Extraneural Tissue Research Articles

Périneuriome extraneural des tissus mous localisé au nez

Perineuriomas are tumours derived from the perineurial cells of the neural sheath. Soft tissue perineuriomas are rare. Herein, we report a case of perineurioma localized to the nose. A 24-year-old adult presented with a cutaneous nodule 1cm in diameter localized on the nose. Histologically, the tumour corresponded to a well-circumscribed fusocellular dermal proliferation organized in a storiform pattern. After surgical removal, the lesion did not recur. Extraneural soft tissue perineurioma is usually a benign nerve sheath tumour composed mainly of perineurial cells. Our case occurred in a 24-year-old Caucasian adult. The tumour generally presents as a unique cutaneous nodule corresponding histologically to a well-delineated dermal fusocellular proliferation organized in a storiform pattern that stains positive for EMA and negative for S100. The tumour is usually localized to the trunk and extremities. Location on the nose as in our patient has been rarely reported. Surgical removal of the tumour is the treatment of choice.

Progressive Cervical Myelopathy as Presentation of Sarcoidosis

A 44-year-old African-American woman was admitted with four months of intermittent “shock-like” sensations in her chest radiating to both arms; she developed left arm weakness just prior to admission. A cervical spine magnetic resonance imaging (MRI) demonstrated intramedullary enhancement from C1 to T1 (Fig. 1 Panel a). Figure 1. Cervical spine magnetic resonance imaging (MRI) of a 44-year-old African-American woman. Panel a: MRI with gadolinium contrast 3 weeks prior to admission. Panel b: MRI with gadolinium contrast after 8 weeks of corticosteroid therapy. Neurologic examination showed 4/5 strength of left wrist flexors and extensors, decreased bilateral light touch and pinprick sensation from C5 to T5, and hyperalgesia bilaterally from T1 to T3. Chest x-ray showed hilar adenopathy. Serum angiotensin converting enzyme level was 191 U/L (normal 9–67). Lumbar puncture was remarkable for a protein of 54 mg/dl (normal 15–45) and glucose of 30 mg/dl (normal 45–80; serum glucose 106). Transbronchial biopsy showed non-caseating granulomas. Sarcoidosis is an idiopathic inflammatory disease characterized by non-caseating granulomas affecting any organ. Neurologic involvement occurs in 5–17 % of sarcoidosis patients, with 0.43 % having spinal cord involvement.1 The most common cerebrospinal fluid findings are elevated protein and hypoglycorrhachia, presumably a manifestation of chronic meningeal inflammation.2 Owing to the invasive nature of spinal cord biopsy, neurosarcoidosis is often diagnosed with extraneural tissue and the appropriate clinical syndrome.3,4 Treatment generally includes immunosuppressive agents. This patient’s neurological deficits and radiographic abnormalities improved with corticosteroids (Fig. ​(Fig.11 Panel b).

Functional diversity of microglia – how heterogeneous are they to begin with?

Microglia serve in the surveillance and maintenance, protection and restoration of the central nervous system (CNS) homeostasis. By their parenchymal location they differ from other CNS-associated myeloid cells, and by origin as well as functional characteristics they are also–at least in part–distinct from extraneural tissue macrophages. Nevertheless, microglia themselves may not comprise a uniform cell type. CNS regions vary by cellular and chemical composition, including white matter (myelin) content, blood–brain barrier properties or prevailing neurotransmitters. Such a micromilieu could instruct as well as require local adaptions of microglial features. Yet even cells within circumscribed populations may reveal some specialization by subtypes, regarding house-keeping duties and functional capacities upon challenges. While diversity of reactive phenotypes has been established still little is known as to whether all activated cells would respond with the same program of induced genes and functions or whether responder subsets have individual contributions. Preferential synthesis of a key cytokine could asign a master control to certain cells among a pool of activated microglia. Critical functions could be sequestered to discrete microglial subtypes in order to avoid interference, such as clearance of endogenous material and presentation of antigens. Indeed, several and especially a number of recent studies provide evidence for the constitutive and reactive heterogeneity of microglia by and within CNS regions. While such a principle of “division of labor” would influence the basic notion of “the” microglia, it could come with the practival value of addressing separate microglia types in experimental and therapeutic manipulations.

