[Interdisciplinary Treatment Of Tumorous And Tumour-Like Lesions Of Peripheral Nerves]. / Interdisziplinäre Behandlung von Raumforderungen in Assoziation zu peripheren Nerven: Tumore und tumorähnliche Läsionen.

Tumorous or tumour-like lesions of peripheral nerves are generally rare, heterogeneous and challenging to diagnose and treat. They may become apparent by a palpable swelling (lump) near nerves, sensory and/or motor deficits, pain to touch or neuropathic pain. In 91% of cases, tumours are benign. The differentiation of entities and their characteristics as well as a function-preserving resection strategy are highly relevant. Misdiagnosis and inadequate treatment can lead to severe deficits and pain syndromes. Benign tumours include schwannomas and neurofibromas, which can occur sporadically but can also be associated with neurogenetic tumour disposition syndromes if they occur more frequently. Rarer benign nerve tumours include perineuriomas, lipomas, aggressive fibrosis (desmoid tumours), paragangliomas and haemangiomas. Ganglion cysts are described as tumour-like lesions. The association of nerve tumours with neurogenetic syndromes and the correct classification of potentially malignant lesions such as MPNST (malignant peripheral nerve sheath tumour) or intermediate stages such as ANNUBPs (atypical neurofibromatous neoplasms with unknown biological potential) pose particular challenges. Interdisciplinarity is highly relevant for clinical treatment and a correct diagnosis. The aim of our work is to provide an overview of the relevant entities, diagnostic evaluation and contemporary treatment strategies based on the current data situation and taking into account the recently published interdisciplinary AWMF S2k guideline "Diagnosis and Treatment of Peripheral Nerve Tumours".

The impact of SARS-Covid-19 pandemic on peripheral nerve surgery - A single centre report.

OBJECTIVE: SARS-Cov-19 pandemic totally changed daily routine work in German hospitals. As hospital capacity was reduced, many surgeries were postponed or even cancelled. On March 25th 2020 the German Society of Neurosurgery (DGNC) published a statement in which urgent non-elective surgeries were defined for each neurosurgical domain, whereas elective interventions were deferred. The present work examines the impact of these Covid strategies focusing on patients with peripheral lesions who were conducted to our department during this period of time. METHODS: All patients who underwent any peripheral nerve surgery at our department from January 2018 until December 2022, were included. The complete range of surgeries including peripheral nerve lesions was examined encompassing compression syndromes, traumatic lesions of brachial plexus, traumatic lesions and tumors of single peripheral nerves. The numbers of surgical procedures were compared before, during and after pandemic. Pearson correlation coefficient was analysed. RESULTS: From 2018 to 2022 the total number of surgical procedures involving peripheral nerves included 2422 procedures. Compression syndromes made up the largest proportion (1433 operations, 59%), followed by peripheral nerve lesions (445 operations, 18%), peripheral nerve tumors (344 operations, 14%) and lesions of the brachial plexus (142 operations, 6%). The average was 40,5 interventions per month, the range was 7-63. Two declines in the number of peripheral nerve surgeries were noted during this period. The first was in April and May 2020 with an average drop of 65% and 41% respectively. In these months the average number of operations was 37. The second decrease was from October 2021 until January 2022, where number of surgeries was reduced by 16%, 36%, 83% and 18% with an average number of 50 operations. Both declines showed a significant and strong correlation with the lower number of compression syndrome treatments (r = 0.952, p < 0.001 and r = 0.968, p < 0.001), while no drop and no significant correlation was found in the treatment of traumatic peripheral nerve injuries (p = 0.769, r = 0.095 and p = 0.243, r = 0.366) and traumatic brachial plexus injuries (p = 0.787, r = 0.088 and p = 0.780, r = 0.09). A weak significant correlation was seen in the treatment numbers of peripheral nerve tumors (p = 0.017, r = 0.672 and p = 0.015, r = 0.67). CONCLUSION: Covid-19 pandemic lead to a significant decrease in the number of nerve decompressions, since, according to the German Society of Neurosurgery, those were considered as elective surgeries.

