Malignant peripheral nerve sheath tumour with divergent epithelioid differentiation in a cat.

Divergent differentiation, mainly towards various subsets of mesenchymal cells, is encountered sporadically in human malignant peripheral nerve sheath tumours (MPNSTs) but this is the first report of epithelioid components within this neoplasm in a cat. An 8-year-old, spayed female Domestic Shorthaired cat was presented for surgical removal of a subcutaneous mass on the right flank. Morphological and immunohistochemical analysis revealed a malignant neoplasm with spindloid cells intermixed with an epithelioid component that had squamous differentiation. There was intense immunolabelling of vimentin, S100 protein, neuron-specific enolase, laminin and glial fibrillary acidic protein in the spindloid cell component and for cytokeratin (CK) AE1/AE3 and CK5/6 in the epithelial elements. Melanoma-associated antigen, desmin, α-smooth muscle actin, CD18, CD31, ionized calcium binding adapter molecule-1 and CK8/18 were not expressed, which helped differentiate the tumour from other feline spindloid cell neoplasms. These features are characteristic of divergent epithelioid differentiation of MPNST.

[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".

Intramuscular Hybrid Nerve Sheath Tumor of the Thigh: Case Report and Literature Review.

BACKGROUND/AIM: Hybrid nerve sheath tumor (HNST) is a benign peripheral nerve sheath tumor with combined features of more than one histological type, such as schwannoma, neurofibroma, and perineurioma. It remains under-recognized in routine clinical practice. Herein, we describe an unusual case of intramuscular HNST of the thigh. CASE REPORT: The patient was a 41-year-old man with no history of trauma who presented with a 3-month history of a palpable mass in the right thigh. Physical examination revealed a 4-cm, elastic hard, mobile, nontender mass. Magnetic resonance imaging exhibited a well-circumscribed intramuscular mass with low-to-intermediate signal intensity on T1-weighted sequences and higher signal intensity peripherally and lower signal intensity centrally, representing a target sign, on T2-weighted sequences. Complete surgical excision of the tumor was carried out. Microscopically, the tumor showed dual histological components of both schwannoma and neurofibroma. Immunohistochemically, the schwannomatous component was strongly and diffusely positive for S-100 protein and negative for CD34, while the neurofibromatous component contained CD34-positive fibroblasts and S-100 protein-positive Schwann cells. Epithelial membrane antigen was negative for both components. These findings were consistent with a diagnosis of HNST (hybrid schwannoma/neurofibroma). The patient had no evidence of local recurrence and no neurological deficit at the final follow-up. CONCLUSION: Although extremely rare, HNST should be included in the extended differential diagnosis of a well-circumscribed, intramuscular soft-tissue mass in the extremities, particularly in young and early middle-aged adults.

Role of catecholamine synthases in the maintenance of cancer stem-like cells in malignant peripheral nerve sheath tumors.

Malignant peripheral nerve sheath tumors (MPNSTs) are malignant tumors that are derived from Schwann cell lineage around peripheral nerves. As in many other cancer types, cancer stem cells (CSCs) have been identified in MPNSTs, and they are considered the cause of treatment resistance, recurrence, and metastasis. As an element defining the cancer stemness of MPNSTs, we previously reported a molecular mechanism by which exogenous adrenaline activates a core cancer stemness factor, YAP/TAZ, through ß2 adrenoceptor (ADRB2). In this study, we found that MPNST cells express catecholamine synthases and that these enzymes are essential for maintaining cancer stemness, such as the ability to self-renew and maintain an undifferentiated state. Through gene knockdown and inhibition of these enzymes, we confirmed that catecholamines are indeed synthesized in MPNST cells. The results confirmed that catecholamine synthase knockdown in MPNST cells reduces the activity of YAP/TAZ. These data suggest that a mechanism of YAP/TAZ activation by de novo synthesized adrenaline, as well as exogenous adrenaline, may exist in the maintenance of cancer stemness of MPNST cells. This mechanism not only helps to understand the pathology of MPNST, but could also contribute to the development of therapeutic strategies for MPNST.

Shaping Our Understanding of Malignant Peripheral Nerve Sheath Tumor: A Bibliometric Analysis of the 100 Most-Cited Articles.