Reduction of neural scarring after peripheral nerve suture: An experimental study about collagen membrane and autologous vein wrapping

The effects of a collagen membrane and a technique of autologous vein wrapping on scar formation after peripheral nerve suture are investigated. Forty-eight sciatic nerves from Wistar rats were transected and repaired, then allocated to a control group C (n=16) and two experimental groups: in group A (n=16) the repair line was covered by the collagen membrane, and in group B (n=16) the repair line was wrapped by an external jugular venous graft. Three months later, it was observed that adhesions in the surrounding tissues were significantly less in groups A and B compared to group C, and significantly less in group A than in the group B. Histological analysis revealed no significant reduction of extraneural or intraneural scar tissue in groups A or B compared to group C. However intraneural fibrosis was significantly less in the group A than in the group B. It was concluded that the collagen membrane was effective in reducing neural scar formation after peripheral nerve suture. Autologous vein wrapping also showed a favorable effect in this indication despite less successful histological outcomes.

Facilitated Cross-Species Transmission of Prions in Extraneural Tissue

Prions are infectious pathogens essentially composed of PrP(Sc), an abnormally folded form of the host-encoded prion protein PrP(C). Constrained steric interactions between PrP(Sc) and PrP(C) are thought to provide prions with species specificity and to control cross-species transmission into other host populations, including humans. We compared the ability of brain and lymphoid tissues from ovine and human PrP transgenic mice to replicate foreign, inefficiently transmitted prions. Lymphoid tissue was consistently more permissive than the brain to prions such as those causing chronic wasting disease and bovine spongiform encephalopathy. Furthermore, when the transmission barrier was overcome through strain shifting in the brain, a distinct agent propagated in the spleen, which retained the ability to infect the original host. Thus, prion cross-species transmission efficacy can exhibit a marked tissue dependence.

脳表ヘモシデリン沈着症とNeuroferritinopathyの神経病理

Neuropathology of superficial hemosiderosis. Gross finding shows diffuse brownish discoloration at the surface of the cerebrum, cerebellum, brainstem and spinal cord. Severe atrophy and necrosis is present in the cerebellum. Extensive deposits of hemosiderin that are well recognized with Berlin blue and ferritin immunohistochemistry are present at the surface and in the superficial parenchyma of the cerebrum, brainstem, cerebellum and spinal cord. Although the pathomechanism of this disease remains unresolved, continuous or recurrent subarachnoid hemorrhage may be important for developing diffuse hemosiderin deposition. Neuroferritinopathy. Intranuclear and intracytoplasmic bodies are seen in glia and subsets of neurons in the central nervous system as well as in extraneural tissue. They are stained by Perls' method for ferric iron. The bodies are immunopositive against antibodies raised against mutated and wild type of ferritin light polypeptide as well as ferritin heavy polypeptide. It is suggested that loss of normal function and gain of toxic function may be crucial for neurodegeneration of neuroferritinopathy. Both diseases could be helpful to understand and clarify the pathomechanism of neurodegeneration associated with iron metabolism.

Classification of Neural Tumors in Laboratory Rodents, Emphasizing the Rat

Neoplasms of the nervous system, whether spontaneous or induced, are infrequent in laboratory rodents and very rare in other laboratory animal species. The morphology of neural tumors depends on the intrinsic functions and properties of the cell type, the interactions between the neoplasm and surrounding normal tissue, and regressive changes. The incidence of neural neoplasms varies with sex, location, and age of tumor onset. Although the onset of spontaneous tumor development cannot be established in routine oncogenicity studies, calculations using the time of diagnosis (day of death) have revealed significant differences in tumor biology among different rat strains. In the central nervous system, granular cell tumors (a meningioma variant), followed by glial tumors, are the most common neoplasms in rats, whereas glial cell tumors are observed most frequently in mice. Central nervous system tumors usually affect the brain rather than the spinal cord. Other than adrenal gland pheochromocytomas, the most common neoplasms of the peripheral nervous system are schwannomas. Neural tumors may develop in the central nervous system and peripheral nervous system from other cell lineages (including extraneural elements like adipose tissue and lymphocytes), but such lesions are very rare in laboratory animals.

