Malignant Peripheral Nerve Sheath Tumors of Cranial Nerves and Intracranial Contents A Clinicopathologic Study of 17 Cases

Malignant peripheral nerve sheath tumors (MPNSTs) arising from cranial nerves or their branches are very uncommon. The literature consists mainly of isolated case reports and small series. We identified 17 such cases in 14 males and 3 females. With one exception, the tumors affected adults (age range 5 to 69y, mean 39, median 32). Sites of involvement included vestibular nerves (n = 6). vagal nerves (n = 4), facial nerves (n = 3) (1 centered in the geniculate ganglion), and 2 unspecified cranial nerves in the posterior fossa. In addition, I tumor involved the optic chiasm (n = 1). Only I tumor arose in brain parenchyma of (frontal lobe). All but 3 lesions were intracranial, live tumors arose in patients who satisfied clinical criteria for neurofibromatosis type 1 (NNI). One patient with a vestibular tumor and presumed NF2 had previously undergone resection of a contralateral vestibular cellular schwannoma. One posterior fossa tumor was a malignant melanotic schwannoma. Four patients had postirradiation malignant peripheral nerve sheath tumors, 2 having been treated for optic chiasm glioma, both being NNI affected. One patient was irradiated for hypothalamic pilocytic astrocytoma and another for cervical Hodgkin disease. Identifiable precursor lesions included schwannoma (n = 4), plexiform neurofibroma (n = 2), and solitary intraneural neurofibroma (n = 2). All tumors were histologically high grade (6 grade III and 10 grade IV). Three tumors showed heterologous elements, 2 osscous, and 1 rhabdomyoblastic. More often scattered than diffuse, S-100 protein staining was noted in 11 of 16 tumors and variable collagen IV staining in 10 of the 16. Immunoreactivity for p53 protein was diffuse and strong in 7 of 11 tumors. Twelve patients died within 17 months to 3 years of diagnosis, 1 was lost to follow-up, 2 are very recent cases, and 2 patients are currently alive, I after 2 recurrences, and another with spinal leptomeningeal metastases. Malignant cranial nerve sheath tumors :ire rare and are associated with the same poor prognosis as those of spinal nerves at other sites

Immunohistochemical detection of EGFRvIII in high malignancy grade astrocytomas and evaluation of prognostic significance

The purpose of this study was to establish an accurate and accessible immunohistochemical (IHC) method for detecting vIII Egf receptor and to assess the prognostic significance of the method as applied to the detection of vIII in malignant astrocytomas. The accuracy of the method was determined by comparing vIII immunoreactivity in formalin-fixed and paraffin-embedded tumor sections versus RT-PCR results from the analysis of RNA extracted from corresponding frozen specimens. RT-PCR revealed vIII transcript in 18 of 44 cases in this series, and IHC analysis of matched formalin-fixed and paraffin-embedded sections showed EGFRvIII reactivity in each of these 18 tumors, as well as 1 additional tumor that was negative for vIII transcript. EGFR amplification was evident in all tumors expressing vIII; none of the 15 tumors lacking amplified EGFR were positive for vIII transcript or vIII protein. IHC analysis for vIII expression was next applied to a large series of anaplastic astrocytomas (AAs) and glioblastoma multiforme (GBMs) from clinical trial patients with complete follow-up and that had been previously examined by FISH for amplified EGFR. Among the GBMs, vIII detection by IHC was determined in 19 of 46 cases (41.3%) with EGFR amplification, and in only 3 of 59 tumors lacking amplified EGFR (5.1%). Among the AAs, vIII expression was observed in 3 of 14 cases with amplified EGFR (21.4%) and in 6 of 49 cases without EGFR amplification (12.2%). GBM and AA patient survival analysis as a function of vIII expression showed contrasting results, with vIII positivity having no association with survival among GBM patients (p = 0.84), but being highly associated with reduced survival among AA patients (p = 0.0016). This latter finding, though quite possibly a result of vIII's association with increasing AA patient age, suggests that vIII IHC will be useful for identifying and/or confirming the identity of malignant astrocytomas whose clinical behavior is consistent with that of GBM