GFA and S 100 protein levels as an index for malignancy in human gliomas and neurinomas.

Human glia-specific proteins S 100 and GFA were quantitated by use of a rocket immunoelectrophoresis technique with monospecific antisera. No relation was found between the S 100 protein content of an astrocytoma and its degree of neoplasia. However, the lower the GFA protein content of the astrocytoma, the more malignant it was. Similarly, the more malignant a neurinoma was, the lower was its S 100 protein content. Therefore, the levels of these proteins might be used as indexes of neoplastic dedifferentiation.

Immunolocalization of laminin in neoplasms of the central and peripheral nervous systems.

Laminin is a basement membrane glycoprotein that is expressed in vitro by immature and neoplastic astrocytes. The expression of laminin in vivo was examined immunohistochemically in normal adult brain and 90 neoplasms of the central and peripheral nervous systems. In normal adult brain, laminin was detected in the vasculature, arachnoid, pial-glial membrane, and choroid plexus. The vasculature in all 90 tumors demonstrated intense laminin immunoreactivity. Deposits of laminin were observed at the glioma-mesenchymal junction in several neoplasms, but never between or within neuroepithelial cells. The glial basement membrane often remained intact although surrounded on both sides by invasive glioma or medulloblastoma. However, there was always fragmentation and disruption of the glial membrane in adjacent fields. Laminin expression by tumor cells was observed in 10/10 schwannomas, 9/10 fibroblastic meningiomas, 3/19 nonfibroblastic meningiomas, and 3/6 mixed glioma-sarcomas. Laminin expression in the normal nervous system and in neuroepithelial neoplasms corresponds to regions of recognized basal lamina formation, including the junction between glial and mesenchymal elements. Although invasive gliomas are able to break down the pial-glial basement membrane and gain access to the perivascular or subarachnoid space, this membrane often remains intact late in the invasive process and may represent a partial barrier to tumor invasion. Laminin may be a useful marker for schwannomas, fibroblastic meningiomas, and vascular neoplasms of the nervous system.

Lipocortin-1 immunoreactivity in central and peripheral nervous system glial tumors.

We examined the cellular distribution of lipocortin-1 (L-1), a major physiologic substrate for the epidermal growth factor receptor/kinase, in 122 central nervous system (CNS) and peripheral nervous system (PNS) neoplasms using the peroxidase-antiperoxidase technique with a polyclonal antibody specific for L-1. Extensive L-1 immunoreactivity was demonstrated in many CNS tumors; in 11 of 21 glioblastoma multiformes, in five of 12 anaplastic astrocytomas, and in five of 14 astrocytomas. Significant numbers of immunoreactive ependymocytes or astrocytes were also seen in six of 13 ependymomas. In contrast, no immunostaining was detected in the oligodendrocytes in any of ten oligodendrogliomas. PNS tumors, found in two of five malignant nerve sheath tumors, 13 of 15 schwannomas, 13 of 17 neurofibromas, and 14 of 15 traumatic neuromas, also contained considerable L-1 immunoreactivity in Schwann cells or mast cells. These findings raise the possibility that L-1 may participate in the proliferation or subsequent differentiation of neoplastic astrocytes, ependymocytes, and Schwann cells.

Malignant peripheral nerve sheath tumor. An immunohistochemical study of 62 cases.

Malignant peripheral nerve sheath tumor (MPNST) commonly presents a diagnostic challenge and may resemble a variety of other soft tissue neoplasms microscopically. The authors have examined 62 examples of MPNST immunohistochemically, using antibodies to S-100 protein, myelin basic protein (MBP), and Leu-7, all of which are potential neural markers. Sixty-eight percent of all cases expressed at least one of these three determinants, representing a higher rate of immunoreactivity than that seen for single nervous system antigens in previous studies. Conjoint reactivity for S-100/Leu-7, S-100/MBP, and MBP/Leu-7 was seen in 34%, 34%, and 24% of cases, respectively. This coexpression of antigens is important, because none of them in isolation is immunospecific for nerve sheath tumors. In addition, stains for epithelial membrane antigen were reactive in two epithelioid tumors in this series, and eight spindle-cell neoplasms demonstrated desmin positivity. Analyses for cytokeratin, carcinoembryonic antigen, and Factor VIII-related antigen were negative in all cases. These results indicate an overlap between the immunocytochemical attributes of malignant peripheral nerve sheath tumors and other soft tissue sarcomas and emphasize the desirability of assessing multiple neural markers in such cases.