From basic concepts to emerging technologies in regional anesthesia

The present article details how our understanding of the basic concepts of regional anesthesia has recently evolved. We will appraise current technological advances and question the commensurate nature of the relationship between tradition and innovation. Ultrasound localization has enhanced our understanding of the needle-nerve relationship. Intraneural injection of local anesthetic may occur with greater frequency than previously thought without inevitably leading to neurological complications. The ratio of neural to non-neural tissue varies both between and within nerves and may be an important determinant of neural injury. Ultrasonographic evidence of intraneural injection is subject to observer expertise and the resolution of the ultrasound image. Current ultrasound resolution capability does not reliably permit differentiation between intrafascicular and extrafascicular drug injection. Perineural electrical impedance may be a determinant of current threshold and conceivably distinguish between intraneural and extraneural tissue. Technology that enhances the sonographic image of both procedure needle and target nerve is the focus of current endeavors in ultrasound innovation.There is inconclusive evidence that the use of ultrasound technology has reduced the incidence of local anesthetic toxicity. Lipid emulsion therapy is now an accepted treatment for systemic local anesthetic toxicity. There are new reports on the development of an ultra long-acting local anesthetic agent that would permit lower doses and superannuate catheter-based continuous regional anesthesia techniques. Over the past decade, our understanding of the fundamental concepts of regional anesthesia continues to be challenged by emerging experimental and clinical evidence.

Intraoral sclerosing perineurioma: a case report and review of the literature

Sclerosing perineurioma is an extraneural soft tissue lesion that has been reported in the extremities of young adults. It is composed of oval epithelioid or plump spindled cells scattered to form ill-defined fascicles in a storiform, whorled, or trabecular pattern and dermal sclerosis represented by thickened collagen bundles in a lamellar array that express epithelial membrane antigen and are negative for S-100 protein. The treatment is surgical excision, and no recurrence or metastases are expected. Herein is presented the first case of intraoral sclerosing perineurioma of the lower lip, emphasizing its histopathologic and immunohistochemical features.

Extraneural Soft Tissue Perineurioma of the Oral Mucosa

A58-year-oldCaucasianfemalepresentedwithapainless,fibroelastic,well-definedmobilesubmucosalnoduleinthelowerbuccalfoldadjacenttotheleftfirstmolar,measuring0.5 cm in diameter. The duration of the lesion was un-knownandthepatientwasotherwisehealthy.Panoramicradiographyshowednobonealterations,buttheassociatedleftfirstmolarwasendodonticallytreated.Withthemainclinicalhypothesisofareactivelymphadenopathy,anexci-sional biopsy was performed under local anesthesia. Thelesionwasayellowishwell-definednodulethatwaseasilydetachedfromtheadjacenttissue(Fig1).Microscopically,itwascomposedofamoderatelycircumscribedbutnonen-capsulated spindle cell proliferation (Fig 2A). The tumorwashypercellularandcomposedofangulatedspindlecellsdisposed in a storiform pattern with some perivascularwhorls (Fig 2B). The cells were thin with scarce eosino-philic cytoplasm, indistinct cell borders, and elongatedwavy-shaped nuclei. Tissue cracking artifact could be ob-servedandtherewerenopleomorphism,mitosis,andne-crosis(Fig2C).Aprovisionaldiagnosisofabenignspindlecellneoplasmofneuraloriginwasestablished,andimmu-nohistochemicalreactionswerecarriedoutusingtheavi-

Detection of High Levels of European Bat Lyssavirus Type‐1 Viral RNA in the Thyroid Gland of Experimentally‐Infected Eptesicus fuscus Bats

Two common bat lyssavirus species have been identified in many European countries: European bat lyssavirus type-1 and -2 (EBLV-1 and EBLV-2). Only limited knowledge on the susceptibility of the natural EBLV-hosts, insectivorous bats, to lyssavirus infection is available. Our study was undertaken to evaluate the susceptibility and pathology associated with an EBLV-1 infection in Eptesicus fuscus following different routes of virus inoculation including intracranial (n = 6), intramuscular (n = 14), oral (n = 7) and intranasal (n = 7). Blood and saliva samples were collected from all bats on a monthly basis. Four bats inoculated intracranially developed rabies with a mean of 11 days to death, whilst seven bats inoculated intramuscularly developed rabies, with an extended incubation period prior to death. We did not observe any mortality in the oral (p.o.) or intranasal (i.n.) groups and both groups had detectable levels of virus neutralizing antibodies (data not shown). Virus shedding was demonstrated in the saliva by virus isolation and the detection of viral RNA in ill bats, particularly immediately prior to the development of disease. In addition, the presence of virus and viral RNA was detected in the thyroid gland in bats challenged experimentally with EBLV-1, which exceeded that detected in all other extra-neural tissue. The significance of detecting EBLV-1 in the thyroid gland of rabid bats is not well understood. We speculate that the infection of the thyroid gland may cause subacute thyroiditis, a transient form of thyroiditis causing hyperthyroidism, resulting in changes in adrenocortical activity that could lead to hormonal dysfunction, thereby distinguishing the clinical presentation of rabies in the rabid host.

