Benign Peripheral Nerve Sheath Tumors Research Articles

Clinical course and predictors of outcome following surgical treatment of benign peripheral nerve sheath tumors, a single center retrospective study

Introduction Peripheral nerve sheath tumors are the most common tumor of the peripheral nerves. In general, surgery has a favorable outcome and is the treatment of choice. However, postoperative neurologic deficits are not uncommon, and predictors of outcome are poorly defined. Objective To evaluate clinical outcomes after surgical treatment of benign peripheral nerve sheath tumors and identify outcome predictors that may affect preoperative decision making and improve surgical outcomes. Method In this single center retrospective study, all patients surgically treated for a benign peripheral nerve sheath tumor between 2005 and 2020 were eligible for inclusion. Medical records and imaging data were reviewed. Studied outcomes were changes in neurological symptoms, pain, and tumor recurrence. Logistic regression was performed to identify possible outcome predictors. Results In total, 81 patients undergoing 85 separate surgeries for benign peripheral nerve sheath tumors were included. The most common preoperative symptoms were local pain (90%) followed by a noticeable mass (78%), radiating pain (72%), sensory deficit (18%), and motor deficit (16%). A postoperative improvement of symptoms was seen in 94% of those with pain, 48% of those with sensory deficits and 78% of those with motor deficits. However, 35% and 9% developed new postoperative sensory and motor deficits, respectively. Multivariable analysis showed complete tumor removal as a predictor of reduced pain (p = 0.033), and younger age and larger tumors were risk factors for persistent or increased sensory deficits (p = 0.002 and p = 0.005, respectively). There were no significant predictors of motor deficits. Neurocutaneous syndromes were associated with increased odds of tumor recurrence on univariable analysis (p = 0.008). Conclusion Surgery of benign peripheral nerve sheath tumors is a safe procedure with a favorable outcome in most cases. Younger age and larger tumors were risk factors for persistent or increased sensory deficits, while complete tumor removal was associated with reduced pain. Patients with neurocutaneous syndromes had a higher rate of tumor recurrence. To further evaluate outcome predictors, we recommend future studies to focus on longer follow-up periods to assess the natural course of postoperative neurological deficits.

SCHWANNOMA OF THE HEAD AND NECK REGION: A CASE SERIES IN A TERTIARY HEALTH CENTRE IN WESTERN ODISHA

Objective: Schwannoma is a benign peripheral nerve sheath tumour. Previously referred to as Neurilemmomas. It is a slow-growing tumour. The commonest site is the limb with a predilection to the upper limb. But, it has a 25–48% predilection for nerves of the head and neck. In the oral cavity, the commonest site is said to be the tongue. Methods: We report three cases of histopathologically diagnosed Schwannoma at unusual sites. The first case was a 52 y old lady with a palpable, firm, painless swelling in the occipital region of the scalp of size 2.0 x 1.0 x 1.0 cm. The second case was a 29 y old woman with a painless scalp swelling of 1 cm by 1 cm. The third case was a 23 y old boy who presented with a slow-growing and painless pedunculated swelling in the posterior pharyngeal wall for a year. All cases showed classical histopathologic pictures on microscopy. Results: All the patients were evaluated pre-operatively and subjected to an excisional biopsy. The post-operative period was uneventful and everything went according to plan for a full year. Conclusion: Schwannomas exhibit a slow growth rate, are present in all age groups, and are not specific to one gender. Extremities are the most common locations to occur, but some rare sites like the scalp, oral cavity, retroperitoneum, and internal viscera also exist. Magnetic resonance imaging (MRI) is helpful in those lesions, providing useful information about the location and nature of the lesion, eliminating differential diagnosis, and thus providing correct management plans.

Silver Nanoparticles Selectively Treat Neurofibromatosis Type 1-Associated Plexiform Neurofibroma Cells at Doses That Do Not Affect Patient-Matched Schwann Cells.

