RARE DISEASE
Benign schwannoma
Benign schwannoma
Benign schwannoma
Synonyms: Neurilemmoma, Neurilemoma, Peripheral fibroblastoma
Synonyms: Neurilemmoma, Neurilemoma, Peripheral fibroblastoma
Synonyms: Neurilemmoma, Neurilemoma, Peripheral fibroblastoma
Drug discovery
3
drugs
With orphan designations
Overview
Benign schwannomas are slow-growing, encapsulated tumors arising from Schwann cells of peripheral nerves, most commonly affecting the vestibular nerve (vestibular schwannoma) or spinal nerves [1][4][16]. Symptoms include localized pain, neurological deficits (numbness, weakness), and cranial nerve dysfunction (hearing loss, tinnitus, imbalance) [6][13][17]. Diagnosis relies on MRI/CT imaging and histopathological confirmation via biopsy [1][16]. Management options include surveillance for asymptomatic tumors, microsurgical resection for symptomatic cases, and stereotactic radiosurgery for inoperable tumors [1][13][19]. Prognosis is excellent post-resection, though rare malignant transformation (<2.5%) occurs, particularly in neurofibromatosis type 2 (NF2) or radiation-exposed patients [11][19][16].
Population
Peak incidence: 65–74 years (spinal) and 45–64 years (vestibular) [2][12].
Male predominance in spinal cases (IRR 0.86 vs. females) [2]; vestibular cases show slight female preference (52.6%) [7].
Associated with NF2 (bilateral vestibular tumors) and schwannomatosis (multiple peripheral tumors) [3][5][16].
Burden
Functional morbidity: Hearing loss (68.8%), facial palsy (82.2%), and balance disorders (91.8%) in vestibular cases [17].
Economic impact: Lifelong surveillance (MRI every 6–12 months) and surgical costs [1][13].
Malignant risk: <2.5% develop MPNSTs, particularly in NF2 or post-radiation cases [11][19].
Therapies
Categories: rare neoplastic diseases, rare neurological diseases
Research Papers
1,727 drug discovery papers about Benign schwannoma, with 2 first-in-class and 5 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
1,727 drug discovery papers about Benign schwannoma, with 2 first-in-class and 5 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
small molecules
2026-06-17 | Repurposing anti-retroviral drugs to treat NF2-related tumours: a protocol for a phase 0 trial (RETREAT).
To date, there is no proven licensed systemic treatment for neurofibromatosis type 2 (NF2)-related schwannomatosis patients. There is a need for more effective, less toxic treatments and, as a rare disease, NF2 is often overlooked in targeted drug development. Subcutaneous schwannomas of the skin (CS) are common in the NF2 population.This trial involves the repurposing of medications already licensed for HIV-ritonavir and lopinavir (Kaletra and Norvir)-that have been shown to reduce tumour growth by reducing cell proliferation in human schwannoma and meningioma tumour cell cultures. The safety and tolerability of these drugs are already known, so they are safe candidates to trial in NF2 patients. This trial is an open-label, phase 0 design. A maximum of 16 participants diagnosed with NF2-related schwannomatosis will be enrolled in this study. Treatment duration is 30 days, with a 30-day follow-up. Biopsies and blood samples will be collected to assess whether the drugs reach the tumours and to analyse the tumour-cell response. The primary outcome is pharmacodynamic response, defined as a statistically significant decrease in biomarker activity in CS biopsy samples at day 30. The sample size calculation is based on the tissue biomarker response. The study was approved by an Ethics Committee (West of Scotland Research Ethics Service (23/WS/0178)), the Health Research Authority (HRA), the Medicines and Healthcare products Regulatory Authority (MHRA) and each of the participating NHS Trust's Research and Development departments. Following analysis of trial data, the trial results will be written up for publication in a peer-reviewed scientific journal and will be disseminated at conferences. ISRCTN10422213.
2026-04-18 | Decoding the Histomorphological and Multi-Omic Characteristics of Melanotic Schwannoma.
Melanotic schwannoma (MS) is a rare peripheral nerve sheath tumor accompanied by melanin deposition and severe refractory pain. However, its molecular pathogenesis remains unclear. This study aimed to explore the histomorphological, transcriptomic, and proteomic characteristics of MS, and to identify key molecules related to melanin production, pain generation, and targeted therapy. Histomorphological characteristics of MS were observed by Luxol Fast Blue (LFB) staining and hematoxylin and eosin (HE) staining in tumor tissues from 3 MS patients. Combined transcriptomic and proteomic analyses were performed to screen differentially expressed genes and proteins. The expression levels of tyrosinase-related protein 1 (TYRP1), transient receptor potential ankyrin 1 (TRPA1), and Bruton's tyrosine kinase (BTK) were validated by quantitative real-time polymerase chain reaction (qRT-PCR), Western blotting, and immunofluorescence staining. Histomorphological examination revealed typical melanin deposition and prominent compression of adjacent nerve fibers in MS. Transcriptomic and proteomic analyses showed activation of the melanin synthesis pathway and transient receptor potential (TRP) channel-related neuroinflammatory pathway. The expression of TYRP1 and TRPA1 was significantly upregulated, suggesting that these related pathways are associated with melanin production and neuropathic pain in MS. In addition, the expression of BTK, a known molecular target of targeted drugs, was significantly increased, suggesting that BTK inhibitors have potential therapeutic effects on MS. This study delineates the histomorphological features, transcriptomic and proteomic profiles of MS. TYRP1, TRPA1, and BTK are identified as key molecules involved in melanogenesis, pain generation, and targeted therapy, respectively. These findings provide novel insights into the pathogenesis and potential therapeutic strategies for MS.
2026-03-28 | Fimepinostat Promotes Apoptosis and Decreases Cytokine Secretion in NF2-Related Human Schwannoma Cells.
There is no approved drug therapy for schwannomas associated with NF2-related schwannomatosis (NF2-SWN). Neither life-saving surgical resection or radiation are curative and can compound the debilitating neurological effects of the schwannomas. We previously identified fimepinostat, a dual histone deacetylase (HDAC)/phosphoinositide-3 kinase (PI3K) inhibitor, as a promising drug candidate with pro-apoptotic effects on NF2-related schwannomas. This preclinical study used the pharmaceutical formulation of fimepinostat to confirm its efficacy in schwannomas and identify pro-apoptotic signaling pathways. Fimepinostat was tested in human schwannoma model cells, patient-derived primary vestibular and non-vestibular schwannoma cells, and in a sciatic nerve allograft model. The signaling pathways leading to caspase-3-dependent apoptosis were elucidated using immune assays, flow cytometry, imaging, proteome, and acetylome analysis. Acute exposure to fimepinostat led to p21-dependent cell cycle inhibition, upregulation of tumor necrosis factor-related apoptosis-inducing ligand receptor 2 (TRAIL R2), and downregulation of tumor necrosis factor receptor 1 (TNFR1), Yes-associated protein (YAP), and inhibitors of apoptosis. Moreover, fimepinostat downregulated cytokine and chemokine secretion increased by merlin loss in schwannoma cells. Fimepinostat is a promising new drug intervention for NF2-SWN patients with the potential to promote tumor regression.
2026-03-20 | Fluorescence‑Navigated Robotic Resection of Pelvic Schwannoma With Hypogastric Nerve Preservation.
To demonstrate the advantages of combining robotic-assisted surgery with Indocyanine Green (ICG) fluorescence imaging in the excision of pelvic retroperitoneal schwannomas, with a particular focus on nerve preservation. Gynecologic unit of a tertiary center. A 47-year-old female presented with severe pelvic pain, characterized as intermittent throughout the day and not exacerbated by positional changes or activity, with no additional complaints other than occasional urinary frequency.Magnetic resonance imaging revealed a 5 cm schwannoma located adjacent to the right internal iliac vein and the right hypogastric nerve. A stepwise narrated video demonstrates the technique using a combined robotic-assisted surgical approach was employed, enhanced by intravenous administration of 6mg ICG at the initiation of retroperitoneal dissection. Real-time ICG fluorescence enabled clear demarcation of the hypervascular schwannoma [1], distinctly contrasting with the non-fluorescent right hypogastric nerve. This contrast facilitated atraumatic nerve lateralization [2],preserving autonomic function and enabling high surgical precision. A focal area of intense fluorescence within the tumor suggested uncapsulated tissue, prompting meticulous inspection of the excision bed, where residual capsular tissue was identified and fully excised from the deep presacral space without vascular injury. The use of robotic instrumentation allowed safe dissection near dense vascular and neural plexuses [3], particularly the internal iliac vein. The specimen and excised residual capsule were extracted transvaginally via posterior colpotomy using an endoscopic retrieval bag, minimizing abdominal trauma and preventing oncologic spillage. The combined use of robotic-assisted surgery and ICG significantly enhances intraoperative visualization, facilitates precise dissection within complex pelvic anatomy, and supports critical nerve preservation during pelvic schwannoma resection. This approach minimizes vascular injury, reduces blood loss, and enables complete tumor excision, including residual capsular tissue, without increasing surgical morbidity and faster recovery. As the first reported case of its kind, this technique demonstrates substantial clinical efficacy and offers valuable guidance for advanced gynecologic surgical practice. VIDEO ABSTRACT.
