Schwannomas are benign encapsulated tumors that may occur in soft tissues, internal organs, or spinal nerve roots. The most commonly affected cranial nerve is the vestibular portion of the eighth nerve. Tumors arising in a nerve root or the vestibular nerve may be associated with symptoms related to nerve root compression, which includes hearing loss in the case of vestibular schwannomas.
Most schwannomas are sporadic, but about 10% are associated with familial neurofibromatosis type 2 (NF2). NF2 patients are at risk of developing multiple schwannomas, meningiomas, and ependymomas (the latter are described in Chapter 23). The presence of bilateral vestibular schwannomas is a hallmark of NF2; despite the name, neurofibromas (described later) are not found in NF2 patients. Affected patients carry a dominant loss of function mutation of the merlin gene on chromosome 22. Merlin is a cytoskeletal protein that functions as a tumor suppressor by facilitating E-cadherin–mediated contact inhibition (Chapter 6). With loss of merlin function, the tumor cells proliferate because contact inhibition is lost. Of note, merlin expression also is disrupted in sporadic schwannomas, possibly because of somatic mutations.
MORPHOLOGYMostschwannomasappearascircumscribedmassesabuttinganadjacentnerve.Onmicroscopicexamination,thesetumorsoftenshowanadmixtureofdenseandlooseareasreferredtoasAntoniAandB,respectively(
Fig.22.7A–B).They arecomprisedofauniformproliferationofneoplasticSchwanncells.InthedenseAntoni A areas,blandspindlecellswithbucklednucleiarearrangedintointersectingfascicles.Thesecellsoftenaligntoproducenuclearpalisading,resultinginalternatingbandsofnuclearandanuclearareascalledVerocaybodies.Axonsarelargelyexcludedfromthetumor.Intheloose,hypocellularAntoni B areas,thespindlecellsarespreadapartbyaprominentmyxoidextracellularmatrix.Thick-walledhyalinizedvesselsoftenarepresent.Hemorrhageorcysticchangesalsoaresometimesseen.
Neurofibromas are benign peripheral nerve sheath tumors. Three important subtypes are recognized:
Localized cutaneous neurofibromas arise as superficial nodular or polypoid tumors. These occur either as solitary sporadic lesions or often as multiple lesions in the context of neurofibromatosis 1 (NF1).
Plexiform neurofibromas grow diffusely within the confines of a nerve or nerve plexus. Surgical enucleation of such lesions is therefore difficult and is often associated with lasting neurologic deficits. Plexiform neurofibromas are virtually pathognomonic for NF1 (discussed later). Unlike other benign nerve sheath tumors, these tumors are associated with a small but real risk of malignant transformation.
Diffuse neurofibromas are infiltrative proliferations that can take the form of large, disfiguring subcutaneous masses. These also are often associated with NF1.
MORPHOLOGYUnlikeschwannomas,neurofibromasarenotencapsulated.Theymayappearcircumscribed,asinlocalized cutaneous neurofibromas, ormayexhibitadiffuselyinfiltrativegrowthpattern.Alsoincontrasttoschwannomas,theneoplasticSchwanncellsinneurofibromaareadmixedwithothercelltypes,includingmastcells,fibroblastlikecells,andperineurial-likecells.Thebackgroundstromaoftencontainsloosewavycollagenbundlesbutalsocanbemyxoidorcancontaindensecollagen(