When biopsy goes wrong: a case series of misdiagnoses and complications from biopsies of masses of unknown origin potentially originating from a peripheral nerve.

OBJECTIVE: Biopsies of peripheral nerve tumors (PNTs) are often used to plan an efficient treatment strategy. However, performing a biopsy is controversial when the mass is likely to be a benign PNT (BPNT). The aim of this study was to evaluate the side effects of biopsies in patients with potential PNTs. METHODS: A retrospective and cross-sectional study was conducted on 24 patients who underwent biopsy of a mass of unknown origin potentially originating from a peripheral nerve (MUOPON), performed in nonspecialty services, and who were later referred to the authors' service for resection of their lesion between January 2005 and December 2022. The patients were evaluated for pain score, presence of a motor or sensory deficit, biopsy diagnosis, and definitive histopathological postsurgical diagnosis. RESULTS: The location of the tumor was supraclavicular in 7 (29.2%) patients, in the axillary region in 3 (12.5%), in the upper limb in 7 (29.2%), and in the lower limb in 7 (29.2%). Twenty-one (87.5%) patients were evaluated by MRI before biopsy, and 3 (12.5%) underwent ultrasound. One patient did not have an examination before the procedure. Based on the biopsy findings, 12 (50%) analyses had an inconclusive histopathological result. The preexisting pain worsened, as measured 1 week after biopsy, in all patients and had remained unchanged at the first evaluation by the authors (median 3 months, range 2-4 months). In 1 case, the open biopsy had to be interrupted because the patient experienced excruciating pain. Four (16.7%) patients developed motor deficits. Subsequent surgery was hampered by scar formation and intratumoral hemorrhage in 5 (20.8%) patients. The initial diagnosis obtained by biopsy differed from the final histopathological diagnosis in all patients, of whom 21 (87.5%) had BPNTs, 2 (8.3%) malignant peripheral nerve sheath tumors, and 1 (4.2%) an ancient schwannoma. CONCLUSIONS: Biopsies of PNTs are controversial and may result in misdiagnosis, neuropathic pain, or neurological deficit due to axonal damage, and they may also hinder microsurgical resection when if performed when not indicated. Indications for biopsy of an MUOPON must be carefully considered, especially if BPNT is a possible diagnosis.

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

OBJECTIVES: To compare MRI features of sporadic and neurofibromatosis syndrome-related localized schwannomas and neurofibromas. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Complete Response to 177 Lu-DOTATATE PRRT in a 9-Year-Old Child With Metastatic Carotid Body Paraganglioma.

ABSTRACT: We present a case involving a 9-year-old boy diagnosed with metastatic carotid body paraganglioma. The metastases were detected in cervical lymph nodes and lungs using 68 Ga-DOTANOC PET/CT imaging. The patient received peptide receptor radionuclide therapy with 177 Lu-DOTATATE. Following 3 treatment cycles, a significant improvement was observed in the metastatic lesions. After 4 cycles, the patient achieved a complete response, with a cumulative administered activity of 16.65 GBq during the therapy. This case underscores the effectiveness of using 177 Lu-DOTATATE in managing metastatic carotid body paraganglioma, offering promising results in terms of tumor regression and overall therapeutic response.

Thoracic Outlet Syndrome Caused by a Primary Tumour in the Brachial Plexus.

Thoracic outlet syndrome (TOS) caused by a primary brachial plexus tumour is very rare. A male politician in his 40s presented with numbness, left limb pain and positive Wright and Roos test results. Magnetic resonance imaging (MRI) revealed a tumour located just below the clavicle, compressing the subclavian artery during left arm elevation. Despite concerns regarding postoperative nerve deficits, surgery was performed because of worsening symptoms during the election campaigns. The pathology report revealed a schwannoma. Few reports have described TOS caused by primary tumours of the brachial plexus. While the decision to perform surgery for primary tumours of the brachial plexus requires careful consideration, surgery may be indicated in cases where the tumour location causes such symptoms. Level of Evidence: Level V (Therapeutic).