Perineurioma: a benign peripheral nerve tumor.

A unique benign peripheral nerve tumor, called a perineurioma, is described in this report. Light and electron microscopy and immunohistochemistry indicate that this tumor was derived from the perineurial cell. We discuss the ultrastructure, histogenesis, and management of this neoplasm.

Gangliocytic paraganglioma in cauda equina region, with biochemical and neuropathological studies. Case report.

Biochemical analysis of a nonfunctional paraganglioma in the cauda equina region demonstrates that its catecholamine content is predominantly dopamine with small amounts of noradrenaline and adrenaline. Scattered mature large neurons characterize the tumor as gangliocytic paraganglioma. Ultrastructural study shows intracytoplasmic neurosecretory granules in the neoplastic cells.

Paraganglioma of the cauda equina. Case report.

An unusual, well demarcated, and encapsulated neoplasm of the cauda equina is presented. At first, the tumor was considered to be a variant of myxopapillary ependymoma, but the reaction for glial fibrillary acidic protein was negative. At the ultrastructural level, the neoplastic cells contained many small dense core vesicles, and the diagnosis of paraganglioma was established. The literature and histogenesis of paraganglioma of the cauda equina is reviewed.

Malignant peripheral nerve sheath tumor and pheochromocytoma. A composite tumor of the adrenal.

An adrenal composite tumor of pheochromocytoma and malignant peripheral nerve sheath tumor (PNST) is described in a 39-year-old woman in whom PNST component appeared to have undergone further malignant degeneration, resulting in a highly anaplastic sarcoma with rapidly progressive clinical course.

[Histogenesis of neurinomas induced in rats by nitrosoethylurea]. / K gistogenezu nevrinom, indutsirovannykh u krys nitrozoétilmochevinoi.

Twenty-five tumors of the peripheral nerves induced in BD rats by N-nitrosoethylurea were studied by peroxidase-antiperoxidase method using specific anti-serum against protein S-100. Eighteen tumors gave positive reactions for S-100 protein, including those with invasive growth. Protein S-100 was always present in cystic neurinomas. No protein was found in seven tumors. It is concluded that most tumors studied originated from Schwann cells, while at least some of them had a connection with the peri(endo)neurium.

[Protein S-100 in spontaneous soft tissue and peripheral nerve neoplasms in rats]. / Belok S-100 v spontannykh opukholiakh miagkikh tkanei i perifericheskikh nervov krys.

16 spontaneous tumors of the peripheral nerves and 18 spontaneous tumors of mesenchymal origin in BDVI rats were studied by peroxidase-antiperoxidase method using anti-serum (DAKOPATT) against protein S-100. The majority of spontaneous peripheral nerve tumors were of cystic histological structure identical to that of cystic neurinomas induced in rats by ethylnitrosourea and almost all of these tumors were S-100 protein positive. The incidence of spontaneous neurinomas in BDVI rats was in some experiments as high as 5%. All tumors of mesenchymal origin (except one lipoma) were S-100 protein negative: 2 fibromas, 6 fibrosarcomas, 3 malignant fibrous histiocytomas, one rhabdomyosarcoma and one hemangioendothelioma. S-100 protein is found, as in human pathology, useful for distinguishing tumors of schwann cell and mesenchymal origin in rats.

Oral nerve sheath myxoma. Report of a case with findings of ultrastructural and immunohistochemical studies.

The first Asian case of oral nerve sheath myxoma is presented, along with the findings of light and electron microscopy, and immunohistochemistry. Ultrastructurally, intracytoplasmic microfilaments and convoluted basement membrane were identified in the tumor cells. Immunohistochemically, S-100 protein and neuron-specific enolase were positive in the tumor cells. These findings may indicate that the tumor is a lesion of Schwann-cell origin. The literature on oral nerve sheath myxoma is also reviewed and discussed.

Granular cell tumor arising in myelinated peripheral nerves. Light and electron microscopy and immunoperoxidase study.

The histologic, immunohistochemical and ultrastructural characteristics of two granular cell tumors arising from the right recurrent laryngeal and left facial nerves are described. S-100 protein was detected both in the nuclei and cytoplasm of the granular cells using the peroxidase-anti-peroxidase method. The ultrastructural findings in both cases support a Schwann cell derivation of the granular cells. It is suggested that the granularity of cells of granular cell tumor may represent a lysosomal disorder affecting most frequently neoplastic and nonneoplastic Schwann cells and occasionally other cells.

