Localized Hypertrophic Neuropathy Research Articles

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.

Localized Hypertrophic Neuropathy as a Neoplastic Manifestation of KRAS-Mediated RASopathy.

Localized hypertrophic neuropathy is a rare Schwann cell proliferation that usually affects single nerves from the extremities, and it is of unclear etiology in its pure form. RASopathies are a defined group of genetic diseases with overlapping clinical features, usually secondary to germline mutations in genes encoding either components or regulators of the RAS/MAPK pathway. Herein, we report an 11-year-old boy presenting with café au lait spots and right leg length discrepancy. A fascicular nerve biopsy of the tibial nerve demonstrated a Schwann cell proliferation with prominent onion-bulb formation, satisfying criteria for localized hypertrophic neuropathy. Molecular genetic analysis demonstrated identical KRAS mutations (c38_40dupGCG) in the peripheral nerve lesion and melanocytes from café au lait spots, but not in blood, supporting a diagnosis of a KRAS-mediated rasopathy with mosaicism. Immunohistochemical staining in the peripheral nerve lesion demonstrated strong pERK staining consistent with downstream MAPK pathway activation. This report suggests that at least a subset of localized hypertrophic neuropathies are bonafide, well-differentiated Schwann cell neoplasms developing through oncogenic RAS signaling, which provides new insights into the controversial entity historically known as localized hypertrophic neuropathy.

Localized hypertrophic neuropathy of the sciatic nerve in children: MRI findings

Localized hypertrophic neuropathy (LHN) of the sciatic nerve in children is a rare condition characterized by a painless neurological deficit in the sciatic nerve territory. To demonstrate the role of MRI using a specific protocol and describe the primary findings in LHN. Imaging in four children (age 2 years to 12 years) is presented. All children presented with lower limb asymmetry. Three had a steppage gait. LHN was confirmed by electrophysiological studies and by MRI of the whole sciatic nerve with a dedicated protocol covering the lumbar spine and the lower limb. There were four direct MRI findings: (1) linear and focal hypertrophy with progressive enlargement of a peripheral nerve or plexus diameter, (2) abnormal hyperintensity of the nerve on T2-weighted images, (3) preserved fascicular configuration, and (4) variable enhancement after intravenous gadolinium administration. In addition there were atrophy and fatty infiltration of innervated muscles. MRI was helpful for determining the extent of lesions and in excluding peripheral nerve compression or tumour. MRI of the whole sciatic nerve is the method of choice for diagnosing LHN of the sciatic nerve.

