Intraneural perineurioma (INP) is a rare, benign peripheral nerve sheath tumour that typically presents in adolescence or early adulthood as a slowly progressive, motor-predominant mononeuropathy or plexopathy. Although its clinicoradiological and histopathological features are well characterised, the genetic basis remains incompletely defined. We retrospectively analysed 10 patients with histologically confirmed INP diagnosed between February 2015 and December 2024. Demographic and clinical data, MRI/MR neurography findings and histopathology (immunohistochemistry and electron microscopy) were analysed. Targeted Sanger sequencing of TRAF7 exons 17-18 (WD40 domain) was performed. Interphase FISH with an EWSR1 (22q12) probe was performed on archival FFPE tissue in a subset. All patients exhibited progressive motor deficits, with at least one muscle group graded ≤ 2 on the MRC scale. Sensory symptoms were present in 8/10 and pain in 4/10. MRI demonstrated fusiform nerve enlargement and homogeneous gadolinium enhancement in all cases, with T2 hyperintensity in 9/10. A pathogenic TRAF7 p.His521Arg variant was identified in 2/9 evaluable tumours (22.2%). Tendon transfer was performed in 7/10 patients as a reconstructive strategy to improve motor function, resulting in heterogeneous functional outcomes. The MRI triad of fusiform enlargement, T2 hyperintensity and homogeneous enhancement strongly supports INP diagnosis and may obviate biopsy in typical cases. Our hotspot-limited assay detected TRAF7 mutations in only 22.2%, underscoring methodological limitations and probable genetic heterogeneity. Despite an indolent imaging appearance, INP frequently causes severe functional impairment requiring reconstructive surgery. Early recognition, structured functional monitoring and risk-adapted intervention are essential to optimise outcomes.

Perineuriomas are rare tumors arising from perineurial cells that form the protective layer surrounding peripheral nerve fascicles. Four types of perineuriomas have been described: (i) intraneural, (ii) soft tissue (extraneural), (iii) sclerosing, and (iv) mucosal. Intraneural perineuriomas are rarely reported nerve sheath tumors that primarily affect the peripheral nerves of the upper and lower extremities. In this report, we present a pediatric case in which the diagnosis of perineurioma was not suspected until lesional tissue was obtained, and the final pathologic diagnosis was made. The patient is a 17-year-old girl who presented with a three-year history of symptoms involving the left upper extremity, including weakness and cramping, which became progressively worse over time. Diagnostic workup included magnetic resonance imaging (MRI), which showed enlargement and contrast enhancement of two of the left brachial plexus nerve trunks, suggestive of an inflammatory or infectious etiology, with schwannoma or neurofibroma also listed as less likely possibilities. An electromyogram (EMG) showed findings concerning for an anterior horn cell process, including amyotrophic lateral sclerosis (ALS). Nerve conduction studies (NCS) demonstrated axonal findings only in motor nerves, and needle EMG demonstrated denervation and fasciculations in multiple muscles. An initial biopsy of the brachial plexus was performed but was non-diagnostic. Ultimately, resection of the involved nerve trunks was performed. The diagnosis of intraneural perineurioma was not suspected preoperatively and was made only after histologic and immunohistochemical examination.

Reports on imaging-based diagnosis of intraneural perineurioma remain limited. This study aimed to summarize the role of ultrasound in diagnosing intraneural perineuriomas to enhance clinical awareness and diagnostic accuracy among clinicians and ultrasonographers. A retrospective study was conducted on 11 patients diagnosed with intraneural perineurioma through surgery or biopsy at our hospital between June 2015 and June 2022. All patients underwent ultrasonography, and their ultrasonographic characteristics were analyzed. All patients presented with isolated mononeuropathy. Sonography revealed fusiform enlargement of the affected nerve. The length of the lesion ranged from 1.5 to 20.0 (5.2 ± 5.4) cm. The intraneural perineuriomas were hypoechoic relative to skeletal muscle. The internal homogeneity was heterogeneous, without posterior acoustic enhancement. The lesion was centrally located within the nerve. The inner epineurium was blurred with a continuous fascicular structure. Two patients had hyperechoic calcifications with posterior acoustic shadows in their lesions. Vascularization assessment using color or power Doppler imaging revealed blood flow in all the tumors. The cross-sectional area of the affected nerves was at least twice as large as that of the contralateral side, with some patients exhibiting up to an eight-fold increase. High-frequency ultrasonography provides important evidence for the clinical diagnosis of intraneural perineurioma. When combined with magnetic resonance imaging and electrophysiological studies, ultrasound can aid in clinical decision-making and facilitate long-term monitoring. Given its accessibility and diagnostic potential, ultrasonography can be one of the preferred imaging examinations for evaluating intraneural perineuriomas.

