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The author addresses the issue of neurofibroma classification and implications for treatment. He emphasizes the importance of understanding that not all neurofibromas are the same and that the key differences between the types of neurofibromas involve which portions of the nerve sheath contribute to the distinctive behavior of the different types of lesions. Endoneurial neurofibromas derive from cellular elements ordinarily restricted to the endoneurium. Perineurial neurofibromas arise within individual fascicles of a nerve and are largely confined thereby, precluding a breach of the epineurium. Epineurial neurofibromas are contained only by the epineurium, and ultimately that portion of the nerve sheath is breached by these lesions. Whether the perineurium is present or breached becomes the key element for exploiting this approach to neurofibroma origins, behaviors, and treatment, surgical and medical. With respect to surgical treatment, perineurial neurofibromas will have clean planes of dissection about the involved nerve. In contrast, endoneurial and epineurial neurofibromas infiltrate adjacent tissues, leading to surgical challenges. With respect to pharmaceutical approaches, the integrity of the perineurium is likely to prove critical: a specific function of the perineurium is to serve as a barrier to various materials, microbiological or chemical. Thus, drugs that might be effective when the perineurium is absent or rent may be less effective (or not effective at all) if the perineurium is intact, as is expected in cases of perineurial neurofibromas.

The genetic predisposition to and histogenesis of neurofibromas and neurofibrosarcoma in neurofibromatosis Type 1