Extra-adrenal paraganglioma of the median nerve.

An extra-adrenal paraganglioma is an uncommon tumour that arises from the paraganglia associated with the autonomous nervous system. A paraganglioma arising in the sensory-somatic nervous system is extremely rare and clinically is easily confused with other neurogenic tumours. We describe a paraganglioma that arose in the median nerve of a 22-year-old woman.

Undifferentiated perivascular cells in myxoid mesenchymal tumors: an ultrastructural study.

The current WHO classification of soft tissue tumors is based on the lineage of differentiation of the proliferating cells. Since mature mesenchymal cells have a broad phenotypic plasticity it has been considered unnecessary to recur to a hypothetical stem cell to explain the origin of these neoplasms. In spite of this assumption, the target cell of the oncogenic mutations in mesenchymal tumors is still a controversial item. Myxoid mesenchymal tumors constitute a heterogeneous group of neoplasms sharing in an ample mucinous matrix that separates neoplastic cells and facilitates their single submicroscopic study under electron microscopy examination. The authors have studied, by electron microscopy, 74 myxoid mesenchymal tumors, including a large variety of nosologic entities, to assess their madurational gradient. In 43 of 74 cases, a common element has been found: medium-sized cells, with high nucleo-cytoplasmic ratio, lacking lineage specific features, which were arranged around the capillary vessels. In some cases, the authors were able to demonstrate gradual differentiation in these cells, as they moved away from the vessels. These features support the hypothesis that at least some mesenchymal tumors originate from perivascular undifferentiated cells. In addition, the findings might contribute to define both topographic and morphologic characteristics of adult stem mesenchymal cells.

[Perineuriomas and other tumors with perineurial differentiation].

This is a review of the literature on the peripheral nerve sheath tumors with perineural differentiation. The authors provide an overview of the clinicopathological, immunohistochemical, ultrastructural, and genetic features of these neoplasms. Emphasis is laid on various morphological variants of perineurioma (intraneural, retifrm, sclerosing, plexiform, atypical, malignant, etc.) and so-called hybrid tumors (schwannoma-perineurioma, neurofibroma-perineurioma).

Unusual metastasis of malignant aortic body tumor to multiple bones in a dog.

Unusual metastasis of malignant aortic body tumor to multiple bones was detected in a 5-year-old female English Setter dog. Radiographs exhibited an abnormal mass in the base of heart and osteolytic lesions in the bodies of T11 and L2 vertebrates, body of right femur, right proximal humoral epiphysis and infraspinous fossa near to the neck of right scapula. At necropsy, multiple tumor masses of various sizes were observed also in the bones as well as the heart base and tracheobronchial lymph node. Tumor masses of L2 and T11 protruded into the vertebral canal and compressed corresponding sites of spinal cord, leading to paraplegia. Histopathologically, the tumor cells, arranged in sheets or nests, were polyhedral, lightly eosinophilic, finely granular cytoplasm with mostly round to oval nucleus and had scattered bizarre giant cells. Ultrastructural study revealed the characteristic findings that tumor cells contained a large number of small, electron-dense, membrane-limited secretory granules in cytoplasm. This is thought to be an extremely rare case having multiple bone metastases of a malignant aortic body tumor.

[Benign intercostal nerve schwannoma simulating pulmonary neoplasm: case report]. / Schwannoma benigno do nervo intercostal simulando neoplastia de pulmão: relato de caso.

A 37 years-old white man, smoker, was interned for having dry cough and pain in the left hemithorax (HE). The exam has show diminished vesicle mumble in the medium third part of the HE. The thorax computer tomography showed expansive nodular lesion of the 7 degrees coster arch projecting within the HE, with density of the bulk part and discreet enhance by the contrast. Imuno-histochemistry was compatible to benign schwannoma. We consider the intercostal benign schwannoma diagnosis must be taken before all the posterior or lateral intrathoracic mass that follows with small syntomathology and absence of clinical manifestation of malignity.