2026-02-24 | Robot-assisted thoracoscopic resection of a posterior mediastinal schwannoma adjacent to the intervertebral foramen using Arista™ AH: A case report.
Posterior mediastinal schwannomas near the intervertebral foramen pose surgical challenges owing to their proximity to critical neurovascular structures. A 19-year-old woman presented with an abnormal shadow on a chest radiograph obtained during a routine health checkup. Magnetic resonance imaging revealed a 3.5-cm mass in the right paravertebral region at the T3-T4 level, suggestive of schwannoma. The tumor was resected via 4-port robot-assisted thoracic surgery. Intraoperatively, the intercostal nerve was found to traverse the tumor and was divided. Arista AH was used to control oozing near the intervertebral foramen. The patient recovered uneventfully and was discharged on postoperative day 8. Pathological examination confirmed schwannoma. She has remained recurrence-free for 12 months. Robot-assisted thoracic surgery enables safe resection of tumors adjacent to the intervertebral foramen. Arista™ AH may provide effective hemostasis in anatomically sensitive areas.
proteins
2026-05-25 | Schwannoma of the tongue: a case report and review of literature
Schwannomas are rare slow growing benign tumors arising from Schwann cells lining the nerve sheaths of myelinated nerves. Only 25 to 48% of the cases occur in the head and neck region with only 1% showing an intraoral origin. We present a case of lingual schwannoma in a 20 year old patient who presented with painless mass on right ventral surface of tongue, which was excised. The final histopathology report revealed a schwannoma. We report this case owing to rarity of disease. Tongue Schwannomas are rare, benign tumors with an excellent prognosis. Histology remains the gold standard for its diagnosis and Malignant transformation is rare after complete surgical excision. Schwannomas should be considered in the differential diagnosis whenever a benign looking mass is seen inside the oral cavity.
2026-05-11 | Abducens Nerve Schwannoma: A Case Report on Extremely Rare Cranial Nerve Tumor.
Abducens nerve (CN VI) schwannomas are exceedingly rare intracranial tumors, constituting less than 10% of all primary cranial nerve schwannomas. This report details the case of a 30-year-old woman presenting with diplopia and progressive visual deterioration due to an abducens nerve schwannoma. Imaging revealed an extra-axial lesion involving the right cavernous sinus and encasing the right internal carotid artery. Surgical resection via frontotemporal craniotomy achieved near-total tumor removal, with histopathological analysis confirming a benign schwannoma. Postoperatively, the patient exhibited persistent right lateral rectus palsy as preoperative status but improvement in diplopia. This case underscores the rarity of abducens nerve schwannomas, the challenges in achieving complete resection due to neurovascular adherence, and the importance of careful surgical planning for optimal patient outcomes.
2026-05-08 | Biallelic germline MBD4 mutations predispose to colorectal polyposis, hypermutated AML, and schwannomas.
Biallelic pathogenic variants in the MBD4 gene have recently been associated with an autosomal recessive cancer predisposition syndrome deemed "MBD4-associated neoplasia syndrome (MANS)". Early reports of individuals with MANS highlight the propensity to develop young onset colorectal polyposis and hyper-mutated acute myeloid leukemia (AML). In the following case series, we present four patients with MANS from three families with polyps and AML, as well as additional features previously less described, such as schwannoma and thyroid cancer. This series increases the total number of reported cases by 27%, with the intention of achieving a more robust understanding of the full phenotypic spectrum of MANS.
2026-03-31 | Solitary Axillary Schwannoma Mimicking a Lymph Node: A Case Study
Schwannoma, also known as neurilemmoma or neurinoma, is a benign, encapsulated tumor of the peripheral nerve sheath that arises from Schwann cells. It is typically a slow-growing, solitary, firm, and well-circumscribed lesion, accounting for approximately 8% of all soft tissue masses. Axillary involvement is rare ; therefore, schwannoma should be considered in the differential diagnosis of axillary and peripheral nerve masses to ensure accurate diagnosis and appropriate management. The clinical presentation may remain asymptomatic for years but can include pain, a palpable mass, or neurological symptoms, particularly in larger lesions. Imaging plays a crucial role in diagnosis, especially magnetic resonance imaging (MRI), with ultrasound serving as a useful adjunct. In this study, we report a case of axillary schwannoma presenting as a painful swelling in the left axillary region, with the definitive diagnosis established postoperatively through histopathological examination of the excised specimen.
2026-02-02 | Cystic orbital schwannoma: A surgeon’s surprise
Schwannomas, also known as neurilemmomas, are benign, encapsulated tumors arising from Schwann cells. Solitary orbital schwannomas are rare, comprising only 1% of orbital neoplasms. We report a case of a 53-year-old woman with unilateral proptosis, radiologically suspected as an intraconal lymphangioma due to fluid levels. Complete surgical excision was performed, and histopathology revealed a cystic schwannoma. This case emphasizes the importance of considering schwannomas in the differential diagnosis of intraconal cystic orbital lesions and highlights the role of histopathological examination in establishing a definitive diagnosis, especially in atypical presentations.
cell therapies
2026-02-26 | The Role of the Obturator Nerve-Acute Nerve Grafting After Resection of a Plexiform Obturator Nerve Schwannoma: A Case Report.
A 45 year-old woman presented with an obturator nerve schwannoma (ONS), which was originally suspected to be a gynecologic malignancy. After thorough workup, the mass and obturator nerve were resected en bloc, and sural nerve grafting was performed. The patient had minimal deficits with return to baseline activities by 7 weeks postoperatively. We guide the reader through the challenging diagnosis of ONS, which may mimic many other intrapelvic masses. The treatment decision of whether to acutely reconstruct the obturator nerve is also discussed, along with implications and functional importance of the nerve in gait and hip motion.
2025-06-24 | Primary culture of inner ear schwannoma.
Vestibulocochlear schwannomas (VS) are benign tumors arising from Schwann cells of the eighth cranial nerve. While VS are commonly located in the internal auditory canal (IAC) or cerebellopontine angle (CPA), a subset occurs within the inner ear, known as inner ear schwannomas (IES). Their location influences management strategies in terms of tumor control, hearing, and vestibular function. Despite the differences between IES and CPA- or IAC-located VS with respect to epidemiology, anatomical pathology, growth behavior, and clinical management, little is known about biological characteristics of IES. We developed a reliable technique for isolation of primary tumor cells from ten IES samples for a standardized application. Cells were isolated, processed and cultured for 28 days. Four samples were further characterized by assessing morphology and stability of schwannoma cells as well as presence of monocytic cells. In all samples, primary cells were successfully cultured and expanded for at least 28 days. Sequential imaging showed characteristic schwannoma cell morphology and a stable growth pattern. While existing protocols had focused on establishing primary cultures of VS in the CPA/IAC so far, this study presents the first successful establishment of primary IES cell cultures from different locations within the inner ear. This work is intended as a proof-of-principle to provide a valuable in vitro model system for investigating biological properties of IES, allowing expansion of small samples of a rare schwannoma subtype and in vitro analysis of new therapeutic approaches.
2025-03-03 | Development of CAR-T cell therapy for NF1/SWN-related nerve sheath tumor treatment.
