Reparative Perineural Hyperplasia in the Gastric Wall: A Histologic Mimic of Perineural Invasion

Reparative perineural hyperplasia is an incidental and probably underreported reactive histologic finding thus far only reported in the setting of healing wounds or adjacent to a dermatofibroma in cutaneous specimens. It is characterized by a focal concentric proliferation of cytologically bland spindled perineurial cells and is hence considered a benign histologic mimic of neoplastic perineural invasion. Thus, it may present a diagnostic pitfall and we therefore consider it as a valuable entity to be aware of. To the best of our knowledge, this brief case report is the first to convey that reparative perineural hyperplasia may also occur in the gastrointestinal tract. It may therefore be a ubiquitous reactive histological phenomenon relating to previous surgical or traumatic wounds in various sites, that is, outside the thus far established setting of skin reexcision specimens.

The Neoplastic Whorls-Soft Tissue Perineurioma

Perineurioma is an exceptional, benign neoplasm entirely composed of neoplastic perineurial cells and arises from the peripheral nerve. Pertaining to location, the neoplasm predominantly demonstrates configurations such as intra-neural or extra-neural, confined to the soft tissue. Perineurioma was initially scripted by Lazarus and Trombetta in 1978 and is additionally nomenclated as localized hypertrophic neuropathy1. Extra-neural soft tissue perineurioma and mucosal (intestinal) perineurioma are frequent, in contrast to intra-neural perineurioma or localized hypertrophic neuropathy subtype1, 2.

The Pebble/Rho1/Anillin pathway controls polyploidization and axonal wrapping activity in the glial cells of the Drosophila eye

During development glial cell are crucially important for the establishment of neuronal networks. Proliferation and migration of glial cells can be modulated by neurons, and in turn glial cells can differentiate to assume key roles such as axonal wrapping and targeting. To explore the roles of actin cytoskeletal rearrangements in glial cells, we studied the function of Rho1 in Drosophila developing visual system. We show that the Pebble (RhoGEF)/Rho1/Anillin pathway is required for glia proliferation and to prevent the formation of large polyploid perineurial glial cells, which can still migrate into the eye disc if generated. Surprisingly, this Rho1 pathway is not necessary to establish the total glial membrane area or for the differentiation of the polyploid perineurial cells. The resulting polyploid wrapping glial cells are able to initiate wrapping of axons in the basal eye disc, however the arrangement and density of glia nuclei and membrane processes in the optic stalk are altered and the ensheathing of the photoreceptor axonal fascicles is reduced.

Varicella Zoster Virus Alters Expression of Cell Adhesion Proteins in Human Perineurial Cells via Interleukin 6

BackgroundIn temporal arteries (TAs) from patients with giant cell arteritis, varicella zoster virus (VZV) is seen in perineurial cells that surround adventitial nerve bundles and form the peripheral nerve-extrafascicular tissue barrier (perineurium). We hypothesized that during VZV reactivation from ganglia, virus travels transaxonally and disrupts the perineurium to infect surrounding cells.MethodsMock- and VZV-infected primary human perineurial cells (HPNCs) were examined for alterations in claudin-1, E-cadherin, and N-cadherin. Conditioned supernatant was analyzed for a soluble factor(s) mediating these alterations and for the ability to increase cell migration. To corroborate in vitro findings, a VZV-infected TA was examined.ResultsIn VZV-infected HPNCs, claudin-1 redistributed to the nucleus; E-cadherin was lost and N-cadherin gained, with similar changes seen in VZV-infected perineurial cells in a TA. VZV-conditioned supernatant contained increased interleukin 6 (IL-6) that induced E-cadherin loss and N-cadherin gain and increased cell migration when added to uninfected HPNCs; anti-IL-6 receptor antibody prevented these changes.ConclusionsIL-6 secreted from VZV-infected HPNCs facilitated changes in E- and N-cadherin expression and cell migration, reminiscent of an epithelial-to-mesenchymal cell transition, potentially contributing to loss of perineurial cell barrier integrity and viral spread. Importantly, an anti-IL-6 receptor antibody prevented virus-induced perineurial cell disruption.

