Melanocytic Schwa n no ma in the Spinal Canal

A case of melanocytic schwannoma, a rare form of schwannian neoplasm, in the thoracolumbar spinal canal of a 52-year-old man is presented. Histopathologically, the tumor was composed of irregularly interlacing spindle-shaped cells showing cystic degeneration, with occasional pigmented tumor cells. The tumor cells showed a low degree of nuclear pleomorphism without any mitotic figures. These histological features were considered to be consistent with a benign schwannian tumor showing pigmentation. Most of the pigments were considered to be melanin histochemically and immunohistochemically. According to the pathological features of the present tumor and those described previously in the literature, the neoplastic Schwann cells were assumed to have melanogenetic capacity, and the concept of the common neural crest origin of Schwann cells and melanocytes appeared to be demonstrated in the present tumor. Acta Pathol Jpn 41: 685–688, 1991.     

Electron microscopic and immunohistochemical studies of gastrointestinal stromal tumors

Sixteen gastrointestinal stromal tumors (GISTs) were studied by immunohistochemical analysis and an ultrastructural procedure. The tumor locations were as follows: esophagus (2), stomach (7), small intestine (3), and large intestine (4). Four of the lesions were classified as malignant, 2 as borderline, and 10 as benign. On the basis of the immunohistochemical analysis, the tumors were classified as follows: 1 as myogenic type, 2 as Schwann cell type, 8 as Cajal cell type (including 2 gastrointestinal autonomic nerve tumors, GANTs), and 5 as mixed-cell type. In each subtype the phenotype was compared to the ultrastructural findings. Myogenic and Schwann cell type revealed ultrastructurally smooth muscle differentiation and schwannian tumor. All 8 tumors of the Cajal cell type revealed interdigitating cytoplasmic processes with occasional clusters of filopodia. Two tumors were subdivided as GANT. Five tumors of mixed-cell type were composed of a mixture of cells with variable myogenic features or variable neural differentiation. We confirmed in this study that immunohistochemical analysis reflected electron microscopic findings.     

Cross-talk between Schwann cells and neuroblasts influences the biology of neuroblastoma xenografts

Neuroblastoma (NB) tumors with abundant schwannian stroma have a differentiated phenotype, low vascularity, and are associated with a favorable prognosis. These observations suggest that cross-talk between Schwann cells and neuroblasts may influence tumor biology. To test this hypothesis, we developed a novel NB xenograft model with infiltrating mouse Schwann cells. Human SMS-KCNR NB cells were injected intrafascicularly (sciatic nerve-engrafted NB, n = 19) or outside the sciatic nerve (control, n = 12). Xenografts were harvested 4 to 12 weeks after tumor cell inoculation for histological studies. Schwann cells were immunostained with S-100 and species-specific p75(NGFR), major histocompatibility complex, and human leukocyte antigen antibodies. The number of proliferating cells, infiltrating Schwann cells, apoptotic cells, differentiated neuroblasts, and blood vessels in the sciatic nerve-engrafted NB tumors were compared to controls. Significantly more Schwann cells were detected in the sciatic nerve-engrafted NB xenografts than controls (P < 0.001). The infiltrating Schwann cells were S-100-positive and reacted with anti-mouse major histocompatibility complex class Ib and p75(NGFR) but not anti-human p75(NGFR) and human leukocyte antigen class I antibodies. The sciatic nerve-engrafted tumors also had lower numbers of proliferating neuroblasts, higher numbers of differentiated neuroblasts and apoptotic cells, and decreased vascular density compared to controls. Our results indicate that infiltrating Schwann cells of mouse origin are capable of promoting human neuroblast differentiation, inducing apoptosis, and inhibiting proliferation and angiogenesis in vivo.     