Neurofibromatosis type 1 (NF1) and schwannomatosis (SWN) are rare genetic disorders with distinct genetic etiologies. Both syndromes are predominantly characterized by the development of multiple benign nerve sheath tumors, which typically arise from cranial/peripheral nerves. The management of NF1/SWN-associated benign nerve sheath tumors pose a substantial clinical challenge. In recent years, immunotherapy has demonstrated significant efficacy in treating various tumors, but its application to NF1/SWN has not been explored. In this study, we first evaluated the feasibility of chimeric antigen receptor (CAR)-T cell therapy for the treatment of benign NF1/SWN-related nerve sheath tumor by analyzing the expression of multiple antigens in 85 tumor samples. Our findings revealed that epidermal growth factor receptor (EGFR/HER1) was highly expressed in most samples, indicating its potential as an ideal target for CAR-T cell therapy. Additionally, TGFβ1 and PDL1, key inhibitory regulators of T cell function within solid tumor microenvironment (TME), were universally overexpressed in these samples, highlighting the immunosuppressive nature of NF1/SWN tumors. To target HER1, we constructed CARs using three distinct scFvs (806, E2 and NEC). All three types of CAR-T cells demonstrated significant tumor-eliminating capability against NF1/SWN tumor cell lines, with 806 CAR-T cells showing the highest efficacy. Considering the immunosuppressive TME, we knocked out TGFBR2 and/or PDCD1 in 806 CAR-T cells using CRISPR/Cas9. Their anti-tumor efficacy was further evaluated using a 3D tumor spheroid model, and the gene-edited 806 CAR-T cells exhibited superior anti-tumor efficacy. In conclusion, we identified HER1 as a target for CAR-T cell therapy in NF1/SWN-related nerve sheath tumors, and developed anti-HER1 CAR-T cells that effectively eliminated NF1/SWN tumor cells, providing a promising therapeutic strategy for patients with these conditions.
2024-10-04 | Excision of large median and ulnar nerve schwannomas: a case series.
Schwannomas are benign, slow-growing tumors originating from Schwann cells in peripheral nerves, commonly affecting the median and ulnar nerves in the forearm and wrist. Surgical excision is the gold standard treatment. This study presents our treatment strategies and outcomes for large-sized ulnar and median nerve schwannomas at the forearm and wrist level. From 2012 to 2023, we enrolled 15 patients with schwannomas over 2 cm in size in the median or ulnar nerve at the forearm and wrist. The study included 12 patients with median nerve schwannomas (mean age: 61 years) and 3 with ulnar nerve schwannomas (mean age: 68 years), with a mean follow-up of 26.9 months. After surgery, all patients with median nerve schwannomas experienced mild, transient numbness affecting fewer than two digits, resolving within six months without motor deficits. Ulnar nerve schwannoma excision caused mild numbness in two patients, also resolving within six months, but all three developed ulnar claw hand deformity, which persisted but improved at the last follow-up. Despite this, patients were satisfied with the surgery due to relief from severe tingling pain. Schwannomas of the median, ulnar, and other peripheral nerves should be removed by carefully dissecting the connecting nerve fascicles to avoid injury to healthy ones. Sensory deficits may occur but are unlikely to significantly impact quality of life. However, in motor-dominant nerves like the ulnar nerve, there is a risk of significant motor deficits that could affect hand function, though not completely. Therefore, thorough preoperative discussion and consideration of interfascicular nerve grafting are essential.
2023-12-16 | Characteristics and Management of Facial Nerve Schwannomas and Hemangiomas.
To characterize facial nerve (FN) schwannomas (FNSs) and FN hemangiomas (FNHs) and their clinical features and management strategies, and to describe the results of cable nerve grafting after FN sectioning during tumor removal. This retrospective study included 84 FNS cases and 42 FNH cases managed between July 1989 and July 2020 at a quaternary referral center for skull base pathology. Clinical details, locations, management, and results of cable nerve grafting at 1 year and during an average period of 3.12 years were evaluated. Sural nerve interpositioning was performed for patients who experienced FN paralysis for less than 1 year and underwent nerve sectioning during tumor removal. FNSs more often involved multiple segments compared with FNHs. The cerebellopontine angle and the mastoid segments were involved in 16 (19.1%) and 34 (40.5%) FNS cases, respectively; however, the cerebellopontine angle and the mastoid segments were involved in 0 and 7 (16.7%) FNH cases, respectively. Sectioned nerves of 99 patients (78.6%) were restored using interposition cable grafting. At the last follow-up evaluation, 56.3% of FNSs and 60.7% of FNHs attained House-Brackmann (HB) grade III. Lower preoperative HB grades were associated with poorer postoperative outcomes. For FNSs, the mean HB grades were 4.13 at 1 year postoperatively and 3.75 at the last follow-up evaluation ( p = 0.001); however, for FNHs, the mean HB grades were 4.04 postoperatively and 3.75 at the last follow-up evaluation. Therefore, extradural coaptation yielded better outcomes. FNSs can occur along any part of the FN along its course, and FNHs are concentrated around the area of geniculate ganglion. The results of cable inter positioning grafts are better in patients with preoperative FN-HB-III or less when compared with higher grades. The outcome of the interpositioning continues to improve even after 1 year in extradural coaptation.
antibodies
2026-07-26 | Hybrid schwannoma-neurofibroma of the upper cervical spine: illustrative case and systematic review of spinal hybrid nerve sheath tumors.
Hybrid peripheral nerve sheath tumors (HPNSTs) are rare benign neoplasms characterized by the coexistence of multiple peripheral nerve sheath lineages, most commonly schwannoma, neurofibroma, and perineurioma. Although increasingly recognized as a distinct pathological entity, spinal involvement remains exceedingly uncommon, posing diagnostic and therapeutic challenges. A systematic review was conducted in accordance with PRISMA guidelines using PubMed, Scopus, and Web of Science from database inception to April 2026. Studies reporting histologically confirmed primary spinal HPNSTs were included. Demographic, clinical, radiological, histopathological, immunohistochemical, and outcome data were extracted and descriptively analyzed. A 25-year-old male presented with a 3-month history of progressive cervical and left shoulder pain accompanied by intermittent numbness. Magnetic resonance imaging revealed a dumbbell-shaped intradural extramedullary lesion at the C1-2 level with foraminal extension and cervical cord compression. Gross total microsurgical resection was achieved through a C1-C2 interlaminar microsurgical approach. Histopathological examination demonstrated a biphasic neoplasm composed of hypercellular schwannomatous nodules and hypocellular neurofibromatous areas within a collagenous and myxoid stroma. Immunohistochemistry revealed diffuse SOX10 positivity within the schwannian component and prominent CD34 reactivity in the neurofibromatous stroma, confirming a hybrid schwannoma-neurofibroma (WHO grade 1). The patient remained neurologically intact without recurrence at 20-month follow-up. Five eligible studies comprising nine spinal HPNST cases were identified. Schwannoma-perineurioma represented the predominant subtype (66.7%), whereas schwannoma-neurofibroma tumors accounted for (33.3%) of cases. Gross total resection was generally associated with favorable outcomes, while recurrence was rarely reported. Spinal HPNSTs are exceptionally rare lesions that remain difficult to diagnose preoperatively because of nonspecific radiological features. Definitive diagnosis relies on histopathological and immunohistochemical confirmation, whereas gross total resection appears to provide favorable outcomes.
2026-06-29 | Ancient Neurilemoma of the Lower Lip Mimicking Malignancy: A case report with Histopathologic Challenge
Neurilemoma, also known as Schwannoma, is a slowgrowing, benign tumor of the nerve sheath that is comparatively rare in the oral cavity. The “Ancient” variant of neurilemomas presents a substantial diagnostic problem, whereas regular neurilemomas exhibit a characteristic biphasic pattern. A 65-year-old woman with a hard, painless lump on his lower lip is the subject of this case report. Significant nuclear atypia and hyperchromasia were found during the initial histopathologic evaluation, which raised the possibility of a spindle cell sarcoma. Nonetheless, a diagnosis of Ancient Neurilemoma was confirmed by the robust S100 positive and lack of mitotic features. This case emphasizes how crucial it is to identify degenerative changes in order to prevent needless, drastic surgery. Bangladesh Journal of Medical Science Vol. 25. Supplementary Issue-2 (2026), Page : S359-S362
2026-06-12 | Medical Therapy for NF2-related Schwannomatosis: A Systematic Review of Current Evidence.