A case report of giant malignant schwannoma of the sciatic nerve associated with neurofibromatosis-1: A CARE-compliant article.

RATIONALE: Neurofibromatosis type 1 (NF1) is an autosomal dominant neurocutaneous syndrome that causes multiple central and peripheral nerve sheath tumors. People with NF1 have a 10% chance of developing malignant peripheral nerve sheath tumors (MPNSTs). Here we report a unique instance of a malignant schwannoma that has remained free of metastasis since its initial removal a decade ago. The malign schwannoma has been infrequently documented in the literature, and remarkably, no instances of such an extensive postoperative time without metastases have ever been described. PATIENT CONCERNS: A 46-year-old male patient with NF had multiple neurofibromas in different parts of his body, underwent surgery about 10 years ago (2013), and was diagnosed histopathologically as MPNST. DIAGNOSES: He was admitted to our institution with a recurrent mass in the posterior third of the proximal thigh and severe pain radiating to the left lower extremity, which presented as sciatic pain (2021). A magnetic resonance imaging and fluorodeoxyglucose-positron emission tomography examination revealed that the tumor was likely malignant. INTERVENTIONS: Surgical excision was performed. OUTCOME: A 10-year follow-up revealed no metastases or neurologic impairment. LESSONS: When articles about benign schwannomas are placed in a separate category, little is written about NF-1-related malignant schwannomas of the sciatic nerve. MPNSTs are high-grade, aggressive sarcomas with a high risk of local recurrence (40%-65%) and metastasis to other body parts. Therefore, among the various benign peripheral nerve sheath tumors in NF-1 patients, the diagnosis of MPNST is crucial.Orthopedic surgeons should be aware that neurofibromas in NF-1 have a significant risk of developing MPNSTs. This study reports the successful treatment of a giant malignant sciatic nerve schwannoma with a long follow-up period without metastasis.

Management of Central and Peripheral Nervous System Tumors in Patients with Neurofibromatosis.

Neurofibromatosis type I (NF1), neurofibromatosis type 2 (NF2), and schwannomatosis represent a diverse group of genetic tumor predisposition syndromes with a shared feature of tumors affecting the peripheral nerve sheaths. PURPOSE OF REVIEW: Many advancements have been made in understanding the biologic underpinnings of these conditions, and in 2016 the first drug was approved by the FDA to treat pediatric symptomatic unresectable plexiform neurofibromas. RECENT FINDINGS: Mek inhibitors have provided a much-needed therapeutic avenue for NF1 patients with unresectable plexiform neurofibromas (PN), both for reduction of tumor bulk and for improvement in symptoms. Selumetinib is the first FDA approved drug for PN, but is only approved for children. Some research suggests that alternative Mek inhibitors and other mixed tyrosine kinase inhibitors may have better efficacy in adults. Vascular endothelial growth factor (VEGF) inhibitor bevacizumab can prolong hearing and delay the need for surgery in NF2 patients with bilateral vestibular schwannomas. This article provides an update regarding considerations and approaches when treating the tumors associated with the neurofibromatoses (NF), including risk and prognosis metrics, clinical trial results, surgical techniques, and radiation therapy recommendations.

Surgery of Schwannoma in the upper limb - sensitivity and specificity of preoperative magnetic resonance imaging and relation between tumour size and symptoms.