BACKGROUND: Malignant peripheral nerve sheath tumors (MPNSTs) are rare yet highly aggressive soft tissue sarcomas of mesenchymal origin, characterized by a heterogeneous pathological spectrum, limited therapeutic options, and high metastatic potential. METHODS: Here, the authors conducted a comprehensive bibliometric analysis of the 100 most-cited MPNST articles by utilizing Elsevier's Scopus to identify all relevant published and indexed articles referring to MPNST, thereby aiming to elucidate the pertinent research findings regarding the disease's pathophysiology and therapeutic advancements. Articles were classified as basic science or clinical and analyzed for various bibliometric parameters. RESULTS: The majority of articles (75%) focused on clinical aspects, reflecting the extensive clinicopathological characterization of MPNSTs. Notable studies investigated prognostic factors, histological and immunohistochemical features, and diagnostic modalities. The identification of loss of function mutations in the polycomb repressive complex 2 emerged as a pivotal role, as it opened avenues for potential targets for novel therapeutic interventions. Newer articles (published in or after 2006) demonstrated higher citation rates, suggesting evolving impact and collaboration. CONCLUSIONS: This bibliometric analysis showed how developments in the understanding of MPNST pathophysiology and the creation of novel therapeutic strategies occurred throughout time. Changes that have been noticed recently could portend future innovative therapeutic approaches.

Malignant peripheral nerve sheath tumor in the kidney of a dog.

A 12-year-old castrated male poodle presented with vomiting and diarrhea. Ultrasonography and computed tomography revealed a protruding mass at the caudal pole of the left kidney. Grossly, the poorly circumscribed abnormal mass was 1.6 × 1.8 × 1.9 cm in size and had multifocal dark-red foci. Microscopically, it was composed of densely or loosely packed variable-sized short spindle or ovoid cells. These neoplastic cells showed high pleomorphism, mitotic figures, and invasive tendency to the adjacent tissue. Immunohistochemically, the neoplastic spindle cells expressed vimentin, S100, neuron-specific enolase, nerve growth factor receptor, and laminin. Therefore, the mass was diagnosed as a malignant peripheral nerve sheath tumor (MPNST). To our knowledge, this is the first report of primary renal MPNST in a dog.

Systematic Characterization of the Clinical and Pathological Features of Schwannomas Harboring SH3PXD2A::HTRA1 Fusion.

The understanding of schwannoma tumorigenesis has been reshaped by the recent identification of SH3PXD2A::HTRA1 fusion in 10% of intracranial/spinal schwannomas. Nonetheless, pathologic features of schwannomas harboring this fusion, as well as its prevalence outside intracranial/spinal locations, have not been characterized. We screened 215 consecutive schwannomas for their clinicopathologic characteristics and fusion status using reverse-transcriptase polymerase chain reaction (RT-PCR). Among 29 (13.5%) fusion-positive schwannomas, the most prevalent location was peripheral somatic tissue (30.7%, 19/62), followed by spinal/paraspinal (18.4%, 7/38), body cavity/deep structures (10%, 2/20), intracranial (1.3%, 1/75), and viscera (0/13). All 8 cellular, 4 microcystic/reticular, and 3 epithelioid schwannomas were fusion-negative, as were 41/42 nonschwannomatous peripheral nerve sheath tumors. Remarkably, a distinct 'serpentine' palisading pattern, comprising ovoid/plump cells shorter than usual schwannian cells in a hyalinized stroma, was identified in most fusion-positive cases and the schwannomatous component of the only fusion-positive malignant peripheral nerve sheath tumor. To validate this finding, 60 additional cases were collected, including 36 with (≥10% arbitrarily) and 24 without appreciable serpentine histology, of which 29 (80.6%) and 2 (8.3%) harbored the fusion, respectively. With percentages of 'serpentine' areas scored, 10% was determined as the optimal practical cut-off to predict the fusion status (sensitivity, 0.950; specificity, 0.943). Fusion positivity was significantly associated with serpentine histology, smaller tumors, younger patients, and peripheral somatic tissue, while multivariate logistic linear regression analysis only identified serpentine histology and location as independent fusion-predicting factors. RNA in situ hybridization successfully detected the fusion junction, highly concordant with RT-PCR results. Gene expression profiling on 18 schwannomas demonstrated segregation largely consistent with fusion status. Fusion-positive cases expressed significantly higher HTRA1 mRNA abundance, perhaps exploitable as a biomarker. In summary, we systematically characterize a series of 60 SH3PXD2A::HTRA1 fusion-positive schwannomas, showing their distinctive morphology and location-specific prevalence for the first time.