An unusual cause of thenar hypertrophy and carpal tunnel syndrome

Carpal tunnel syndrome (CTS) is characterized by classic symptoms of paresthesias in the median distribution and weakness that is sometimes accompanied by thenar atrophy. We describe an unusual case presenting with thenar hypertrophy. A 52 year-old, right-handed man presented with 10 years of intermittent paresthesias in the left median nerve distribution and difficulty snapping the fingers. Driving and typing worsened his symptoms. His examination revealed increased thenar bulk without focal masses (Fig. 1A). A Tinel sign was present. Sensory exam did not elicit significant abnormalities. Mild thenar weakness was noted. Electrodiagnostic studies revealed prolonged distal motor latency (7.9 ms), decreased compound motor action potential amplitude compared to the right (left 5.1 mV, right 9.2 mV) and absent left median sensory nerve action potential. Ulnar studies and F-wave latencies were normal. Needle EMG of abductor pollicis brevis showed increased insertional activity, 1+ fibrillation potentials, 2+ positive sharp waves, 3+ fasciculation potentials, increased motor unit potential (MUP) amplitude, reduced MUP recruitment and increased firing rate. Studies were consistent with left focal median neuropathy at the wrist. Figure 1 A) Thenar eminence in the symptomatic left hand is appreciably larger compared to the right. B) MR axial T1 weighted non-fat saturated image reveals linear strands of hyperintense fat (arrow) infiltrating the thenar muscles. C) MR axial fat saturated ... To further elucidate the etiology of thenar hypertrophy, MRI of the hand and wrist was performed to assess structural detail. MRI revealed linear strands of fat infiltrating thenar muscles (Fig. 1B), which was different from diffuse fibrofatty change associated with advanced muscle atrophy. There was globular enlargement of the median nerve with linear cable-like appearance of the nerve fascicles with surrounding fat. The enlargement measured 1.2 × 1.6 centimeters and was consistent with lipofibromatous hamartoma (LFH) (Fig. 1C). He underwent decompression of the nerve. Nerve enlargement and swelling was noted at the time surgery but fibrofatty change was not appreciated because of intact epineurium. Three months post-operatively, paresthesias improved. However, imaging revealed no change in the size of the median nerve mass (Fig. 1D). This case is instructive because thenar hypertrophy led to imaging, which revealed LFH. Thenar hypertrophy could result from either pseudohypertrophy or true hypertrophy related to spontaneous activity, increased work of remaining fibers, and fiber stretching 2, 3. Chronic denervation and spontaneous activity on needle EMG raises the possibility of true thenar hypertrophy. The focal, band-like pattern of fatty infiltration in thenar muscles suggests extension of LFH. If the fatty replacement were due to severe muscle atrophy, then significant clinical weakness and diffuse fibrofatty change should be present. To our knowledge, we describe the first case of thenar pseudohypertrophy likely due to extension of median nerve LFH. Besides LFH, localized hypertrophic neuropathy has been reported in hereditary sensory motor neuropathy type 1, Refsum syndrome and diabetic neuropathy 4. However, a “cable-like” appearance of the median nerve is pathognomonic for LFH and arguably nullifies the need for biopsy 5. Additionally, LFH have a predilection for the median nerve 6. The etiology of LFH is unknown. There are many proposed mechanisms including a post-traumatic reactive process, congenital and association with neurofibromatosis 7. Surgical treatment of the tumor is debated. Mass excision can lead to sensory deficits 6. In our case, an initial conservative decompression procedure resulted in improvement in sensory symptoms. LFH of the median nerve should be considered for patients who present with CTS and clinical thenar pseudohypertrophy.

Localized hypertrophic neuropathy: a case report and review of the literature

The case is presented of a 71-year-old man with a 6-year history of symptoms suggestive of carpal tunnel syndrome, which did not improve despite two surgical procedures. On further investigation, a fusiform enlargement of the median nerve was found above the elbow, which was found on biopsy to be localized hypertrophic neuropathy (LHN). This case is the first to be described affecting the median nerve. The literature regarding LHN is reviewed, with discussion of the differential diagnoses and possible etiology of this rare lesion.

Intraneural Perineurioma: A Systematic Review With Illustrative Cases

Intraneural perineurioma may be confused with other "onion bulb" Schwann cell entities (localized hypertrophic neuropathy, reactive/demyelinating processes, or inherited polyneuropathies of Charcot-Marie-Tooth/Dejerine Sottas) due to similar clinical, radiologic, and histologic features. Perineurial and Schwann cells can only be differentiated by ultrastructure and immunohistochemsitry. To identify and summarize the clinicopathologic features of true cases of intraneural perineurioma from the English language literature. A systematic review was performed on definitive intraneural perineuriomas identified through Medline. Baylor College of Medicine-affiliated hospitals' anatomic pathology databases yielded 2 illustrative intraneural perineurioma cases. Intraneural perineurioma inclusion criteria consisted of characteristic histology and confirmation of perineurial cell lineage by either immunohistochemistry (epithelial membrane antigen positive, S100 protein negative) and/or ultrastructural analysis (thin cytoplasmic processes with an incomplete basal lamina, poorly formed tight junctions, and pinocytotic vesicles). Clinicopathologic data were extracted from all identified articles, with subsequent statistical analysis of the following parameters: age, sex, race, tumor location, tumor size, duration of symptoms prior to diagnosis, treatment modalities and outcomes measures, follow-up assessment for tumor recurrence and metastasis, clinical features (history of trauma, motor/sensory abnormalities, clinical/family history), and diagnostic workup (routine histology, immunohistochemistry, ultrastructural analysis, and molecular/cytogenetic characteristics). Intraneural perineurioma is a neoplastic proliferation of perineurial cells with unique immunohistochemistry and ultrastructural features, and it is distinct from other onion bulb Schwann cell-derived entities. Despite harboring molecular abnormalities of the long arm of chromosome 22, intraneural perineurioma has not been associated with neurofibromatosis. Intraneural perineurioma is a benign peripheral nerve sheath tumor that does not recur or metastasize.

