LMNA-NTRK1 rearranged mesenchymal tumor (lipofibromatosis-like neural tumor) mimicking pigmented dermatofibrosarcoma protuberans.

We present the case of a 31-year-old female with a 1.5 cm pigmented nodule on the scalp. Histopathological examination revealed a proliferation of relatively bland spindle cells and pigmented dendritic cells, with interspersed lymphoid follicles diffusely infiltrating the adipose tissue. The microscopic differential diagnosis included pigmented dermatofibrosarcoma protuberans (DFSP). The spindle cells showed S-100 and CD34 labeling but were negative for SOX-10. Immunohistochemical stain for pan-TRK was positive, while fluorescence in-situ hybridization for PDGFB gene rearrangement was negative. Targeted RNA sequencing revealed an LMNA-NTRK1 (exon2/exon10) fusion. This molecular result coupled with the histopathological findings and immunohistochemical profile supported the diagnosis of the recently characterized NTRK-rearranged spindle cell neoplasm termed "lipofibromatosis-like neural tumor (LPF-NT)." These neoplasms typically occur in superficial soft tissue and are characterized by a distinctive immunoprofile (CD34+, S-100+, SOX10-). Histopathological differential diagnosis for LPF-NT tumors includes lipofibromatosis, DFSP, low-grade malignant peripheral nerve sheath tumor, and spindle cell/desmoplastic melanoma. The pigmented dendritic cells reminiscent of pigmented DFSP and lymphoid follicles noted in our case have not been previously reported in LPF-NT, thus expanding the morphological spectrum of this entity. LMNA-NTRK1 fusion serves both as a diagnostic and therapeutic biomarker, as cases with advanced disease may be amenable to targeted therapy using tyrosine kinase inhibitors.

Neurogenic Tumors of the Mediastinum.

Neurogenic tumors represent a broad ill-defined category of neoplasms that includes tumors of Schwann cell and/or neuroblastic derivation, as well as neoplasms that typically develop in the central nervous system, but rarely present in ectopic sites including the mediastinum. Neurogenic tumors may occur at many different anatomic sites, but the mediastinum represents a uniquely challenging site given the complex anatomy. Additionally, some of these neoplasms may present with multicentric involvement in the context of genetic syndromes, including NF1, NF2 and schwanomatosis. Most of these develop in posterior structures, often in association with paraspinal structures. Fine needle biopsy/small biopsies play an important role in the diagnosis of these neoplasms, given its record of safety and the increased applicability of ancillary testing to these smaller samples at the present time. In this review we focus on the major categories of neurogenic tumors that may be encountered in the mediastinum, including schwannoma, neurofibroma, malignant peripheral nerve sheath tumors, ganglioneuroma and ganglioneuroblastoma, as well as rarer members of this category. We discuss diagnostic approaches applicable to small cytologic and tissue samples and relevant differential diagnoses.

A systematic review reporting quality of radiomics research in neuro-oncology: toward clinical utility and quality improvement using high-dimensional imaging features.

BACKGROUND: To evaluate radiomics analysis in neuro-oncologic studies according to a radiomics quality score (RQS) system to find room for improvement in clinical use. METHODS: Pubmed and Embase were searched up the terms radiomics or radiogenomics and gliomas or glioblastomas until February 2019. From 189 articles, 51 original research articles reporting the diagnostic, prognostic, or predictive utility were selected. The quality of the methodology was evaluated according to the RQS. The adherence rates for the six key domains were evaluated: image protocol and reproducibility, feature reduction and validation, biologic/clinical utility, performance index, a high level of evidence, and open science. Subgroup analyses for journal type (imaging vs. clinical) and biomarker (diagnostic vs. prognostic/predictive) were performed. RESULTS: The median RQS was 11 out of 36 and adherence rate was 37.1%. Only 29.4% performed external validation. The adherence rate was high for reporting imaging protocol (100%), feature reduction (94.1%), and discrimination statistics (96.1%), but low for conducting test-retest analysis (2%), prospective study (3.9%), demonstrating potential clinical utility (2%), and open science (5.9%). None of the studies conducted a phantom study or cost-effectiveness analysis. Prognostic/predictive studies received higher score than diagnostic studies in comparison to gold standard (P < .001), use of calibration (P = .02), and cut-off analysis (P = .001). CONCLUSIONS: The quality of reporting of radiomics studies in neuro-oncology is currently insufficient. Validation is necessary using external dataset, and improvements need to be made to feature reproducibility, demonstrating clinical utility, pursuits of a higher level of evidence, and open science.