To synthesize the available evidence on medical therapies investigated for the management of NF2-related vestibular schwannomas (VS). Systematic review. Not applicable. NF2-related VS patients. Systemic medical therapies. Tumor control and hearing outcomes. Thirty studies met inclusion criteria: 18 investigated bevacizumab, 5 mTOR inhibitors, 5 tyrosine kinase inhibitors (TKIs), and 2 the vascular endothelial growth factor receptor (VEGFR) vaccine. Bevacizumab demonstrated the most consistent activity, with hearing improvement in up to 61% of patients, stable hearing in up to 84%, and tumor response in up to 60% (Level 4 evidence). Outcomes for mTOR inhibitors were variable, with 1 study stopped for futility, while others reported up to 100% hearing and tumor stability (Level 4 evidence). Five different TKIs showed hearing improvement rates ranging from 17 to 60% and tumor responses of 10 to 23.5% (Level 4 evidence). The VEGFR vaccine appeared safe and immunologically active, with radiologic and hearing improvement in one-third of patients (Level 4 evidence). Bevacizumab remains the most studied and clinically active systemic therapy for NF2-related VS, although evidence is largely nonrandomized. Other systemic therapies have demonstrated variable results in terms of hearing outcomes or tumor control. High-quality prospective and randomized controlled trials are needed to clarify efficacy, durability, and comparative effectiveness.
2026-05-25 | Multiple Peripheral Schwannomas of the Upper Limb – A Case Report
Schwannomas are the most common benign tumors of peripheral nerves, typically presenting as solitary, slow-growing lesions. Multiple schwannomas are rare and may indicate underlying syndromic conditions. We report a 68-year-old woman presenting with multiple upper limb nodules. MRI revealed well-defined lesions with T1 isointensity, T2 hyperintensity, and heterogeneous gadolinium enhancement. Surgical excision confirmed benign schwannoma. MRI is essential for evaluation, but histopathological confirmation remains mandatory.
2026-04-15 | Incidental Intracranial Schwannoma With High 68 Ga-PSMA Uptake on PET/CT.
A 67-year-old man with newly diagnosed prostate adenocarcinoma underwent 68 Ga-PSMA PET/CT for initial staging. In addition to intense focal uptake in the prostate gland consistent with the primary tumor, the scan demonstrated heterogeneous PSMA uptake in the inferior-anterior region of the left temporal lobe adjacent to the left cavernous sinus. Further evaluation of this intracranial lesion with brain MRI raised a differential diagnosis between prostate cancer metastasis and cavernous sinus meningioma. Ultimately, surgical resection and histopathologic analysis established the diagnosis of schwannoma.
other
2025-03-09 | Gene therapy and genome-editing for schwannoma in NF2-related schwannomatosis: current understanding and future directions.
NF2-related schwannomatosis (NF2-SWN) is a rare genetic disorder characterized by bilateral vestibular schwannomas. NF2-SWN represents a difficult management problem with most patients facing substantial morbidity and reduced life expectancy. Gene therapy involves replacing a faulty gene or adding a new gene in an attempt to cure disease or improve the patient's condition. Several studies of gene therapy for NF2-SWN have utilized adeno-associated viral vector serotype-1 (AAV1) to deliver apoptosis-inducing enzyme, the pore-forming protein gasdermin-D, apoptosis-associated speck-like protein containing a caspase recruitment domain, and functional merlin causing schwannoma regression in a xenograft mouse model. These studies support the potential therapeutic efficacy of gene therapy against NF2-SWN. Currently, gene therapy approaches primarily include bystander-killing effect by inducing immune responses, gene replacement or augmentation therapy, and gene knockdown and replacement combination approach through genome-editing technology. Although these gene therapeutic strategies have shown potential in preclinical animal model studies, they still face many specific challenges apart from the traditional challenges in gene therapy, such as immunogenicity, delivery vector, manufacturing, and long-term effects of treatments. In this article, we discuss the current understanding and future directions of gene therapy and genome-editing for schwannoma in NF2-SWN.
2024-07-17 | Phase I/II Study of a Vascular Endothelial Growth Factor Receptor Vaccine in Patients With NF2-Related Schwannomatosis.
The humanized antivascular endothelial growth factor (VEGF) antibody bevacizumab (Bev) is efficacious for the treatment of NF2-related schwannomatosis (NF2), previously known as neurofibromatosis type 2. This study evaluated the safety and efficacy of a VEGF receptor (VEGFR) vaccine containing VEGFR1 and VEGFR2 peptides in patients with NF2 with progressive schwannomas (jRCTs031180184). VEGFR1 and VEGFR2 peptides were injected subcutaneously into infra-axillary and inguinal regions, once a week for 4 weeks and then once a month for 4 months. The primary end point was safety. Secondary end points included tolerability, hearing response, imaging response, and immunologic response. Sixteen patients with NF2 with progressive schwannomas completed treatment and were assessed. No severe vaccine-related adverse events occurred. Among the 13 patients with assessable hearing, word recognition score improved in five patients at 6 months and two at 12 months. Progression of average hearing level of pure tone was 0.168 dB/mo during the year of treatment period, whereas long-term progression was 0.364 dB/mo. Among all 16 patients, a partial response was observed in more than one schwannoma in four (including one in which Bev had not been effective), minor response in 5, and stable disease in 4. Both VEGFR1-specific and VEGFR2-specific cytotoxic T lymphocytes (CTLs) were induced in 11 patients. Two years after vaccination, a radiologic response was achieved in nine of 20 assessable schwannomas. This study demonstrated the safety and preliminary efficacy of VEGFR peptide vaccination in patients with NF2. Memory-induced CTLs after VEGFR vaccination may persistently suppress tumor progression.
2024-02-14 | Gene-targeted therapy for neurofibromatosis and schwannomatosis: The path to clinical trials.
Numerous successful gene-targeted therapies are arising for the treatment of a variety of rare diseases. At the same time, current treatment options for neurofibromatosis 1 and schwannomatosis are limited and do not directly address loss of gene/protein function. In addition, treatments have mostly focused on symptomatic tumors, but have failed to address multisystem involvement in these conditions. Gene-targeted therapies hold promise to address these limitations. However, despite intense interest over decades, multiple preclinical and clinical issues need to be resolved before they become a reality. The optimal approaches to gene-, mRNA-, or protein restoration and to delivery to the appropriate cell types remain elusive. Preclinical models that recapitulate manifestations of neurofibromatosis 1 and schwannomatosis need to be refined. The development of validated assays for measuring neurofibromin and merlin activity in animal and human tissues will be critical for early-stage trials, as will the selection of appropriate patients, based on their individual genotypes and risk/benefit balance. Once the safety of gene-targeted therapy for symptomatic tumors has been established, the possibility of addressing a wide range of symptoms, including non-tumor manifestations, should be explored. As preclinical efforts are underway, it will be essential to educate both clinicians and those affected by neurofibromatosis 1/schwannomatosis about the risks and benefits of gene-targeted therapy for these conditions.
2023-11-01 | Schwannomatosis: a Realm Reborn: year one.
In 2022, an international consensus recommendation revised the nomenclature for neurofibromatosis type 2 ( NF2 ) and Schwannomatosis (SWN), now grouped under the umbrella term Schwannomatosis, and defined new diagnostic criteria. This review describes the molecular criteria for diagnosis of schwannomatosis and the subsequent diagnosis strategy, while setting out the most recent advances in our understanding of the natural history, pathology, molecular biology and treatment of schwannomatosis-associated tumors, including schwannomas, meningiomas and ependymomas. Somatic mutation screening should become a new standard for the diagnosis of NF2 -, LTZTR1 -, SMARCB1 - and 22q-schwannomatosis to discriminate those conditions. Constitutional events in NF2 -Schwannomatosis have a major influence on disease severity and justifiably motivate ongoing efforts on gene replacement therapy research. On the other hand, underlying mechanisms of disease severity and associated pain remain largely unknown in non- NF2 -SWN and independent of germline mutation. Research efforts therefore focus on pain relief in ongoing trials and the discovery of new molecular mechanisms underlying schwannoma tumorigenesis/pain/neuropathies.
2022-05-31 | A Critical Overview of Targeted Therapies for Vestibular Schwannoma.
