Collection of Rare Peripheral Nerve Tumors-Insights from the German Registry.

The most common peripheral nerve tumors are of a benign nature and include schwannoma or neurofibroma. In rare cases, other tumors or non-tumorous lesions can mimic peripheral nerve tumors clinically or radiologically. Based on data from the multicentric German Peripheral Nerve Tumor Registry (PNTR), which encompasses current information on 315 surgically treated patients from three high-volume centers, we present 61 cases of rare tumors and lesions that mimic tumors associated with peripheral nerves. This cohort displays considerable heterogeneity, featuring a broad spectrum of morphological features and biological potentials. Histopathological diagnoses include various intrinsic peripheral nerve tumors such as malignant peripheral nerve tumors (MPNSTs) (n = 13), perineurioma (n = 17), and hybrid nerve sheath tumors (HPNSTs, comprising schwannoma/perineurioma and schwannoma/neurofibroma) (n = 14), as well as atypical neurofibromatous neoplasm with unknown biological potential (ANNUBP) (n = 1). Additionally, the cohort encompasses extrinsic tumorous lesions like lymphoma (n = 3), lymphangioma (n = 2), hemangioma (n = 2), solitary fibrous tumor (n = 2), metastatic disease (n = 1), and single cases of other rare tumor entities (n = 6). An overview of the underlying pathology, imaging features, and clinical presentation is provided, with a brief description of each entity. A definitive preoperative differentiation between benign peripheral nerve tumors and rare intrinsic and extrinsic tumors is often not possible. Clinical examination and subtle imaging clues can at least indicate the possibility of a rare entity. The basic requirement is close cooperation between radiologists, neurologists, neuropathologists, and neurosurgeons at a specialized center to develop a multidisciplinary concept and offer the patient the best therapeutic approaches.

Malignant perineurioma derived from the retroperitoneum with an aggressive clinical course: a case report.

BACKGROUND: Malignant perineurioma is a rare malignant counterpart of perineurioma derived from perineural cells. Resection is the primary option for the treatment of malignant perineuriomas; however, patients often develop recurrence after resection, and effective treatment for advanced or recurrent lesions needs to be established. This report describes a 51-year-old female with a rare malignant perineurioma in the retroperitoneum, which contributing valuable insights to the literature. CASE PRESENTATION: The patient presented with abdominal distension and the imaging work-up revealed a huge hemorrhagic tumor in the retroperitoneum and obstruction of inferior vena cava by the tumor. The patient underwent surgery retrieving the tumor combined with left hemiliver and retrohepatic vena cava, which confirmed the diagnosis of a malignant perineurioma based on histopathological and immunohistochemical examination. Cancer gene panel testing identified mutations in NF2. Radiotherapy was administered for peritoneal dissemination 2 months after surgery, and the patient died from disease progression 6 months after surgery. CONCLUSIONS: This rare case highlights the challenges in managing retroperitoneal malignant perineuriomas. The aggressive characteristics and limited treatment options for advanced malignant perineuriomas underscore the need for understanding the pathogenesis and developing effective systemic therapies. The identification of an NF2 mutation provides significant insights into potential therapeutic target.

Peripheral nerve tumors.

The chapter is focused on the neoplastic peripheral nerve lesions, which primarily involve "cranial and paraspinal nerves," as outlined in the CNS volume (WHO_Classification_of_Tumours_Editorial_Board, 2021). These include classic peripheral nerve sheath tumors such as schwannoma, neurofibroma, intraneural perineurioma, and malignant peripheral nerve sheath tumors, with their variants as well as new and more precisely defined entities, including hybrid nerve sheath tumors and malignant melanotic nerve sheath tumor (previously melanotic schwannoma).

Gastric Perineurioma: A Rare Entity with Molecular Analysis and Literature Review.