Neurofibromatosis Type 1 (NF1) is a common neurogenic condition characterized by heterozygous loss of function mutations in the neurofibromin gene. NF1 patients are susceptible to the development of neurofibromas, including plexiform neurofibromas (pNFs), which occurs in about half of all cases. Plexiform neurofibroma are benign peripheral nerve sheath tumors originating from Schwann cells after complete loss of neurofibromin; they can be debilitating and also transform into deadly malignant peripheral nerve sheath tumors (MPNSTs). Here, our data indicates that silver nanoparticles (AgNPs) may be useful in the treatment of pNFs. We assessed the cytotoxicity of AgNPs using pNF cells and Schwann cells derived from the same NF1 patient. We found that AgNPs are selectively cytotoxic to pNF cells relative to isogenic Schwann cells. We then examined the role of neurofibromin expression on AgNP-mediated cytotoxicity; restoration of neurofibromin expression in pNF cells decreased sensitivity to AgNP, and knockdown of neurofibromin in isogenic Schwann cells increased sensitivity to AgNP, outlining a correlation between neurofibromin expression and AgNP-mediated cytotoxicity. AgNP was able to selectively remove pNF cells from a co-culture with patient-matched Schwann cells. Therefore, AgNPs represent a new approach for clinical management of NF1-associated pNF to address significant clinical need.

Coincidence of chronic rhinosinusitis with nasal polyps and neurofibroma

Background: Nasal polyps are painless inflammatory lesions originated from around the middlemeatus or paranasal sinus cavity; while neurofibroma is benign peripheral nerve sheath tumor. Purpose:To report a rare case of neurofibroma concurrently with nasal polyps in chronic rhinosinusitis. Casereport: A 64-year-old female with chief complaint congestion on the right nose cavity. There was a mass on both nasal cavities. Patient diagnosed with benign mass at right nasal cavity and chronic rhinosinusitis with nasal polyps at left nasal cavity; with a differential diagnosis of chronic rhinosinusitis with bilateral nasal polyps. Computer tomography scan results showed homogeneous isodense lesion in the right nasal cavity, and mucosal thickening in left nasal cavity and maxillary sinus. Patient was managed with total extirpation of the bilateral nasal cavity mass and functional endoscopic sinus surgery. Pathological examination revealed neurofibroma in the right nasal cavity and polyps in the left nasal cavity. Clinical question: “How to differentiate inflammation with tumor of nasal and paranasal sinuses? Is there a causal relationship?” Review method: Literature searching was performed with the keywords “nasal cavity neurofibroma”, AND “nasal polyps”, AND ”chronic rhinosinusitis” through database Google Scholar, PubMed, and hand searching/e-book. Result: There were 11 literatures published in the last 5 years, and 7 articles relevant with the subject. Conclusion: Chronic rhinosinusitis with nasal polyps, along with neurofibroma on nasal cavity is a rare co-incidence, and there was no correlation between those lesions. Pathological examination is a gold standard in differentiating a definite diagnosis of neurofibromas and polyps.Keywords: nasal cavity neurofibroma, nasal polyps, chronic rhinosinusitis

Discrimination of benign, atypical, and malignant peripheral nerve sheath tumors in neurofibromatosis type 1 using diffusion-weighted MRI.

