A peripheral nerve sheath tumor (PNST) is a neoplasm arising from a peripheral nerve or showing nerve sheath differentiation. PNSTs may be subdivided into benign and malignant (MPNST) variants. Several distinct benign subtypes have been recognized, including schwannoma (neurilemoma, neurinoma), neurofibroma, and perineurioma.

The etiology of PNSTs is usually unknown. However, several hereditary disorders are known to predispose to benign and malignant PNSTs, notably neurofibromatosis type 1 (NF1) and neurofibromatosis type 2 (NF2), both of which are inherited in an autosomal dominant fashion. NF1 (also known as von Recklinghausen disease) is caused by mutations in the NF1 gene on chromosome 17 and is characterized by several phenotypic features including multiple neurofibromas and MPNSTs. The incidence of MPNST is in general rare, but half of all cases arise in NF1 patients. NF2, caused by muations in the NF2 gene on chromosome 22, predisposes to schwannomas, predominantly affecting the spine and the intracranial nerves.

All ages and both sexes may be affected by PNSTs. Sporadic MPNSTs are most common between 40 and 50 years of age, while those occurring in the setting of NF1 are diagnosed some 10 years earlier. In total, MPNSTs account for 5-10% of all soft tissue sarcomas.

Benign PNSTs rarely recur after surgery. MPNST, on the other hand, is often a highly aggressive tumor, and more than 60% of the patients die of the disease.

Molecular cytogenetic - clinical correlation MPNST: One study has reported poor overall patient survival associated with simultaneous gain of 17q and 7p.

Molecular genetic findings
Schwannoma : The frequent finding of deletions at 22q suggests that this chromosome arm harbors one or more tumor suppressor loci of importance for schwannoma development. Focussing on the NF2 locus, loss of this tumor suppressor gene has been demonstrated in one third to half of all schwannomas investigated. The importance of this gene in schwannomas is further supported by the finding of biallelic inactivating mutations in up to two thirds of the cases.
Neurofibroma : Biallelic inactivation of the NF1 gene in 17q has been demonstrated.
MPNST : The basis for MPNST occurring in the setting of NF1 is presumed to be biallelic inactivation of the NF1 gene. Indeed, allelic imbalance at the NF1 locus in 17q is commonly (20-50% of the cases) detected in sporadic as well as NF1-associated MPNSTs. Due to the large size of this gene, however, it has been difficult to identify the mutation in the non-deleted copy in but a few cases. From studies of neurofibromas in NF1 patients, showing frequent deletion of the wild-type allele, it is obvious that NF1 inactivation is not sufficient for malignant transformation. Molecular genetic investigations aiming at disclosing mechanisms of importance for tumor progression have revealed that MPNSTs often display disruption of the RB1 pathway. Thus, the CDKN2A locus in 9p21 often displays loss of heterozygosity, and the gene itself is homozygously deleted or otherwise rendered functionally inactive. Also the CDKN2B and RB1 tumor suppressor genes may be inactivated in a subset of MPNSTs. Alternatively, dominantly acting genes in the RB1 pathway ­ CDK4, MDM2, and CCND2 ­ may be overexpressed or amplified. In a study of 12 MPNSTs, changes in one or more of these dominantly or recessively acting genes were found in 11 cases. The TP53 gene, on the other hand, seems to be biallelically affected in only a small proportion of MPNSTs.