Intraneural Perineuriomas Research Articles

TRAF7-mutated Fibromyxoid Spindle Cell Tumors Are Associated With an Aggressive Clinical Course and Harbor an Undifferentiated Sarcoma Methylation Signature: A Molecular and Clinicopathologic Study of 3 Cases.

TRAF7 somatic mutations are rare and have been reported in meningiomas, intraneural perineuriomas, and mesotheliomas. Triggered by an index case of an unclassified low-grade mesenchymal tumor with TRAF7 mutation as the only genetic alteration, we searched our files and identified 2 additional cases with similar features. The tumors arose in 2 females and 1 male, aged 63 to 75 years old (median: 67y). They were infiltrative deep soft tissue masses involving the shoulder, chest wall, and thigh, measuring 7.0 to 9.1cm in greatest dimensions. One tumor was locally aggressive, and 2 were associated with lung and bone metastases. The tumors displayed alternating fibrous and myxoid stroma with mild to moderate cellularity and consisted of uniform spindle cells with open chromatin, inconspicuous nucleoli and scant cytoplasm. Significant mitotic activity or necrosis were not present. However, the metastatic tumor of 1 case showed an epithelioid morphology and brisk mitotic activity. Immunohistochemically, the tumors showed nonspecific and focal smooth muscle actin or CD34 expression. By DNA sequencing, all 3 cases harbored TRAF7 missense mutations involving the C-terminal WD40 domains as the only somatic mutations, showed nonrecurrent focal copy number alterations, and were negative for gene fusions by targeted RNA sequencing. On methylation profiling, the tumors clustered with the undifferentiated sarcoma and myxofibrosarcoma methylation classes and were distinct from morphologic mimics. On follow-up (5 to 36mo), 2 patients died of disease following aggressive chemotherapeutic regimens. We describe a novel TRAF7- mutated mesenchymal tumor characterized by aggressive clinical behavior despite the histologic appearance of a low-grade fibromyxoid spindle cell tumor.

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.

Perineurioma: A Rare Entity of Peripheral Nerve Sheath Tumors.

Intraneural perineurioma is a rare tumor entity. It is a benign, very slow growing peripheral nerve sheath tumor that typically occurs in children and young adults. Motor deficits and muscle atrophy are classic presenting symptoms, while sensory deficits are rare at the onset of the disease. Recommended treatment strategies are lacking. We have evaluated the clinical follow-up and our experience with treatment of this rare entity. A total of 30 patients with intraneural perineuriomas were assessed retrospectively. Demographic data, clinical symptoms, diagnostic examinations, therapy strategies, and clinical outcome were analyzed. Descriptive statistical methods were used for evaluation. The mean age was 22 years. Eleven women and 19 men were affected. The lesion occurred in the area of the upper extremity in 16 patients and in the area of the lower extremity in 14 patients. The most frequently affected nerve was the sciatic nerve, followed by the radial nerve. All patients showed a motor deficit to some extent. Seventy percent (n = 21) revealed atrophy, 43.3% (n = 13) had sensitive deficits, and 17% (n = 5) suffered of pain. Fascicle biopsies were performed in 26 patients (87%). In four patients (13%), the tumor was completely resected and then reconstructed via nerve grafts. Seventy percent of the patients (n = 21) received a magnetic resonance imaging (MRI) within 5 years postoperatively, in which no progress was shown. To diagnose perineurioma, it is essential to take a biopsy of an enlarged, nonfunctional fascicle. Furthermore, a long-distance epineuriotomy to decompress the hypertrophic fascicle is reasonable. To preserve the nerves' residual function, a complete resection is not recommended. Results after grafting are poor. One reason for this might be residual tumor cells along the nerve that cannot be visualized. Malignant transformation is not yet reported and tumor growth is stable for years.

Association of intraneural perineurioma with neurofibromatosis type 2.