Spinal cord sarcoidosis: report of seven cases

Spinal cord involvement in sarcoidosis is rare, occurring in <1% of patients with sarcoidosis. We report seven cases of spinal cord sarcoidosis, seen in two French hospitals over a 13-year period. Presentation of disease, methods of diagnosis and response to treatment, with quantification according to the reduction of the modified Rankin scale (MRS), were noted. Six patients presented insidious paresthesias or weakness and one a sudden paraplegia. Average MRS at diagnosis was to 2. Spine MRI showed one or several intramedullary lesions in all cases. Diagnosis was confirmed by extra-neural tissue biopsies in all cases, including mediastinoscopy (two patients), coelioscopy (one patient), bronchoscopy (one patient), salivary gland biopsy (one patient) and skin biopsy (two patients). The average follow-up for the group was 49.4 months. All patients responded to corticosteroid therapy with a median reduction of MRS of one point. Five patients received immunosuppressive therapy: cyclophosphamide (two patients), methotrexate (two patients), azathioprine (one patient), mycophenolate mofetyl (one patient), with an inconstant benefit. Patients who received cyclophosphamide presented severe fungaemia. Based on our study and literature analysis, we propose an algorithm for treatment of spinal cord sarcoidosis.

Compression of the radial nerve at the elbow by a ganglion: two case reports

IntroductionRadial nerve compression by a ganglion in the radial tunnel is not common. Compressive neuropathies of the radial nerve in the radial tunnel can occur anywhere along the course of the nerve and may lead to various clinical manifestations, depending on which branch is involved. We present two unusual cases of ganglions located in the radial tunnel and requiring surgical excision.Case presentationA 31-year-old woman complained of difficulty in fully extending her fingers at the metacarpophalangeal joint for 2 weeks. Before her first visit, she had noticed a swelling and pain in her right elbow over the anterolateral forearm. The extension muscle power of the metacarpophalangeal joints at the fingers and the interphalangeal joint at the thumb had decreased. Sonography and magnetic resonance imaging of the elbow revealed a cystic lesion located at the area of the arcade of Frohse. A thin-walled ovoid cyst was found against the posterior interosseous nerve during surgical excision. Pathological examination was compatible with a ganglion cyst. The second case involved a 36-year-old woman complaining of numbness over the radial aspect of her hand and wrist, but without swelling or tumor in this area. The patient had slightly decreased sensitivity in the distribution of the sensory branch of the radial nerve. There was no muscle weakness on extension of the fingers and wrist. Surgical exposure defined a ganglion cyst in the shoulder of the division of the radial nerve into its superficial sensory and posterior interosseous components. There has been no disease recurrence after following both patients for 2 years.ConclusionCompression of nerves by extraneural soft tissue tumors of the extremities should be considered when a patient presents with progressive weakness or sensory changes in an extremity. Surgical excision should be promptly performed to ensure optimal recovery from the nerve palsy.