Neurofibromatosis type 1 (NF1) is associated with the development of benign (BPNST) and malignant (MPNST) peripheral nerve sheath tumors. Recently described atypical neurofibromas (ANF) are considered pre-malignant precursor lesions to MPNSTs. Previous studies indicate that diffusion-weighted magnetic resonance imaging (DW-MRI) can reliably discriminate MPNSTs from BPNSTs. We therefore investigated the diagnostic accuracy of DW-MRI for the discrimination of benign, atypical, and malignant peripheral nerve sheath tumors. In this prospective explorative single-center phase II diagnostic study, 44 NF1 patients (23 male; 30.1 ± 11.8 years) underwent DW-MRI (b-values 0-800s/mm²) at 3T. Two radiologists independently assessed mean and minimum apparent diffusion coefficients (ADCmean/min) in areas of largest tumor diameters and ADCdark in areas of lowest signal intensity by manual contouring of the tumor margins of 60 BPNSTs, 13 ANFs, and 21 MPNSTs. Follow-up of ≥ 24 months (BPNSTs) or histopathological evaluation (ANFs + MPNSTs) served as diagnostic reference standard. Diagnostic ADC-based cut-off values for discrimination of the three tumor groups were chosen to yield the highest possible specificity while maintaining a clinically acceptable sensitivity. ADC values of pre-malignant ANFs clustered between BPNSTs and MPNSTs. Best BPNST vs. ANF + MPNST discrimination was obtained using ADCdark at a cut-off value of 1.6 × 10-3 mm2/s (85.3% sensitivity, 93.3% specificity), corresponding to an AUC of 94.3% (95% confidence interval: 85.2-98.0). Regarding BPNST + ANF vs. MPNST, best discrimination was obtained using an ADCdark cut-off value of 1.4 × 10-3 mm2/s (83.3% sensitivity, 94.5% specificity). DW-MRI using ADCdark allows specific and noninvasive discrimination of benign, atypical, and malignant nerve sheath tumors in NF1.

Primary Rectal Perineurioma: A Rare Incidental Finding

Abstract Perineurioma is a rare benign peripheral nerve sheath tumor which can occur intraneurally or uncommonly in the extraneural soft tissues. The majority of the perineuriomas of the gastrointestinal tract occur distal to the splenic flexure as polypoid pedunculated or sessile lesions. Lesions are often discovered incidentally during routine colonoscopy for cancer screening. Diagnosis is mainly histological with the majority of the cases showing mucosal/submucosal bland spindle cell proliferation with expression of perineurial markers. We report a rare case of rectal perineurioma in a 42-year-old female who presented with the complaint of intermittent episodes of painless rectal bleed associated with defecation. A pedunculated polypoid lesion in the rectum measuring 12 mm in greatest dimension was seen on colonoscopy. The patient underwent endoscopic mucosal resection of the mass. Microscopically, the lesion showed proliferation of spindle cells with oval-to-spindle nuclei, bland chromatin, and moderate amount of pale to eosinophilic cytoplasm with indistinct cell borders. Overlying mucosa showed hyperplastic crypt epithelium. Spindle cells were positive for epithelial membrane antigen and CD 34 and negative for S100, with low Ki-67 marked cycling cell population (<1.0%) and negative Progesterone receptor (PR) and CD 117, these features confirming the diagnosis of perineurioma.

Spatial Gene-Expression Profiling Unveils Immuno-oncogenic Programs of NF1-Associated Peripheral Nerve Sheath Tumor Progression.

Plexiform neurofibromas (PNF) are benign peripheral nerve sheath tumors (PNST) associated with neurofibromatosis type 1 (NF1). Despite similar histologic appearance, these neoplasms exhibit diverse evolutionary trajectories, with a subset progressing to malignant peripheral nerve sheath tumor (MPNST), the leading cause of premature death in individuals with NF1. Malignant transformation of PNF often occurs through the development of atypical neurofibroma (ANF) precursor lesions characterized by distinct histopathologic features and CDKN2A copy-number loss. Although genomic studies have uncovered key driver events promoting tumor progression, the transcriptional changes preceding malignant transformation remain poorly defined. Here we resolve gene-expression profiles in PNST across the neurofibroma-to-MPNST continuum in NF1 patients and mouse models, revealing early molecular features associated with neurofibroma evolution and transformation. Our findings demonstrate that ANF exhibit enhanced signatures of antigen presentation and immune response, which are suppressed as malignant transformation ensues. MPNST further displayed deregulated survival and mitotic fidelity pathways, and targeting key mediators of these pathways, CENPF and BIRC5, disrupted the growth and viability of human MPNST cell lines and primary murine Nf1-Cdkn2a-mutant Schwann cell precursors. Finally, neurofibromas contiguous with MPNST manifested distinct alterations in core oncogenic and immune surveillance programs, suggesting that early molecular events driving disease progression may precede histopathologic evidence of malignancy. If validated prospectively in future studies, these signatures may serve as molecular diagnostic tools to augment conventional histopathologic diagnosis by identifying neurofibromas at high risk of undergoing malignant transformation, facilitating risk-adapted care.