Schwannoma with features mimicking neuroblastoma: report of two cases with immunohistochemical and ultrastructural findings

OBJECTIVE: A study of two cases of a rare variant of benign schwannoma showing areas mimicking neuroblastoma/peripheral primitive neuroectodermal tumour (PNET). METHODS: Sections of formalin fixed, paraffin embedded specimens were studied by tinctorial stains and immunohistochemistry, and the tissue retrieved from formalin was examined by electronmicroscopy in one case. RESULTS: The tumours were small and subcutaneous. Both showed features of benign schwannoma; one had a multinodular plexiform pattern. In addition, rosette-like structures consisting of collagenous cores surrounded by small round cells or slightly larger epithelioid cells were present. Tumour cells were positive for S100 protein, Leu7, and in one case GFAP, but were negative for neurofilament protein, synaptophysin, and MIC2. Type IV collagen surrounded individual cells. Electronmicroscopy in case 2 confirmed schwannian features (lamina, processes) and failed to show features of neuroblastoma (neuroendocrine granules). CONCLUSIONS: Benign schwannomas may contain rosette-like structures mimicking neuroblastoma/PNET. The techniques used confirmed schwannian differentiation only and eliminated neuroblastoma/PNET. These uncommon variants should be recognised by practising histopathologists to avoid erroneous diagnoses and inappropriate treatment.     

Malignant peripheral nerve sheath tumors: an immunohistochemical study in relation to ultrastructural features.

The constituent cells in malignant peripheral nerve sheath tumors were examined by studying the expression of immunohistochemical markers for Schwann cells and perineurial cells in relation to ultrastructural features in 12 malignant peripheral nerve sheath tumors. Ultrastructural studies demonstrated mixed proliferation of Schwann cells, perineurial cells, fibroblastic cells, and primitive cells in many malignant peripheral nerve sheath tumors. Expression of S-100 protein was well correlated with Schwann cell-like differentiation of tumor cells. However, Leu-7 and epithelial membrane antigen, which have been considered to be specific to Schwann cells and perineurial cells, respectively, were common to Schwann cells, perineurial cells, and primitive cells. The common immunophenotypic expression suggests a close relationship among these cell types. The unusual expression of cytokeratin could be explained by the plasticity of intermediate filament expression.     

Myoepithelioma of the Retroperitoneum

An abdominal mass detected in a 36-year-old man was thought from radiologic studies to be a renal neoplasm, but at surgery the kidney was found to be uninvolved. The 9.5-cm retroperitoneal tumor was resected totally and found to be encapsulated, and it appeared to be benign by light microscopy. The pattern of the spindle cells throughout the tumor suggested a cellular schwannoma, but immunocytochemical and ultrastructural studies did not support schwannian differentiation and instead revealed epithelial and smooth muscle features compatible with a myoepithelioma.     

Plexiform Soft Tissue Tumor Composed Predominantly of Perineurial Fibroblasts (Perineurioma)

A 15-year-old girl presented with a small, indolent mass near the knee joint. Light microscopy revealed a peculiar myxoid plexiform tumor composed of cytologically bland cells. Interpretation of the initial biopsy material was controversial. Subsequent immunohistochemical studies revealed tumor cells to be strongly reactive for epithelial membrane antigen (EMA) and negative for S-100 protein. Ultrastructural studies revealed tumor cells with long, thin, bipolar cell processes and discontinuous basal laminae. They had no epithelial or histiocytoid features. Admixed among the tumor cells were Schwann cells, but they represented a rare and scattered component of the overall cell population. These features are most consistent with a so-called perineurioma and contrast with those of plexiform neurofibroma and traumatic neuroma (two lesions strongly positive for S-100 protein and showing a distinctive EMA immunoreactivity pattern with focal peripheral staining of neural bundles).     