Intraneural perineurioma in a child with Beckwith-Wiedemann syndrome

To the authors' knowledge, this is the first report of an intraneural perineurioma in a child with Beckwith-Wiedemann syndrome. Intraneural perineurioma, previously known as localized hypertrophic neuropathy, is a rare benign peripheral nerve sheath tumor arising from perineurium. This report adds a new entity in the spectrum of tumor formation in Beckwith-Wiedemann syndrome.

A series of 146 peripheral non—neural sheath nerve tumors: 30-year experience at Louisiana State University Health Sciences Center

This is a retrospective review of 146 surgically treated benign and malignant peripheral non-neural sheath tumors (PNNSTs). Tumor classifications with patient numbers, locations of benign PNNSTs, and surgical techniques and adjunctive treatments are presented. The results of a literature review regarding tumor frequencies are presented. One hundred forty-six patients with 111 benign and 35 malignant PNNSTs were treated between 1969 and 1999 at the Louisiana State University Health Sciences Center (LSUHSC). The benign tumors included 33 ganglion cysts, 16 cases of localized hypertrophic neuropathy, 12 lipomas, 12 tumors of vascular origin, and 11 desmoid tumors. There were four each of lipofibrohamartomas, myositis ossificans, osteochondromas, and ganglioneuromas; two each of meningiomas, cystic hygromas, myoblastoma or granular cell tumors, triton tumors, and lymphangiomas; and one epidermoid cyst. The locations of benign PNNSTs were the following: 33 in the brachial plexus region, 39 in an upper extremity, one in the pelvic plexus, and 38 in a lower extremity. The malignant PNNSTs included 35 surgically treated carcinomas, 15 of which originated in the breast and nine in the lung. There were two melanomas metastatic to nerve and one tumor each that had metastasized from the bladder, rectum, skin, head and neck, and thyroid, and from a primary Ewing sarcoma. There was a single lymphoma that had metastasized to the radial nerve and one chordoma and one osteosarcoma, each of which had metastasized to the brachial plexus. There were more benign PNNSTs than malignant ones. Benign tumors were relatively equally distributed in the brachial plexus region and upper and lower extremities, with the exception of the pelvic plexus, which had only one tumor.

Hypertrophic inflammatory neuropathy involving bilateral brachial plexus

BACKGROUND The present case is an example of hypertrophic inflammatory neuropathy (HIN). This entity is a rare tumor-like, chronic inflammatory, focal or multifocal, mainly demyelinating neuropathy of unknown origin, most frequently involving the brachial plexus. CASE DESCRIPTION The authors describe a 67-year-old man presenting with a nodular mass in his right supraclavicular fossa. A nodular mass grossly resembling a schwannoma originating from a single nerve fascicle was surgically removed from the right C6 spinal nerve. Histologically, endoneurial edema, fibrosis, focal chronic inflammation, and extensive “onion bulb” formation were seen. Electron microscopy studies and immunohistochemistry proved that the onion bulb-forming cells were schwannian in nature and that the whorls of onion bulbs surrounded a generally demyelinated axon. Three months following surgery the patient developed acute painless paralysis of his right biceps brachii muscle that rapidly reversed; after that he remained neurologically asymptomatic. MRI revealed multiple fusiform mass lesions involving the brachial plexus bilaterally. Electrophysiologic studies demonstrated a bilateral, asymmetrical, mainly demyelinating neuropathy involving the brachial plexus; they failed to reveal any abnormality suggestive of generalized neuropathy. CONCLUSION HIN is different from other focal tumor-like neuropathies and in particular from localized hypertrophic neuropathy (LHN).

Resection and graft repair for localized hypertrophic neuropathy.