Surgical treatment of posterior mediastinal neurogenic tumors.

BACKGROUND: Posterior mediastinal neurogenic tumors are among the most frequent mediastinal masses in adults. These tumors may be dumbbell shaped, extending into the spinal canal, exclusively paraspinal or apical tumors extending in the cervical region. In this report, we present our experience in the surgical resection of these tumors and discuss the surgical strategies for such tumors. METHODS: A retrospective analysis was performed of 121 patients who underwent surgery for posterior mediastinal neurogenic tumors at our department during the period 2009 to 2016. Seventy-four tumors were excised via video-assisted thoracic surgery (VATS). Other approaches included thoracotomy, supraclavicular incision, supraclavicular incision plus thoracotomy/VATS, and a posterior approach with laminectomy combined with thoracotomy/VATS. RESULTS: Tumors were resected completely in 119 cases and partially in two. The majority of the tumors were benign nerve sheath tumors. No recurrence developed during postoperative median follow-up period of 31 months. CONCLUSION: Most posterior neurogenic tumors can be resected via VATS. Thoracotomy is the appropriate surgical approach for large tumors. A supraclavicular approach is recommended for tumors extending in the cervical region, and this can be combined with VATS or thoracotomy in case of larger masses. A posterior approach could be used for patients with dumbbell tumors.

Demographic, Clinical and Histopathological Features of Oral Neural Neoplasms: A Retrospective Study.

Intraoral neural neoplasms though unusual may be clinically significant. The aim of this study was to categorize and evaluate oral neural tumors in a large oral pathology biopsy service. With IRB approval, a retrospective search of all neural neoplasms of the oral cavity in the archives of the University of Florida Oral Pathology Biopsy Service spanning from 1994 to 2015 was performed. Extraoral cases as well as cases with insufficient patient information were excluded. A total of 340 out of 164,578 submitted specimens in a 22 year period (0.2%) were included with a mean age of 43.3 years (range: 6-89), and 44% male and 56% female. The most commonly affected locations were: tongue (37.5%), palate (22%), lip (19%), and gingiva (14%). The microscopic diagnoses rendered, in descending order of frequency were: neurofibromas (NFs): 123 (36%), granular cell tumor (GCT): 108 (32%), schwannomas: 61 (17%), palisaded encapsulated neuromas: 39 (11%), benign neural lesion not otherwise specified: 8 (2%), and mucosal neuroma c/w multiple endocrine neoplasia type 2B (MEN 2B): 1 (< 0.5%). Six cases of NF reported a history of neurofibromatosis Type 1 (NF 1). Four cases showed multifocal lesions. Immunohistochemical staining was performed on equivocal cases (25% of the lesions) and all were confirmed by their S-100 positivity. Intraoral neural neoplasms, though uncommon should be in the differential diagnosis of oral soft tissue entities and specific consideration to syndromal linkage is paramount as this may impact patient management.

Primary mediastinal melanotic schwannian tumors: A clinicopathological and immunohistochemical study of 5 cases.

Mediastinal neurogenic tumors are unusual and more so is the presence of melanotic neurogenic tumors. We present five cases of mediastinal melanotic neurogenic tumors. The patients are five men between the ages of 34 and 43 years (average: 38.5 years). All patients presented with non-specific symptoms that included back pain and cough. Diagnostic imaging revealed the presence of a posterior mediastinal mass without connection to the spinal canal, and surgical resection was accomplished in all of the patients. Histologically, the five tumors showed a spindle epithelioid cellular proliferation, nuclear atypia, mitotic activity, and melanin deposition. Histochemical stain for Fontana Masson clearly demonstrated the presence of melanin pigment in all the cases, while S-100 protein was only focally positive in tumor cells. Other immunohistochemical stains including SOX-10, MITF, HMB-45, and Melan A were negative. Clinical follow-up showed that two patients died 22 and 30 months after initial diagnosis; one remains alive, 6 months after initial diagnosis; two patients were lost to follow up. Melanotic neurogenic tumors represent a diagnostic challenge for pigmented thoracic tumors and careful analysis of the morphology and immunohistochemistry is required to lead to proper diagnosis.

