Pseudo-onion Bulb Research Articles

What is new in intraneural perineurioma?

Since the initial description of intraneural (IN) perineurioma in 1964, advances in the understanding of the clinical presentation, diagnostic imaging, pathologic features, and genetic underpinnings have changed how this pathology is managed. IN perineuriomas are rare, benign peripheral nerve sheath tumors, most frequently coming to clinical attention when patients present with painless, progressive weakness or sensory loss in adolescence or young adulthood. The gold standard of diagnosis has traditionally been with targeted tissue biopsy demonstrating "pseudo-onion bulb" formation with positive epithelial membrane antigen (EMA) staining. However, modern magnetic resonance imaging is allowing some patients to forgo biopsy. Recent genetic studies of IN perineuriomas have demonstrated common TRAF7 point mutations and rare NF2 mutations, which may present targets for diagnosis or therapy in the future. Current advances have allowed for us to provide improved patient counseling with informed understanding for various clinical scenarios. With the workup and diagnosis now clearly defined, the next frontier is for improving the lives of patients with IN perineuriomas through the interaction between restoration of functional deficits and advances in our understanding of the genetics of this entity.

Letter to editor: Orofacial overgrowth with peripheral nerve enlargement and perineuriomatous pseudo-onion bulb proliferations is part of the PIK3CA-related overgrowth spectrum.

The data summarized in this letter provide further evidence that the pathogenic mechanism underlying peripheral nerve enlargement as a phenotypic manifestation in PROS (PIK3CA-related overgrowth spectrum) may be genetically distinct from that of intraneural perineuriomas or soft tissue perineuriomas.

Orofacial overgrowth with peripheral nerve enlargement and perineuriomatous pseudo-onion bulb proliferations is part of the PIK3CA-related overgrowth spectrum.

SummaryIndividuals with orofacial asymmetry due to mucosal overgrowths, ipsilateral bone and dental aberrations with perineurial hyperplasia and/or perineuriomatous pseudo-onion bulb proliferations, comprise a recognizable clinical entity. In this article, we describe three individuals with this clinical entity and mosaic PIK3CA variants c.3140A>G (p. His1047Arg), c.328_330delGAA (p. Glu110del), and c.1353_1364del (p.Glu453_Leu456del). We conclude that the identification of these mosaic variants in individuals with orofacial asymmetry presenting histopathologically perineurial hyperplasia and/or intraneural pseudo-onion bulb perineurial cell proliferations supports the inclusion of this clinical entity in the PIK3CA-related overgrowth spectrum.

Intraneural perineurioma – a retrospective study of 19 patients

Introduction Intraneural perineurioma is a benign neoplasm of peripheral nerve sheath with perineurial cell origin that typically affects teenagers and young adults and tends to result in a motor-predominant neuropathy. It is very rare lesion due to lack of familiarity among clinicians, lack of precise pathological diagnosis and uncertainties regarding its cause. The aim of our study is to present the epidemiology, clinical presentation, way of diagnosis and our management plan. Study materials Clinical monocentric study. Patients diagnosed as intraneural perineurioma tumor and managed by the same team of surgeons between 2009–2014. Methodology Nineteen patients were retrospectively chart reviewed. We included all patients with diagnoses of Intraneural perineurioma by MRI and or biopsy with morphological, immunohistochemical staining study confirmation. We classified patients by gender, age, symptoms, tumor localization, radiological aspect, management and pathological confirmation. Results Sex ratio was 10 males to 9 females with mean age of 31.2 (15–64). Weakness was presented in all cases with sensory component in 10 patients (52.6%). The ratio of upper limb to lower limb was 9–10 with 4 brachial plexus. All patients underwent MRI with 16 patients had nerves enlargement and 5 presented with typical fusiform tumor, hypointense to isointense on T1-weighted images and hyperintense on T2-weighted images. Eighteen patients were operated for excision biopsy and or palliative treatment for their motor deficit. Seventeen patients had pathological confirmation with a morphological pseudo-onion bulb shape and or specific immunohistochemical assay of (+) EMA and (−) s 100. One patient had only palliative treatment without excision biopsy. Discussion Our data confirms the equal penetration to both sex and upper to lower limbs. It confirms motor involvement of the tumor however, it shows high sensory component that can be accompanied in this type of tumors. MRI can show typical aspect but most of the time, it is nonspecific enlargement. A unique surgical strategy for each nerve lesion involvement was proposed and because of the benignity of the tumor, the surgical treatment focused to optimize the functional outcome. This study represents one of the most important and large clinical series of intraneural perineurioma in the literature. Conclusion Prospective studies with long-term follow-up are needed for this under diagnosed tumor. Its genetic and biochemical mechanism is still unknown.