Malignant granular cell tumor of the right sciatic nerve. Report of an autopsy case with electron microscopic, immunohistochemical, and enzyme histochemical studies.

An autopsy case of a malignant granular cell tumor of the right sciatic nerve was reported. The surgically excised malignant granular cell tumor of a 43-year-old women showed a close relationship with the sciatic nerve, and postmortem examination disclosed extensive metastases. Electron microscopic observations of the material obtained at surgery revealed many diagnostic granules containing myelin figures, as well as basement membrane-like structures around some of the tumor cells. Electron microscopic acid phosphatase staining suggested that the granules could be of a lysosomal origin. Immunohistochemical investigation showed the presence of S-100 protein in the tumor cells, a finding which is believed to be specific for the nervous system. And, focally, the cytoplasmic processes accompanied by basement membrane mimicked Schwann cells. This evidence suggested the highly malignant nature of the malignant granular cell tumor of probable Schwann cell origin.

Collagen synthesis in cells cultured from v. Recklinghausen's neurofibromatosis.

Subcutaneous tumors of a patient with v. Recklinghausen's neurofibromatosis contained about 31% collagen calculated on the basis of lipid-free dry weight. Slices of the tumors synthesized collagen at a rate (4.7-8.5% from total protein) which was higher than that of the skin slices (2.8-5.9%). Neurofibromatosis cells were cultured from tumors of two patients. They synthesized relatively much more collagen than cultures of skin fibroblasts of the same patient or of healthy age-matched control persons. The second patient's cultures were studied in detail. The cell densities of these cultures were higher and expressed more variation than the densities of control skin fibroblasts. Ion exchange cellulose chromatograms, SDS-polyacrylamide gel electrophoresis and 3-hydroxyproline analysis of the radioactive proteins made by the cultures indicate that most of the collagenous proteins resembled type I collagen. High proliferative capacity and high collagen synthesis of selected neurofibromatosis cells explains the growth of solid tumors.

[DNA cytofluorometric analysis of nerve sheath tumors].

The present study was undertaken to clarify the ploidy patterns of peripheral nerve sheath tumors by determining nuclear DNA content of the individual tumor cells using PI-DNA cytofluorometry (NIKON SPM-RF1-D), and to investigate the relation between the ploidy patterns and histopathological findings. Most of the solitary neurilemmomas and neurofibromas studied were found to be associated with euploid-polyploidization, almost without DNA synthetic cells. It was also shown that the number of polyploid cells increased in accordance with an increase in the frequency of cells having large, atypical nuclei in histological picture, regardless of the natures of cellular arrangements. Malignant schwannomas, however, were composed of many polyploid and aneuploid cells with an increase of DNA synthetic cells, indicating their active cell proliferation. Thus, the ploidy patterns of nerve sheath tumors were remarkably different between benign and malignant ones. Furthermore, a case of multiple schwannoma suspected to be a variant of von Recklinghausen's disease, showed euploid-polyploidization with many DNA synthetic cells, indicating a ploidy pattern intermediate between benign and malignant tumors. This tumor thus appears to be a premalignant tumor or in the early stages of malignancy.

[Malignant peripheral neuroectodermal tumors. Histological and immunohistological conditions in 41 cases]. / Maligne periphere neuroektodermale Tumoren. Histologische und immunohistochemische Befunde an 41 Fällen.

In view of the personal observation that malignant peripheral neuroectodermal tumours (MPNT) can present different histological growth patterns, 41 cases of MPNT were histologically and immunohistochemically studied. The median age of the 41 patients was 15 years (range: 9 months - 23 years). There were 27 males and 14 females. Most tumours (23/41) were located in the thoracopulmonary region. In 31/41 cases there was bone as well as soft tissue involvement. The following histopathological patterns were found: Ewing's sarcoma-like (n = 7), atypical Ewing's sarcoma-like (n = 4), neuroblastoma-like (n = 8), rhabdomyosarcoma-like (n = 8), and hemangiopericytoma-like (n = 1). In 2 cases combined patterns were noted, one tumour being characterized by neuroblastoma-like and Burkitt's lymphoma-like features. Most cases of MPNT differed from the cytological features of typical Ewing's sarcoma in that they contained hyperchromatic nuclei with distinct nucleoli. Some reticulin fibrils were found in between the cells of some cases. Immunohistochemically, 19/23 cases reacted positively to vimentin, 29/32 to neuron specific enolase (NSE), 16/28 to protein S-100, and 1/9 to glial fibrillary acidic protein. 12/24 cases reacted positively to NSE and protein S-100. Neurofilaments and desmin were not found in the formalin fixed material of the present study. The results show that most cases of MPNT can be distinguished from typical Ewing's sarcoma by cytological and histological findings. Differential diagnosis from atypical Ewing's sarcoma, neuroblastoma, and rhabdomyosarcoma is possible by immunohistochemistry.

