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.

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.

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.

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.

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.

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.

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.

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.

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.

Glomus-like bodies within a neurofibroma: a novel neoplasm arising in neurofibromatosis type 1 or a coincidence?

Neurofibromatosis type 1 is a relatively common genetic disorder with variable phenotypes. Tumors with features of both glomus tumors and neurofibromas are exceedingly rare in literature. Herein, we report a not yet described neoplasm with features of both a glomangioma/glomus tumor and a neurofibroma arising in a patient with segmental neurofibromatosis. Our case report supports the theory of a common lineage/ancestor cell between neurofibromas and glomus tumors and adds it to the spectrum of neoplasms that may arise in the setting of Von Recklinghausen's disease.

Intraoperative esophagoscopy provides accuracy and safety in video-assisted thoracoscopic enucleation of benign esophageal submucosal tumors.

Benign esophageal tumors are rare; complete surgical resection is essential for the management of the submucosal tumors. Larger, symptomatic, or non-diagnostic lesions should be resected for both diagnostic and therapeutic indications. Video-assisted thoracic surgery has become a popular treatment in the field of thoracic surgery; however, thoracoscopic esophageal surgery may lead to an increase in operative complications. The effect and safety of thoracoscopic surgery for esophageal submucosal lesions were evaluated. A retrospective study evaluated patients undergoing thoracoscopic treatment of benign submucosal tumors. Between March 2011 and December 2013, 17 patients underwent thoracoscopic resection of benign submucocal tumors. Intraoperative esophagoscopy was performed for tumor localization by transillumination and confirmation of mucosal integrity after enucleation in every patient. Median patient age was 47 years (range 30-65). The median surgery time was 170 minutes (range 80-429). The median tumor size was 3.8 cm (range 1.3-9). The median hospital stay was 4 days (range 2-12). There were 16 leiomyoma and 1 neurogenic tumor. There was one case of conversion to thoracotomy because of residual tumor after enucleation. Mucosal injuries occurred in three patients, two accidentally and one intentionally; each patient was treated with primary repair and confirmed integrity with flexible esophagoscopy at operating room. The small sized tumor with intraoperative esophagoscopy could be localized. Esophagoscopic assistance was necessary in eight patients to have better idea where to make myotomy. There were no major morbidities such as postoperative leakage or mortality. Esophageal submucosal tumors can be treated safely with thoracoscopic surgery. However, intraoperative esophagoscopy allows accurate tumor localization, direction of esophageal access incision, and decreases complications during VATS enucleation of esophageal submucosal tumors.

Soft tissue sarcoma misdiagnosed as benign peripheral neurogenic tumor.

BACKGROUND: Because of the distinctive clinical and MR findings associated with benign peripheral neurogenic tumors (BPNTs), they are commonly diagnosed without histological confirmation. As such, they are one of the most frequently misdiagnosed entities among the soft tissue sarcomas (STSs) that undergo initial unplanned excision. In this study, we investigate the characteristics of STSs misdiagnosed as BPNTs. METHODS: We present a series of nine STS patients with an initial preoperative diagnosis of BPNT (BPNT-STS), and compare their clinical and MR findings to those of the 18 genuine BPNT patients, matched for site, depth, and size of tumors as well as related nerves. RESULTS: Among the nine BPNT-STS cases, the most common histological diagnosis was synovial sarcoma (n = 4). Six patients (67 %) had deep-seated tumors; four patients (44 %) had tumors 5 cm or greater in size. BPNT-STS patients were more likely to experience pain (78 % vs. 22 %) and shorter symptom duration (9 vs. 55 months) compared to BPNT patients. A target sign on MR imaging was observed only in BPNT patients (0 % vs. 50 %), whereas peritumoral edema was found only in BPNT-STS patients (33 % vs. 0 %). CONCLUSIONS: If a tumor suggestive of a BPNT is painful, with a relatively short symptom duration, and presents with peritumoral edema without a definite target sign on MR images, the possibility of an STS must be considered.

A probabilistic assessment of the diagnosis of paraganglioma/pheochromocytoma based on clinical criteria and biochemical/imaging findings.

UNLABELLED: Paragangliomas (PGL) and pheochromocytomas (P) are rare neural-crest-derived neoplasms. Very recently guidelines on diagnosis and treatment of PGL/P have been presented by the US Endocrine Society. In the following overview we assessed the implementation of these guidelines with probabilistic reasoning (calculating with Fagan nomograms the post-test probability of PGL/P for a given pre-test probability). CONCLUSION: Biochemical evaluation of PGL/P showed excellent diagnostic characteristics with post-test probabilities that are very different from the pre-test probabilities, thus a positive biochemical test is usually indicative of disease whereas a negative one usually rules out disease. The post-test probabilities of anatomical and functional imaging modalities (i.e. in nuclear medicine) were different from the pre-test probabilities but to a lesser degree than the biochemical tests; furthermore in biochemically-proven PGL/P a negative imaging modality is not useful, while a positive one may indicate only one of multiple foci of metastatic/extra-adrenal disease. Thus, regarding imaging modalities, they should be combined in order to get the most of their characteristics for the localization of PGL/P.