Neurofibromatosis type 2 (NF2) is a genetic disorder characterized by mutations of the NF2 tumor suppressor gene that predisposes patients to develop multiple tumors in the peripheral and central nervous system. The most common neoplasms associated with the disease are schwannomas and meningiomas. Both have been shown to contain abnormalities in chromosome 22 and the NF2 gene, suggesting a genetic component to their pathogenesis. Perineuriomas are rare benign tumors arising from the perineural cells. They are commonly classified as intraneural and soft tissue perineuriomas. Several studies have reported mutations in genes on chromosome 22 in both types of perineuriomas, and there are reports of soft tissue perineuriomas associated with NF2 gene mutations. Despite this, perineuriomas are not considered as part of the NF2 constellation of tumors. The electronic medical records were searched for patients with a radiologic or pathologic diagnosis of intraneural perineurioma. Patients with clinical signs and genetic testing consistent with a diagnosis of NF2 were further evaluated. Of 112 patients meeting inclusion criteria, there were two cases of intraneural perineurioma in patients with NF2 treated at our institution (1.8%). We include a third patient treated at another facility for whom we performed a virtual consultation. The rarity of both NF2 and perineuriomas could explain the rarity of perineuriomas in the setting of NF2. Furthermore, there is divergent intraneural and soft tissue perineurioma somatic mutation pathogenesis, and there may be cytogenetic overlap between perineuriomas and multiple tumor syndromes. Our observed occurrence of intraneural perineurioma in the setting of NF2 in several patients provides further evidence of a potential link between the NF2 gene and the development of intraneural perineurioma.

Limb Undergrowth in Intraneural Perineuriomas: An Under-Recognized Association

Intraneural (IN) perineuriomas are a rare benign hypertrophic nerve tumor, most frequently occurring in young patients. Patients with IN perineurioma have been anecdotally found to have limb undergrowth; however, this has not been systematically evaluated. Archived electronic records from 1990 to 2018 from a single institution were reviewed for pathology or radiology reports documenting a diagnosis of IN perineurioma. This identified 111 patients; 3 patients with IN perineurioma of cranial nerves were excluded. We further reviewed the 108 patients and identified those with a documented limb length discrepancy (LLD) or hand/foot size discrepancy (HFD) and tried to correlate findings with nerve-territory distribution. Twenty-seven (25.0%) patients had either LLD or HFD. Nine patients had only an LLD, 6 patients had only an HFD, and 12 patients had both. Patients with undergrowth were significantly younger at diagnosis than patients without (6.14 vs. 22.9 years, respectively). Although there was a trend toward a greater incidence of LLD in lower extremity IN perineuriomas, this was not statistically significant. Patients with proximal IN perineuriomas had a higher incidence of LLD or HFD than patients with distal IN perineuriomas. The difference between the 2 groups was statistically significant (P < 0.0001). All instances of undergrowth were explained by nerve-territory bone innervation. Limb undergrowth occurs in the affected nerve territory and is likely under-reported in patients with IN perineuriomas. Within our series, patients with documented LLD and HFD were likely to be significantly younger at diagnosis than patients without undergrowth.

Modern treatment of perineuriomas: a case-series and systematic review

BackgroundPerineuriomas are rare benign peripheral nerve sheath tumours of perineurial cell origin and can be classified into intraneural and extraneural perineuriomas. They most commonly present a mononeuropathy of gradual onset and slow progression, resulting in progressive neurological deficits like hypoesthesia or motor weakness. Therapy is still variable. Aim of the study was to compare our surgical treatment and our follow-up regime including high-resolution nerve sonography with the current literature to evaluate best treatment of perineuriomas.MethodsRetrospective analysis of our dataset “peripheral nerve lesion” to identify patients suffering from perineuriomas between 01.01.2012 until 31.12.2018. Surgical treatment and the follow-up examination of three patients were described. Additionally, a systematic review including PubMed, the Cochrane Collaboration Library, Scopus and Google Scholar was performed for literature published between January 1, 1990 and October 31, 2019 independently by 2 authors.ResultsIn the first case, the left ulnar nerve was affected. In the second case, the left peroneal nerve and in the third case the right median nerve was affected. High-resolution nerve sonography was performed in each case. All patients underwent interfascicular neurolysis combined with a targeted fascicular biopsy under electrophysiological monitoring. Neurological deficits improved subsidized by rehabilitation. Surgical therapy and the neurological outcome were compared with literature. Systematic review revealed 22 articles, which met the inclusion criteria. Therefore, demographics, surgical treatment and neurological outcome of 77 patients were analysed.ConclusionsPerineuriomas are rare benign nerve sheath tumours with a slow progression, sometimes difficult to diagnose. Decompression and neurolysis may improve neurological deficits. High resolution nerve sonography might serve as a helpful additional diagnostic tool in this process.