BACKGROUND: Benign peripheral nerve tumours consist of different types, most commonly Schwannomas. Preoperative Magnetic Resonance Imaging (MRI) is commonly performed before surgery and Pathoanatomical Diagnosis (PAD) confirms the diagnosis. Our aims were to study the utility of MRI and the relation between tumour size and symptoms. METHODS: Retrospectively, patients, surgically treated for benign nerve tumours between 2008 and 2019, were identified and preoperative MRI, with measurement of tumour size, PAD, symptoms, peroperative details, and symptomatic outcomes of surgery, were analysed. RESULTS: The sensitivity and specificity to correctly identify Schwannomas with preoperative MRI were 85% and 50%, respectively, based on 30 Schwannomas and nine neurofibromas that were identified. Tumour size did not affect the presence of preoperative symptoms, but patients with sensory dysfunction at last follow-up had larger Schwannomas (p < 0.05). Symptoms as a palpable tumour, paraesthesia and pain improved by surgical excision (p < 0.001, p < 0.001 and p < 0.012, respectively), but sensory and motor dysfunction were common postoperatively. No malignant peripheral nerve sheath tumours (MPNST) were found. Using a surgical microscope, instead of only loop magnification, lowered the risk of perioperative nerve injuries (p < 0.05), but did not further diminish postoperative symptoms. CONCLUSIONS: Early and accurate diagnosis of Schwannomas is valuable for adequate presurgical preparation and prompt surgical intervention. Preoperative examination with MRI has a high sensitivity, but low specificity; although recent advancement in MRI technology indicates improvement in diagnostic precision. Surgical excision is preferably performed early in conjunction with symptomatic debut to improve outcome.

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.

Plexiform neurofibroma (Hamartoma) of the median nerve: A two-case report.

Plexiform neurofibroma is a benign peripheral nerve-sheath tumor, rarely involving major nerves of the extremities. In the literature, there are no clear treatment strategies for plexiform neurofibroma of major peripheral nerves. Our experience encountered two patients with plexiform neurofibroma of the median nerve, presenting with a palmar mass and symptoms of carpal tunnel compression. Preoperatively, plexiform neurofibroma was diagnosed on MRI and clinical examination. Both patients also experienced significant neurological deterioration, with finger numbness and increased nerve/tumor size. Potential malignant transformation was also considered. For these reasons, resection of the involved area of the nerve and repair were indicated. In both patients, intraoperative pathological diagnosis was plexiform neurofibroma. The 45-year-old male patient refused further surgery after carpal tunnel release, which was performed under axillary block. One year postoperatively, nerve compression symptoms decreased moderately. In the other patient, a 7-year-old boy, a significantly enlarged area of the median nerve was resected, and neurorrhaphy was performed. One year postoperatively, median nerve motor-sensory functions recovered completely. Four years postoperatively, no enlargement of the residual tumor was observed.

Cytoplasmic HIF-2α as tissue biomarker to identify metastatic sympathetic paraganglioma.

Pheochromocytomas (PCCs) and paragangliomas (PGLs) are rare neuroendocrine tumors. PGLs can further be divided into sympathetic (sPGLs) and head-and-neck (HN-PGLs). There are virtually no treatment options, and no cure, for metastatic PCCs and PGLs (PPGLs). Here, we composed a tissue microarray (TMA) consisting of 149 PPGLs, reflecting clinical features, presenting as a useful resource. Mutations in the pseudohypoxic marker HIF-2α correlate to an aggressive tumor phenotype. We show that HIF-2α localized to the cytoplasm in PPGLs. This subcompartmentalized protein expression differed between tumor subtypes, and strongly correlated to proliferation. Half of all sPGLs were metastatic at time of diagnosis. Cytoplasmic HIF-2α was strongly expressed in metastatic sPGLs and predicted poor outcome in this subgroup. We propose that higher cytoplasmic HIF-2α expression could serve as a useful clinical marker to differentiate paragangliomas from pheochromocytomas, and may help predict outcome in sPGL patients.

7T for clinical imaging of benign peripheral nerve tumors: preliminary results.

PURPOSE: MRI has become an essential diagnostic imaging modality for peripheral nerve pathology. Early MR imaging for peripheral nerve depended on inferred nerve involvement by visualizing downstream effects such as denervation muscular atrophy; improvements in MRI technology have made possible direct visualization of the nerves. In this paper, we share our early clinical experience with 7T for benign neurogenic tumors. MATERIALS: Patients with benign neurogenic tumors and 7T MRI examinations available were reviewed. Cases of individual benign peripheral nerve tumors were included to demonstrate 7T MRI imaging characteristics. All exams were performed on a 7T MRI MAGNETOM Terra using a 28-channel receive, single-channel transmit knee coil. RESULTS: Five cases of four pathologies were selected from 38 patients to depict characteristic imaging features in different benign nerve tumors and lesions using 7T MRI. CONCLUSION: The primary advantage of 7T over 3T is an increase in signal-to-noise ratio which allows higher in plane resolution so that the smallest neural structures can be seen and characterized. This improvement in MR imaging provides the opportunity for more accurate diagnosis and surgical planning in selected cases. As this technology continues to evolve for clinical purposes, we anticipate increasing applications and improved patient care using 7T MRI for the diagnosis of peripheral nerve masses.

