed in one of our patients is part of spinal NF1 phenotype or part of a phenotype where spinal root neurofibromas are seen along with plexiform neurofibroma. The involvement of sympathetic chain and brachial plexus in the nearby area of the spinal involvement also fits with the spinal NF1 phenotype. However, this is in contrast with the previously described MNFSR and/or MNFSR/Spinal Neurofibromatosis phenotypes [5, 9].
We believe that the patients in our cohort belonged to true mosaic/segmental NF1 , since we found pathogenic mutation in the tumor with lack of pathogenic mutation in the blood. This is different from the classical NF1 in which NF1 pathogenic mutation is found in both the blood and the tumor. It is possible that patients had mild to classical NF1 phenotype which was superimposed by more aggressive NF1 manifestations (i.e., bilateral spinal root tumors). Nevertheless, there is a high likelihood that the NF1 pathogenic mutation could not be detected either in the blood or in the tumor, hence more extensive genomic analysis like WES and/or WGS should be carried out.
True spinal NF1 has a relentless and progressive course, while mosaic/segmental phenotype has a more indolent and slower course . Hence, if the patients present in their early ages they should be closely observed, in contrast if they present in the later stages there is more likelihood of a benign course. Genetic testing would certainly help to better characterize these individuals, or at least, to exclude or confirm NF1 pathogenic mutations . Although Selumetinib  has proven effective in plexiform neurofibromas within the context of classical NF1, there are currently no reports on its use in spinal NF1 and/or mosaic phenotypes.