INTRANEURAL PERINEURIOMA - A CLONAL NEOPLASM ASSOCIATED WITH ABNORMALITIES OF CHROMOSOME-22

The nature of perineurioma, variably termed ''localized hypertrophic n europathy,'' ''intraneural neurofibroma,'' and ''hypertrophic intersti tial neuritis'' has long been an issue of contention. Most authors con sider it a neoplasm, but some a reactive process. Eight clinically and morphologically typical perineuriomas were studied by histologic, imm unohistochemical and ultrastructural methods, One perineurioma was sub ject to tissue culture and cytogenetic study and another to fluorescen ce in situ hybridization (FISH) analysis, The patients, 3 males and 5 females, ranged in age from 11 to 38 years, All tumors were intraneura l, and involved extremities (2 sciatic, 1 median, 1 femoral, 1 peronea l, 1 brachial plexus, 1 ulnar, and 1 radial). Neurologic symptoms, mot or in all cases and sensory in 4, were present from I month to 7 years (mean 1.2 years). Fusiform, segmental nerve enlargement was clinicall y apparent in only two patients, but was evident on MRI in five of eig ht patients, Lesion length ranged from 3.5 to 30 cm, the largest invol ving the sciatic nerve from the obturator foramen to the knee. One les ion involved two nerve roots, but no association with a phakomatosis w as noted, Treatment consisted of biopsy in six cases and resection in tao cases. Histologically, pseudo-onion bulbs composed of epithelial m embrane antigen-reactive, S-100 protein-negative perineurial cells sur rounded myelinated or nonmyelinated nerve fibers. Many were accompanie d 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 anti gen labelling index ranged from 4% to 17%. Staining for p53 antigen in six cases showed no (2 of 6), rare (2 of 6), or scattered (2 of 6) im munoreactive nuclei. Cytogenetic analysis in one case demonstrated a c hromosomally abnormal clone, Each of 16 metaphases was abnormal; the t umor cells appeared to be homozygously deficient for the region 22q11. 2qter. In another case, 53% of interphase nuclei showed three FISH sig nals with a chromosome 14/22 probe, thus suggesting either monosomy fo r the centromere of chromosome 14 or that of chromosome 22. On the bas is of this study, the authors conclude that (1) perineuriomas represen t a clonal neoplastic lesion rather than a reactive process; (2) most perineuriomas are localized and self-limited, but that occasional exam ples 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) a lterations in the tumor suppressor gene p53, although unlikely to be t he cause of perineurioma, may contribute to their continued growth, La stly, the authors suggest the spectrum of perineurial cell neoplasms b e expanded to include not only the rare, extraneural soft tissue varia nt, but intraneural perineurioma as well.