Formulation of surgical management recommendations for localized hypertrophic mononeuropathy has been difficult because of the infrequency of the lesion, lack of precise pathological diagnosis, and uncertainties regarding its cause. The purpose of this retrospective review of the Louisiana State University (LSU) experience with this unusual neuropathy was to evaluate the efficacy of lesion resection and interposition grafting in its management. The charts of 15 patients operated on at LSU during a 15-year period with a pathological diagnosis of localized hypertrophic neuropathy were reviewed. Hypertrophic lesions were located on major named peripheral nerves of the extremities, distributed equally to the upper and lower extremities. Family history was negative for all patients, and entrapment or trauma, other than previous surgery, were unlikely by symptom location or history. Weakness was the most common presentation. The mean length of symptoms was 76 months. Atrophy, sensory loss, Tinel's sign, focal tenderness, and a mass were found in the majority of patients. Preoperative electrophysiological studies showed chronic denervational changes in all patients. At surgery, if no action potential or one of low amplitude was recorded across the lesion, the lesion was resected and an autologous nerve graft measuring from 3.5 to 8.5 cm in length was interposed. During follow-up periods of 1 or more years, seven of nine patients with localized hypertrophic mononeuropathy treated with graft repairs were either unchanged or improved. Localized hypertrophic mononeuropathy is a progressive process associated with pathological nerve changes that correlate with eventual severe functional loss. If intraoperative histological examination shows onion bulb neuropathy and intraoperative nerve action potentials confirm a nonfunctioning or poorly functioning segment, lesion resection with interposition graft repair provides the possibility of some degree of recovery.

Intraneural Perineurioma:A Clonal Neoplasm Associated With Abnormalities of Chromosome 22

The nature of perineurioma, variably termed "localized hypertrophic neuropathy," "intraneural neurofibroma," and "hypertrophic interstitial neuritis" has long been an issue of contention. Most authors consider it a neoplasm, but some a reactive process. Eight clinically and morphologically typical perineuriomas were studied by histologic, immunohistochemical and ultrastructural methods. One perineurioma was subject to tissue culture and cytogenetic study and another to fluorescence in situ hybridization (FISH) analysis. The patients, 3 males and 5 females, ranged in age from 11 to 38 years. All tumors were intraneural, and involved extremities (2 sciatic, 1 median, 1 femoral, 1 peroneal, 1 brachial plexus, 1 ulnar, and 1 radial). Neurologic symptoms, motor in all cases and sensory in 4, were present from 1 month to 7 years (mean 1.2 years). Fusiform, segmental nerve enlargement was clinically apparent in only two patients, but was evident on MRI in five of eight patients. Lesion length ranged from 3.5 to 30 cm, the largest involving the sciatic nerve from the obturator foramen to the knee. One lesion involved two nerve roots, but no association with a phakomatosis was noted. Treatment consisted of biopsy in six cases and resection in two cases. Histologically, pseudo-onion bulbs composed of epithelial membrane antigen-reactive, S-100 protein-negative perineurial cells surrounded myelinated or nonmyelinated nerve fibers. Many were accompanied by their S-100 protein-positive Schwann sheaths. Some whorls lacked a central axon. A single mitosis was noted in one case. The MIB-1 antigen labelling index ranged from 4% to 17%. Staining for p53 antigen in six cases showed no (2 of 6), rare (2 of 6), or scattered (2 of 6) immunoreactive nuclei. Cytogenetic analysis in one case demonstrated a chromosomally abnormal clone. Each of 16 metaphases was abnormal; the tumor cells appeared to be homozygously deficient for the region 22q11.2qter. In another case, 53% of interphase nuclei showed three FISH signals with a chromosome 14/22 probe, thus suggesting either monosomy for the centromere of chromosome 14 or that of chromosome 22.(ABSTRACT TRUNCATED AT 400 WORDS)

Localized Hypertrophic Neuropathy (LHN): As Expert Quiz published in Vol. 185, 418–419 (1989)

