Intraneural perineurioma: A clonal neoplasm associated with abnormalities of chromosome 22

The nature of perineurioma, variably termed 'localized hypertrophic neuropathy),' 'intraneural neurofibroma,' and 'hypertrophic interstitial neuritis' has long been an issue of contention. Most lost authors consider it a neoplasm, but some a reactive process. Eight clinically and morphologically typical perineuriomas were studied by histologic, immunohistochemical and ultrastructural methods. One perineurioma was subject to tissue culture and cytogenetic study and another to fluorescence in situ hybridization (FISH)) analysis. The patients. 3 males and 5 females, ranged in age from 11 to 38 years. All tumors were intraneural, and involved extremities (2 sciatic, 1 median, 1 femoral, 1 peroneal, 1 brachial plexus. I ulnar, and 1 radial). Neurologic symptoms, motor in all cases and sensor) in 4, were present from 1 month to 7 years (mean 1.2 years). Fusiform, segmental near enlargement was clinically apparent in only two patients, but was evident on MRI in five of eight patients. Lesion length ranged from 3.5 to 30 cm, the largest involving the sciatic nerve from the obturator foramen to the knee. One lesion involved two nerve roots, but no association with a phakomatosis was noted. Treatment consisted of biopsy in six cases and resection in two cases. Histologically, pseudo-onion bulbs composed of epithelial membrane antigen-reactive, S-100 protein-negative perineurial cells surrounded myelinated or nonmyelinated nerve fibers. Many were accompanied by their S-100 protein-positive Schwann sheaths. Some whorls lacked a central axon. A single mitosis was noted in one case. The MIB-1 antigen labelling index ranged from 4% to 17%. Staining for p53 antigen in six eases showed no (2 of 6), rare (2 of 6), or scattered (2 of 6) immunoreactive nuclei. Cytogenetic analysis in one case demonstrated a chromosomally abnormal clone. Each of th metaphases was abnormal; the tumor cells appeared to be homozygously deficient for the region 22q11.2qter. In another case, 53% of interphase nuclei showed three FISH signals with a chromosome 14/22 probe, thus suggesting either monosomy for the centromere of chromosome 14 or that of chromosome 22. On the basis of this study, the authors conclude that (1) perineuriomas represent a clonal neoplastic lesion rather than a reactive process; (2) most perineuriomas are localized and self-limited, but that occasional examples show extensive intraneural spread; (3) despite their slow growth and the presence of only rare mitoses, elevated proliferation indices attest to ongoing cell multiplication; (4) a gene on chromosome 22 may play a role in the pathogenesis of perineurioma, perhaps the same one implicated in the development of other nerve sheath tumors; and (5) alterations in the tumor suppressor gene p53, although unlikely to be the cause of perineurioma, may contribute to their continued growth. Lastly, the authors suggest the spectrum of perineurial cell neoplasms be expanded to intraneural as well.