Neural and neurogenic tumours of the gastroenteropancreaticobiliary tract.

Neural lesions occur uncommonly in the gastroenteropancreaticobiliary tract. However, due to the growing number of screening colonoscopy procedures, polypoid neural lesions of the colon are being recognised increasingly and range from benign tumours to high-grade malignant neoplasms. Morphological variability of neural tumours can be wide, although some entities share pathological features, and, as such, these lesions can be diagnostically challenging. We review the spectrum of pathology of neural tumours in the gastroenteropancreaticobiliary tract, with the goal of providing a practical approach for practising surgical pathologists.

Multinodular and vacuolating neuronal tumors in epilepsy: dysplasia or neoplasia?

Multinodular and vacuolating neuronal tumor (MVNT) is a new pattern of neuronal tumour included in the recently revised WHO 2016 classification of tumors of the CNS. There are 15 reports in the literature to date. They are typically associated with late onset epilepsy and a neoplastic vs. malformative biology has been questioned. We present a series of ten cases and compare their pathological and genetic features to better characterized epilepsy-associated malformations including focal cortical dysplasia type II (FCDII) and low-grade epilepsy-associated tumors (LEAT). Clinical and neuroradiology data were reviewed and a broad immunohistochemistry panel was applied to explore neuronal and glial differentiation, interneuronal populations, mTOR pathway activation and neurodegenerative changes. Next generation sequencing was performed for targeted multi-gene analysis to identify mutations common to epilepsy lesions including FCDII and LEAT. All of the surgical cases in this series presented with seizures, and were located in the temporal lobe. There was a lack of any progressive changes on serial pre-operative MRI and a mean age at surgery of 45 years. The vacuolated cells of the lesion expressed mature neuronal markers (neurofilament/SMI32, MAP2, synaptophysin). Prominent labelling of the lesional cells for developmentally regulated proteins (OTX1, TBR1, SOX2, MAP1b, CD34, GFAPδ) and oligodendroglial lineage markers (OLIG2, SMI94) was observed. No mutations were detected in the mTOR pathway genes, BRAF, FGFR1 or MYB. Clinical, pathological and genetic data could indicate that MVNT aligns more with a malformative lesion than a true neoplasm with origin from a progenitor neuro-glial cell type showing aberrant maturation.

Assessment of paraspinal neurogenic tumors with diffusion-weighted MR imaging.

PURPOSE: To assess paraspinal neurogenic tumors with diffusion-weighted MR imaging. METHODS: Retrospective analysis was done upon 34 patients with paraspinal neurogenic tumors that underwent diffusion-weighted MR imaging. The ADC values of the mediastinal neurogenic tumors were calculated and correlated with biopsy results. RESULTS: The ADC of benign paraspinal neurogenic tumors (1.5 ± 0.28 × 10-3 mm2/s) was significantly higher (P = 0.001) than that of malignant peripheral nerve sheath tumors (0.995 ± 0.198 × 10-3 mm2/s). Selection of 1.15 × 10-3 mm2/s as a cut-off point for differentiating malignant from benign neurogenic tumors revealed an area under the curve of 0.885, an accuracy of 91.1%, a sensitivity of 90.9%, and specificity of 91.3%. There was significant difference (P = 0.04) in the ADC of schwannomas (1.55 ± 0.29 × 10-3 mm2/s) from neurofibromas (1.33 ± 0.08 × 10-3 mm2/s). The cut-off ADC value of 1.44 × 10-3 mm2/s was used to differentiate schwannomas and neurofibromas with an area under the curve of 0.86, an accuracy of 82.6%, a sensitivity of 100%, and a specificity of 76.5%. CONCLUSION: Diffusion-weighted MR imaging is imaging parameter that can be used for differentiation of benign from malignant paraspinal neurogenic tumors.

Multinodular and vacuolating neuronal tumor of the cerebrum. A rare entity. New case and review of the literature.