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

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

Asymmetry of thalamic hypometabolism on FDG-PET/CT in neurofibromatosis type 1: Association with peripheral tumor burden.

BACKGROUND AND PURPOSE: Thalamic hypometabolism is a consistent finding in brain PET with F-18 fluorodeoxyglucose (FDG) in patients with neurofibromatosis type 1 (NF1). However, the pathophysiology of this metabolic alteration is unknown. We hypothesized that it might be secondary to disturbance of peripheral input to the thalamus by NF1-characteristic peripheral nerve sheath tumors (PNSTs). To test this hypothesis, we investigated the relationship between thalamic FDG uptake and the number, volume, and localization of PNSTs. METHODS: This retrospective study included 22 adult NF1 patients (41% women, 36.2 ± 13.0 years) referred to whole-body FDG-PET/contrast-enhanced CT for suspected malignant transformation of PNSTs and 22 sex- and age-matched controls. Brain FDG uptake was scaled voxelwise to the individual median uptake in cerebellar gray matter. Bilateral mean and left-right asymmetry of thalamic FDG uptake were determined using a left-right symmetric anatomical thalamus mask. PNSTs were manually segmented in contrast-enhanced CT. RESULTS: Thalamic FDG uptake was reduced in NF1 patients by 2.0 standard deviations (p < .0005) compared to controls. Left-right asymmetry was increased by 1.3 standard deviations (p = .013). Thalamic hypometabolism was higher in NF1 patients with ≥3 PNSTs than in patients with ≤2 PNSTs (2.6 vs. 1.6 standard deviations, p = .032). The impact of the occurrence of paraspinal/paravertebral PNSTs and of the mean PNST volume on thalamic FDG uptake did not reach statistical significance (p = .098 and p = .189). Left-right asymmetry of thalamic FDG uptake was not associated with left-right asymmetry of PNST burden (p = .658). CONCLUSIONS: This study provides first evidence of left-right asymmetry of thalamic hypometabolism in NF1 and that it might be mediated by NF1-associated peripheral tumors.

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.

Coefficient of variation of T2-weighted MRI may predict the prognosis of malignant peripheral nerve sheath tumor.

BACKGROUND: We investigated whether non-enhancement MRI features, including measurement of the heterogeneity of the tumor with MR T2 imaging by calculating coefficient of variation (CV) values, were associated with the prognosis of non-metastatic malignant peripheral nerve sheath tumors (MPNST). METHODS: This retrospective study included 42 patients with MPNST who had undergone surgical resection (mean age, 50 years ± 21; 20 male participants). Non-enhancement MR images were evaluated for signal intensity heterogeneity on T1- and T2-weighted imaging, tumor margin definition on T1- and T2-weighted imaging, peritumoral edema on T2-weight imaging, and CV. We measured the signal intensities of MR T2-weighted images and calculated the corresponding CV values. CV is defined as the ratio of the standard deviation to the mean. The associations between factors and overall survival (OS) were investigated via the Kaplan-Meier method with log-rank tests and the Cox proportional hazards model. RESULTS: The mean CV value of MR T2 images was 0.2299 ± 0.1339 (standard deviation) (range, 0.0381-0.8053). Applying receiver operating characteristics analysis, the optimal cut-off level for CV value was 0.137. This cut-off CV value was used for its stratification into high and low CV values. At multivariate survival analysis, a high CV value (hazard ratio = 3.63; 95% confidence interval = 1.16-16.0; p = 0.047) was identified as an independent predictor of OS. CONCLUSION: The CV value of the signal intensity of heterogenous MPNSTs MR T2-weighted images is an independent predictor of patients' OS.

A Case of Superficial Papular Neuroma: A Rare Neural Neoplasm.

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

Malignant triton tumor of uterus: A case report and literature review.

