myelin-basic-protein and Neurofibroma

Neurofibromatosis type 1 (NF-1, von Recklinghausen's disease) is characterized by the focal accumulation of Schwann-like cells (SLC) to form subcutaneous and plexiform neurofibromas and schwannomas. The aim of the present study was to determine whether NF-SLC are competent to differentiate in the presence of axons. Five dermal neurofibromas from five patients with NF-type 1 were enzymatically dissociated and the resultant cells were co-cultured with fetal rat dorsal root ganglion neurons. The cultures were studied by indirect immunofluorescence microscopy using antibodies against galactocerebroside (galC), P0 glycoprotein, human nerve growth factor receptor (NGFR) and human myelin-associated glycoprotein (MAG). SLC were strongly NGFR+ but galC- and MAG-SLC for the 2 weeks of coculture. After 3 weeks in vitro, SLC-NGFR was down-regulated but some of the spindle shaped cells had become galC+. MAG-SLC first appeared after 5 weeks in vitro but P0 glycoprotein was never detected when studied up to 6 weeks. Our data demonstrate that axons induce SLC to down-regulate surface NGFR and to express some myelin components in a qualitatively normal fashion.

Topics: Animals; Antibodies, Monoclonal; Axons; Cell Differentiation; Cells, Cultured; Female; Galactosylceramides; Ganglia, Spinal; Immunohistochemistry; Myelin Basic Protein; Nervous System Neoplasms; Neurofibroma; Pregnancy; Rats; Rats, Inbred Strains; Receptors, Cell Surface; Receptors, Nerve Growth Factor; Schwann Cells

A case of schwannomatosis is described, including clinical, pathological and biochemical features. A 16-year-old male patient was admitted because of multiple subcutaneous tumors without family history. No café au lait spots were found. Magnetic resonance images (MRI) revealed multiple tumors of cranial and spinal nerves. The tumors in the scalp, right forearm and left spinal nerve at the level of C5 were excised out surgically. The pathological study of all tumor specimens showed a typical appearance of schwannoma with Antoni A and B tissues but not that of neurofibroma. Electrophoretic study of the extract from the tumor detected a basic protein at a molecular weight of 18.5 KD, which has been reported to be a tumor marker protein of benign schwannoma. From these findings, this patient had the features of schwannomatosis, clearly distinguished from those of neurofibromatosis.

Topics: Adolescent; Biomarkers, Tumor; Cranial Nerve Neoplasms; Diagnosis, Differential; Electrophoresis; Humans; Magnetic Resonance Imaging; Male; Molecular Weight; Myelin Basic Protein; Neoplasms, Second Primary; Neurilemmoma; Neurofibroma; Spinal Cord Neoplasms

Nine examples of a cellular peripheral neural tumor (CPNT) were identified in a review of 139 peripheral nerve sheath neoplasms in children, which included 60 neurofibromas and 16 malignant peripheral nerve sheath tumors. The mean age at diagnosis of these nine patients was 7 years, with six presenting in the first decade of life and four were noted at birth. The male:female ratio was 0.5. Topographically, the tumors were located in the extremities, 4; head and neck, 3; and trunk, 2. One or another stigmata of von Recklinghausen's neurofibromatosis (VRN) was present in four patients. After initial resection, seven children remained well, but two developed a recurrence; the histology was identical to the original tumor in one case but overt malignant transformation had occurred in the second. This case was the only tumor-related death in this series. The CPNT was a circumscribed but nonencapsulated mass measuring 1.8-7.5 cm in greatest dimension in the subcutaneous and deep soft tissues and had a compact spindle cell pattern, occasional mitoses, and minor foci of typical neurofibroma. Immunohistochemical staining revealed vimentin expression in all seven cases, Leu-7 in six, myelin basic protein and S-100 protein in five, desmin in one, and actin in none. In contrast to neurofibroma and malignant peripheral nerve sheath tumors, CPNT tended to occur earlier, either congenitally or in the first decade, and slightly more commonly in females. The anatomical distribution and pattern of immunoreactivity were similar to neurofibroma. However, the cellularity and mitotic activity of these neoplasms were sufficiently disquieting as to raise concerns about the prognosis, and in one case, the tumor behaved in an unequivocally malignant fashion. When a peripheral neural tumor with the pathologic features described in this study is encountered, wide excision and careful clinical follow-up are recommended.