Vestibular schwannoma (VS) is a benign tumor that originates from Schwann cells in the vestibular component. Surgical treatment for VS has gradually declined over the past few decades, especially for small tumors. Gamma knife radiosurgery has become an accepted treatment for VS, with a high rate of tumor control. For neurofibromatosis type 2 (NF2)-associated VS resistant to radiotherapy, vascular endothelial growth factor (VEGF)-A/VEGF receptor (VEGFR)-targeted therapy (e.g., bevacizumab) may become the first-line therapy. Recently, a clinical trial using a VEGFR1/2 peptide vaccine was also conducted in patients with progressive NF2-associated schwannomas, which was the first immunotherapeutic approach for NF2 patients. Targeted therapies for the gene product of SH3PXD2A-HTRA1 fusion may be effective for sporadic VS. Several protein kinase inhibitors could be supportive to prevent tumor progression because merlin inhibits signaling by tyrosine receptor kinases and the activation of downstream pathways, including the Ras/Raf/MEK/ERK and PI3K/Akt/mTORC1 pathways. Tumor-microenvironment-targeted therapy may be supportive for the mainstays of management. The tumor-associated macrophage is the major component of immunosuppressive cells in schwannomas. Here, we present a critical overview of targeted therapies for VS. Multimodal therapy is required to manage patients with refractory VS.
small molecules
2026-06-17 | Repurposing anti-retroviral drugs to treat NF2-related tumours: a protocol for a phase 0 trial (RETREAT).
To date, there is no proven licensed systemic treatment for neurofibromatosis type 2 (NF2)-related schwannomatosis patients. There is a need for more effective, less toxic treatments and, as a rare disease, NF2 is often overlooked in targeted drug development. Subcutaneous schwannomas of the skin (CS) are common in the NF2 population.This trial involves the repurposing of medications already licensed for HIV-ritonavir and lopinavir (Kaletra and Norvir)-that have been shown to reduce tumour growth by reducing cell proliferation in human schwannoma and meningioma tumour cell cultures. The safety and tolerability of these drugs are already known, so they are safe candidates to trial in NF2 patients. This trial is an open-label, phase 0 design. A maximum of 16 participants diagnosed with NF2-related schwannomatosis will be enrolled in this study. Treatment duration is 30 days, with a 30-day follow-up. Biopsies and blood samples will be collected to assess whether the drugs reach the tumours and to analyse the tumour-cell response. The primary outcome is pharmacodynamic response, defined as a statistically significant decrease in biomarker activity in CS biopsy samples at day 30. The sample size calculation is based on the tissue biomarker response. The study was approved by an Ethics Committee (West of Scotland Research Ethics Service (23/WS/0178)), the Health Research Authority (HRA), the Medicines and Healthcare products Regulatory Authority (MHRA) and each of the participating NHS Trust's Research and Development departments. Following analysis of trial data, the trial results will be written up for publication in a peer-reviewed scientific journal and will be disseminated at conferences. ISRCTN10422213.
2026-04-18 | Decoding the Histomorphological and Multi-Omic Characteristics of Melanotic Schwannoma.
Melanotic schwannoma (MS) is a rare peripheral nerve sheath tumor accompanied by melanin deposition and severe refractory pain. However, its molecular pathogenesis remains unclear. This study aimed to explore the histomorphological, transcriptomic, and proteomic characteristics of MS, and to identify key molecules related to melanin production, pain generation, and targeted therapy. Histomorphological characteristics of MS were observed by Luxol Fast Blue (LFB) staining and hematoxylin and eosin (HE) staining in tumor tissues from 3 MS patients. Combined transcriptomic and proteomic analyses were performed to screen differentially expressed genes and proteins. The expression levels of tyrosinase-related protein 1 (TYRP1), transient receptor potential ankyrin 1 (TRPA1), and Bruton's tyrosine kinase (BTK) were validated by quantitative real-time polymerase chain reaction (qRT-PCR), Western blotting, and immunofluorescence staining. Histomorphological examination revealed typical melanin deposition and prominent compression of adjacent nerve fibers in MS. Transcriptomic and proteomic analyses showed activation of the melanin synthesis pathway and transient receptor potential (TRP) channel-related neuroinflammatory pathway. The expression of TYRP1 and TRPA1 was significantly upregulated, suggesting that these related pathways are associated with melanin production and neuropathic pain in MS. In addition, the expression of BTK, a known molecular target of targeted drugs, was significantly increased, suggesting that BTK inhibitors have potential therapeutic effects on MS. This study delineates the histomorphological features, transcriptomic and proteomic profiles of MS. TYRP1, TRPA1, and BTK are identified as key molecules involved in melanogenesis, pain generation, and targeted therapy, respectively. These findings provide novel insights into the pathogenesis and potential therapeutic strategies for MS.
2026-03-28 | Fimepinostat Promotes Apoptosis and Decreases Cytokine Secretion in NF2-Related Human Schwannoma Cells.
There is no approved drug therapy for schwannomas associated with NF2-related schwannomatosis (NF2-SWN). Neither life-saving surgical resection or radiation are curative and can compound the debilitating neurological effects of the schwannomas. We previously identified fimepinostat, a dual histone deacetylase (HDAC)/phosphoinositide-3 kinase (PI3K) inhibitor, as a promising drug candidate with pro-apoptotic effects on NF2-related schwannomas. This preclinical study used the pharmaceutical formulation of fimepinostat to confirm its efficacy in schwannomas and identify pro-apoptotic signaling pathways. Fimepinostat was tested in human schwannoma model cells, patient-derived primary vestibular and non-vestibular schwannoma cells, and in a sciatic nerve allograft model. The signaling pathways leading to caspase-3-dependent apoptosis were elucidated using immune assays, flow cytometry, imaging, proteome, and acetylome analysis. Acute exposure to fimepinostat led to p21-dependent cell cycle inhibition, upregulation of tumor necrosis factor-related apoptosis-inducing ligand receptor 2 (TRAIL R2), and downregulation of tumor necrosis factor receptor 1 (TNFR1), Yes-associated protein (YAP), and inhibitors of apoptosis. Moreover, fimepinostat downregulated cytokine and chemokine secretion increased by merlin loss in schwannoma cells. Fimepinostat is a promising new drug intervention for NF2-SWN patients with the potential to promote tumor regression.
2026-03-20 | Fluorescence‑Navigated Robotic Resection of Pelvic Schwannoma With Hypogastric Nerve Preservation.
To demonstrate the advantages of combining robotic-assisted surgery with Indocyanine Green (ICG) fluorescence imaging in the excision of pelvic retroperitoneal schwannomas, with a particular focus on nerve preservation. Gynecologic unit of a tertiary center. A 47-year-old female presented with severe pelvic pain, characterized as intermittent throughout the day and not exacerbated by positional changes or activity, with no additional complaints other than occasional urinary frequency.Magnetic resonance imaging revealed a 5 cm schwannoma located adjacent to the right internal iliac vein and the right hypogastric nerve. A stepwise narrated video demonstrates the technique using a combined robotic-assisted surgical approach was employed, enhanced by intravenous administration of 6mg ICG at the initiation of retroperitoneal dissection. Real-time ICG fluorescence enabled clear demarcation of the hypervascular schwannoma [1], distinctly contrasting with the non-fluorescent right hypogastric nerve. This contrast facilitated atraumatic nerve lateralization [2],preserving autonomic function and enabling high surgical precision. A focal area of intense fluorescence within the tumor suggested uncapsulated tissue, prompting meticulous inspection of the excision bed, where residual capsular tissue was identified and fully excised from the deep presacral space without vascular injury. The use of robotic instrumentation allowed safe dissection near dense vascular and neural plexuses [3], particularly the internal iliac vein. The specimen and excised residual capsule were extracted transvaginally via posterior colpotomy using an endoscopic retrieval bag, minimizing abdominal trauma and preventing oncologic spillage. The combined use of robotic-assisted surgery and ICG significantly enhances intraoperative visualization, facilitates precise dissection within complex pelvic anatomy, and supports critical nerve preservation during pelvic schwannoma resection. This approach minimizes vascular injury, reduces blood loss, and enables complete tumor excision, including residual capsular tissue, without increasing surgical morbidity and faster recovery. As the first reported case of its kind, this technique demonstrates substantial clinical efficacy and offers valuable guidance for advanced gynecologic surgical practice. VIDEO ABSTRACT.
2026-02-24 | Robot-assisted thoracoscopic resection of a posterior mediastinal schwannoma adjacent to the intervertebral foramen using Arista™ AH: A case report.