A Retrospective Analysis of High Resolution Ultrasound Evaluation of the "Split Fat Sign" in Peripheral Nerve Sheath Tumors.

Peripheral nerve sheath tumors (PNST) comprise schwannomas and neurofibromas. The finding of increased adipose tissue around benign PNSTs has been described as the "split fat sign" on magnetic resonance imaging exams, which is suggestive of an intramuscular or intermuscular location of the tumor. However, few studies have described this sign as a salient ultrasound feature of PNSTs. The main purpose of this study was to retrospectively evaluate the presence of increased fatty tissue deposition around benign PNSTs diagnosed by high-resolution ultrasound. In addition, we aimed to corroborate the presence of vascularization around the affected area. A retrospective analysis of ten cases of PNSTs and two cases of post-traumatic neuromas diagnosed by high-resolution ultrasound was performed with a Logiq® P8 ultrasound with a 2-11 MHz multifrequency linear probe L3-12-D (central frequency: 10 MHz). Localized types of neurofibromas and schwannomas in any location were seen as predominantly hypoechoic tumors with an oval or fusiform shape. Exiting and entering nerves (tail sign) were observed in six cases, showing localized lesions both in intermuscular and subcutaneous locations. The presence of increased hyperechoic tissue (the split fat sign) was noted in cases of solitary intermuscular and intramuscular peripheral nerve sheath tumors, mainly the schwannomas. Though small tumors did not demonstrate the tail sign, the increase in adipose tissue and vascularity on US was well demonstrated. In conclusion, the nerve in continuity forms the basis of the ultrasonographic diagnosis of PNSTs. However, high-resolution US can convincingly demonstrate the increased presence of fat in the upper and lower poles as well as circumferentially in intermuscular or intramuscular benign PNSTs.

Hybrid peripheral nerve sheath tumours: MRI features with pathological correlation in 24 cases.

To describe the MRI features of histologically proven hybrid peripheral nerve sheath tumours (HPNST). A retrospective analysis of the MRI features of 24 histologically proven cases of HPNST over 7 years. Demographic data obtained from clinical records included age, gender, and date of diagnosis. Two readers independently assessed MRI studies and assessed the following features: involvement of a major nerve, intramuscular location, lesion morphology, entering nerve sign, exiting nerve sign, target sign, fascicular sign, split fat sign, and ancient change (cystic change). Inter-observer agreement was assessed with Cohen's kappa coefficient. Histological diagnosis was based on either image-guided needle biopsy or resection histology. The study included 9 males and 15 females with mean age 50 years (range: 24-78 years). Nine tumours (35%) involved a major nerve including spinal roots (5), radial (1), median (1), tibial (1), and axillary (1), while 5 (21%) tumours were intramuscular. The mean tumour size was 4.2 cm (standard deviation of 2.4 cm). The frequency of MRI features was as follows: lobular contour (71%; 17/24), ancient change (38%; 9/24), fascicular sign (17%; 4/24), entering nerve sign (21%; 5/24), exiting nerve sign (13%; 3/24), target sign (13%; 3/24), and split fat sign (8%; 2/24). Inter-observer agreement was high, ranging from 0.7 to 0.83. HPNST infrequently demonstrate the classical MRI signs of benign peripheral nerve sheath tumours, but commonly have a lobular morphology and can show ancient/cystic change. This is the first study in the literature analysing the MRI features of histologically proven HPNST. HPNST infrequently shows the classical MRI signs that would be expected with benign peripheral nerve sheath tumours although commonly have a lobular morphology and show cystic change.

Targeted Muscle Reinnervation and Regenerative Peripheral Nerve Interfaces for Prophylactic Pain Control in Neurofibromatosis Type 1 Amputees.