Topics: Actins; Adolescent; Adult; Antigens, Differentiation; CD57 Antigens; Child; Child, Preschool; Desmin; Female; Humans; Immunohistochemistry; Infant; Male; Myelin Basic Protein; Neoplasms, Nerve Tissue; Neurofibroma; S100 Proteins; Vimentin

Neurofibromas are often clinically, as well as histologically, indistinguishable from completely neurotized melanocytic nevi. We tested the hypothesis that immunologic markers would differentiate the perineural fibroblasts and Schwann cells of neurofibromas from the neurotized cells of melanocytic origin. We examined eight partially neurotized acquired melanocytic nevi, three partially neurotized congenital melanocytic nevi, and five neurofibromas, with antibodies directed against S-100 protein, Leu-7(HNK-1), glial fibrillary acid protein (GFAP), and myelin-basic protein (MBP). A histologic diagnosis of neurofibroma was based on identification of a dermal proliferation of spindle-shaped cells with wavy nuclei, in a background of loose reticulated collagen. Neurotized nevi were diagnosed upon recognition of scattered nests of type A or B nevus cells, surrounded by basement membrane, present in the papillary dermis of lesions otherwise indistinguishable from neurofibromas. The congenital nevi were all large melanocytic nevi known to be present at birth. S-100 stained the majority of neoplastic cells in all neurofibromas, neurotized acquired nevi, and neurotized congenital nevi. Neurofibromas showed focal staining for Leu-7, GFAP, and MBP. In contrast, neurotized acquired and congenital nevi failed to express these markers. We believe that Leu-7, GFAP, and MBP may be helpful in differentiating neurofibromas from completely neurotized melanocytic nevi. The differences in the immunohistochemical profiles of neurofibromas and neurotized nevi support the concept that these neoplasms are histogenically distinct, despite their similar histologic appearance.

Topics: Antigens, Differentiation; Antigens, Surface; Biomarkers, Tumor; Cell Transformation, Neoplastic; Glial Fibrillary Acidic Protein; Humans; Immunohistochemistry; Killer Cells, Natural; Melanocytes; Myelin Basic Protein; Neurofibroma; Nevus, Pigmented; S100 Proteins; Skin Neoplasms; Staining and Labeling

One hundred and two cases of benign nerve sheath tumors (NSTs) were studied with a combined approach using routine light microscopy (LM), immunohistochemistry (IH) for myelin basic protein (MBP) and S-100 protein as well as transmission electron microscopy (TEM) with the aim of obtaining greater insight into the true nature of these neoplasms, and also to establish the importance of IH and TEM in their diagnosis. Myelin basic protein was not identified in any of these tumors, whereas S-100 protein was positive to a variable degree in both schwannomas and neurofibromas. TEM revealed that Schwann cells predominated in tumors which were strongly positive for S-100 protein and appeared as schwannomas by LM. However, neurofibromas showing a variable patchy positivity for S-100 were composed of an admixture of Schwann cells, fibroblast-like cells and intermediate cells considered to be modified Schwann cells. Perineurial cells in typical form were not seen. It is concluded that all NSTs are basically of Schwann cell origin and that the intermediate cells and fibroblast-like cells are variants of Schwann cells. The different morphological appearances and biological behaviour of schwannomas and neurofibromas may be related to some other factors like micro-environment or genetic predisposition. Further, both IH, especially for S-100 protein, and TEM play an important role in establishing their diagnosis.

Topics: Cranial Nerve Neoplasms; Humans; Immunohistochemistry; Microscopy; Microscopy, Electron; Myelin Basic Protein; Neoplasms, Nerve Tissue; Neurilemmoma; Neurofibroma; S100 Proteins; Schwann Cells; Skin Neoplasms; Spinal Cord Neoplasms

The collective expression of five antigens produced in immature or mature myelin-producing glia was evaluated in nerve sheath tumors and spindle cell sarcomas with histologic features of schwannomas. Myelin-associated glycoprotein (Leu-7), myelin basic-protein (MBP), S100-protein, and, in most cases, glial-fibrillary acidic-protein (GFAP) and HLA-DR/Ia (LN3) immunoreactivity were evaluated immunohistochemically using commercially available antibodies on 53 benign nerve sheath tumors and 12 sarcomas. Leu-7 immunoreactivity was detected by a monoclonal antibody in 12 of 16 schwannomas, 12 of 20 neurofibromas, and 17 of 17 traumatic neuromas. No Leu-7 positivity was seen in the sarcomas. Distinct heavy MBP immunoreactivity, assessed using polyclonal antibodies, was identified only in all 17 traumatic neuromas. Extensive S100-protein positivity was seen in 15 of 16 schwannomas, 17 of 20 neurofibromas, and 17 of 17 traumatic neuromas. Extensive LN3 immunoreactivity was seen in Schwann cells of 50% of the nerve sheath tumors analyzed; however, it was also present in associated interdigitating reticulum cells; GFAP immunoreactivity was not detected. These data suggest that Leu-7 is an important marker of Schwann cell neoplasms, although it is not superior to S100 protein. Moreover, combined immunohistochemical evaluation of potential Schwann cell markers including Leu-7, MBP, GFAP, and LN3 using commercially available antibodies offers no advantage over analysis of S100-protein immunoreactivity alone.