Perineurial-like Cells and EMA Expression in the Suprachoroidal Region of the Human Eye

The suprachoroidal region of the eye comprises vascular channels, melanocytes, and thin fibroblasts with elongated cytoplasm that are positioned directly adjacent to the densely collagenous sclera. Morphological similarities between these suprachoroidal fibroblasts and arachnoid cells and perineurial cells have been recognized, but whether these fibroblasts have a perineurial cell-like immunophenotype is not known. To further examine the relationship of these three cell types, we investigated the comparative expression of epithelial membrane antigen (EMA), the tight junction protein claudin-1, glucose transporter-1 (Glut-1), and CD34 in suprachoroidal fibroblasts, arachnoid of the optic nerve sheath, and perineurium of ciliary nerves in eight human eye specimens. Granular, diffuse, and cytoplasmic EMA expression was seen in suprachoroidal fibroblasts, but this was not contiguous with the similar pattern of EMA expression in adjacent perineurium and arachnoid. CD34 expression in suprachoroidal fibroblasts was also seen, similar to arachnoid and perineurium. Claudin-1 and Glut-1 were not consistently expressed in suprachoroidal fibroblasts, distinguishing them from perineurial cells in particular and suggesting that these fibroblasts do not arise directly from adjacent arachnoid or perineurium. Nonetheless, the overlapping morphology and protein expression suggest phenotypic similarities in these cells that protect and support adjacent retina, optic nerve, and peripheral nerve.

Can Intraneural Perineuriomas Occur Intradurally? An Anatomic Perspective

BACKGROUND: Intraneural perineuriomas are rare, benign lesions produced by the neoplastic proliferation of perineurial cells. They typically present in adolescents and affect nerves of the limbs. In our experience, we have not encountered a single case of classic intraneural perineurioma at an intradural location. OBJECTIVE: To determine whether intraneural perineuriomas could occur intradurally, given the prevalence of intradural nerve sheath tumors, and explain our findings with an anatomic perspective. METHODS: We retrospectively reviewed the high-resolution magnetic resonance images of 56 patients from an institutional registry of patients with intraneural perineurioma. All cases were analyzed for signs of proximal extension toward spinal nerves, roots, and spinal cord. A literature review was performed. The clinical, radiological, and histopathological features of potential intradural lesions were critically appraised against strict criteria for a diagnosis of classic intraneural perineurioma. RESULTS: Fifteen of 56 (27%) patients with intraneural perineurioma had a proximal localization in the lumbosacral or brachial plexus. Not a single case occurred proximal to the dorsal root ganglia (DRG). One case of trigeminal intraneural perineurioma occurred distal to the gasserian ganglion. A literature review did not reveal any convincing cases of classic intraneural perineuriomas occurring in an intraspinal intradural location and revealed only 1 possible case in an intracranial intradural location. CONCLUSION: Based on our study, the occurrence of classic intraneural perineuriomas intradurally is exceedingly rare, if at all present. This may be related to the paucity of perineurial cells at the nerve root level and reciprocal interactions between neuroglial cells at the central-to-peripheral transition zones.

Expression Of Cytokeratin 18 In The Peripheral Nerves

The perineurium constitutes the basis for the regulation of endoneurial fluid homeostasis. In the work presented here, cytokeratin 18, as an immunohistochemical marker for epithelial cells, was used to identify the perineurium in the peripheral nerves of two species. Two organs, rich in peripheral nerves, were used; the tongue of the bull and the ductus deferens of the male goat. Special attention was paid to one of the the nerve sheath cells - the perineurial cells of myelinated nerves in the skeletal muscle of the tongue and in the smooth muscle in the wall of the ductus deferens. A positive reaction to cytokeratin 18 was found in the perineurial cells of the perineurial sheath in the nerves of various sizes. No difference in the reactivity was observed between the peripheral nerves of the tongue and that of the ductus deferens.

The almost-invisible perineurioma

Intraneural perineurioma is a rare, benign slow-growing lesion arising from the perineurial cells that surrounds the peripheral nerve fibers. Typically it presents during childhood and young adulthood as a motor mononeuropathy. MRI plays an essential role in the diagnosis and localization of the lesion, which appears as a fusiform enlargement of the nerve fascicles that enhances intensely with gadolinium. Despite the typical clinical and radiological features, intraneural perineurioma remains largely underdiagnosed because of the lack of familiarity with this entity, but also as a result of technical limitations with conventional MRI that is typically performed as a screening test over a large field of view and without contrast sequences. The purpose of this article is to present the pitfalls and pearls learned from years of experience in the diagnosis and management of this relatively rare condition. Clinical suspicion and detailed neurological examination followed by high-quality electrophysiological studies (EPS) must lead to an adequate preimaging localization of the lesion and narrowing of the imaging area. The use of high-resolution (3-T) MRI combined with gadolinium administration will allow adequate visualization of the internal anatomy of the nerve and help in differentiating other causes of neuropathy. In cases where the lesion is not recognized but clinical suspicion is high, possible errors must be assessed, including the EPS localization, area of imaging, MRI resolution, and slice thickness.