Périneuriome intraneural du nerf sciatique

Intraneural perineurioma is a benign tumor developed from the perineurium and responsible for localized nerve hypertrophy. This uncommon tumor is characterized by a proliferation of perineural cells with a "pseudo-onion bulb" pattern. We report a sciatic nerve intraneural perineurioma in a 39-year-old patient.

Surgical removal of intraneural perineurioma arising in the brachial plexus using an interfascicular dissection technique.

Surgical removal of intraneural perineurioma arising in the brachial plexus using an interfascicular dissection technique.

On Pseudo-Onion Bulb Intraneural Proliferations of the Non-Major Nerves of the Oral Mucosa

Perineurial cells (PCs) participate in reactive and neoplastic processes, of the latter pure perineurial being intraneural (IP) and soft tissue perineuriomas with oral examples being reported in both. In our review of over 500 peripheral nerve sheath tumors including granular cell tumor, we identified a single ostensible case of IP occurring on the tongue of a 45-year-old African-American male that was characterized by classic perineurial pseudo-onion bulbs (PsOb), proliferating PCs among these PsOb, sclerosis apparently due to long term duration and a plexiform pattern. We have also encountered 37 examples of apparently reactive, hyperplastic or traumatic, PsOb intraneural pseudoperineuriomatous proliferation (IPP) simulating microscopically some of the properties of IP. The majority of the lesions occurred in women and close to 80% affected the tongue. Three microscopic patterns were appreciated. Type I lesions were those where IPP was seen only focally, type II where it was seen in roughly half of the lesion, and type III where the majority of the lesional tissue or the lesion itself was characterized by IPP. Immunohistochemically, IPP featured PsOb with generally a single layer of PCs decorated by epithelial membrane antigen, glut-1 or claudin-1, and decreased numbers of S-100 positive Schwann cells. The number of axons was not apparently altered. A prominent collagenous intraneural component was occasionally evident among PsOb and the affected nerve featured discontinuous or absent perineurial envelop. While type I and II IPP can be distinguished from IP, the distinction from type III lesions can be problematic. However, the discontinuity of the perineurium of the affected nerve, the spacing and collagenization among PsOb, the limited perineurial cell layer defining the pseudo-onion bulbs, the absence of proliferating PCs between PsObs and the decreasing number of Schwann cells may be of help in the distinction from IP.

Intraneural perineurioma of the tongue: report of a case and review of the literature

An intraneural perineurioma arising in the tongue of a 34-year-old woman is presented. Histologically, the tumor was composed of numerous pseudo-onion bulb structures, formed by whorled proliferation of spindle cells around axons. Immunohistochemically, the spindle cells were positive for epithelial membrane antigen (EMA) but negative for S-100 protein, indicating that the tumors cells were derived from perineurial cells.

Intraneural reticular perineurioma of the hypoglossal nerve

Intraneural perineurioma or reticular perineurioma, which is 1 variant of extraneural perineurioma, has been rarely reported in the head and neck region. We report a case of a 52-year-old woman who wasseen with a swelling in the neck. A mass was found located on the medial aspect of the left submandibular gland and was palpated with a sponge-like texture. The mass was seen as a homogenous semisolid lesion on CT and ultrasound examination. Surgical exploration revealed expansion of the hypoglossal nerve. Microscopically, the tumor showed both pseudo-onion bulb, which is a feature of intraneural perineurioma, and reticular pattern with microcysts, which is a feature of reticular variant of extraneural perineurioma. The tumor cells were immunopositive for epithelial membrane antigen and human erythrocyte glucose transporter-1 (GLUT-1). An intraneural reticular perineurioma of the hypoglossal nerve should be included in the differential diagnosis of submandibular swelling.