Topics: Antigens, Differentiation, T-Lymphocyte; Antigens, Neoplasm; Fibrosarcoma; Glial Fibrillary Acidic Protein; Histocompatibility Antigens Class II; Humans; Immunohistochemistry; Leiomyosarcoma; Myelin Basic Protein; Myelin Proteins; Myelin Sheath; Myelin-Associated Glycoprotein; Neoplasm Proteins; Nervous System Neoplasms; Neurilemmoma; Neurofibroma; S100 Proteins; Sarcoma; Schwann Cells

Immunohistochemical localization of tissue specific or cell-specific antigenic markers in neoplastic cells has become an increasingly important tool in the pathologic diagnosis of tumors. The myelin-specific proteins of peripheral nervous system myelin, because they are normally synthesized in Schwann cells, are potentially useful markers for neoplasms arising from peripheral nerves. The authors carried out immunohistochemical studies on 18 cases of Schwann cell neoplasms, including schwannomas, neurofibromas, and granular cell tumors, to determine whether two myelin-specific proteins, myelin basic protein and P2 protein, were present in neoplastic Schwann cells. None of these tumors showed immunostaining for either myelin basic protein or P2 protein in neoplastic cells. In contrast, S-100 protein, which is a well established marker for normal and neoplastic Schwann cells, was localized by immunohistochemistry to neoplastic cells in all 18 neoplasms. Therefore, although myelin basic protein and P2 protein are known to be Schwann-cell-specific proteins, they do not appear to be expressed commonly in neoplastic Schwann cells.

Topics: Histocytochemistry; Humans; Immunologic Techniques; Myelin Basic Protein; Myelin P2 Protein; Neoplasms, Muscle Tissue; Neurilemmoma; Neurofibroma; S100 Proteins; Schwann Cells; Skin Neoplasms; Soft Tissue Neoplasms

The presence of myelin basic protein (MBP) within a skin neoplasm would support its derivation from Schwann's cells, since this substance is routinely present within Schwann's cells in the peripheral nervous system. Using a monoclonal antibody prepared against MBP and an unlabeled antibody peroxidase-antiperoxidase assay, we surveyed a variety of skin lesions suspected of being derived from Schwann's cells to determine whether MBP was present. Myelin basic protein was detected within the cytoplasm of cells composing benign solitary schwannoma (neurilemmoma) and neurofibroma, confirming the association of these lesions with proliferation of Schwann's cells. Myelin basic protein was not found in a variety of intradermal and compound nevus cell nevi nor in malignant melanoma. This negative finding supports electron microscopic evidence suggesting that nevus cells have no relationship to Schwann's cells even though some nevus cell arrangements suggest Schwann's cell derivation under the light microscope.

Topics: Animals; Antibodies, Monoclonal; Histocytochemistry; Humans; Immunoenzyme Techniques; Melanoma; Mice; Mice, Inbred BALB C; Myelin Basic Protein; Neurilemmoma; Neurofibroma; Nevus, Pigmented; Skin Neoplasms; Swine

The presence and distribution of nervous-system-specific protein (S-100 protein), peripheral nerve myelin proteins (P2 protein and P0 protein) that have not been given any attention in the field of tumor pathology, and striated muscle-related proteins (myoglobin and myosin) were studied in 18 cases of granular cell tumor by the peroxidase-antiperoxidase method. The granular cells of all cases were negatively stained with anti-striated-muscle-related protein antiserums. On the other hand, they were positively stained with anti-S-100 protein, P2 protein, and P0 protein antiserums. The distribution of P2 protein and P0 protein corresponded with that of characteristic PAS-positive granules on serial sections. Angular bodies in the interstitial cells were also positively stained with anti-P2 protein antiserum and anti-P0 protein antiserum. These results further support the hypothesis that the granular cell tumor is derived from Schwann cells and also suggest that myelin proteins are major core proteins of the characteristic granules and angular bodies of interstitial cells. The biologic significance of these results in relation to myelinogenesis is also discussed.

Topics: Adult; Aged; Child; Cytoplasmic Granules; Female; Humans; Immunoenzyme Techniques; Male; Middle Aged; Myelin Basic Protein; Myelin P0 Protein; Myelin P2 Protein; Myelin Proteins; Neoplasm Proteins; Neoplasms, Muscle Tissue; Nerve Tissue Proteins; Neurilemmoma; Neurofibroma; Periodic Acid-Schiff Reaction; S100 Proteins