BACKGROUND: Multinodular and vacuolating neuronal tumor has been recently described and included in the World Health Organization Classification of Tumors of The Central Nervous System, even though its consideration as a true tumor is controversial. Patients with these lesions usually present with refractory seizures and inconclusive imaging findings that may be confused with other more common diagnoses such as dysembryoplastic neuroepithelial tumors or low-grade gliomas. Therefore, surgical resection is warranted to reach a pathologic diagnosis and seizure control. To the best of our knowledge, only 16 cases have been published in the English literature. CASE DESCRIPTION: We present the case of a 52-year-old male who presented at our institution with a 2-year-history of absence of seizures. Brain MRI showed a T2-hyperintense lesion with no contrast enhancement affecting his temporal lobe. Temporal craniotomy and microsurgical resection was scheduled. The procedure was uneventful and a grayish, gluey mass was sent for pathologic analysis. The tumor was formed by immature neuronal cells organized in nodules with a vacuolated matrix. A thorough immunohistochemical analysis showed positivity for: Protein Gene Product 9.5. ATRX. OLIG2. SOX10. p16. Nestin. Synaptophysin. The findings were consistent with multinodular and vacuolating neuronal tumor. The patient has been seizure-free after surgery and with no signs of tumor progression. CONCLUSION: We present a thorough review addressing this uncommon tumor along with a description of the 17th reported case of MVNT, a tumor that was described for the first time in 2013. Further studies and case studies are necessary to establish a well-defined morphological and immunohistochemical profile along with knowledge about its natural history.

Glycolipids: Essential regulator of neuro-inflammation, metabolism and gliomagenesis.

Gene knockout mice of glycosyltransferases have clearly showed roles of their products in the bodies, while there are examples where phenotype of knockout was much less severe than expected probably due to functional redundancy. The most striking novel finding obtained from ganglioside-deficient mice was that progressive inflammatory reaction took place, leading to neurodegeneration. In particular, dysfunction of complement-regulatory proteins due to deteriorated architecture of lipid rafts seemed to be essential mechanisms for the inflammation. Furthermore, roles of gangliosides in neurons were demonstrated by neuron-specific transgenic of B4galnt1 with genetic background of B4galnt1 deficiency. From study of gene knockout mice of St8sia1, new roles of b-series gangliosides in leptin secretion from adipocytes, and roles of a-series gangliosides in leptin receptor, ObR in hypothalamus were demonstrated, leading to apparent intact balance of energy. Essential roles of b-series gangliosides in malignant properties of gliomas were also shown, suggesting their roles in the regulation of inflammation and proliferation in nervous tissues. How to apply these findings for the control of newly discovered patients with ganglioside deficiency remains to be investigated. This article is part of a Special Issue entitled Neuro-glycoscience, edited by Kenji Kadomatsu and Hiroshi Kitagawa.

The survival outcome and prognostic factors for distal cholangiocarcinoma following surgical resection: a meta-analysis for the 5-year survival.

PURPOSE: To assess the available evidence on the prognostic factors for the 5-year survival for patients with distal cholangiocarcinoma (DCC) following surgical resection. METHODS: We performed a comprehensive search of abstracts included in databases where relevant studies were published between January 2000 and August 2015. Risk ratios (RRs), 95 % confidence intervals (95 % CIs), and random-effects model were calculated using RevMan 5.3 software. RESULTS: A total of 23 observational studies involving 2063 patients with DCC were analyzed. The meta-analysis showed that postoperative adjuvant chemotherapy was not confirmed as a prognostic factor, with similar 5-year survival rates between those receiving and not receiving chemotherapy (RR 0.71; 95 % CI 0.21-2.36; P = 0.57). Perineural invasion (RR 0.51; 95 % CI 0.40-0.64; P < 0.00001), lymph node metastasis (RR 0.51; 95 % CI 0.38-0.70; P < 0.0001), positive resection margin status (RR 2.11; 95 % CI 1.36-3.30; P = 0.001), and not-well-differentiated adenocarcinoma (RR 1.77; 95 % CI 1.39-2.25; P < 0.00001) were associated with shorter survival. CONCLUSIONS: Perineural invasion, lymph node metastasis, resection margin status, and tumor differentiation were the significant prognostic factors for the 5-year survival.

Intrathoracic neurogenic tumor with malignant transition-20 years operation experience in a medical center of China.