Intraneural perineurioma is a rare peripheral nerve sheath tumor characterized by localized proliferation of perineurial cells. The literature consists predominantly of case reports and institutional series, with inconsistent and confusing nomenclature. We present a pooled analysis of all reported cases of intraneural perineurioma in the literature.A systematic search of PubMed, MEDLINE, Embase, and Scopus was performed according to PRISMA guidelines to identify all reported cases of intraneural perineurioma in the literature. Individual cases were pooled and analyzed for demographics, clinical features, and outcomes.A total of 172 cases were identified across 72 studies, of which 149 were found in major peripheral nerves and their branches. Median age of patients at diagnosis and onset of symptoms was 18 years (interquartile range [IQR], 12–34 years) years and 13.5 years (IQR, 8–26 years), respectively, with 54.4% (81/149) being female. The most common sites were the sciatic nerve or its branches (41.9%), median nerve (13.5%), radial nerve (12.2%), and brachial plexus (12.2%). Most patients were managed conservatively (52.9%; 72/136). Among those managed conservatively with available follow-up (n = 31), median follow-up was 11 months, and most (67.7%, n = 21) reported no change in neurologic status, although worsening was noted in 29.0% (9/31). Among surgically managed cases (n = 64), the most common intervention was resection with or without repair (62.5%; 40/64), neurolysis (25%; 16/64), or tendon transfers without resection (12.5%; 8/64). No lesion recurred after surgical resection.Intraneural perineurioma represents a benign focal lesion presenting with weakness and atrophy affecting adolescents and young adults. Most cases are managed nonoperatively and surgical treatment strategies are varied.

The Enigmatic Perineurial Cell and Its Participation in Tumors and in Tumorlike Entities

The perineurial cells that make up the perineurium of peripheral nerve fascicles are characterized by distinct ultrastructural features, including non-branching thin cytoplasmic processes coated by an external lamina and joined at their ends by a tight junction, few organelles, actin and vimentin filaments, and numerous pinocytotic vesicles. Perineurial cells are immunoreactive for vimentin and epithelial membrane antigen (EMA) but not for the Schwann cell markers S-100 protein and Leu-7. The cytogenesis of the perineurium remains disputable, with morphologic, immunohistochemical, and experimental evidence supporting origin from the fibroblast, Schwann cell, and arachnoid cap cell. Ultrastructural studies more recently supported by immunolocalization of EMA have detected hyperplastic and neoplastic perineuriallike cells in a number of pseudoneoplastic lesions and true neoplasms, notably localized hypertrophic neuropathy, neurofibromas of various types, and perineurioma.

Soft tissue tumors.

Selection de resumes interessant les acquisitions nouvelles en pathologie tumorale des tissus mous au cours des annees 88 et 89: description de 2 nouvelles entites. La tumeur fibrohistiocytaire plexiforme et le myofibroblastome palissadique, distinction entre haemangiome epithelioide et maladie de KIMURA et interet de l'anticorps anti EMA comme outil diagnostique courant dans le cadre des tumeurs des tissus mous

Perineurioma as the cause of localized hypertrophic neuropathy

Clinical, electrodiagnostic, and morphological studies were performed on three patients with localized hypertrophic neuropathy (LHN). LHN is characterized clinically by slowly progressive motor mononeuropathy without significant pain or numbness. Nerve conduction studies and needle electrode examination show severe focal motor and sensory axonal loss. Morphological findings in the localized areas of enlarged nerves are different from those of generalized hypertrophic neuropathy, entrapment neuropathy, and neurofibroma, and consist of primary perineurial cell hyperplasia. The tumor is thus a perineurioma. This rare tumor can occur both in generalized neurofibromatosis and in isolated form and appears to be the cause of localized hypertrophic neuropathy.

Macrodactyly and localized hypertrophic neuropathy.

A case of focal hypertrophic neuropathy involving the left median nerve associated with macrodactyly of the left thumb is reported. The pathologic picture showed classic onion bulb formation caused by proliferation of Schwann cell processes, collagen, and fibroblasts. An unusual feature of the ultrastructural aspects of the disorder, to our knowledge not previously recognized, was the participation of processes from one Schwann cell in the formation of several onion bulbs. Although the relationship of the focal hypertrophic neuropathy to the macrodactyly remains speculative, it is tentatively attributed to disturbed trophic functions of peripheral nerves. Onion bulb formation, although not usually clinically apparent at birth, might arise in utero, since the macrodactyly in our patient was noted in infancy.