Schwannoma benigno do nervo intercostal simulando neoplastia de pulmão: relato de caso / Benign intercostal nerve schwannoma simulating pulmonary neoplasm: case report

Homem de 37 anos, branco, tabagista, foi internado com tosse seca e dor no hemitórax esquerdo (HE). Ao exame, macicez e murmúrio vesicular diminuído no terço médio do HE. A tomografia axial computadorizada de tórax revelou lesão expansiva nodular do 7º arco costal, projetando-se para o interior do HE, com densidade de parte mole e discreto realce pelo contraste. A histologia e a imuno-histoquímica foram compatíveis com schwannoma benigno. Consideramos que o diagnóstico de schwannoma benigno intercostal deve ser aventado ante toda massa intratorácica posterior ou lateral que curse com escassa sintomatologia e ausência de manifestações clínicas de malignidade.

Intraneural perineurioma involving the ulnar nerve.

Intraneural perineurioma is a rare peripheral nerve sheath tumor consisting of intraneural proliferation of neoplastic perineurial cells. Clinical and pathological findings of a perineurioma involving the ulnar nerve is presented. A 7-year-old girl presented with a 2 year history of weakness and atrophy of the right hand muscles. Physical examination and imaging study revealed a pea-sized tumor in the ulnar side of the right forearm. At surgery, a fusiform swelling of the ulnar nerve was found and an excisional biopsy of the lesion was performed. Light microscopy revealed numerous whorls consisting of concentric layers of spindle cells encircling the nerve fibers. The proliferating cells were immunoreactive for vimentin, epithelial membrane antigen and glucose transporter protein 1 (Glut1), but negative for S-100 protein and CD34. Ultrastructural examination revealed features of perineurial cell differentiation. The current study suggests that Glut1 is a useful marker of intraneural perineurioma.

Ultrastructural studies of gastrointestinal stromal tumors.

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors in the gastrointestinal tract (GIT). Although interstitial cells of Cajal has been suggested as origin of this tumor, the cytological and ultrastructural features of GISTs are heterogeneous and unclear. A total 10 cases of normal gastrointestinal tissue (control), 13 GISTs of the stomach (8), small intestine (3), mesocolon (1) and liver (1), and 2 gastrointestinal autonomic nervous tumor (GANT) of small intestine were ultrastructurally studied. Normal interstitial cells of Cajal (ICC) were abundantly present around the myenteric plexuses or individually scattered through the wall of GIT. ICC was characterized by slender cytoplasmic processes, well-developed endoplasmic reticulum (ER), mitochondria, Golgi apparatus, caveolae and intermediate filaments. The GISTs and GANTs had overlapping ultrastructures. The most common and important ultrastructural features of GISTs were rich villous cytoplasmic processes, dispersed intermediate filaments and abundant SER, and those of GANTs were neurosecretory granules and skenoid fibers. Compared with ICC, the GISTs and GANTs had remarkably reduced caveolae and gap junctions. Our study suggested that ultrastructural analysis gives much information to investigate lineage differentiation of neoplastic cells and make a differential diagnosis of these tumors from other mesenchymal tumors and between GISTs and GANTs.

Intraneural synovial sarcoma: two cases.

We report two cases of intraneural synovial sarcoma. The first patient is a 46-year-old female who presented for several months with soft-tissue mass in the right infra-auricular region. The second patient is a 11-year-old girl who fell and then presented with pain in the area innervated by the right C7 spinal root and a nodule identified in the nerve root foramina. Both lesions were of small size and presented with features of synovial sarcoma. A biphasic variant was found in case 1 and a monophasic variant was present in case 2. Immunohistochemical studies were performed to confirm the diagnosis, excluding the main differential diagnoses, namely schwannoma and malignant peripheral nerve sheath tumor. Ultrastructural study was performed in case 2 allowing exclusion of other possible diagnoses. Molecular studies were performed on paraffin-embedded tissue in both cases and revealed the known characteristic t(X;18)(SYT-SSX) translocation.

Low grade malignant peripheral nerve sheath tumour: varied cytological and histological patterns.