Described in 2013, intraneural pseudoperineuriomatous proliferations (IPP) present perineurial cells concentrically surrounding the axon-Schwann cell complexes, forming pseudo-onion bulbs. Different from intraneural perineuriomas, rare neoplasms with differentiation of perineural cells, IPP are reactive, associated with fibrosis, and frequently diagnosed histologically as traumatic neuroma (TN). The aim of this study was to characterize IPP by exploring its clinicopathological features and differentiating it from the main neural lesions that are part of the histopathological differential diagnosis through a retrospective study in six Brazilian Oral Pathology laboratories. Cases diagnosed as IPP, TN and intraneural perineuriomas were selected from the archives of the participating centers. Data on age, sex, race, symptoms, site, size, and clinical features and diagnosis were obtained from histopathological reports. Hematoxylin and eosin-stained slides were then re-evaluated by two examiners. Finally, statistical tests were performed to assess the association between clinical, pathological and demographic characteristics (p < 0.05). After reclassification, 152 TN, 48 IPP and no case of intraneural perineurioma were diagnosed. Clinically, IPP and TN are similar, but IPP affects younger individuals, presents less reported pain, and is more commonly found on the tongue, while TN is frequently observed on the lip, alveolar ridge, and mental foramen. Both lesions typically present as fibrous nodules, often clinically misdiagnosed as fibrous hyperplasia. IPP is fibrous in all cases, more superficial in the mucosa, less frequently associated with adipose tissue and inflammation. These features may assist clinical dentists and pathologists in differentiating lesions. Although histologically similar, pathologists should note the perineural cell proliferation in IPP to avoid confusion with TN (a common reactive lesion) or intraneural perineurioma (a rare neoplastic lesion).

Several cutaneous neurovascular stromal lesions are clinically and pathologically ill-defined entities. They are known by different nomenclatures, often unrecognized, misinterpreted, and confused with other skin lesions. Reports have documented cases of palmar and oral lesions in both children and adults. There is uncertainty regarding their true prevalence, clinicopathologic characteristics, and classification. Our aim is to highlight the salient histopathologic, histochemical, and immunohistochemical features of acral nodular tumors showing perineuriomatous differentiation. We found 3 teenagers (0.2%) [2 females, 1 male, average age: 13 years] with hand nodules out of 1331 patients with cutaneous and oral polypoid lesions. They were isolated, asymptomatic, nontraumatic, subcentimetric, palmar, digital nodules with an average duration of 5 years. They demonstrated dermal-based anomalous growths composed of thick tortuous neurovascular bundles and collagenous fibrovascular stroma. Masson trichome demarcated micronodular and plexiform neurovascular bundles showing concentric onion-bulb whorls ensheathed in collagenous fibrovascular stroma. Elastic fibers were absent. Alcian blue demonstrated intraneural mucinous alteration and loose interstitial myxoid mesenchyme. CD31, ERG, and smooth muscle actin highlighted small intraneural capillary-sized, and larger venous and arteriolar interstitial vasculatures. CD34 decorated the interstitial mesenchyme. S100, SOX10, and neurofilament revealed sparse neural components, whereas EMA and GLUT1 highlighted prominent perineurial components within the neurovascular bundles and onion-bulb micronodules. The findings suggest that cutaneous intraneural pseudoperineurioma nodules may represent a distinct clinicopathologic entity among traumatic neuromas, resembling cutaneous intraneural perineurioma. Further validation studies are necessary because of the small size of the case series and the lack of molecular genetic studies.