Intraneural perineurioma of the third cranial nerve: occurrence and identification

Intraneural perineurioma is a true but rare neoplasm that originates from perineurial cells and mainly affects peripheral nerves. It must be distinguished from other hypertrophic neuropathies that are either inflammatory or demonstrate an onion-bulb formation that originates from Schwann cells. Complying with this strict definition, only three additional cases of cranium-related perineurioma have been identified: two lesions arose extracranially and involved cranial nerves, and one occurred intracranially but did not involve a nerve. The authors describe a 27-year-old woman who presented with left third cranial nerve palsy and was found to harbor a mass lesion in the superior orbital fissure and cavernous sinus. After subtotal resection had been performed, pathological studies confirmed the presence of perineurial tumor cells in a pseudo-onion bulb formation. The cells stained positively for epithelial membrane antigen but not for S100 protein, clearly distinguishing the disease from one that originates in Schwann cells.

Intraneural reticular perineurioma of the neck

Perineuriomas are infrequent tumors that may be intraneural or extraneural in soft tissue with no apparent relation with a nerve. Some cases of soft tissue perineurioma may have a retiform pattern, but this pattern has not been described to date in intraneural perineurioma. We report a case of a unique perineurioma arising in a nerve of the neck that had a distinctive reticular pattern and was intraneural. The patient was a 21-year-old woman who had a lump on the left side of the neck abutting the vena jugularis. The tumor had features of both reticular perineurioma and intraneural perineurioma with pseudo-onion bulb pattern. The tumor cells were positive for epithelial membrane antigen. The patient is free of tumor 6 months after operation. Ann Diagn Pathol 7: 120-123, 2003.

Phenotypical features of a Moroccan family with autosomal recessive Charcot-Marie-Tooth disease associated with the S194X mutation in the GDAP1 gene.

The first locus for demyelinating autosomal recessive Charcot-Marie-Tooth (ARCMT) disease was identified in 8q13, where mutations in GDAP1 have been found. Mutations in the same gene have been detected in families with axonal ARCMT disease. To determine the clinical, electrophysiologic, and morphologic characteristics of a consanguineous Moroccan family with ARCMT disease associated with the S194X mutation in the GDAP1 gene. Four patients from a consanguineous Moroccan family were examined clinically and electrophysiologically. In one patient, a morphometric and ultrastructural study of a peroneal nerve biopsy sample was performed. Mutation in the coding region of the GDAP1 gene was identified by direct sequencing. Neuropathy was evident early in childhood, walking was delayed in one patient, and onset of symptoms occurred before 18 months in the others. The phenotype was severe: foot deformities and disabilities involving the hands and feet developed toward the end of the first decade, followed by involvement of proximal muscles in the lower limbs, leading to loss of autonomy. Electrophysiologic findings were consistent with an axonal form of CMT disease: motor nerve conduction velocities, recordable in one patient only, were greater than 40 m/sec. Sensory nerve action potentials were either abolished or substantially reduced in amplitude. The morphologic data supported the diagnosis of axonal neuropathy, showing a marked reduction in myelinated fibers and signs of axonal regeneration, including frequent pseudo-onion bulb formations. The 4 patients in this family were homozygous for the S194X mutation in the GDAP1 gene. Electrophysiologic and pathological findings support the hypothesis of an axonal disorder in this ARCMT family with the S194X mutation in the GDAP1 gene.

Histopathological features of X-linked Charcot-Marie-Tooth disease in 8 patients from 6 families with different connexin32 mutations.

There is still confusion as to whether X-linked Charcot-Marie-Tooth disease (CMTX) is primarily an axonal disorder or is primarily demyelinating. Eight symptomatic patients, 7 males and 1 female, from 6 families with identified connexin32 mutations underwent a superficial peroneal nerve biopsy. Quantitative and ultrastructural studies were performed, and histopathological lesions in these 8 patients proved to be quite homogeneous. The myelinated fiber count was within normal values or only moderately decreased. In 7 cases, the distribution of myelinated fibers was unimodal due to a loss of large fibers, coexisting with numerous clusters of small regenerating fibers. At ultrastructural level, these clusters were often surrounded by flattened Schwann cell processes giving an aspect of "pseudo-onion bulb" formation. There was no "naked axon" (ie, demyelinated axon), and real "onion bulb" formations composed of flattened Schwann cell processes surrounding an isolated myelinated fiber were discrete and not numerous. Macrophages laden with myelin debris were scarce or absent in the endoneurium. Several fibers appeared discretely hypomyelinated and the calculated g-ratio was scarcely higher than the mean control value. Lesions of unmyelinated fibers were absent in 7 cases and mild in one. Given that the primary defect concerns connexin32, we think that the histopathological features observed in our patients correspond to primary hypomyelination rather than to ongoing demyelination. The associated axonal degeneration might be secondary to defective axon-Schwann cell interactions.