Fig.22.7D ).Plexiform neurofibromas involvemultiplefasciclesofindividualaffectednerves(
Fig.22.7C ).Diffuse neurofibromas showanextensiveinfiltrativepatternofgrowthwithinthedermisandsubcutisoftheskin.
NF1 is an autosomal dominant disorder caused by mutations in the tumor suppressor neurofibromin, encoded on the long arm of chromosome 17 (17q). Neurofibromin is a negative regulator of the potent oncoprotein Ras (Chapter 6). Loss of neurofibromin function and the resulting Ras hyperactivity appear to be a cardinal feature of NF1associated tumors. As would be anticipated for a tumor suppressor gene, the sole normal NF1 allele is mutated or silenced in tumors arising in the setting of NF1. These include neurofibromas of all three main types, malignant peripheral nerve sheath tumors, “optic gliomas,” and other glial tumors. In addition, patients with NF1 exhibit learning disabilities, seizures, skeletal abnormalities, vascular abnormalities with arterial stenoses, pigmented nodules of the iris (Lisch nodules), and pigmented skin lesions (axillary freckling and café-au-lait spots) in various degrees.
Malignant peripheral nerve sheath tumors are neoplasms seen in adults that typically show evidence of Schwann cell derivation and sometimes a clear origin from a peripheral nerve. They may arise from transformation of a neurofibroma, usually of the plexiform type. About one-half of such tumors arise in patients with NF1, and 3% to 10% of all patients with NF1 develop a malignant peripheral http://ebooksmedicine.net
Fig. 22.7 Schwannomaandplexiformneurofibroma.(A–B)Schwannoma.Asseenin(A),schwannomasoftencontaindensepinkAntoniAareas(left) andloose,paleAntoniBareas(right),aswellashyalinizedbloodvessels(right).(B)AntoniAareawiththenucleioftumorcellsalignedinpalisadingrows.(C–D)Plexiformneurofibroma.Multiplenervefasciclesareexpandedbyinfiltratingtumorcells(C),whichathigherpower(D)areseentoconsistofblandspindle cellsadmixedwithwavycollagenbundleslikenedtocarrotshavings.
nerve sheath tumor during their lifetimes. Histologically, these tumors are highly cellular and exhibit features of overt malignancy, including anaplasia, necrosis, infiltrative growth pattern, pleomorphism, and high proliferative activity.
Traumatic neuroma is a nonneoplastic proliferation associated with a previous injury leading to transection of a peripheral nerve. Such injuries activate a regenerative program (see
Fig. 22.1 ) characterized by sprouting and elongation of processes from the proximal axonal stump. With severe injuries that disrupt the perineurial sheath, these new processes may “miss” their target, the distal end of the transected nerve. The misguided elongating axonal processes can induce a reactive proliferation of Schwann cells, leading to the formation of a painful localized nodule that consists of a haphazard mixture of axons, Schwann cells, and connective tissue.
Inmostperipheralnervesheathtumors,theneoplasticcellsshowevidenceofSchwanncelldifferentiation.
PeripheralnervesheathtumorsareimportantfeaturesofthefamilialtumorsyndromesNF1andNF2.
Schwannomasandneurofibromasarebenignnervesheathtumors.
Schwannomasarecircumscribed,usuallyencapsulatedtumorsthatabutthenerveoforiginandareafeatureofNF2.