BACKGROUND: A small number of malignant peripheral nerve sheath tumours (MPNSTs) are low grade, and the nature of these low grade tumours has never been systematically assessed. AIMS: To describe the clinicopathological, immunohistochemical, and ultrastructural features of low grade MPNST and to discuss the main differential diagnoses. METHODS: Four cases of low grade MPNST were studied, including one coexistent with neurofibromatosis type 1. The tumours were analysed with respect to nuclear atypia, cellularity, nuclear enlargement, hyperchromasia, mitotic rate, and necrosis. Immunohistochemistry was performed by standard techniques, and an ultrastructural study was performed on one tumour. RESULTS: The ages of the patients ranged from 32 to 72 years (mean, 58). Two were male and two were female. Three tumours occurred in the deep tissue, including one in the retroperitoneum, and one was located in the dermal and subcutaneous tissue. The maximum diameters of the tumours ranged from 3.5 to 8.0 cm. Microscopically, all tumours showed moderate hypercellularity, an increased nuclear to cytoplasmic ratio, and hyperchromasia, but exhibited varied growth patterns, including those that were atypical neurofibroma-like, low grade fibromyxoid sarcoma-like, low grade epithelioid, and haemangiopericytoma-like. All tumours showed immunoreactivity for S-100 protein and vimentin. CONCLUSIONS: These findings suggest that careful clinical and histological evaluation, along with S-100 protein immunostaining, are essential for the accurate diagnosis of low grade MPNST.

Pigmented vagal paraganglioma.

Paragangliomas are uncommon and those arising from the vagal trunk are rarer. Pigmented extra-adrenal paragangliomas are still rarer and reported sites of occurrence are the uterus, spine, retroperitoneum, bladder, mediastinum and orbit. The presence of abundant pigment in a cervical paraganglion has not been reported previously. We report one such unusual case of pigmented vagal paraganglioma that arose from the vagal trunk below the nodose ganglion, had massive central necrosis and showed hypovascularity on angiography. The unusual features and difficulties in the diagnosis of such cases are discussed.

Soft tissue perineuriomas in children: report of three cases and review of the literature [corrected].

Perineuriomas (PN) are uncommon, slowly growing, usually benign tumors composed of well-differentiated perineural cells. Two variants are recognized: intraneural perineuriomas and soft tissue perineurioma, which includes a sclerosing subset of tumors. They are usually reported in the adult population. We present three cases of soft tissue perineuriomas in children. One was located in the deep soft tissue of the retroperitoneum in a 14-year-old girl, the second one in the left thumb of a 14-year-old boy, and the third one in the index finger of a 16-year-old boy. This report, which describes the clinicopathologic, immunohistochemical, and ultrastructural features of these tumors, should alert pathologists to the occurrence of perineuriomas in children. A review of the English language literature on perineuriomas in children is also included.

Alpha-synuclein immunoreactivity in normal and neoplastic Schwann cells.

Alpha-synuclein is known to play an important role in several neurodegenerative diseases. Moreover, it is expressed in central nervous system neuronal tumors, and another member of the synuclein family, gamma-synuclein, is overexpressed in breast and ovarian carcinomas. However, the expression of alpha-synuclein has not been reported hitherto in the peripheral nervous system (PNS). In the present study, we investigated normal PNS tissue and schwannomas in human postmortem and biopsy samples using both immunocytochemistry and immunoelectron microscopy with antibodies against alpha-, beta- and gamma-synuclein. In normal PNS tissue, Schwann cells, but not axons or myelin, were immunopositive for alpha-synuclein. In schwannomas, almost all of the tumor cells showed diffuse cytoplasmic staining for alpha-synuclein (30 cases). Ultrastructurally, alpha-synuclein immunoreactivity was found in the cytoplasm of normal and neoplastic Schwann cells, in association with the plasma membrane, ribosomes, rough endoplasmic reticulum, small vesicles, Golgi apparatus and the nuclear outer membrane. No beta- or gamma-synuclein immunoreactivity was found in those cells. These results indicate that in the PNS, alpha-synuclein is a useful marker of Schwann cells and that it is not involved in tumorigenesis.