Neurofibromatosis type 1 (NF1) is an inherited multisystem disorder that affects one in 2500 to one in 5000 people. Neurofibromas are the second-most common benign peripheral nerve sheath tumors arising from Schwann cells and are associated with neurofibromatosis. Chronic pain and opioid use is elevated in patients with NF1 when neurofibromas are associated with sensory nerves. Surgical excision is the primary treatment of neurofibromas when they become large, malignant, or painful, but they are associated with high rates of recurrence. Targeted muscle reinnervation and regenerative peripheral nerve interfaces are two prophylactic surgical techniques that are used to prevent neuroma-associated residual limb and phantom pain in amputees. Both techniques stimulate physiologic regeneration of the nerve via trophic stimulus from denervated muscle. This case report describes two patients with NF1 who underwent targeted muscle reinnervation and/or regenerative peripheral nerve interfaces at the time of amputation. Despite the abnormality of the peripheral nerves involved, both patients had excellent postoperative outcomes with minimal pain. This experience advocates for the use of prophylactic nerve management techniques in neurofibromatosis patients despite baseline nerve pathology.

MRI features of benign peripheral nerve sheath tumors: how do sporadic and syndromic tumors differ?

To compare MRI features of sporadic and neurofibromatosis syndrome-related localized schwannomas and neurofibromas. In this retrospective study, our pathology database was searched for "neurofibroma" or "schwannoma" from 2014 to 2019. Exclusion criteria were lack of available MRI and intradural or plexiform tumors. Qualitative and quantitative anatomic (location, size, relationship to nerve, signal, muscle denervation) and functional (arterial enhancement, apparent diffusion-weighted coefficient) MRI features of sporadic and syndrome-related tumors were compared. Statistical significance was assumed for p < 0.05. A total of 80 patients with 64 schwannomas (sporadic: 42 (65.6%) v. syndrome-related: 22 (34.4%)) and 19 neurofibromas (sporadic: 7 (36.8%) v. syndrome-related: 12 (41.7%)) were included. Only signal heterogeneity (T2W p=0.001, post-contrast p=0.03) and a diffused-weighted imaging target sign (p=0.04) were more frequent with schwannomas than neurofibromas. Sporadic schwannomas were similar in size to syndrome-related schwannomas (2.9±1.2cm vs. 3.7±3.2 cm, p = 0.6), but with greater heterogeneity (T2W p = 0.02, post-contrast p = 0.01). Sporadic neurofibromas were larger (4.6±1.5cm vs. 3.4±2.4 cm, p = 0.03) than syndrome-related neurofibromas, also with greater heterogeneity (T2W p=0.03, post-contrast p=0.04). Additional tumors along an affected nerve were only observed with syndrome-related tumors). There was no difference in apparent diffusion coefficient values or presence of early perfusion between sporadic and syndrome-related tumors (p > 0.05). Although syndrome-related and sporadic schwannomas and neurofibromas overlap in their anatomic, diffusion and perfusion features, signal heterogeneity and presence of multiple lesions along a nerve are differentiating characteristics of syndrome-related tumors.

Identification of potential common genetic modifiers ofneurofibromas: a genome-wide association study in1333 patients with neurofibromatosis type 1.

Neurofibromatosis type 1 (NF1) is characterized by the highly variable and unpredictable development of benign peripheral nerve sheath tumours: cutaneous (cNFs), subcutaneous (scNFs) and plexiform (pNFs) neurofibromas. To identify neurofibroma modifier genes, in order to develop a database of patients with NF1. All patients were phenotypically evaluated by a medical practitioner using a standardized questionnaire and the causal NF1 variant identified. We enrolled 1333 patients with NF1 who were genotyped for > 7 million common variants. A genome-wide association case-only study identified a significant association with 9q21.33 in the pNF phenotype in the discovery cohort. Twelve, three and four regions suggestive of association at the P ≤ 1 × 10-6 threshold were identified for pNFs, cNFs and scNFs, respectively. Evidence of replication was observed for 4, 2 and 6 loci, including 168 candidate modifier protein-coding genes. Among the candidate modifier genes, some were implicated in the RAS-mitogen-activated protein kinase pathway, cell-cycle control and myelination. Using an original CRISPR/Cas9-based functional assay, we confirmed GAS1 and SPRED2 as pNF and scNF candidate modifiers, as their inactivation specifically affected NF1-mutant Schwann cell growth. Our study may shed new light on the pathogenesis of NF1-associated neurofibromas and will, hopefully, contribute to the development of personalized care for patients with this deleterious and life-threatening condition.