Chronic Wasting Disease in a Wisconsin White-Tailed Deer Farm

In September 2002, chronic wasting disease (CWD), a prion disorder of captive and wild cervids, was diagnosed in a white-tailed deer (Odocoileus virginianus) from a captive farm in Wisconsin. The facility was subsequently quarantined, and in January 2006 the remaining 76 deer were depopulated. Sixty animals (79%) were found to be positive by immunohistochemical staining for the abnormal prion protein (PrP(CWD)) in at least one tissue; the prevalence of positive staining was high even in young deer. Although none of the deer displayed clinical signs suggestive of CWD at depopulation, 49 deer had considerable accumulation of the abnormal prion in the medulla at the level of the obex. Extraneural accumulation of the abnormal protein was observed in 59 deer, with accumulation in the retropharyngeal lymph node in 58 of 59 (98%), in the tonsil in 56 of 59 (95%), and in the rectal mucosal lymphoid tissue in 48 of 58 (83%). The retina was positive in 4 deer, all with marked accumulation of prion in the obex. One deer was considered positive for PrP(CWD) in the brain but not in the extraneural tissue, a novel observation in white-tailed deer. The infection rate in captive deer was 20-fold higher than in wild deer. Although weakly related to infection rates in extraneural tissues, prion genotype was strongly linked to progression of prion accumulation in the obex. Antemortem testing by biopsy of recto-anal mucosal-associated lymphoid tissue (or other peripheral lymphoid tissue) may be a useful adjunct to tonsil biopsy for surveillance in captive herds at risk for CWD infection.

Cerebral and Peripheral Amyloid Phagocytes— an Old Liaison with a New Twist

In this month's issue of Nature Medicine, Town et al. suggest that peripheral macrophages invading the brain reduce cerebral amyloidosis and thus may play a key role in the pathogenesis of Alzheimer's disease (AD). This observation intensifies the longstanding controversy of whether mononuclear cells such as macrophages and/or microglial cells are beneficial or detrimental in AD.

Cutaneous Lipomatous Sclerosing Perineurioma

Sclerosing perineurioma is a variant of extraneural soft tissue perineurioma that occurs in the distal extremities of young adults. They are composed of small, plump, spindle-shaped, or epithelioid perineurial cells that coexpress epithelial membrane antigen (EMA), glut-1, claudin 1, collagen type IV, laminin, and are negative for S-100 protein. Once locally excised, sclerosing perineurioma does not recur or metastasize. Adipocytic component has been observed occasionally in peripheral nerve sheath tumors. In particular, only one report has previously detailed histopathological features of a superficial soft tissue perineurioma harboring lipomatous areas. Herein, we report a unique case of sclerosing perineurioma showing adipocytic component. Knowledge of this phenomenon is important to reach a correct diagnosis and to avoid unnecessary aggressive local excision.

Enzymatic detergent treatment protocol that reduces protease-resistant prion protein load and infectivity from surgical-steel monofilaments contaminated with a human-derived prion strain

The unconventional nature of the infectious agent of prion diseases poses a challenge to conventional infection control methodologies. The extraneural tissue distribution of variant and sporadic Creutzfeldt-Jakob disease has increased concern regarding the risk of prion disease transmission via general surgical procedures and highlighted the need for decontamination procedures that can be incorporated into routine processing. In this study, the ability of preparations of enzymatic medical instrument cleaners to reduce the infectivity associated with a rodent-adapted strain of human prion disease, previously reported to be resistant to decontamination, was tested. Efficient degradation of the disease-associated prion protein by enzymatic cleaning preparations required high treatment temperatures (50-60 degrees C). Standard decontamination methods (1 M NaOH for 1 h or autoclaving at 134 degrees C for 18 min) reduced infectivity associated with the human-derived prion strain by less than 3 log10 LD50. In contrast, a 30 min treatment with the optimized enzymatic cleaning preparation protocols reduced infectivity by more than 3 log10 LD50 and when used in conjunction with autoclave cycles eliminated detectable levels of infectivity. The development of prion decontamination procedures that are compatible with routine cleaning and sterilization of medical and surgical instruments may reduce the risk of the transmission of prion disease in general surgery.

Myelin Proteolipid Protein (PLP) as a Marker Antigen of Central Nervous System Contaminations for Routine Food Control