BACKGROUND: Perineuriomas of the gastrointestinal tract are benign neoplasms that commonly develop in the distal colon and are identified during screening colonoscopy; however, perineuriomas of the stomach are exceedingly rare and less frequently identified. Differentiating gastric perineuriomas from other more serious gastric neoplasms is critical to avoid unnecessarily aggressive treatments. Thus far, only six patients with gastric perineurioma have been described, and the molecular characterization of this entity is still lacking. CASE PRESENTATION: We report a 52-year-old woman who presented with abdominal pain and gastric acid reflux and was found to have a 1.5 cm subepithelial gastric neoplasm composed of bland spindle cells displacing the gastric glands with no cytologic atypia or mitotic activity, suggesting a benign spindle cell neoplasm. Immunohistochemical analysis showed reactivity for perineurial markers glucose transporter-1 and epithelial membrane antigen, consistent with benign gastric perineurioma. DNA extracted from the tissue was used for a capture-based target sequence enrichment panel followed by Illumina next-generation sequencing and targeted bioinformatic analysis for oncogenic alterations within defined disease-associated target regions. No sequence variants in the BRAF gene were identified. CONCLUSIONS: This rare case of gastric perineurioma helps solidify our understanding of how to discern various types of gastric neoplasms through traditional laboratory analysis alongside genetic sequencing approaches. Although extremely rare, gastric perineurioma should be kept in the differential diagnosis when assessing spindle cell gastric tumors to avoid unnecessary therapies, and physicians should understand the molecular characteristics of benign versus malignant tumors.

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

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

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.

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.

Diagnosis and Treatment of Peripheral and Cranial Nerve Tumors with Expert Recommendations: An EUropean Network for RAre CANcers (EURACAN) Initiative.

The 2021 WHO classification of the CNS Tumors identifies as "Peripheral nerve sheath tumors" (PNST) some entities with specific clinical and anatomical characteristics, histological and molecular markers, imaging findings, and aggressiveness. The Task Force has reviewed the evidence of diagnostic and therapeutic interventions, which is particularly low due to the rarity, and drawn recommendations accordingly. Tumor diagnosis is primarily based on hematoxylin and eosin-stained sections and immunohistochemistry. Molecular analysis is not essential to establish the histological nature of these tumors, although genetic analyses on DNA extracted from PNST (neurofibromas/schwannomas) is required to diagnose mosaic forms of NF1 and SPS. MRI is the gold-standard to delineate the extension with respect to adjacent structures. Gross-total resection is the first choice, and can be curative in benign lesions; however, the extent of resection must be balanced with preservation of nerve functioning. Radiotherapy can be omitted in benign tumors after complete resection and in NF-related tumors, due to the theoretic risk of secondary malignancies in a tumor-suppressor syndrome. Systemic therapy should be considered in incomplete resected plexiform neurofibromas/MPNSTs. MEK inhibitor selumetinib can be used in NF1 children ≥2 years with inoperable/symptomatic plexiform neurofibromas, while anthracycline-based treatment is the first choice for unresectable/locally advanced/metastatic MPNST. Clinical trials on other MEK1-2 inhibitors alone or in combination with mTOR inhibitors are under investigation in plexiform neurofibromas and MPNST, respectively.

Perineurioma of the sciatic nerve with reticular, microcystic, and pseudolipoblastic features: illustrative case.

BACKGROUND: Perineuriomas are peripheral nerve sheath tumors that are composed of benign, localized proliferations of perineural cells and further subclassified as intraneural or extraneural (soft tissue) based on their relationship to the histological boundaries of the nerve. Multiple histological variants have been described, and herein the authors present the first known case of a pseudolipoblastic perineurioma affecting the nerve. OBSERVATIONS: A 52-year-old woman presented with a 5-year history of progressive, severe left buttock pain radiating down to the top of her foot and ankle, without any associated weakness, with a large mass in her sciatic nerve noted on magnetic resonance imaging (MRI). She underwent resection, which demonstrated a pseudolipoblastic perineurioma of the sciatic nerve, an unusual histological subtype composed of perineurial cells with an abundant clear intracytoplasmic background. Postoperatively, her pain resolved, and follow-up MRI showed no tumor persistence or recurrence. LESSONS: On imaging, this lesion had a benign appearance, with areas suggestive of subacute hemorrhage, and was associated with a nerve. Although the distinctive morphological features of this lesion may suggest liposarcoma, careful morphological evaluation and appropriate immunohistochemical studies allow its correct classification.

GAB1::ABL1 fusions define a distinctive soft tissue neoplasm, with variable perineurial differentiation, and a predilection for children and young adults.