Malignant triton tumor (MTT) is a highly aggressive malignant neoplasm, classified as a variant of malignant peripheral nerve sheath tumor with rhabdomyoblastic differentiation. There are few reports that MTT occurred in urogenital system. In the present study, we report the first MTT occurring in the uterus. A 57-year-old woman came to the emergency department due to persistent vaginal bleeding for 2 months. The gynecological palpation found that a club-shaped excrescence existed in the vagina about 7 cm × 3 cm × 3 cm. The mass located in the lower segment of the uterus and the cervix was confirmed by gynecological vaginal ultrasound and magnetic resonance imaging, which was preliminarily diagnosed as cervical carcinoma. After neoplasm punch biopsy, the pathological diagnosis was malignant triton tumor. The patient finally lost follow-up. This is the first report about MTT in the uterus and suggests that pathological biopsy combined with imaging examination is necessary for the diagnosis of rarely MTT.

Epithelioid malignant peripheral nerve sheath tumour of the ulnar nerve around the elbow: a diagnostic and therapeutic challenge.

Epithelioid malignant peripheral nerve sheath tumour (EMPNST) is a rare histological subtype of malignant peripheral nerve sheath tumour (MPNST), accounting for 5% to 17% of MPNSTs. The clinical and MRI findings of EMPNST mimic those of nerve abscesses, similar to the presentation in Hansen's disease. We present one such case with this kind of diagnostic dilemma. Intraoperative findings suggest a tumour changed the course of management subsequently. The development of neurological deficits postoperatively after tumour resection was a reconstructive challenge. To provide motor power and sensation through a procedure that provides a complete functional outcome for a young patient, distal nerve transfers were chosen. This provided an improvement in the quality of life and hastened the neurological recovery of the involved limb. Level of evidence: V.

A malignant peripheral nerve-sheath tumor: A CARE case report.

INTRODUCTION: Malignant peripheral nerve-sheath tumor (MPNST) is an extremely rare sarcoma of the nasal cavity and paranasal sinuses. Non-specific clinical and radiological presentation and challenging histological diagnosis make it little known by physicians. We describe a case of maxillary sinus MPNST, following CARE guidelines. CASE REPORT: A 62-year-old woman consulted for swelling of the right cheek and hard palate with several months' progression. CT and MRI revealed a tissue mass in the right maxillary sinus with osteolysis of the orbital and maxillary floors, hard palate and lateral and medial walls of the maxillary sinus. Biopsy confirmed diagnosis of low-grade MPNST. After total resection and 60Gy adjuvant radiotherapy, 2-year follow-up showed no signs of recurrence. CONCLUSION: MPNST in the nasal cavity and paranasal sinuses is very rare. Because of a high risk of recurrence, wide resection should be implemented, possibly completed by radiotherapy if resection cannot be complete because of proximity to at-risk structures.

Surgical and oncologic outcomes in dogs with malignant peripheral nerve sheath tumours arising from the brachial or lumbosacral plexus.

Malignant peripheral nerve sheath tumours (MPNST) of a plexus nerve or nerve root cause significant morbidity and present a treatment challenge. The surgical approach can be complex and information is lacking on outcomes. The objective of this study was to describe surgical complication rates and oncologic outcomes for canine MPNST of the brachial or lumbosacral plexus. Dogs treated for a naïve MPNST with amputation/hemipelvectomy with or without a laminectomy were retrospectively analysed. Oncologic outcomes were disease free interval (DFI), overall survival (OS), and 1- and 2-year survival rates. Thirty dogs were included. The surgery performed was amputation alone in 17 cases (57%), and amputation/hemipelvectomy with laminectomy in 13 cases (43%). Four dogs (13%) had an intraoperative complication, while 11 dogs (37%) had postoperative complications. Histologic margins were reported as R0 in 12 dogs (40%), R1 in 12 dogs (40%), and R2 in five dogs (17%). No association was found between histologic grade and margin nor extent of surgical approach and margin. Thirteen dogs (46%) had recurrence. The median DFI was 511 days (95% CI: 140-882 days). The median disease specific OST was 570 days (95% CI: 467-673 days) with 1- and 2-year survival rates of 82% and 22% respectively. No variables were significantly associated with recurrence, DFI, or disease specific OST. These data show surgical treatment of plexus MPNST was associated with a high intra- and postoperative complication rate but relatively good disease outcomes. This information can guide clinicians in surgical risk management and owner communication regarding realistic outcomes and complications.