Aplasia Cutis Congenita With Cutaneous Meningioma: A Rare Case.

ABSTRACT: Cutaneous meningioma, characterized by ectopic meningothelial cells in the dermis or subcutis, is a rare neoplasm. Generally, the most common location for cutaneous meningioma is the scalp. We report a case of cutaneous meningioma presenting as soft, light red, atrophic, and smooth patches with central blue spots. On histological examination, the tumor consisted largely of epithelioid cells, whorls, nests, and syncytial sheets of meningothelial cells. HMB-45, Melan-A, and S100 were negative; epithelial membrane antigen and somatostatin receptor 2 were positive. Ultimately, histopathologic examination and immunohistochemistry results supported a diagnosis of cutaneous meningioma. In addition, dermal dysplasia was observed above the tumor, manifested by thinning of the dermis and loss of appendages. No abnormalities were found on brain magnetic resonance imaging. Cutaneous meningioma is an extremely rare tumor, and its manifestation as an atrophic patch is even rarer. There have been mainly clinical reports of cutaneous meningioma. This was a rare case of focal aplasia cutis congenita with cutaneous meningioma. For cutaneous meningioma to be diagnosed earlier, there needs to be greater public awareness about the condition.

Rare peripheral nerve tumor of the median nerve.

Peripheral nerve tumors of the median nerve are uncommon. We present a case of a large atypical intraneural perineurioma of the median nerve. In our case, a 27-year-old man with a history of Asperger's and Autism who was diagnosed with a lipofibromatous hamartoma of the median nerve after a biopsy and treated conservatively presented to clinic due to the slowly growing size of his lesion. He was treated with excision of the lesion with associated resection of healthy median nerve and extensor indicis pollicis oppponenplasty. The pathology of the excision reported the lesion as an intraneural perineurioma instead of a lipofibromatous hamartoma perhaps presenting evidence of a reactive process.

[Histological and molecular characteristics of tumours of the peripheral nervous system]. / Histologische und molekularpathologische Besonderheiten von Tumoren des peripheren Nervensystems.

Tumours of the peripheral nervous system occur sporadically in adults and except for a minority of entities, these tumours are usually benign. The most common are nerve sheath tumours. Because these tumours grow in direct proximity or even invade peripheral nerve bundles, they can lead to severe pain and motion deficits. From the neurosurgical perspective these tumours are technically challenging, and especially for tumours with an invasive growth pattern complete resection may not be possible. Peripheral nervous system tumours that are associated with tumour syndromes such as neurofibromatosis type 1 and 2 or schwannomatosis are a particular clinical challenge. The goal of the current article is to present histological and molecular characteristics of peripheral nervous system tumours. Furthermore, future targeted therapy strategies are presented.

Comparison of 18 F-FDOPA and 18 F-MFBG PET/CT Images of Metastatic Pheochromocytoma.

ABSTRACT: A 30-year-old man with pheochromocytoma was hospitalized for hemoptysis without inducement. CT revealed a mass in the left lung, and biopsy pathology under the bronchoscope suggested that it was a pheochromocytoma metastasis. To further identify the location of the metastatic lesions, the patient was enrolled in a clinical trial and underwent 18 F-FDOPA and 18 F-MFBG PET/CT. Images from both examinations showed similar lesions. However, the lesions differed in that the uptake of some lesions was significantly higher with 18 F-FDOPA than with 18 F-MFBG, whereas the para-aortic lesion was active in 18 F-MFBG but not in 18 F-FDOPA.