Although well known as a fusion partner in hematological malignancies, fusion genes involving the ABL proto-oncogene 1 (ABL1), mapping to chromosomal region 9q34.12, have only been anecdotally reported in five soft tissue tumors. These neoplasms have been variously reported as perineurioma, angiofibroma, and solitary fibrous tumor, and all have harbored a GAB1::ABL1 gene fusion; however, the nosology and clinicopathological characteristics of soft tissue tumors carrying this rare fusion have not been delineated. We herein describe eight tumors containing the GAB1::ABL1 fusion and review previously reported cases in a series to define their morphological spectrum, address immunohistochemical evidence for a line of differentiation, with special reference to the presence or absence of a perineurial immunophenotype, and gather insight into their behavior. The patients included four females and four males, aged 13-37 years (median, 24 years). Two cases each originated in the shoulder area, trunk, hands, and lower extremities, with a size range of 1.5-8 cm (median, 3.4 cm). Four tumors were deep and four superficial. All tumors were morphologically similar, being composed of bland fibroblast-like spindle to ovoid cells diffusely arranged in a paucivascular fibrous to fibromyxoid stroma with variable resemblance to soft tissue perineurioma. Mitotic activity was generally low (0-8 mitoses in 10 high-power fields [HPFs]; median, 1). All lesions had at least focally infiltrative margins, but they otherwise lacked pleomorphism and necrosis. Immunohistochemistry showed focal reactivity for CD34 (5/7), epithelial membrane antigen (EMA) (3/8), claudin1 (2/3), GLUT1 (4/6), and S100 (2/7); other markers, including MUC4 (0/7), desmin (0/9), and smooth muscle actin (SMA) (0/4), were negative. RNA sequencing revealed a GAB1::ABL1 fusion in all cases with exon 6 of GAB1 fused to exon 2 of ABL1. Treatments included various forms of surgical intervention in seven cases; one tumor was biopsied only. Limited follow-up was available for five patients. One tumor regrew rapidly within 1 month to 1.5 cm after an initial marginal excision and was re-excised with close margins. Four patients were disease-free at 1, 3, 14, and 25 months of follow-up. Metastases have not, to date, been observed. This series characterizes "GAB1::ABL1 fusion-positive spindle cell neoplasm" as a distinct entity, with overlapping features with soft tissue perineurioma and predilection for children and young adults.

Plexal intraneural perineurioma: an analysis of the clinicoradiologic presentation of this rare variant.

PURPOSE: Intraneural (IN) perineurioma is a rare benign peripheral nerve sheath tumor, typically presenting as a painless, progressive mononeuropathy in adolescents. A rare plexal variant has been described, although there are little data describing its clinicoradiologic features. Herein, we present the largest case series of plexal IN perineuriomas reported in the literature. METHODS: Electronic medical records (EMR) from 1990 to 2022 from a single academic institution were reviewed for a diagnosis of IN perineurioma involving the brachial or lumbosacral plexus. This identified 18 patients, of which 17 had available MR imaging. We reviewed the EMR for demographics, clinical presentation, imaging characteristics, and surgical outcomes. RESULTS: Eighteen patients were identified. Most patients were male (11/18, 61%) and first developed symptoms at the age of 9.6 years (range 7 months to 55 years). Diagnosis occurred on average at the age of 22 years (4-57 years), which is significantly earlier than distal IN perineurioma (p = 0.0096). All patients (100%, 17/17) presented with motor polyneuropathy and muscular atrophy in multiple nerve distributions, with associated sensory loss (12/17, 71%). Most plexal lesions occurred in the brachial plexus (66%, 12/18). Five (29%, 5/17) patients presented with a hand/foot discrepancy, and 5 patients (29%) had a limb length discrepancy. Five patients underwent tendon transfer, of which two had failure of tendon transfer at most recent follow-up (50%, 2/4) due to progression of neurologic loss affecting the donors. Of patients managed nonoperatively, 87% of patients (6/7) with follow-up information demonstrated disease progression with worsening motor function or sensory loss, and 2 patients demonstrated progression on imaging at most recent follow-up. CONCLUSIONS: Plexal perineurioma represents an uncommon variant of IN perineurioma that presents as a progressive motor and sensory polyneuropathy in childhood or early adolescence. Surgical management remains controversial, and tendon transfer tends to result in poor long-term surgical outcomes.

Benign peripheral nerve tumors: Analysis of 89 FNA cases emphasizing diagnostic accuracy and their morphologic spectrum.