Posterior mediastinal schwannomas near the intervertebral foramen pose surgical challenges owing to their proximity to critical neurovascular structures. A 19-year-old woman presented with an abnormal shadow on a chest radiograph obtained during a routine health checkup. Magnetic resonance imaging revealed a 3.5-cm mass in the right paravertebral region at the T3-T4 level, suggestive of schwannoma. The tumor was resected via 4-port robot-assisted thoracic surgery. Intraoperatively, the intercostal nerve was found to traverse the tumor and was divided. Arista AH was used to control oozing near the intervertebral foramen. The patient recovered uneventfully and was discharged on postoperative day 8. Pathological examination confirmed schwannoma. She has remained recurrence-free for 12 months. Robot-assisted thoracic surgery enables safe resection of tumors adjacent to the intervertebral foramen. Arista™ AH may provide effective hemostasis in anatomically sensitive areas.
proteins
2026-05-25 | Schwannoma of the tongue: a case report and review of literature
Schwannomas are rare slow growing benign tumors arising from Schwann cells lining the nerve sheaths of myelinated nerves. Only 25 to 48% of the cases occur in the head and neck region with only 1% showing an intraoral origin. We present a case of lingual schwannoma in a 20 year old patient who presented with painless mass on right ventral surface of tongue, which was excised. The final histopathology report revealed a schwannoma. We report this case owing to rarity of disease. Tongue Schwannomas are rare, benign tumors with an excellent prognosis. Histology remains the gold standard for its diagnosis and Malignant transformation is rare after complete surgical excision. Schwannomas should be considered in the differential diagnosis whenever a benign looking mass is seen inside the oral cavity.
2026-05-11 | Abducens Nerve Schwannoma: A Case Report on Extremely Rare Cranial Nerve Tumor.
Abducens nerve (CN VI) schwannomas are exceedingly rare intracranial tumors, constituting less than 10% of all primary cranial nerve schwannomas. This report details the case of a 30-year-old woman presenting with diplopia and progressive visual deterioration due to an abducens nerve schwannoma. Imaging revealed an extra-axial lesion involving the right cavernous sinus and encasing the right internal carotid artery. Surgical resection via frontotemporal craniotomy achieved near-total tumor removal, with histopathological analysis confirming a benign schwannoma. Postoperatively, the patient exhibited persistent right lateral rectus palsy as preoperative status but improvement in diplopia. This case underscores the rarity of abducens nerve schwannomas, the challenges in achieving complete resection due to neurovascular adherence, and the importance of careful surgical planning for optimal patient outcomes.
2026-05-08 | Biallelic germline MBD4 mutations predispose to colorectal polyposis, hypermutated AML, and schwannomas.
Biallelic pathogenic variants in the MBD4 gene have recently been associated with an autosomal recessive cancer predisposition syndrome deemed "MBD4-associated neoplasia syndrome (MANS)". Early reports of individuals with MANS highlight the propensity to develop young onset colorectal polyposis and hyper-mutated acute myeloid leukemia (AML). In the following case series, we present four patients with MANS from three families with polyps and AML, as well as additional features previously less described, such as schwannoma and thyroid cancer. This series increases the total number of reported cases by 27%, with the intention of achieving a more robust understanding of the full phenotypic spectrum of MANS.
2026-03-31 | Solitary Axillary Schwannoma Mimicking a Lymph Node: A Case Study
Schwannoma, also known as neurilemmoma or neurinoma, is a benign, encapsulated tumor of the peripheral nerve sheath that arises from Schwann cells. It is typically a slow-growing, solitary, firm, and well-circumscribed lesion, accounting for approximately 8% of all soft tissue masses. Axillary involvement is rare ; therefore, schwannoma should be considered in the differential diagnosis of axillary and peripheral nerve masses to ensure accurate diagnosis and appropriate management. The clinical presentation may remain asymptomatic for years but can include pain, a palpable mass, or neurological symptoms, particularly in larger lesions. Imaging plays a crucial role in diagnosis, especially magnetic resonance imaging (MRI), with ultrasound serving as a useful adjunct. In this study, we report a case of axillary schwannoma presenting as a painful swelling in the left axillary region, with the definitive diagnosis established postoperatively through histopathological examination of the excised specimen.
2026-02-02 | Cystic orbital schwannoma: A surgeon’s surprise
Schwannomas, also known as neurilemmomas, are benign, encapsulated tumors arising from Schwann cells. Solitary orbital schwannomas are rare, comprising only 1% of orbital neoplasms. We report a case of a 53-year-old woman with unilateral proptosis, radiologically suspected as an intraconal lymphangioma due to fluid levels. Complete surgical excision was performed, and histopathology revealed a cystic schwannoma. This case emphasizes the importance of considering schwannomas in the differential diagnosis of intraconal cystic orbital lesions and highlights the role of histopathological examination in establishing a definitive diagnosis, especially in atypical presentations.
cell therapies
2026-02-26 | The Role of the Obturator Nerve-Acute Nerve Grafting After Resection of a Plexiform Obturator Nerve Schwannoma: A Case Report.
A 45 year-old woman presented with an obturator nerve schwannoma (ONS), which was originally suspected to be a gynecologic malignancy. After thorough workup, the mass and obturator nerve were resected en bloc, and sural nerve grafting was performed. The patient had minimal deficits with return to baseline activities by 7 weeks postoperatively. We guide the reader through the challenging diagnosis of ONS, which may mimic many other intrapelvic masses. The treatment decision of whether to acutely reconstruct the obturator nerve is also discussed, along with implications and functional importance of the nerve in gait and hip motion.
2025-06-24 | Primary culture of inner ear schwannoma.
Vestibulocochlear schwannomas (VS) are benign tumors arising from Schwann cells of the eighth cranial nerve. While VS are commonly located in the internal auditory canal (IAC) or cerebellopontine angle (CPA), a subset occurs within the inner ear, known as inner ear schwannomas (IES). Their location influences management strategies in terms of tumor control, hearing, and vestibular function. Despite the differences between IES and CPA- or IAC-located VS with respect to epidemiology, anatomical pathology, growth behavior, and clinical management, little is known about biological characteristics of IES. We developed a reliable technique for isolation of primary tumor cells from ten IES samples for a standardized application. Cells were isolated, processed and cultured for 28 days. Four samples were further characterized by assessing morphology and stability of schwannoma cells as well as presence of monocytic cells. In all samples, primary cells were successfully cultured and expanded for at least 28 days. Sequential imaging showed characteristic schwannoma cell morphology and a stable growth pattern. While existing protocols had focused on establishing primary cultures of VS in the CPA/IAC so far, this study presents the first successful establishment of primary IES cell cultures from different locations within the inner ear. This work is intended as a proof-of-principle to provide a valuable in vitro model system for investigating biological properties of IES, allowing expansion of small samples of a rare schwannoma subtype and in vitro analysis of new therapeutic approaches.
2025-03-03 | Development of CAR-T cell therapy for NF1/SWN-related nerve sheath tumor treatment.
Neurofibromatosis type 1 (NF1) and schwannomatosis (SWN) are rare genetic disorders with distinct genetic etiologies. Both syndromes are predominantly characterized by the development of multiple benign nerve sheath tumors, which typically arise from cranial/peripheral nerves. The management of NF1/SWN-associated benign nerve sheath tumors pose a substantial clinical challenge. In recent years, immunotherapy has demonstrated significant efficacy in treating various tumors, but its application to NF1/SWN has not been explored. In this study, we first evaluated the feasibility of chimeric antigen receptor (CAR)-T cell therapy for the treatment of benign NF1/SWN-related nerve sheath tumor by analyzing the expression of multiple antigens in 85 tumor samples. Our findings revealed that epidermal growth factor receptor (EGFR/HER1) was highly expressed in most samples, indicating its potential as an ideal target for CAR-T cell therapy. Additionally, TGFβ1 and PDL1, key inhibitory regulators of T cell function within solid tumor microenvironment (TME), were universally overexpressed in these samples, highlighting the immunosuppressive nature of NF1/SWN tumors. To target HER1, we constructed CARs using three distinct scFvs (806, E2 and NEC). All three types of CAR-T cells demonstrated significant tumor-eliminating capability against NF1/SWN tumor cell lines, with 806 CAR-T cells showing the highest efficacy. Considering the immunosuppressive TME, we knocked out TGFBR2 and/or PDCD1 in 806 CAR-T cells using CRISPR/Cas9. Their anti-tumor efficacy was further evaluated using a 3D tumor spheroid model, and the gene-edited 806 CAR-T cells exhibited superior anti-tumor efficacy. In conclusion, we identified HER1 as a target for CAR-T cell therapy in NF1/SWN-related nerve sheath tumors, and developed anti-HER1 CAR-T cells that effectively eliminated NF1/SWN tumor cells, providing a promising therapeutic strategy for patients with these conditions.