A new human malignant peripheral nerve sheath tumour-cell line, HS-sch-2, harbouring p53 point mutation.

Only a few human malignant peripheral nerve sheath tumour (MPNST)-cell lines have been reported, and their characteristics have not been fully established. In this study, we established a new human cell line, HS-Sch-2, from an MPNST of the ordinary type which arose in a 54-year-old woman without von Recklinghausen's disease. This cell line was characterized by chromosome analysis, immunohistochemistry, ultrastructural examination, and direct sequencing of the p53 gene. The HS-Sch-2 cells have grown for more than 48 months in vitro, and exhibited hypotriploid karyotypes with complex chromosome abnormalities lacking a specific pattern. Histological features of the heterotranplanted nude mouse tumours were essentially the same as those of the original MPNST, with positive reactions for S-100 protein and neuron-specific enolase but not for epithelial membrane antigen, fibronectin or CD34. Ultrastructural examination in vivo revealed intricate interdigitation of long cytoplasmic processes and basal lamina-like structures. In addition, direct sequencing of the p53 gene detected a point mutation from CGT to CAT at codon 273 in exon 8. This HS-Sch-2 cell line, which exhibits distinctive morphological characteristics of MPNST and a p53 point mutation, will be useful for biological and pathological investigations of MPNST.

End-to-side anastomosis of transected nerves to prevent neuroma formation.

Neuroma can be painful and physically and psychologically disabling. Among the many methods of treatment available, one of the more successful is centrocentral nerve union with an autologous graft. However, it cannot be used in small nerves that lack two fascicles. This study evaluated neuroma prevention in an end-to-side anastomosis, a new technique applicable to all nerves. The lateral branch of the right sciatic nerve in 20 rats was transected at the midthigh level. The proximal segment was looped back to the main nerve and an end-to-side epineural anastomosis was performed. The lateral branch of the left sciatic nerve was transected to serve as a control, and the proximal nerve stump was closed by interrupted epineural sutures. The animals were sacrificed 12 weeks after the operation. Histologic analysis of specimens from the 12 controls showed neuroma formation. Specimens from 12 side-to-end anastomoses contained regenerated nerve tissues and formed smaller masses compared with that of the controls. The regenerated tissues at the anastomoses were orientated more orderly than were tissues from the controls in 75% of cases. The differences were statistically significant. Electron microscopic study on specimens from the remaining eight controls showed the presence of abundant large abnormal myelinated fibers (10-15 microns) with thick irregular myelin sheaths scattered among smaller myelinated fibers (2-10 microns) that had thin myelin sheaths. In the remaining eight end-to-side anastomoses, large abnormal myelinated fibers were absent. The myelinated fibers were 2 to 10 microns in diameters and had a normal appearance with thin myelin sheaths. End-to-side anastomosis formed a smaller mass of regenerated nerve tissues. Ultrastructurally they were formed better and orientated more orderly resembling normal nerve.

Cytokeratins expression in paragangliomas of the cauda equina.

BACKGROUND: Paragangliomas rarely involve the cauda equina region. In this location, these tumors can show misleading morphological features such as trabecular or papillary growth patterns and variable expression of cytokeratins. METHODS: We comparatively studied the immunohistochemical and ultrastructural patterns of 3 paragangliomas of the cauda equina (PCE) and of 8 paragangliomas from other sites. RESULTS: All the paragangliomas expressed neuroendocrine markers (neuron-specific enolase, chromogranin A, synaptophysin and neurofilament protein). In PCE, chief cells exhibited a strong positivity with a broad spectrum anti-cytokeratin antibody. The staining was diffuse in the cytoplasm or had a paranuclear dot-like disposition. In other sites, only one paraganglioma showed a focal expression of cytokeratins. At ultrastructural level, chief cells of PCE contained characteristic dense core granules and intermediate-sized filaments sometimes grouped in paranuclear whorls. CONCLUSION: The dual immunophenotype of PCE, paraganglionic and epithelial, must be recognized in order to distinguish these tumors from, for example, a metastasis of a neuroendocrine carcinoma. PCE are slow-growing tumors and have mostly a favorable prognosis after complete surgical excision.

