Neurofibromatous neuropathy: An ultrastructural study

Neurofibromatosis 1 (NF1) is a common genetic disorder characterized by the presence of neurofibromas arising from the proliferation of Schwann cells (SC) and perineurial cells. At variance with NF2, the incidence of an associated polyneuropathy is very low in NF1, and its histopathological features are poorly characterized. We report the sporadic case of a 46-year-old woman presenting with bilateral subclavicular painful masses. MRI showed bilateral plexiform lesions extending from cervical roots to the elbows; a malignant nature of lesions was ruled out by PET-TC. A biopsy of the larger lesion had histological features of plexiform neurofibroma. Although the patient had no peripheral nerve symptoms, nerve conduction studies documented a sensory-motor polyneuropathy, which was confirmed by sural nerve biopsy. Electron microscopy showed dramatic loss of large and small myelinated, as well as unmyelinated axons together with numerous regeneration clusters. An increased number of fibroblast cell processes and a large amount of collagen fibrils characterized the endoneurium. A combined involvement of myelinating and non-myelinating SC was evidenced by the high frequency of alterations such as: irregularities and degradation figures of myelin, lipofuscin deposition, pseudo-onion bulb structures and collagen pockets substituting unmyelineted axons. These changes suggest that in neurofibromatous neuropathy, a widespread axonal degeneration takes place independently of the presence of tumoral infiltration, possibly due to an impairment in SC-axon cross-talk.