INTRODUCTION: Benign peripheral nerve tumors (BPNTs) are a heterogenous group of soft tissue tumors that include a variety of nerve sheath tumors, granular cell tumor (GCT), and ganglioneuroma. Only a few large studies exist on cytopathology and diagnostic accuracy using fine-needle aspiration (FNA) biopsy for this set of neoplasms. MATERIALS AND METHODS: Both surgical and cytopathology files were searched for cases of BPNT. FNA biopsy was performed using standard techniques. RESULTS: Eighty-nine cases from 88 patients (male:female = 1:1; age range: 16-85 years, mean age, 51 years) met inclusion criteria. FNA sites included extremities (58, 65%), head/neck (14, 16%), deep (9, 10%), and trunk (8, 10%). Aspirates were from primary neoplasms in all but one instance. There were 65 schwannomas, seven neurofibromas, seven perineuriomas, seven GCTs, and three ganglioneuromas/neuromas. Aspirates of schwannoma, GCT, neurofibroma (NF), and perineurioma (PN) were correctly diagnosed in 86%, 100%, 29%, and 0% of cases, respectively. Five tumors (6%) were interpreted as either a specific sarcoma or suspicious for sarcoma. Remaining aspirates were classified as spindle cell neoplasm, salivary gland neoplasm, and nondiagnostic. Cytologic features for schwannoma, NF, PN, and ganglioneuroma showed spindle cell-dominant smears arranged mainly in syncytial clusters. GCT aspirates contained a population of epithelioid cells harboring coarsely granular cytoplasm and bare nuclei. Immunohistochemical (IHC) staining in 55 (62%) cases showed S-100 expression in 95%. CONCLUSION: FNA biopsy coupled with IHC is reliable in correctly classifying schwannoma and GCT, but less so for NF. Perineurioma can be mistaken for sarcoma.

Gastric Perineurioma: A Case Report and Review of the Literature.

Perineuriomas of the gastrointestinal tract, formerly known as benign fibroblastic polyps, most commonly occur as polyps on screening colonoscopy, particularly in the distal colon. Gastric examples are exceedingly rare. We report the sixth patient with a gastric perineurioma in a 57-year-old female. Histologically, the lesion was composed of bland spindle cells without cytologic atypia or mitotic activity located in the gastric lamina propria. The spindled cells were strongly positive for GLUT1 and focally reactive for epithelial membrane antigen (EMA). The morphologic and immunophenotypic findings were those of gastric perineurioma.

RREB1::MRTFB fusion-positive extra-glossal mesenchymal neoplasms: A series of five cases expanding their anatomic distribution and highlighting significant morphological and phenotypic diversity.

The RREB1::MRTFB (former RREB1::MKL2) fusion characterizes ectomesenchymal chondromyxoid tumors (EMCMT) of the tongue. Only five molecularly confirmed extra-glossal EMCMT cases have been reported recently; all occurring at head and neck or mediastinal sites. We herein describe five new cases including the first two extracranial/extrathoracic cases. The tumors occurred in three male and two female patients with an age ranging from 18 to 61 years (median, 28). Three tumors were located in the head and neck (jaw, parapharyngeal space, and nasopharyngeal wall) and two in the soft tissue (inguinal and presacral). The tumor size ranged from 3.3 to 20 cm (median, 7). Treatment was surgical without adjuvant treatment in all cases. Two cases were disease-free at 5 and 17 months; other cases were lost to follow-up. Histologically, the soft tissue cases shared a predominant fibromyxoid appearance, but with variable cytoarchitectural pattern (cellular perineurioma-like whorls and storiform pattern in one case and large polygonal granular cells embedded within a chondromyxoid stroma in the other). Two tumors (inguinal and parapharyngeal) showed spindled to ovoid and round cells with a moderately to highly cellular nondescript pattern. One sinonasal tumor closely mimicked nasal chondromesenchymal hamartoma (NCMH). Mitotic activity was low (0-5 mitoses/10 hpfs). Immunohistochemical findings were heterogeneous with variable expression of S100 (2/5), EMA (2/3), CD34 (1/4), desmin (1/4), and GFAP (1/3). Targeted RNA sequencing revealed the same RREB1::MRTFB fusion in all cases, with exon 8 of RREB1 being fused to exon 11 of MRTFB. This study expands the topographic spectrum of RREB1::MRTFB fusion-positive mesenchymal neoplasms, highlighting a significant morphological and phenotypic diversity. Overall, RREB1::MRTFB-rearranged neoplasms seem to fall into two subcategories: tumors with lobulated, chondroid, or myxochondroid epithelioid morphology (Cases 2 and 3) and those with more undifferentiated hypercellular spindle cell phenotype (Cases 1, 4, and 5). Involvement of extracranial/extrathoracic sites and the NCMH-like pattern are novel. The biology of these likely indolent or benign tumors remains to be verified in the future.