A Case of Superficial Papular Neuroma: A Rare Neural Neoplasm

Abstract: A case of 67-year-old male patient with superficial papular neuroma (SPN) on the occiput is reported. This is the second report of SPN and the first with clinical images. Histologically, in the superficial dermis and periadnexa, the specimen exhibits a nodule of bland spindle cells with an S-shaped and spindle nucleus, surrounded by eosinophilic collagen fibers and scattered mast cells, which forms focally peripheral nerve-like structures. Lichen simplex chronicus-like changes are observed. Immunostaining result revealed that the tumor cells are positive for S-100, neurofilament, collagen IV, and CD34 but negative for Melan A, epithelial membrane antigen, and glial fibrillary acidic protein. Histological differential diagnosis includes prurigo nodularis, neurotized nevus, benign peripheral nerve sheath tumor, such as neurofibroma or schwannoma, a type of neuroma, such as traumatic neuroma, mucosal neuroma, and palisaded encapsulated neuroma, or a type of neural hamartoma. A careful histological investigation will enable dermatopathologists to make a diagnosis of SPN.

Malignant and Benign Peripheral Nerve Sheath Tumors in a Single Center: Value of Clinical and Ultrasound Features for the Diagnosis of Malignant Peripheral Nerve Sheath Tumor Compared With Magnetic Resonance Imaging.

This study aimed to investigate the combined use of ultrasonography and clinical features for the differentiation of malignant peripheral nerve sheath tumors (MPNST) from benign peripheral nerve sheath tumors (BPNST) and to compare the efficacy of ultrasonography with that of magnetic resonance imaging (MRI). This retrospective study included 28 MPNSTs and a control group of 57 BPNSTs. All patients underwent an ultrasound scan using the Logiq E9 (GE Health Care, Milwaukee, WI) or EPIQ7 equipment (Philips Medical System, Bothell, WA). A 3.0-T MRI machine (Ingenia; Philips Healthcare, Best, the Netherlands) was used for scanning, and conventional MRI was performed on different regions based on the patient's clinical situation. The following variables were evaluated: palpable mass, pain, nerve symptoms, maximum diameter, location, shape, boundary, encapsulation, echogenicity, echo homogeneity, presence of a cystic component, calcification, target sign, posterior echo, and intertumoral vascularity of the tumors. The diagnostic efficacy of ultrasonography and clinical factors was compared with that of MRI. Independent factors for predicting MPNST versus BPNST were also assessed. The parameters of location, shape, boundary, encapsulation, and vascularity were significantly different between MPNSTs and BPNSTs. Multiple logistic regression analysis showed that shape, boundary, and vascularity were independent predictors of MPNSTs. The sensitivity, specificity, and Youden index of the three clinical and ultrasound factors (shape, boundary, and vascularity) were 0.89, 0.81, and 0.69, respectively, whereas those of MRI were 0.71, 0.89, and 0.61, respectively. No significant differences in the area under the curve (AUC) of the three combined clinical and ultrasound factors and those of MRI were found (P > .05). MRI was useful in the differential diagnosis between MPNSTs and BPNSTs. However, the combination of clinical and ultrasound diagnoses can achieve the same effect as MRI, including shape, boundary, and vasculature.

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.

