15 - Tumors of Peripheral Nerve

Peripheral nerves are complex tissues composed of a variety of cellular elements, specifically Schwann cells, perineurial cells, and neuronal processes (axons), enveloped by connective tissue elements. Neoplasms originating from peripheral nerve often recapitulate the phenotype of underlying cell elements and range from benign, circumscribed tumors easily cured by surgery (e.g., schwannoma), locally aggressive neoplasms with potential for malignant degeneration (e.g., plexiform neurofibromas), to overtly malignant, highly aggressive neoplasms (malignant peripheral nerve sheath tumors, MPNST). The proper diagnosis of these tumors not only has therapeutic implications but is also increasingly relevant to genetic counseling given their association with multisystemic genetic syndromes, including neurofibromatosis types 1 and 2, schwannomatosis, Carney Complex, and multiple endocrine neoplasia type IIB. Recent concepts in peripheral nerve tumor classification are covered in this review, including the increasing recognition of tumors with hybrid features. Although there have been no major recent changes in the overall diagnostic categories of nerve sheath tumors, our basic understanding of these tumors has been accelerated by comprehensive genomic studies. Malignant peripheral nerve sheath tumors have recently been found to have frequent mutations in components of the polycomb repressive complex 2 (SUZ12, EED), resulting in consistent epigenetic alterations, particularly loss of histone H3K27 trimethylation. All these findings have translated into diagnostic biomarkers useful in surgical pathology diagnosis, including immunohistochemical antibodies recognizing loss of neurofibromin and H3K27 trimethylation. In summary, peripheral nerve sheath tumors represent a heterogeneous group, with important diagnostic challenges that are important to recognize.