Trigeminal hybrid nerve sheath tumor - a case report and literature review.

BACKGROUND: Hybrid nerve sheath tumors (HNST) contain elements of more than one established sub-type of nerve sheath tumor and have been recently recognized in the 2016 WHO classification of central nervous system tumors. While common in the peripheral nerves and extracranial branches of cranial nerves, only one case has been previously documented of an intracranial HNST arising from a cranial nerve. CASE DESCRIPTION: We describe a large, multi-compartmental intracranial hybrid nerve sheath tumor arising from the trigeminal nerve in a 22-year-old lady who presented with clinical and radiological features suggestive of a right cerebellopontine angle mass. Histopathological examination following retrosigmoid excision of the tumor revealed histological and immunohistochemical features of a schwannoma and a perineurioma. CONCLUSIONS: HNSTs are likely to be underreported in the intracranial region. The clinical course of these tumors and the reason for their occurrence in this location are not known.

Hybrid tumors with perineurioma components: a systematic review of the literature and illustrative case.

PURPOSE: Hybrid peripheral nerve sheath tumors (HPNST) are a newly recognized class of peripheral nerve sheath tumor, composed of at least two areas characteristic of perineurioma, schwannoma, or neurofibroma. The literature consists only of case reports and small series; therefore, we present an illustrative case and an analysis of all reported cases of HPNST with a perineurioma component in the literature. METHODS: A systematic search of the literature was performed to identify all reported cases of hybrid perineurioma-schwannoma or perineurioma-neurofibroma in the world's literature. Individual cases were analyzed for demographics, clinical features, imaging, and outcomes. RESULTS: A total of 159 cases were identified across 41 studies. Hybrid tumors tended to present in mid-adulthood (median 38.5 years), predominantly affected females (57%, 89/156), as a painless (63%, 63/100) mass, or swelling. Ten patients (10/74, 14%) had a history of neurofibromatosis 1, and 2 patients a history of neurofibromatosis 2 (2/74, 3%). The majority (78%, 122/157) of cases occurred superficially, most commonly in the lower extremity (25%, 39/157). Perineurioma-schwannoma was the most reported (86%, 137/159) pathologic diagnosis, with 3 cases presenting with malignant features. Two cases reocurred after resection. CONCLUSION: HPNST tend to occur in mid-adulthood and present as slowly progressive, painless, superficial masses, with a heterogeneous appearance on imaging. These entities pose a unique diagnostic challenge and likely remain under-recognized in the literature and current clinical practice. They pose low risk of recurrence or malignant transformation, and future work regarding the association with neurofibromatosis and genetic profiles is needed.

Value of ultrasound in the diagnosis of intraneural perineurioma / 中华超声影像学杂志

Objective:To investigate the value of ultrasound in the diagnosis of intraneural perineurioma.Methods:From June 2015 to June 2022, 11 patients with intraneural perineurioma confirmed by surgery or biopsy in Provincial Hospital Affiliated to Shandong First Medical University were retrospectively collected, all of whom underwent high-frequency ultrasound examination. Clinical data and sonographic characteristics were collected. The maximum cross-sectional area of the affected nerve was recorded and compared with the corresponding site of the contralateral nerve.Results:All the 11 cases of intraneural perineurioma were single neuropathy. The sonogram showed that the affected nerve was spindle shaped and thickened. There was a statistical difference between the maximum cross-sectional area of the thickened intraneural perineurioma and the corresponding site of the contralateral nerve [(0.158±0.043)cm vs (0.044±0.012)cm, t=8.669, P<0.001]. The fascicles of the affected nerve were thickened with loss of normal fascicular definition, but there were still hyperechoic linear separation among the fascicles. Conclusions:High-frequency ultrasound may be a valuable technique for the diagnosis of intraneural perineurioma.