Clinical and Radiological Follow-up of Intraneural Perineuriomas.

Management of intraneural perineuriomas remains controversial, largely due to the lack of knowledge regarding the natural history of these lesions. To describe the typical radiological growth pattern of intraneural perineuriomas and to determine how the pattern of growth relates to clinical progression. We performed a retrospective review of the magnetic resonance imaging (MRI) studies and serial clinical examinations of a cohort of patients with biopsy-proven intraneural perineuriomas who had 2 MRI studies at least 2 yr apart. The outcome of interest was radiological growth in length or width of the intraneural perineurioma. Radiological growth was tested for association with clinical progression. Twenty patients were included in the study. By width, the lesions were on average larger on repeat imaging (P=.009). By absolute length, the lesions were on average longer on repeat imaging (P=.02). By lesion:landmark ratio, there was no difference in length of the lesions between sequential images (P=.09), with 10 (50%) lesions being shorter and 7 (35%) showing no change. No lesions grew to involve a new nerve or division of a nerve on sequential imaging. None of the variables tested were associated with clinical progression. We found that intraneural perineuriomas only rarely grow in length, do not grow to involve new nerves or nerve divisions, and growth does not correlate with clinical progression. These findings have significant ramifications for management of these tumors.

Extraneural perineurioma: CT and MRI imaging characteristics.

To examine the CT and MRI characteristics of extraneural perineuriomas. With IRB approval, our institutional imaging database was retrospectively reviewed for cases of pathologically proven extraneural perineuriomas. CT and MRI features were recorded, correlative imaging analyzed, and the electronic medical record cross-referenced. We identified ten patients [(seven males, three females, mean age 49.4 ± 18.3years (range, 16-70years)]. All cases were pathologically confirmed. Nine cases were conventional soft tissue extraneural perineuriomas, including one with "reticular" features and one with histologic features of malignancy; the tenth case contained admixed Schwann cells (hybrid perineurioma/schwannoma). Six out of ten patients underwent CT and ten of ten MRI evaluation. Nine out of ten MRIs were performed with IV contrast. Five lesions were subcutaneous, four intermuscular, and one intramuscular. Mean lesion diameter was 4.3 ± 2.7cm (range, 0.9-10.2cm). Nine out of ten lesions were well circumscribed; one had irregular margins. On CT, five of six were hypodense and one isodense compared to skeletal muscle. Most lesions were T1 isointense (5/10) or hypointense (4/10) and T2 hyperintense (7/10) relative to skeletal muscle, and demonstrated solid enhancement (6/9). There was no evidence of muscular denervation on any MRI exam, and a nerve of origin was identified in two out of ten cases. Extraneural perineuriomas have a distinctly different imaging appearance from intraneural perineuriomas, manifesting as rounded or ovoid soft tissue masses, without evidence of muscular denervation, and usually without an apparent nerve of origin. Because these features mimic other benign and malignant soft tissue lesions, including sarcomas, biopsy or excision is needed for definitive diagnosis.

Recurrent Genomic Alterations in Soft Tissue Perineuriomas.