Assessment of the malignant potential of mitogen stimulated human Schwann cells.

Human Schwann cells (SCs) can be isolated and expanded with mitogens using cell culture techniques. These cells have been demonstrated to promote axonal regrowth in both the central and peripheral nervous system. Primary rat SCs can be immortalized with long-term exposure to mitogens. Transplantation of these cells into an autogenic host sciatic nerve results in the formation of tumors. Human cells are, in general, relatively more resistant to malignant transformation, but any potential risk for inducing tumor after transplantation of SCs in humans must be excluded. In this study, the malignant potential of mitogen expanded human SCs injected into the sciatic nerve of immunodeficient mice was investigated. Human SCs were isolated from human peripheral nerves and placed in cell culture, expanded with mitogens (heregulin and forskolin) for many passages (0-6 times), and then injected within the sciatic nerve of Severe Combined Immunodeficient (SCID) rat or mice. As a positive control for tumor formation in this xenograft model, human glioma cells were also injected. The proliferation index (PI) of the human SCs gradually decreased with each passage in cell culture. SC purity remained stable until the 6th passage, and then decreased significantly for older passages, so that the cultures were over-grown with fibroblasts. The incidence for rat or human glioma cells to induce tumors was 100% and 92%, respectively. In contrast, there was no tumor induced by human primary or mitogen expanded SCs. Demyelination, remyelination and formation of connective sheath at the injection site were observed in some cases after injection of the human SCs. Thus, mitogen-expanded human SCs do not produce tumors when transplanted in vivo, which suggests that these cells are safe, and deserve further study towards their use in clinical transplantation.

Perineurial malignant peripheral nerve sheath tumor (MPNST): a clinicopathologic, immunohistochemical, and ultrastructural study of seven cases.

Most malignant peripheral nerve sheath tumors (MPNST) are schwannian in nature. The pathologic features of MPNST with perineurial cell differentiation remain to be characterized. To determine the clinicopathologic, immunohistochemical, and ultrastructural characteristics of perineurial MPNST, 121 MPNST from the Mayo Clinic Tissue Registry were examined. Of these 23 spindle cell tumors with long processes disposed in whorls or storiform patterns, features typical of perineurioma, were studied. On the basis of immunohistochemistry (epithelial membrane antigen+/S-100-), 5 perineurial MPNST were identified among 23 tumors selected. These and two previously characterized perineurial MPNST are the subject of this study. None of seven tumors was associated with NF-1. Patients included five males and two females ranging in age from 11 to 83 years (mean, 45.7 years). The tumors measured 1.5 to 30 cm (mean, 9.1 cm) and arose in the extremities (two), trunk (two), face (one), mediastinum (one), and retroperitoneum (one). Only one tumor was nerve associated (phrenic nerve). All tumors were surgically removed. No encapsulation or neurofibroma components were noted. Necrosis was seen in three lesions. Four tumors were classified as high-grade malignant and three as low grade. Mitotic indices varied from 1 to 85/10 high-power fields (median, 16). Immunoreactivities included epithelial membrane antigen (100%), vimentin (100%), Leu-7 (57%), and CD34 (14%). Stains for S-100 protein, muscle markers, and cytokeratin were nonreactive. Ultrastructurally, perineurial-like cells were noted in three tumors and cells intermediate between perineurial and Schwann cells in one. Four tumors recurred and two metastasized; no deaths of disease were noted at follow-ups of 28 to 98 months (mean, 66.9). In conclusion, 4% of MPNST show perineurial cell differentiation. An NF-1 association has yet to be described. Nerve involvement is infrequent. Their immunophenotype (epithelial membrane antigen+/S-100-) frequently indicates ultrastructural perineurial differentiation. The prognosis of perineural MPNST appears to be more favorable than that of conventional MPNST.