Plexiform Soft Tissue Tumor Composed Predominantly of Perineurial Fibroblasts (Perineurioma)

A 15-year-old girl presented with a small, indolent mass near the knee joint. Light microscopy revealed a peculiar myxoid plexiform tumor composed of cytologically bland cells. Interpretation of the initial biopsy material was controversial. Subsequent immunohistochemical studies revealed tumor cells to be strongly reactive for epithelial membrane antigen (EMA) and negative for S-100 protein. Ultrastructural studies revealed tumor cells with long, thin, bipolar cell processes and discontinuous basal laminae. They had no epithelial or histiocytoid features. Admixed among the tumor cells were Schwann cells, but they represented a rare and scattered component of the overall cell population. These features are most consistent with a so-called perineurioma and contrast with those of plexiform neurofibroma and traumatic neuroma (two lesions strongly positive for S-100 protein and showing a distinctive EMA immunoreactivity pattern with focal peripheral staining of neural bundles).     

Melanocytic schwannoma. Light-and electron microscopic findings on the morphology, diagnosis, and differential diagnosis

A melanocytic schwannoma was extirpated from the posterior mediastinum of a ten-year old girl The tumor consisted of cells which were spindle-shaped to polygonal in shape. Spindle-shaped cells were arranged in short, somewhat curved fascicles. In some areas a strand-like arrangement of cells gave rise to an epithelioid appearance. Typical features of benign schwannomas such as nuclear palisading and myxoid texture were absent. The essential histologic hallmarks were melanin deposition and the presence of small psammoma body-like, calcified spherules. Electron microscopic examination confirmed the schwannian differentiation of the tumor cells. These features included interlocking cellular processes, along with a tendency to display the wrap-around phenomenon and a sometimes multi-layered lamina externa. Intracytoplasmic melanin synthesis was evidenced by demonstration of melanosomes in different phases of maturation. The differential diagnosis is discussed with particular emphasis on the need to distinguish this tumor from malignant melanoma. Melanocytic schwannomas should be regarded as potentially malignant. The tendency and degree of invasiveness, mitotic frequency and the ability of tumor cells to form lamina externa have the greatest prognostic value.     

STUDY ON THE ULTRASTRUCTURE AND ACETYLCHOLINESTERASE ACTIVITY IN VON RECKLINGHAUSEN'S NEUROFIBROMATOSIS

The cutaneous nodules obtained from seven patients with von Reckling-hausen's neurofibromatosis were investigated by electron microscopy, and ultrastructural localization of acetylcholinesterase activity was demonstrated in the nerve fibers of this tumor for the first time using Karnovsky's thiocholine method. The enzymatic activity was mainly found in unmyelinated fibers, exactly associated with their axonal membranes, the interspace between the apposing axonal and Schwann cell membrane, and some different mesaxons, which indicated their cholinergic nature. Almost all myelinated fibers and some unmyelinated fibers did not possess the activity. The relationship between axon and Schwann cell was quite similar to that of normal peripheral nervous system, but two striking alterations of the nerves existed: One is the dissociation of unmyelinated fibers, and the other is the degenerative changes of the axon and the myelin sheath. As the evidence of schwannian proliferation, onion bulb formations and collagen pockets were observed. Some signs of fibroblastic proliferation were also found.
From the present study and the review of the literature, the probable histogenesis of this disease was discussed.     

Cellular Schwannoma of the Bronchus

A cellular schwannoma in a bronchus of a 64-year-old female is reported with immunocytochemical and ultrastructural observations. One previous case arising in the lung has been reported. The tumor formed a 3-cm exophytic mass in a segmental bronchus. Pneumonectomy was performed. The tumor was moderately cellular and devoid of Verocay bodies, and the spindle cells were immunoreactive for S-100 protein. Electron microscopy revealed schwannian features that were less developed than in a classic schwannoma.     