Perineuriomas are rare nerve sheath tumors, divided into intraneural and extraneural (soft tissue) types. Intraneural perineuriomas frequently contain TRAF7 mutations, and rarely, chr22q12 deletions. While chr22q losses can occur in soft tissue perineuriomas, comprehensive high-resolution molecular profiling has not been reported in these tumors and TRAF7 status is unknown. We used whole-exome sequencing and OncoScan single nucleotide polymorphism (SNP) array to evaluate 14 soft tissue perineuriomas. Thirteen cases showed 2 or more chromosomal abnormalities, composed primarily of large deletions. Recurrent chr22q deletions, containing the NF2 locus (n=6) and the previously unreported finding of chr17q deletions, with the NF1 locus (n=4) were frequent events and were mutually exclusive in all but1 case. In addition, 5 cases had varying chr2 deletions; and 4 cases had chr6 deletions. A chr10 deletion (previously reported in the sclerosing variant of soft tissue perineurioma) was observed in one case and another case had chr7 chromothripsis as the sole chromosomal abnormality. No TRAF7 mutations or alterations were identified in any case and no other evaluated gene (MAF<0.0001) had recurrent, deleterious mutations in >2 cases. The molecular genetic profiles showed no association with patient sex, age, tumoral histology or anatomic site. OncoScan SNP array analysis was performed on 10 cases and showed high concordance with the whole exome data, validating the large-scale deletions, duplications, and chr7 chromothripsis findings. In soft tissue perineuriomas, recurrent 22q12 deletions (with NF2) and 17q11 deletions (with NF1) appear to be mutually exclusive events, and alterations in NF1 or NF2 likely contribute to perineurioma pathogenesis, similar to other nerve sheath tumors. Moreover, the lack of TRAF7 mutations in soft tissue perineuriomas indicates divergent pathogenetic mechanisms from those of intraneural perineuriomas.

Clinicoradiological features of intraneural perineuriomas obviate the need for tissue diagnosis.

This study aimed to define a set of clinicoradiological parameters with a high specificity for the diagnosis of intraneural perineurioma, obviating the need for operative tissue diagnosis. The authors retrospectively reviewed MR images obtained in a large cohort of patients who underwent targeted fascicular biopsy and included only those patients for whom the biopsy yielded a diagnosis. Clinical and radiological findings were then tested for their ability to predict a tissue diagnosis of intraneural perineurioma. The authors propose a new set of diagnostic criteria, referred to as the Perineurioma Diagnostic Criteria. The sensitivity, specificity, positive predictive value, and negative predictive value of several clinicoradiological methods of diagnosis were compared. A total of 195 patients who underwent targeted fascicular biopsy were included in the cohort, of whom 51 had a tissue diagnosis of intraneural perineurioma. When the clinicoradiological methods used in this study were compared, the highest sensitivity (0.86), negative predictive value (0.95), and F1 score (0.88) were observed for the decision trees generated in C5.0 and rPart, whereas the highest specificity (1.0) and positive predictive value (1.0) were observed for the Perineurioma Diagnostic Criteria. This study identified clinical and radiological features that are associated with a diagnosis of perineurioma. The Perineurioma Diagnostic Criteria were determined to be the following: 1) no cancer history, 2) unifocal disease, 3) moderate to severe hyperintensity on T2-weighted MR images, 4) moderate to severe contrast enhancement, 5) homogeneous contrast enhancement, 6) fusiform shape, 7) enlargement of the involved nerves, and 8) age ≤ 40 years. Use of the Perineurioma Diagnostic Criteria obviates the need for tissue diagnosis when all of the criteria are satisfied.

Can Intraneural Perineuriomas Occur Intradurally? An Anatomic Perspective.

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. To determine whether intraneural perineuriomas could occur intradurally, given the prevalence of intradural nerve sheath tumors, and explain our findings with an anatomic perspective. 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. 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. 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.

Genomic analysis reveals frequent TRAF7 mutations in intraneural perineuriomas.

Intraneural perineuriomas are benign peripheral nerve sheath tumors that cause progressive debilitating focal extremity weakness. The etiology of perineuriomas is largely unknown. We utilized whole exome sequencing, copy number algorithm evaluation, and high-resolution whole genome microarray to investigate for a genetic causal link to intraneural perineuriomas. Ten of 16 (60%) tumor cases had mutations in the WD40 domain of TRAF7, the same location for causal mutations of meningiomas. Two additional perineurioma cases had large chromosomal abnormalities in multiple chromosomes, including chromosome 22q. This study identifies a common cause for intraneural perineuriomas and an unexpected shared pathogenesis with intracranial meningiomas. Ann Neurol 2017;81:316-321.

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.