THE IMPORTANCE OF IMMUNOHISTOCHEMICAL STUDIES IN THE DIAGNOSIS OF CANCER OF UNKNOWN PRIMARY ORIGIN.

The purpose of the research is to give a comparative diagnostic characteristic to tumors of unknown primary origin by admission diagnosis and morphological diagnosis. 162 treated cases with tumors of unknown primary at Oncologic Dispensary for 5 years were analyzed in details. Besides clinical, instrumental, cytological, morphological methods, immunnohistochemical research of tumors was carried out by avidin-biotin-peroxydase tecnics. The cases with poorly differentiated carcinoma (33,3±4,3%) and lymphoproliferative disorders (27,2±3,5%) prevailed among the cases with tumors of unknown primary by histological research. High degree of noncoincidence of cytologic and histological diagnoses (χ2=515, р=0,00001), histological and immunohistochemical diagnoses (χ2=378, р=0,00001), cytologic and immunohistochemical diagnoses (χ2=556, р=0,00001) were revealed. Cytologic overdiagnosis of undifferentiated carcinoma by 13,6% (р<0,05) and hypodiagnosis of benign diseases by 4,4% (р<0,05) and histological overdiagnosis of poorly differentiated carcinoma by 11,1% (р<0,05) and hypodiagnostics of tumors of nerve tissue by 8,0% (р<0,05) are marked, that points to the necessity of making immunohistochemical research in the cases of given pathology. Statistically significant connection of mean degree between diagnoses of poorly differentiated tumors made by cytologic, histological and immunohistochemical investigation is revealed.

Intrathoracic neurogenic tumors.

BACKGROUND: Intrathoracic neurogenic tumors are uncommon neoplasms arising from nerve tissues. This study reports on our 24-year single-center experience with intrathoracic neurogenic tumors. PATIENTS AND METHODS: We retrospectively analyzed the postoperative pathological records of 19,378 operations performed in our clinic between January 1988 and December 2011 and included cases with diagnosis of neurogenic tumors. RESULTS: The study included 149 patients (90 females and 59 males) with an average age of 24.5 years (7 months to 77 years). The study group comprised 29 infants and children, and 120 adults. Of the patients, 72 had benign schwannomas, 10 malignant schwannomas, 17 neurofibromas, 24 ganglioneuromas, 9 ganglioneuroblastomas, 4 neuroblastomas, 9 primitive neuroectodermal tumors, and 4 paragangliomas. Concerning the location of these lesions, 131 were located in the posterior mediastinum, 8 in the lung parenchyma, 5 in the chest wall, 3 in the anterior mediastinum, and 2 in the thoracic inlet. The majority of nerve cell tumors were in infants and children (79.3%), whereas the nerve sheath tumors most commonly occurred in adults (78.3%). There were 117 benign and 32 malignant tumors across all age groups. The rate of malignancy was 41.4% in infants and children, compared with 16.7% in adults. Symptoms were seen in 65% of the adult patients and 79.3% of the infant and children patients. Seven tumors were associated with von Recklinghausen's disease. In six patients (4.0%), the tumor showed an intraspinal extension. Surgical resection of the tumor was complete in 142 of 149 patients (95.3%). CONCLUSION: The treatment of choice for malignant and benign thoracic neurogenic tumors is complete resection. The objective of resection is to avoid local invasion, facilitate differential histopathological diagnosis to determine other treatment options, and to prevent malignant degeneration.

Braided pattern in a dermatofibrosarcoma protuberans: a potential mimicker of neural neoplasms.

Dermatofibrosarcoma protuberans (DFSP) is a dermal and subcutaneous slow-growing tumor of intermediate malignancy. Different histological variants of DFSP have been described, depending on cellular and stromal peculiarities. Here, we report the histological features of a DFSP in which cells were frequently arrayed in cords and fascicles that were interweaved, conforming a peculiar braided pattern. This finding might pose difficulties in the differential diagnosis with neural neoplasms and expands the morphological spectrum of DFSP.

Spectrum of superficial nerve-related tumor and tumor-like lesions: MRI features.

Superficial soft-tissue masses arising from skin appendages, metastasis, and inflammatory lesions have been widely reported. However, nerve-related superficial mass-like lesions other than peripheral nerve sheath tumors are less commonly described. High resolution magnetic resonance imaging (MRI) is an excellent non-invasive tool for the evaluation of such lesions. In this article, the authors discuss the entire spectrum of these lesions and also outline a systemic diagnostic approach.

Challenges with defining response to antitumor agents in pediatric neuro-oncology: a report from the response assessment in pediatric neuro-oncology (RAPNO) working group.

Criteria for new drug approval include demonstration of efficacy. In neuro-oncology, this is determined radiographically utilizing tumor measurements on MRI scans. Limitations of this method have been identified where drug activity is not reflected in decreased tumor size. The RANO (Response Assessment in Neuro-Oncology) working group was established to address limitations in defining endpoints for clinical trials in adult neuro-oncology and to develop standardized response criteria. RAPNO was subsequently established to address unique issues in pediatric neuro-oncology. The aim of this paper is to delineate response criteria issues in pediatric clinical trials as a basis for subsequent recommendations.