Spreading transmissible spongiform encephalopathies (TSE) have been widely attributed to transmission by ingestion of mammalian central nervous system (CNS) tissue. Reliable exclusion of this epidemiological important route of transmission relies on an effective surveillance of food contamination. Here, myelin proteolipid protein (PLP) is identified as a specific and largely heat-resistant marker for detection of food contaminations by CNS tissue. PLP is a component of oligodendritic glial sheaths of neuronal processes that is specifically expressed in the CNS. A highly selective polyclonal antibody was developed directed against an epitope present in the full-length PLP protein, but absent from the developmentally regulated splice variant DM-20. In combination with a hydrophobic extraction of PLP from tissue samples, the antibody reliably detected PLP from spinal cord, cerebellum, and cortex of different mammalian species. Consistent with earlier reports on PLP expression, no cross-reactivity was observed with peripheral nerve or extraneural tissue, except for a very faint signal obtained with heart. When applied to an artificial CNS contamination present in sausages, the antibody reliably detected a low concentration (1%) of the contaminant. Application of heat, as used during conventional sausage manufacturing, led to a predominant alteration of arginine residues in the PLP protein and a partial loss of immunoreactivity. In contrast, a stretch of hydrophilic amino acids(112-122) proved to be heat-resistant, preserving the immunogenicity of this PLP epitope during heating. Taken together, the excellent CNS specificity of PLP immunodetection and the presence of a heat-resistant epitope have permitted the development of a highly sensitive immunoassay for CNS contamination in routine food control.

Perineurioma: a clinicopathological study of eight cases

Perineuriomas (PN) are uncommon, benign neoplasms that mimic a number of benign and malignant soft tissue lesions. There are two main forms: a rare intraneural PN (IPN), and a relatively more common extraneural soft tissue PN (STPN) including a conventional form (STPNc), sclerosing (SPN), reticular and lipomatous variants. Their diagnosis requires immunohistochemical (IHC) and/or ultrastructural (US) confirmation of perineurial cell differentiation. This study aims to review the clinicopathological features of eight PN we encountered recently, to raise awareness of PN as an entity and to highlight the differential diagnoses which include potentially aggressive lesions. Clinical, histological, IHC and US features of seven STPN and one IPN were studied. The eight PN arose in the limbs of six females and two males aged 30-58 years. Five STPN occurred in subcutis, one intramuscularly and one intradermally. The STPN were well-circumscribed, multinodular growths. STPNc contained bland spindle cells with long cytoplasmic processes arranged in lamellae, storiform patterns and whorls. Three SPN were acrally located and additionally contained small epithelioid cells in cords and clusters in a myxohyaline stroma with extensive sclerosis. One SPN had giant collagen rosettes of spiral collagen. The IPN showed 'pseudo-onion bulbs' of perineurial cells. All PN were at least focally EMA positive, six of eight were Claudin-1 positive and all were S100 protein negative. Common US features were organelle-poor cell processes, many pinocytotic vesicles, sparse intermediate filaments, and tight junctions and patchy external lamina. There were no recurrences (follow-up 1-49 months). PN has a variable morphology and can mimic many benign, borderline and malignant lesions, the differential diagnoses of which are discussed. When confronted with a subcutaneous (in particular) spindle and/or epithelioid cell lesion, EMA/Claudin-1 stains and/or US are essential to identify PN and thereby avoid inappropriately aggressive therapy.

March 2003: A 41‐year‐old female with a solitary lesion in the liver

The March COM. A 41-year-old woman presented in 1997 with diffuse abdominal pain, meteorism and intermittent diarrhea. Imaging studies revealed a focal rounded lesion in the liver. Although there was no history of progesterone or estrogen therapy, the radiographic appearance was considered to be suggestive of adenoma. The lesion was monitored by ultrasound until October 2000 when a resection was performed because of the presumed risk of a malignant transformation. H&E stained sections revealed an ectopic ependymoma that was strongly positive for GFAP. The surrounding hepatic tissue was negative for GFAP. An extensive search for a CNS manifestation or any other extraspinal localization was unrevealing. We believe we have encountered the first case of an ectopic ependymoma presenting as a solitary hepatic lesion in the absence of CNS disease. Ependymomas generally arise in the CNS in relation to the ventricular system. Extraneural metastasis from ependymomas may occasionally occur even years after detection and treatment of the primary lesion and have been the subject of several reports. In contrast, there are only anecdotal reports of primary extraneural "ectopic" ependymomas. So far those rare cases have only been found in close vicinity to the neural axis, eg, in the sacrococcygeal region, the posterior mediastinum or the ovaries and are there thought to originate from embryonic remnant cells around the neural tube. Distant metastases of ependymomas invading or arising within the extraneural lumbosacral soft tissue may occur in this situation. Here, we report what appears to be the first case of a primary ectopic ependymoma originating in the liver, with no signs of CNS or other systemic involvement.