P02.14.B SPATIAL TRANSCRIPTOMIC ARCHITECTURE OF TUMOURS OF THE PERIPHERAL NERVOUS SYSTEM

Abstract BACKGROUND Studies into the genetics of peripheral nerve tumors have been focused on their association with known gene mutations and syndromes as well as on the tumor microenvironment of malignant peripheral nerve sheath tumors. Still, not many advances have been made into clarifying the structure and diverse pathophysiology of these tumors. Here we present spatially resolved transcriptomic profiling of benign and malignant entities and describe the topographical architecture of the neoplastic and microenvironmental diversity. MATERIAL AND METHODS We employed spatially resolved transcriptomics using the 10X Visium technology from paraffine embedded specimens. We included hybrid peripheral nerve sheath tumors (HPNSTs) plexiform neurofibromas and malignant peripheral nerve sheath tumors (MPNST). Computational analysis was employed by the SPATA2 toolbox. Transcriptomic niches were identified by graph-based spatial clustering. Correlation of histomorphological features and transcriptomic programs was performed by a co-expression network-based analysis. RESULTS We identified hub genes associated with neurofibroma and schwannoma histopathology across primary pathologies and discovered that neurofibroma regions of HPNSTs exhibited unique transcriptional programs marked by a significant higher local accumulation of bone-derived macrophages and lymphoid cells compared to primary neurofibromas. A novel marker, Apolipoprotein D (APOD), was found to accurately identify neurofibroma subregions in HPNSTs, which was confirmed by immunostaining in a control cohort. In MPNSTs, we observed a high grade of inter- and intrapatient heterogeneity driven by unique transcriptional niches and genetic variability. Subsequent pathway analysis revealed distinct oncogenic signaling driver across regional niches along with variance in immune infiltration. Our findings highlight the disbalance between histological annotation and actual tumor cell abundance in MPNSTs indicated by inferred copy number alterations. CONCLUSION Our integrated analysis pipeline revealed distinct transcriptional signatures and cellular interactions within benign PNSTs, including neurofibromas and hybrid peripheral nerve sheath tumors (HPNSTs) and sought to expose the tumor heterogeneity of MPNST and identify various cancer niches. Our study underscores the potential of spatially resolved transcriptomics as a powerful tool for advancing our understanding of PNST biology, and ultimately improving diagnosis, prognosis, and treatment strategies.

Benign peripheral nerve sheath tumors: an interdisciplinary diagnostic and therapeutic challenge

A benign peripheral nerve sheath tumor (bPNST) is a rare lesion associated with peripheral nerval structures. Symptoms may be heterogeneous, complicating diagnosis finding. Additionally, management concepts of bPNST may vary. In some cases, initial misdiagnosis leads to mistreatment resulting in severe functional deficits and chronic pain syndromes. Therefore, we analyzed patients treated for bPNST in our specialized institution with a primary focus on prior misdiagnosis and possible mistreatment. Patients with bPNSTs (schwannomas, neurofibromas, hybrid nerve sheath tumors, and perineuriomas) treated at the Neurosurgical Department between January 1, 2015, and July 31, 2021, were included. Assessment of demographics, tumor entity, tumor location, symptoms, the interval between the onset of symptoms and surgery, involved medical specialties, and outpatients’ treatment, with particular focus on initial misdiagnosis and inappropriate medical treatment, was performed. Eighty-five patients were included in the final analysis with schwannoma being the most prevalent histopathological diagnosis (schwannoma (75.3%, n=64), neurofibroma (12.9%, n=11), hybrid nerve sheath tumor (5.9%, n=5), and perineurioma (5.9%, n=5)). An incorrect primary diagnosis was detected in 44.7% (n=38), leading to suboptimal or insufficient treatment in these cases. Of those, 28.9% (n=11/38) were treated suboptimal, while 18.5% (n=7/38) underwent unnecessary invasive diagnostics. Inappropriate surgery based on prior misdiagnosis, which led to severe neurological deficits in all these cases, was reported in 26.3% (n=10/38). For the first time, our data shows the quantity and impact of incorrect initial diagnosis in bPNST causing a delay in causative treatment or resulting in unnecessary or potentially harmful treatment.