Olfactory neuroblastoma. Clinical course, light microscopic and ultrastructural findings in 3 cases

Olfactory neuroblastomas are considered to be a clinicopathological entity, but they may show variable histologic pictures. The light and electron microscopic features of 3 cases as examples for the possible range of morphological findings are presented. This report is also aimed at defining essential diagnostic features, at discussing the differential diagnosis and finally at making pathologists more familiar with these rare tumors. The clinical appearance of the three cases was more or less typical for olfactory neuroblastomas. The leading symptom in all patients was a nasal obstruction. Light microscopically, the neuroblast-like tumor cells were arranged in sheaths or nests. Only in case 1 there were some Flexner rosettes, and especially in case 2 numerous Homer-Wright pseudo-rosettes could be found. Somewhat spindled cells with resemblance to Schwann cells were recognized in case 1 and 3. Neither argyrophilia nor argentaffinity could be demonstrated. Neuroblast-like tumor cells in case 2 contained glycogen intracytoplasmically. The diagnostically essential electron microscopic characteristics were neurite-like cellular processes and neurosecretory granules within the cytoplasm. Corresponding to light microscopic findings in cases 1 and 3, cells with features of Schwann cells could be identified. From the literature and the results presented here the conclusion can be drawn, that in nearly all cases a definite diagnosis is possible if besides the histologic picture also clinical data and, if necessary, ultrastructural and immunohistochemical findings are considered. The most important light microscopic criteria are a fine-fibrillary intercellular substance and the occurrence of Homer-Wright pseudo-rosettes. The differential diagnosis of olfactory neuroblastomas with special regard to electron microscopic findings is discussed and some remarks on the clinical behaviour are added.     

Study on the ultrastructure and acetylcholinesterase activity in von Recklinghausen's neurofibromatosis.

The cutaneous nodules obtained from seven patients with von Recklinghausen's neurofibromatosis were investigated by electron microscopy, and ultrastructural localization of acetylcholinesterase activity was demonstrated in the nerve fibers of this tumor for the first time using Karnovsky's thiocholine method. The enzymatic activity was mainly found in unmyelinated fibers, exactly associated with their axonal membranes, the interspace between the apposing axonal and Schwann cell membrane, and some different mesaxons, which indicated their cholinergic nature. Almost all myelinated fibers and some unmyelinated fibers did not possess the activity. The relationship between axon and Schwann cell was quite similar to that of normal peripheral nervous system, but two striking alterations of the nerves existed: One is the dissociation of unmyelinated fibers, and the other is the degenerative changes of the axon and the myelin sheath. As the evidence of schwannian proliferation, onion bulb formations and collagen pockets were observed. Some signs of fibroblastic proliferation were also found. From the present study and the review of the literature, the probable histogenesis of this disease was discussed.     

A case of hyalinizing spindle cell tumor with giant rosettes in the presacral region. Immunohistochemical and ultrastructural study

Hyalinizing spindle cell tumor with giant rosettes is a slowly growing tumor with a risk of local recurrence in case of incomplete surgical excision that could be regarded as a distinctive type of low-grade fibroblastic tumor. We report a case involving the presacral area. This tumor was composed of areas of bland spindle cell proliferation with a fascicular pattern in a fibrous or myxoid stroma, intermixed with giant rosettes consisting of rounded cells surrounding a central collagen core. The tumor expressed vimentin, and, for cells comprising the rosettes, S-100 protein, NSE and CD-57. These latter cells exhibited ultrastructural features of Schwann cells, the tumoral cells of fascicular area exhibiting features of fibroblastic cells. Flow cytometry showed DNA-aneuploidy and a very low S-phase fraction. This tumor appeared to be composed of two cellular components, fibroblastic and Schwann cells, located, at the opposite of neurofibroma, in two distinct areas.     

Neurogenic sarcomas in patients with neurofibromatosis (von Recklinghausen's disease)