Histopathologic and immunohistochemical study of malignant tumors of peripheral nerve sheath (malignant schwannoma).

Histologic and immunochemical analyses were performed on 38 cases and 33 cases of malignant tumors of the peripheral nerve sheath, respectively. The histologic features consisted of either closely packed or loosely arranged interlacing fascicles of slender spindle cells that showed a wavy pattern. Although no characteristic findings indicative of neurogenic differentiation could be confirmed with anti-S-100-protein, a fair number of positive cells were seen in the area where the tumor cells were loosely arranged and displayed a wavy pattern. When anti-neuron-specific enolase (NSE) and anti-neurofilament antibody (68K, 200K) were applied, they were found to be positive in cells differentiating to ganglion cells and in epithelial cells. Since S-100-protein-positive cells indicate a differentiation to Schwann cells and NSE-positive cells and neurofilament-positive cells to nerve cells, it was concluded that immunohistochemistry can serve as an effective supplementary method for the diagnosis of malignant tumors of the peripheral nerve sheath.

Dermal nerve sheath myxoma: a study of three cases.

Three cases of dermal nerve sheath myxoma have been studied by light microscopy, histochemistry and immunohistochemistry. The pertinent literature has been reviewed. This lesion, which is a rare benign tumour of probable nerve sheath origin, arises most often in young adults and shows a predeliction for females. Histologically it has a characteristic appearance. Histochemically, the heteroglycan content of the mucoid matrix is more in keeping with a cartilaginous lesion. The histogenesis and differential diagnosis are discussed.

Gamma-enolase and glial fibrillary acidic protein in nervous system tumors. An immunohistochemical study using specific monoclonal antibodies.

A large series of central and peripheral nervous system tumors was studied for the presence of glial fibrillary acidic protein (GFAP) and gamma-enolase (neuron-specific enolase, NSE), using specific monoclonal antibodies (mAbs). Occurrence in and specificity of GFAP to glial and mixed tumors was confirmed and depended on the malignancy grade and features such as meningeal invasion. Using a well-characterized mAb, gamma-enolase was demonstrated in neuronal, as well as in a whole range of non-neuronal tumors. This lack of specificity of gamma-enolase prohibits its use as an exclusive neuronal marker. Nevertheless quantization or comparison with other types of enolases could still prove to be useful in well-defined situations. The advantages inherent to mAbs and a highly sensitive detection system turn GFAP stainings into a specific and readily reproducible technique.

Neutral glycosphingolipids and ceramide composition of ethylnitrosourea-induced rat neural tumors: accumulation of ceramide in tumors.

Experimental rat neural tumors in offspring were induced transplacentally by a single injection of a chemical carcinogen, ethylnitrosourea, 20 mg/kg body weight, in the tail vein of the mother. The neutral glycosphingolipid, sulfatide, and ceramide composition of the tumors and the normal tissues from which the tumors originated is described. The content of nonhydroxy fatty acid (NFA) and hydroxy fatty acid (HFA) containing ceramide in all the neural tumors so far examined was significantly increased compared with the corresponding normal neural tissue. Some 8 to 18 mol% of total neutral glycolipids was as ceramide in neurinomas, oligodendrogliomas, and meningiomas. Lactosylceramide in normal neural tissues was about 1 mol% of the total neutral glycosphingolipids. In various neural tumors lactosylceramide increased up to 8 mol%. NFA- and HFA-containing cerebrosides constitute 94-100% of the neutral glycosphingolipids in normal neural tissues. In various neural tumors the mol percent of cerebrosides was significantly reduced. A high performance liquid chromatographic method was modified to analyze simultaneously ceramides, cerebrosides, and higher neutral glycosphingolipids.