2024-10-04 | Excision of large median and ulnar nerve schwannomas: a case series.
Schwannomas are benign, slow-growing tumors originating from Schwann cells in peripheral nerves, commonly affecting the median and ulnar nerves in the forearm and wrist. Surgical excision is the gold standard treatment. This study presents our treatment strategies and outcomes for large-sized ulnar and median nerve schwannomas at the forearm and wrist level. From 2012 to 2023, we enrolled 15 patients with schwannomas over 2 cm in size in the median or ulnar nerve at the forearm and wrist. The study included 12 patients with median nerve schwannomas (mean age: 61 years) and 3 with ulnar nerve schwannomas (mean age: 68 years), with a mean follow-up of 26.9 months. After surgery, all patients with median nerve schwannomas experienced mild, transient numbness affecting fewer than two digits, resolving within six months without motor deficits. Ulnar nerve schwannoma excision caused mild numbness in two patients, also resolving within six months, but all three developed ulnar claw hand deformity, which persisted but improved at the last follow-up. Despite this, patients were satisfied with the surgery due to relief from severe tingling pain. Schwannomas of the median, ulnar, and other peripheral nerves should be removed by carefully dissecting the connecting nerve fascicles to avoid injury to healthy ones. Sensory deficits may occur but are unlikely to significantly impact quality of life. However, in motor-dominant nerves like the ulnar nerve, there is a risk of significant motor deficits that could affect hand function, though not completely. Therefore, thorough preoperative discussion and consideration of interfascicular nerve grafting are essential.
2023-12-16 | Characteristics and Management of Facial Nerve Schwannomas and Hemangiomas.
To characterize facial nerve (FN) schwannomas (FNSs) and FN hemangiomas (FNHs) and their clinical features and management strategies, and to describe the results of cable nerve grafting after FN sectioning during tumor removal. This retrospective study included 84 FNS cases and 42 FNH cases managed between July 1989 and July 2020 at a quaternary referral center for skull base pathology. Clinical details, locations, management, and results of cable nerve grafting at 1 year and during an average period of 3.12 years were evaluated. Sural nerve interpositioning was performed for patients who experienced FN paralysis for less than 1 year and underwent nerve sectioning during tumor removal. FNSs more often involved multiple segments compared with FNHs. The cerebellopontine angle and the mastoid segments were involved in 16 (19.1%) and 34 (40.5%) FNS cases, respectively; however, the cerebellopontine angle and the mastoid segments were involved in 0 and 7 (16.7%) FNH cases, respectively. Sectioned nerves of 99 patients (78.6%) were restored using interposition cable grafting. At the last follow-up evaluation, 56.3% of FNSs and 60.7% of FNHs attained House-Brackmann (HB) grade III. Lower preoperative HB grades were associated with poorer postoperative outcomes. For FNSs, the mean HB grades were 4.13 at 1 year postoperatively and 3.75 at the last follow-up evaluation ( p = 0.001); however, for FNHs, the mean HB grades were 4.04 postoperatively and 3.75 at the last follow-up evaluation. Therefore, extradural coaptation yielded better outcomes. FNSs can occur along any part of the FN along its course, and FNHs are concentrated around the area of geniculate ganglion. The results of cable inter positioning grafts are better in patients with preoperative FN-HB-III or less when compared with higher grades. The outcome of the interpositioning continues to improve even after 1 year in extradural coaptation.
antibodies
2026-07-26 | Hybrid schwannoma-neurofibroma of the upper cervical spine: illustrative case and systematic review of spinal hybrid nerve sheath tumors.
Hybrid peripheral nerve sheath tumors (HPNSTs) are rare benign neoplasms characterized by the coexistence of multiple peripheral nerve sheath lineages, most commonly schwannoma, neurofibroma, and perineurioma. Although increasingly recognized as a distinct pathological entity, spinal involvement remains exceedingly uncommon, posing diagnostic and therapeutic challenges. A systematic review was conducted in accordance with PRISMA guidelines using PubMed, Scopus, and Web of Science from database inception to April 2026. Studies reporting histologically confirmed primary spinal HPNSTs were included. Demographic, clinical, radiological, histopathological, immunohistochemical, and outcome data were extracted and descriptively analyzed. A 25-year-old male presented with a 3-month history of progressive cervical and left shoulder pain accompanied by intermittent numbness. Magnetic resonance imaging revealed a dumbbell-shaped intradural extramedullary lesion at the C1-2 level with foraminal extension and cervical cord compression. Gross total microsurgical resection was achieved through a C1-C2 interlaminar microsurgical approach. Histopathological examination demonstrated a biphasic neoplasm composed of hypercellular schwannomatous nodules and hypocellular neurofibromatous areas within a collagenous and myxoid stroma. Immunohistochemistry revealed diffuse SOX10 positivity within the schwannian component and prominent CD34 reactivity in the neurofibromatous stroma, confirming a hybrid schwannoma-neurofibroma (WHO grade 1). The patient remained neurologically intact without recurrence at 20-month follow-up. Five eligible studies comprising nine spinal HPNST cases were identified. Schwannoma-perineurioma represented the predominant subtype (66.7%), whereas schwannoma-neurofibroma tumors accounted for (33.3%) of cases. Gross total resection was generally associated with favorable outcomes, while recurrence was rarely reported. Spinal HPNSTs are exceptionally rare lesions that remain difficult to diagnose preoperatively because of nonspecific radiological features. Definitive diagnosis relies on histopathological and immunohistochemical confirmation, whereas gross total resection appears to provide favorable outcomes.
2026-06-29 | Ancient Neurilemoma of the Lower Lip Mimicking Malignancy: A case report with Histopathologic Challenge
Neurilemoma, also known as Schwannoma, is a slowgrowing, benign tumor of the nerve sheath that is comparatively rare in the oral cavity. The “Ancient” variant of neurilemomas presents a substantial diagnostic problem, whereas regular neurilemomas exhibit a characteristic biphasic pattern. A 65-year-old woman with a hard, painless lump on his lower lip is the subject of this case report. Significant nuclear atypia and hyperchromasia were found during the initial histopathologic evaluation, which raised the possibility of a spindle cell sarcoma. Nonetheless, a diagnosis of Ancient Neurilemoma was confirmed by the robust S100 positive and lack of mitotic features. This case emphasizes how crucial it is to identify degenerative changes in order to prevent needless, drastic surgery. Bangladesh Journal of Medical Science Vol. 25. Supplementary Issue-2 (2026), Page : S359-S362
2026-06-12 | Medical Therapy for NF2-related Schwannomatosis: A Systematic Review of Current Evidence.
To synthesize the available evidence on medical therapies investigated for the management of NF2-related vestibular schwannomas (VS). Systematic review. Not applicable. NF2-related VS patients. Systemic medical therapies. Tumor control and hearing outcomes. Thirty studies met inclusion criteria: 18 investigated bevacizumab, 5 mTOR inhibitors, 5 tyrosine kinase inhibitors (TKIs), and 2 the vascular endothelial growth factor receptor (VEGFR) vaccine. Bevacizumab demonstrated the most consistent activity, with hearing improvement in up to 61% of patients, stable hearing in up to 84%, and tumor response in up to 60% (Level 4 evidence). Outcomes for mTOR inhibitors were variable, with 1 study stopped for futility, while others reported up to 100% hearing and tumor stability (Level 4 evidence). Five different TKIs showed hearing improvement rates ranging from 17 to 60% and tumor responses of 10 to 23.5% (Level 4 evidence). The VEGFR vaccine appeared safe and immunologically active, with radiologic and hearing improvement in one-third of patients (Level 4 evidence). Bevacizumab remains the most studied and clinically active systemic therapy for NF2-related VS, although evidence is largely nonrandomized. Other systemic therapies have demonstrated variable results in terms of hearing outcomes or tumor control. High-quality prospective and randomized controlled trials are needed to clarify efficacy, durability, and comparative effectiveness.
2026-05-25 | Multiple Peripheral Schwannomas of the Upper Limb – A Case Report
Schwannomas are the most common benign tumors of peripheral nerves, typically presenting as solitary, slow-growing lesions. Multiple schwannomas are rare and may indicate underlying syndromic conditions. We report a 68-year-old woman presenting with multiple upper limb nodules. MRI revealed well-defined lesions with T1 isointensity, T2 hyperintensity, and heterogeneous gadolinium enhancement. Surgical excision confirmed benign schwannoma. MRI is essential for evaluation, but histopathological confirmation remains mandatory.