OBJECTIVE: Malignant peripheral neurogenic tumor is always found in large peripheral nerve of the extremities, however, benign peripheral neurogenic tumors of chest is an uncommon disorder, furthermore, malignant transition is even rare. So far, few cases have been reported. We studied 45 neurogenic thoracic tumors patients with malignant transition. METHODS: We retrospectively reviewed clinical data of 45 malignant neurogenic thoracic tumors from 1992 to 2012, including 11 (24.44%) cases of borderline tumors (group X), 13 cases of (28.88%) low-grade malignant tumor (group L), and 21 cases (46.66%) of malignant tumors (group M). Specifically, we reviewed the clinical characteristics, surgical approach, postoperative outcome, complications and prognosis of these patients. RESULTS: All tumors are located in the thoracic cavity, and arising from sympathetic or spinal nerve or their branches from the lung or posterior mediastinum. The patients from groups X and L had more complete resection than group M. Unfortunately, one patient was dead intra operatively in Group M. Group M had more recurrence than groups X and L. Our results indicates that, the survival rate may be correlated with tumor size, malignant degree (P=0.018), tumor recurrence and incomplete resection (P<0.05). CONCLUSION: The most effective treatment method for these tumors is early identification and resection by minimally invasive surgery during benign stage. In addition, regarding low-grade malignant tumor, non-radical surgery could also be responsible for the low survival rate.

Extracranial head and neck neurogenic tumors: report of 47 cases.

UNLABELLED: Extracranial head and neck neurogenic tumors are rare and usually revealed by histological examination. The aim of this study was to review the clinical, radiological and therapeutic particularities of these tumors. METHODS: This retrospective study concerns 47 patients with neurogenic tumors of the head and neck, operated on between 1989 and 2011 (22 years period). All patients had complete physical examination and ultrasonography was performed when a cervical extension was found. CT scan and MRI were performed in 16 cases. Minimum follow up was 4 years. RESULTS:   A sinusonasal tumor was found in 9 cases and a cervical mass was seen in 28 cases. Parapharyngeal extension was observed in two cases. Two patients had tympano-jugular glomic tumors and 8 of them had a cervical soft tissue tumor. Complete surgical resection was performed in 46 patients. Histological examination revealed a benign tumor in 91% of cases (n=43), 24 of them were schwannomas. Malignant tumors were seen in 4 cases: esthesioneuroblastoma (3 cases) and malignant schwannoma (1 case). These patients received post operative radiotherapy. After surgery, two patients had Claude Bernard Horner syndrome and one had a definitive facial nerve palsy. CONCLUSION: Extracranial head and neck neurogenic tumors may have several aspects depending on their localisation and their histological type. Surgery, when performed, should be complete with minimum complications.

Cutaneous manifestations in neuro-oncology: clinically relevant tumor and treatment associated dermatologic findings.

Skin findings are a rare but important aspect of the evaluation and management of patients with tumors of the nervous system. Skin findings have the highest prevalence in genetic tumor syndromes termed neuro-genodermatoses, which include neurofibromatosis type 1 (NF1), neurofibromatosis type 2 (NF2), and tuberous sclerosis. Skin changes are observed in patients with non-syndromic nervous system malignancy, often as a result of pharmacotherapy. The skin may also manifest findings in paraneoplastic conditions that affect the nervous system, providing an early indication of underlying neoplasm, including dermatomyosistis, neuropathic itch, and brachioradial pruritus. In this article, we review the major cutaneous findings in patients with tumors of the brain, spine, and peripheral nervous system focusing on (1) cutaneous manifestations of genetic and sporadic primary nervous system tumor syndromes, and (2) paraneoplastic neurological syndromes with prominent cutaneous features.

Migration of Transformed Bone Marrow-Derived Cells with Peripheral Neural Tumor Traits In Vivo.

The identification of the original cells in tumors may allow for measures that protect the original cells and prevent tumor formation. In the present study, we isolated a subpopulation of cells with the features of neural tumor cells from transformed BMDCs in vitro. These neural tumor cells expressed the markers of neural tumor progenitor cells and differentiated neural tumor cells in vitro. Moreover, the subcloned cells from transformed BMDCs could migrate to distant tissues and drive peripheral neural tumors in vivo. Therefore, our results further verify that transformed mouse BMDCs are a potential source of peripheral neural tumors.