Subperiosteal Schwannoma of the Humerus: A Case Report and Review of Literature

There are numerous conditions that arise from the surface of bones including both neoplastic and non-neoplastic entities. Schwannoma had been reported to be one of those conditions originating from the bone surface with variable proposed theories on it’s origin. We present a unique case of subperiosteal schwannoma arising from the humerus in a 40 years old female with history of painful swelling for two years. Radiograph showed cortically based lytic lesion located in the lateral distal humeral metaphysis with periosteal reaction and cortical scalloping. MRI showed the same juxtacortical lesion with a large extraosseous soft tissue component. It demonstrates intermediate T1 signal intensity and high signal intensity on T2 weighted images with intense enhancement. US guided biopsy showed benign peripheral nerve sheath tumour, consistent with schwannoma. The patient underwent complete rescetion with no complications or documented recurrence till the latest follow-up. In conclusion, subperiosteal schwannoma should be kept in the differential diagnosis in patients presenting with bone surface lesions associated with unexplained vague pain and swelling for a prolonged period of time.

Single Stage Nasal Reconstruction for Solitary Neurofibroma Isolated in the Columella.

Neurofibromas are benign peripheral nerve sheath tumors that can originate from several elements of peripheral nerves, including axons, Schwann cells, endoneurial fibroblasts, and perineurial cells. The occurrence of a solitary neurofibroma in the external nose, especially that isolated in the nasal columella, is extremely rare. To the best of our knowledge, only 4 cases of solitary neurofibromas in the external nose have been reported in the English literature: on the nasal dorsum, tip, and pyriform aperture, all originating from the trigeminal nerve. We report the first case of a solitary neurofibroma isolated in the nasal columella, which we found in an otherwise healthy 42-year-old man. We completely resected this tumor with a negative resection margin and performed reconstruction with a bilateral spreader graft and caudal septal extension graft using autologous septal cartilage. The postoperative course was successful in both cosmetic and functional results, with no sensory changes at the 1-year follow-up. Surgical treatment for this lesion was challenging due to the cosmetically obvious location and high rate of recurrence. A review of the literature highlights the clinical and histological characteristics, differential diagnosis, and management of solitary neurofibroma of the external nose.

A Spectrum of Histomorphological and Immunohistochemical Expression Profiles of S-100, CD56 and Calretinin in Benign Peripheral Nerve Sheath Tumours.

Peripheral nerve sheath tumours comprise benign tumours; namely schwannomas and neurofibromas, and onlyrarely comprise hybrid benign tumours and their malignant counterpart, malignant peripheral nerve sheath tumours (MPNST). There may be diagnostic difficulties in histopathology analysis, especially in core needle biopsies where there is a limited amount of tissue. Immunohistochemistry (IHC) can play a beneficial role, especially in atypical and cellular histological variants and rarely hybrid tumours. A total of 45 cases of benign peripheral nerve sheath tumours were included in the study; there were 27 cases of neurofibroma including variants like plexiform and cellular neurofibromas and 18 cases of schwannomas including variants like ancient schwannoma and cellular schwannoma. Immunohistochemical staining (IHC) on these tumour tissues using S-100, CD56 and calretinin was done and scoring was done based on extent and intensity. No significant differences were observed between neurofibromas and schwannomas on patient age and anatomical locations of these tumours. IHC results did not show statistically significant patterns of expression of S-100 protein between the schwannoma and neurofibromas groups (p=0.75).CD56 protein was expressed strongly (3+) in90% of cases of schwannoma and negative in 86% of neurofibromas, the differential expression between the two groups was found to be statistically significant (p <0.0001). Calretinin was positive in 39% of schwannomas including one case of cellular schwannoma and negative in all (100%) cases of neurofibroma while the differential expression of calretinin between schwannoma and neurofibroma groups was found to be statistically significant (p < 0.005). Our study shows that S-100 does not show differential expression between schwannomas and neurofibromas. CD56 could be a potentially useful IHC marker to aid in the diagnosis of peripheral nerve sheath tumours with significantly higher expression in schwannomas compared to neurofibromas. Calretinin was also found to be preferentially expressed in schwannomas, though the difference is statistically significantly lower compared to CD56.A panel of all these markers could be used for accurate diagnosis.