Summary Thirteen soft tissue neurogenic sarcomas from twelve patients with neurofibromatosis (Von Recklinghausen's disease) were ultrastructurally examined. Electron microscopic studies revealed a wide spectrum of morphological manifestations varying from schwannian to fibroblastic, histiocytic, fibrohistiocytic and relatively undifferentiated cellular proliferations. A similar variation on light microscopic appearances has been previously reported in these neurogenic sarcomas. Neurogenic sarcomas occurring in patients with neurofibromatosis (Von Recklinghausen's disease), represent a heterogenous group of neoplasms with various patterns of differentiation identified ultrastructurally. The morphologic expressions of these neurogenic neoplasms can be conceptualized as a disorderly growth of the various peripheral nerve cellular components, or, as has been previously suggested, as a result of the multipotential nature and metaplastic ability of Schwann cells. S-100 protein immunohistochemistry was only positive in those neoplasms ultrastructurally proven to represent schwannian cellular proliferations.This study serves to document the range of fine structure that may be found in neurogenic sarcomas, to correlate the ultrastructural findings with the light microscopic appearance of these tumors, to determine the specificity of the electron microscopic findings, and immunohistochemistry for S-100 protein and assess their possible value in differential diagnosis.     

PERINEURIAL CELL TUMOR AND THE SIGNIFICANCE OF THE PERINEURIAL CELLS IN NEUROFIBROMA

The authors attempted to clarify the exact cell components of neurofibroma by immunohistochemical and ultrastructural studies. Materials were randomly selected, 40 cases of neurilemoma and neurofibroma (-tosis) in addition to 2 cases of tumors composed exclusively of perineurial cells and three cases of normal peripheral nerve. The applied markers included antisera of S-100 protein for Schwann cells, blood coagulation factor XIIIa for endoneurial fibroblasts or perineurial cells, and laminin and collagen type IV for the basement membrane. S-100 protein was demonstrated only in normal or neoplastic Schwann cells, but not in perineurial cells. On the other hand, factor XIIIa was often recognized in endoneurial fibroblasts and perineurial cells, but not in Schwann cells. Neurofibroma was basically composed of a mixture of Schwann cells, perineurial cells, and endoneurial fibroblasts, the population of each type of cell differing according to the case and area within a given tumor. Perineurial cell tumor exclusively composed of perineurial cells, though rare, appears to be a definite entity, and its characteristic histological and ultrastructural features were described.     

Perineurial cell tumor and the significance of the perineurial cells in neurofibroma

The authors attempted to clarify the exact cell components of neurofibroma by immunohistochemical and ultrastructural studies. Materials were randomly selected, 40 cases of neurilemoma and neurofibroma (-tosis) in addition to 2 cases of tumors composed exclusively of perineurial cells and three cases of normal peripheral nerve. The applied markers included antisera of S-100 protein for Schwann cells, blood coagulation factor XIIIa for endoneurial fibroblasts or perineurial cells, and laminin and collagen type IV for the basement membrane. S-100 protein was demonstrated only in normal or neoplastic Schwann cells, but not in perineurial cells. On the other hand, factor XIIIa was often recognized in endoneurial fibroblasts and perineurial cells, but not in Schwann cells. Neurofibroma was basically composed of a mixture of Schwann cells, perineurial cells, and endoneurial fibroblasts, the population of each type of cell differing according to the case and area within a given tumor. Perineurial cell tumor exclusively composed of perineurial cells, though rare, appears to be a definite entity, and its characteristic histological and ultrastructural features were described.     

Benign nerve sheath tumors: a light microscopic, electron microscopic and immunohistochemical study of 102 cases.

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.     

Malignant melanoma of soft parts: an ultrastructural study of four cases

Malignant melanomas of soft parts from 4 patients were studied by light microscopy, immunocytochemistry for S-100 protein, and electron microscopy. Each patient presented with a deep soft tissue mass in an extremity. Histologically, the tumors were composed of epithelioid and spindle cells, and in one, neoplastic giant cells were present. The tumors did not stain for melanin but were all positive for S-100 protein. Ultrastructurally, premelanosomes were identified in every tumor and in a cell line established from one tumor. Schwann cell features were present in one of the tumors. Although the clinical presentation of malignant melanoma of soft parts is similar to that of epithelioid sarcoma and synovial sarcoma, the combined light microscopic, immunocytochemical, and ultrastructural features should serve to distinguish it from other soft tissue sarcomas.