2026-04-15 | Incidental Intracranial Schwannoma With High 68 Ga-PSMA Uptake on PET/CT.
A 67-year-old man with newly diagnosed prostate adenocarcinoma underwent 68 Ga-PSMA PET/CT for initial staging. In addition to intense focal uptake in the prostate gland consistent with the primary tumor, the scan demonstrated heterogeneous PSMA uptake in the inferior-anterior region of the left temporal lobe adjacent to the left cavernous sinus. Further evaluation of this intracranial lesion with brain MRI raised a differential diagnosis between prostate cancer metastasis and cavernous sinus meningioma. Ultimately, surgical resection and histopathologic analysis established the diagnosis of schwannoma.
other
2025-03-09 | Gene therapy and genome-editing for schwannoma in NF2-related schwannomatosis: current understanding and future directions.
NF2-related schwannomatosis (NF2-SWN) is a rare genetic disorder characterized by bilateral vestibular schwannomas. NF2-SWN represents a difficult management problem with most patients facing substantial morbidity and reduced life expectancy. Gene therapy involves replacing a faulty gene or adding a new gene in an attempt to cure disease or improve the patient's condition. Several studies of gene therapy for NF2-SWN have utilized adeno-associated viral vector serotype-1 (AAV1) to deliver apoptosis-inducing enzyme, the pore-forming protein gasdermin-D, apoptosis-associated speck-like protein containing a caspase recruitment domain, and functional merlin causing schwannoma regression in a xenograft mouse model. These studies support the potential therapeutic efficacy of gene therapy against NF2-SWN. Currently, gene therapy approaches primarily include bystander-killing effect by inducing immune responses, gene replacement or augmentation therapy, and gene knockdown and replacement combination approach through genome-editing technology. Although these gene therapeutic strategies have shown potential in preclinical animal model studies, they still face many specific challenges apart from the traditional challenges in gene therapy, such as immunogenicity, delivery vector, manufacturing, and long-term effects of treatments. In this article, we discuss the current understanding and future directions of gene therapy and genome-editing for schwannoma in NF2-SWN.
2024-07-17 | Phase I/II Study of a Vascular Endothelial Growth Factor Receptor Vaccine in Patients With NF2-Related Schwannomatosis.
The humanized antivascular endothelial growth factor (VEGF) antibody bevacizumab (Bev) is efficacious for the treatment of NF2-related schwannomatosis (NF2), previously known as neurofibromatosis type 2. This study evaluated the safety and efficacy of a VEGF receptor (VEGFR) vaccine containing VEGFR1 and VEGFR2 peptides in patients with NF2 with progressive schwannomas (jRCTs031180184). VEGFR1 and VEGFR2 peptides were injected subcutaneously into infra-axillary and inguinal regions, once a week for 4 weeks and then once a month for 4 months. The primary end point was safety. Secondary end points included tolerability, hearing response, imaging response, and immunologic response. Sixteen patients with NF2 with progressive schwannomas completed treatment and were assessed. No severe vaccine-related adverse events occurred. Among the 13 patients with assessable hearing, word recognition score improved in five patients at 6 months and two at 12 months. Progression of average hearing level of pure tone was 0.168 dB/mo during the year of treatment period, whereas long-term progression was 0.364 dB/mo. Among all 16 patients, a partial response was observed in more than one schwannoma in four (including one in which Bev had not been effective), minor response in 5, and stable disease in 4. Both VEGFR1-specific and VEGFR2-specific cytotoxic T lymphocytes (CTLs) were induced in 11 patients. Two years after vaccination, a radiologic response was achieved in nine of 20 assessable schwannomas. This study demonstrated the safety and preliminary efficacy of VEGFR peptide vaccination in patients with NF2. Memory-induced CTLs after VEGFR vaccination may persistently suppress tumor progression.
2024-02-14 | Gene-targeted therapy for neurofibromatosis and schwannomatosis: The path to clinical trials.
Numerous successful gene-targeted therapies are arising for the treatment of a variety of rare diseases. At the same time, current treatment options for neurofibromatosis 1 and schwannomatosis are limited and do not directly address loss of gene/protein function. In addition, treatments have mostly focused on symptomatic tumors, but have failed to address multisystem involvement in these conditions. Gene-targeted therapies hold promise to address these limitations. However, despite intense interest over decades, multiple preclinical and clinical issues need to be resolved before they become a reality. The optimal approaches to gene-, mRNA-, or protein restoration and to delivery to the appropriate cell types remain elusive. Preclinical models that recapitulate manifestations of neurofibromatosis 1 and schwannomatosis need to be refined. The development of validated assays for measuring neurofibromin and merlin activity in animal and human tissues will be critical for early-stage trials, as will the selection of appropriate patients, based on their individual genotypes and risk/benefit balance. Once the safety of gene-targeted therapy for symptomatic tumors has been established, the possibility of addressing a wide range of symptoms, including non-tumor manifestations, should be explored. As preclinical efforts are underway, it will be essential to educate both clinicians and those affected by neurofibromatosis 1/schwannomatosis about the risks and benefits of gene-targeted therapy for these conditions.
2023-11-01 | Schwannomatosis: a Realm Reborn: year one.
In 2022, an international consensus recommendation revised the nomenclature for neurofibromatosis type 2 ( NF2 ) and Schwannomatosis (SWN), now grouped under the umbrella term Schwannomatosis, and defined new diagnostic criteria. This review describes the molecular criteria for diagnosis of schwannomatosis and the subsequent diagnosis strategy, while setting out the most recent advances in our understanding of the natural history, pathology, molecular biology and treatment of schwannomatosis-associated tumors, including schwannomas, meningiomas and ependymomas. Somatic mutation screening should become a new standard for the diagnosis of NF2 -, LTZTR1 -, SMARCB1 - and 22q-schwannomatosis to discriminate those conditions. Constitutional events in NF2 -Schwannomatosis have a major influence on disease severity and justifiably motivate ongoing efforts on gene replacement therapy research. On the other hand, underlying mechanisms of disease severity and associated pain remain largely unknown in non- NF2 -SWN and independent of germline mutation. Research efforts therefore focus on pain relief in ongoing trials and the discovery of new molecular mechanisms underlying schwannoma tumorigenesis/pain/neuropathies.
2022-05-31 | A Critical Overview of Targeted Therapies for Vestibular Schwannoma.
Vestibular schwannoma (VS) is a benign tumor that originates from Schwann cells in the vestibular component. Surgical treatment for VS has gradually declined over the past few decades, especially for small tumors. Gamma knife radiosurgery has become an accepted treatment for VS, with a high rate of tumor control. For neurofibromatosis type 2 (NF2)-associated VS resistant to radiotherapy, vascular endothelial growth factor (VEGF)-A/VEGF receptor (VEGFR)-targeted therapy (e.g., bevacizumab) may become the first-line therapy. Recently, a clinical trial using a VEGFR1/2 peptide vaccine was also conducted in patients with progressive NF2-associated schwannomas, which was the first immunotherapeutic approach for NF2 patients. Targeted therapies for the gene product of SH3PXD2A-HTRA1 fusion may be effective for sporadic VS. Several protein kinase inhibitors could be supportive to prevent tumor progression because merlin inhibits signaling by tyrosine receptor kinases and the activation of downstream pathways, including the Ras/Raf/MEK/ERK and PI3K/Akt/mTORC1 pathways. Tumor-microenvironment-targeted therapy may be supportive for the mainstays of management. The tumor-associated macrophage is the major component of immunosuppressive cells in schwannomas. Here, we present a critical overview of targeted therapies for VS. Multimodal therapy is required to manage patients with refractory VS.
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3 orphan drug designations for Benign schwannoma.
3 orphan drug designations for Benign schwannoma.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
Salmonella enterica, subsp. enterica, serovar Typhimurium, strain YS1646, live | other | EMA | 2022-07-18 | — | Premier Research Group S.L. |
Live attenuated Salmonella enterica Serovar Typhimurium (S. Typhimurium) | gene therapies | FDA | 2022-05-10 | — | Mulberry Biotherapeutics, Inc. |
N-hydroxy-4-(3-methyl-2-(S)phenyl-butyrylamino)benzamide | small molecules | EMA | 2012-06-06 | — | Propharma Group The Netherlands B.V. |
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