Glut-1, Best Immunohistochemical Marker for Perineurial Cells

Sir, historically, transmission electron microscopy (TEM) was used to characterize perineurial cells and to confirm the diagnosis of perineuriomas. Perineurial cells typically present thin and long cytoplasmic processes containing numerous pinocytotic vesicles, with the external surface coated by a discontinuous basal lamina, and well-developed tight junctions at points of cells contact. With the advent of immunohistochemistry, epithelial membrane antigen (EMA) became a useful marker for perineurial cells, substituting the laborious and time consuming preparations for TEM. EMA is a non-specific antibody positive in many cells and tissues including perineurial cells, and although its expression in perineuriomas is faint and/or focal, it is the most widely used marker for this neural lesion. Afterwards it was noted that Claudin-1, a tight junction protein, was also positive in perineurial cells and that it could also be useful for the diagnosis of perineuriomas [1, 2]. Glut-1, an erythrocyte glucose transporter, was then reported to be also expressed in perineurial cells [3, 4] and in perineurioma, for the first time in five cases of sclerosing perineurioma [5]. This was not a surprise, since Glut-1 is positive not only for erythrocytes, but also for epithelial intercellular junctions. Perineurial cells are found in the perineurial sheath of normal nerves. Neurofibromas besides axons, Schwann cells and endoneurial fibroblasts can show perineurial cells, mainly at the periphery, probably representing remains of the perineurial sheath [1]. Perineuriomas either intra or extraneural are characterized by the proliferation of perineurial cells, and express the three above cited immunohistochemical markers [2, 6]. We revised 10 cases of oral perineuriomas and 15 cases of oral neurofibromas. Normal nerves present at the periphery of these lesions were also evaluated. Eight cases of perineurioma were classified as intraneural and two as extraneural, while 11 neurofibromas were diffuse and four were plexiform. All of them were immunostained with EMA (clone E29, 1:100; DAKO), Claudin-1 (polyclonal, 1:100; BioSystems) and Glut-1 (polyclonal, 1:100; BioSystems). Retrieval antigen was made in a microwave oven using a 10 mM citrate buffer (pH 6.0), followed by overnight incubation with primary antibodies. For visualization the streptavidin biotin system was used (LSAB + HRP, Dako). The reaction was developed with diaminobenzidine hydrochloride (Sigma, St Louis, MO) and was lightly counterstained with Carazzi hematoxylin. The intensity of the staining was determined subjectively by three oral pathologists, as weak, medium and strong, considering comparatively the three markers used. Neurofibromas showed positive areas mainly at the periphery of the tumors and/or surrounding isolated nerve fascicles. Normal nerves were uniformly positive on the perineurial sheath. Intraneural perineuriomas showed the typical concentric pattern around axons, while in the extraneural type the cells were more diffusely marked. In all cases of normal nerves, neurofibromas and perineuriomas, the expression of EMA and Claudin-1 was weak and diffuse, and sometimes difficult to identify. On the other hand Glut-1 showed always strong and evident expression (Figs. 1, ​,2).2). Higher and lower concentrations of primary antibodies were tested in known positive controls, but it did not improve the results of the three markers used. However, independent of the dilution when comparing the markers, always EMA and Claudin-1 showed weaker expression than Glut-1. Considering the antibodies used and pattern of expression, Glut-1 appears to be a more sensitive immunomarker than EMA and Claudin-1 for perineurial cells, and therefore the preferable marker to distinguish perineuriomas from morphologic mimics. Also, as erythrocytes are ubiquitous practically in all histologic preparations, they serve as a useful internal control for Glut-1. Fig. 1 Perineurial cells of normal nerve fiber, positive for Glut-1, Claudin-1 and EMA. a Strong and evident expression of Glut-1 highlighting the perineurial sheath. Erythrocytes inside various vessels are strongly positive serving as internal control. b Similar ... Fig. 2 Perineurial cells in intraneural perineurioma, positive for Glut-1, Claudin-1 and EMA. a Strong Glut-1 positivity in concentric pattern surrounding axons. b Similar area showing lesser and more focal expression of Claudin-1 than the seen with Glut-1. ...

Intraneural Perineurioma of Unilateral Radial and Median Nerves Manifesting With Long-Standing Focal Amyotrophy in a 14-Year-Old-Boy

Intraneural perineuriomas are rare tumors of the peripheral nerves with unique immunohistochemical findings. In this report, we highlight the clinical and imaging findings of an adolescent male with histologically proven intraneural perineurioma involving multiple nerves. The salient features included a clinically progressive course, imaging evidence of involvement of long segments of multiple nerves, enlargement of individual fascicles within the affected nerves, and intense contrast enhancement of the enlarged fascicles. The identification of enlarged fascicles with intense contrast enhancement within the affected and distended nerve segments may aid in distinguishing intraneural perineurioma from other tumors affecting the peripheral nerves.

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.

Cutaneous Intraneural Perineurioma

Perineuriomas are benign neoplasms composed of perineurial cells. Classically, perineuriomas are divided into 2 distinct clinicopathologic entities, known as intraneural and extraneural perineuriomas. Intraneural perineuriomas, first described as interstitial hypertrophic neuritis, involve the major nerve trunks, causing motor or sensory deficits. Here, we report a case of a 42-year-old man presenting a lesion on the second finger of the right hand. The patient did not refer any previous trauma, tenderness, or sensorial nerve deficit. Histologic analysis showed a plexiform dermal lesion composed of enlarged nerve fascicles due to proliferation of spindle perineurial cells, arranged in onion-bulb-like structures. The proliferating cells showed positive membranous staining for epithelial membrane antigen and were negative for S100 protein, which highlighted residual Schwann cells. Fluorescence in situ hybridization studies revealed the loss of one signal for chromosome 22 probe in 15% of the spindle cells. In our report, we present the first case of cutaneous intraneural perineurioma, a benign tumor, which expands the morphological spectrum of cutaneous neural lesions.

Intraneural Perineurioma of the Sciatic Nerve in Early Childhood

Intraneural perineurioma is an uncommon benign neoplasm characterized by focal perineural cell proliferation. The typical course is indolent, with gradual onset and slow progression of motor loss. In early childhood, uncertainty concerning the time of onset can lead to difficulty in distinguishing this potential treatable lesion from congenital and other causes of nerve palsy. In the present case, clinical presentation, electrophysiologic findings, and magnetic resonance imaging findings in a child were compatible with intraneural perineurioma of the lumbosacral trunk and sciatic nerve. Initially, peroneal neuropathy was suspected. The case illustrates that sciatic intraneural perineuriomas do occur in early childhood, and that traction on the sciatic nerve may result in earlier damage to the peroneal nerve than to the tibial nerve, thus mimicking a more peripheral lesion.

A Rare Peripheral Nervous System Tumor: Soft Tissue Perineurioma of the Hallux

Perineuriomas are rare tumors of the peripheral nervous system that occur as either intraneural or extraneural lesions. Intraneural perineuriomas generally affect the major nerve branches in the upper extremity, whereas extraneural perineuriomas have a predilection for the subcutaneous tissues of the lower extremities. In this article, we describe the case of an adult patient who had a perineurioma localized to the foot. 4.

Intraneural Perineuriomas; a Rare Entity. Clinical, Surgical and Neuropathological Details in the Management of these Lesions

Perineuriomas are rare benign peripheral nerve sheath tumors, which have only been included in the WHO classification system since 2000. They are divided into intraneural perineuriomas and soft tissue tumors. Intraneural perineuriomas were previously known as localized hypertrophic neuropathies. Because of their rarity there are only case reports in the literature. Between 1992 and 2006 surgery was performed on four patients suffering from intraneural perineuriomas in our hospital. All patients were males, aged five, ten, twenty and twenty-nine years old. One of the tumors occurred in the ulnar nerve, one in the common peroneal part of the sciatic nerve and two of them in the radial nerve. In a retrospective study the clinical, electrophysiological and imaging data of the patients was analyzed. Two of these patients had previously been treated with decompression and neurolysis of the nerve for the suspicion of a nerve compression syndrome. Revisions were necessary following progressive neurological deterioration postoperatively. Explorations of the nerves showed nerve tumors. The tumors were resected and nerve grafting was performed. These tumors tend to affect the nerves of the upper extremities in children or young adults. The predominant symptom is a slow-progressive paralysis. Two of the four patients showed a partial improvement of their motor and sensorial nerve deficits in the long-term follow-up following complete tumor resection and interpositional autologous nerve grafts. No relapse could be observed. In cases of slow-progressive neurological deficits of a peripheral nerve in young patients the differential diagnosis should include the intraneural perineuriomas.