RETRACTED ARTICLE: Ulnar malignant peripheral nerve sheath tumour diagnosis in a mixed-breed dog as a model to study human: histologic,immunohistochemical, and clinicopathologic study

Canine Malignant Peripheral Nerve Sheath Tumors (MPNSTs) are uncommonly reported in the ulnar, since they are underestimated relative to the more common spindle cell tumours of soft tissue. In dogs, MPNST accounts for 27% of nervous system tumours. In man, MPNST represents 5-10% of all soft tissue sarcomas and is often associated with neurofibromatosis type 1 (NF-1).An 8-year-old, 9 kg, female mixed-breed dog with a subcutaneous mass on the upper right side of the ulnar region was presented to the small animal research and teaching hospital of Tehran University. The dog was anorexic with general weakness. The mass (7 × 4 cm) was removed surgically and processed routinely. Microscopically, the mass was composed of highly cellular areas with a homogeneous population of round or spindle cells, high cellular pleomorphism, high mitotic index and various morphologic patterns. Furthermore, spindle cells arranged in densely or loosely sweeping fascicles, interlacing whorls, or storiform patterns together with wavy cytoplasm, nuclear palisades, and round cells were arranged in sheets or cords with a meshwork of intratumoral nerve fibers. In addition, in this case the presence of neoplastic cells within the blood vessels was observed. Immunohistochemically, tumor was positive for vimentin and S-100 protein. The histopathologic features coupled with the S-100 and vimentin immunoreactivity led to a diagnosis of malignant neurofibroma.To the best of our knowledge, primary ulnar MPNST has not been reported in animals. This is the first documentation of an ulnar malignant peripheral nerve sheath tumour in a dog.

Virtual slides

The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1310907815984587

     

Brain metastases as primary manifestation of a melanocytic malignant peripheral nerve sheath tumor in a 60-year-old man

Background  

Malignant peripheral nerve sheath tumors are rare tumor entities that originate from peripheral nerve sheaths and have an unfavorable prognosis. Metastatic spread to the cerebral parenchyma is absolutely rare. This case report describes the clinical course in a 60-year-old man whose tumor came to medical attention because of a seizure.     

Cell-free DNA ultra-low-pass whole genome sequencing to distinguish malignant peripheral nerve sheath tumor (MPNST) from its benign precursor lesion: A cross-sectional study

BackgroundThe leading cause of mortality for patients with the neurofibromatosis type 1 (NF1) cancer predisposition syndrome is the development of malignant peripheral nerve sheath tumor (MPNST), an aggressive soft tissue sarcoma. In the setting of NF1, this cancer type frequently arises from within its common and benign precursor, plexiform neurofibroma (PN). Transformation from PN to MPNST is challenging to diagnose due to difficulties in distinguishing cross-sectional imaging results and intralesional heterogeneity resulting in biopsy sampling errors.Methods and findingsThis multi-institutional study from the National Cancer Institute and Washington University in St. Louis used fragment size analysis and ultra-low-pass whole genome sequencing (ULP-WGS) of plasma cell-free DNA (cfDNA) to distinguish between MPNST and PN in patients with NF1. Following in silico enrichment for short cfDNA fragments and copy number analysis to estimate the fraction of plasma cfDNA originating from tumor (tumor fraction), we developed a noninvasive classifier that differentiates MPNST from PN with 86% pretreatment accuracy (91% specificity, 75% sensitivity) and 89% accuracy on serial analysis (91% specificity, 83% sensitivity). Healthy controls without NF1 (participants = 16, plasma samples = 16), PN (participants = 23, plasma samples = 23), and MPNST (participants = 14, plasma samples = 46) cohorts showed significant differences in tumor fraction in plasma (P = 0.001) as well as cfDNA fragment length (P < 0.001) with MPNST samples harboring shorter fragments and being enriched for tumor-derived cfDNA relative to PN and healthy controls. No other covariates were significant on multivariate logistic regression. Mutational analysis demonstrated focal NF1 copy number loss in PN and MPNST patient plasma but not in healthy controls. Greater genomic instability including alterations associated with malignant transformation (focal copy number gains in chromosome arms 1q, 7p, 8q, 9q, and 17q; focal copy number losses in SUZ12, SMARCA2, CDKN2A/B, and chromosome arms 6p and 9p) was more prominently observed in MPNST plasma. Furthermore, the sum of longest tumor diameters (SLD) visualized by cross-sectional imaging correlated significantly with paired tumor fractions in plasma from MPNST patients (r = 0.39, P = 0.024). On serial analysis, tumor fraction levels in plasma dynamically correlated with treatment response to therapy and minimal residual disease (MRD) detection before relapse. Study limitations include a modest MPNST sample size despite accrual from 2 major referral centers for this rare malignancy, and lack of uniform treatment and imaging protocols representing a real-world cohort.ConclusionsTumor fraction levels derived from cfDNA fragment size and copy number alteration analysis of plasma cfDNA using ULP-WGS significantly correlated with MPNST tumor burden, accurately distinguished MPNST from its benign PN precursor, and dynamically correlated with treatment response. In the future, our findings could form the basis for improved early cancer detection and monitoring in high-risk cancer-predisposed populations.

Jeffrey J. Szymanski and colleagues investigate the use of cell-free DNA ultra-low-pass whole genome sequencing to distinguish the malignant peripheral nerve sheath tumor (MPNST) from its benign precursor lesion in patients with Neurofibromatosis type 1 in United States.     

Molecular structure in peripheral dog breeds: Portuguese native breeds as a case study

Genetic variability in purebred dogs is known to be highly structured, with differences among breeds accounting for ∼30% of the genetic variation. However, analysis of the genetic structure in non-cosmopolitan breeds and local populations is still limited. Nine Portuguese native dog breeds, and other peripheral dog populations (five) with regional affinities, were characterized using 16 microsatellites and 225 amplified fragment length polymorphism (AFLP) markers, and the pattern of genetic differentiation was investigated. Although the level of breed differentiation detected is below that of other dog breeds, there is in most cases a correlation between breed affiliation and molecular structure. AFLP markers and Bayesian clustering methods allowed an average of 73.1% of individuals to be correctly assigned to source populations, providing robust genotypic assessment of breed affiliation. A geographical genetic structure was also detected, which suggests a limited influence of African dogs on the Iberian breeds. The sampling effect on the estimation of population structure was evaluated and there was a 2.2% decrease in genetic differentiation among breeds when working animals were included. Genetic diversity of stray dogs was also assessed and there is no evidence that they pose a threat to the preservation of the gene pool of native dog breeds.     

Evaluation of myelin sheath and collagen reorganization pattern in a model of peripheral nerve regeneration using an integrated histochemical approach

Peripheral nerves are complex histological structures that can be affected by a variety of conditions with different degree of axonal degeneration and demyelination. For the study of peripheral nerve regeneration in pathology and tissue engineering, it is necessary to evaluate the regeneration, remyelination and extracellular matrix reorganization of the neural tissue. Currently, different histochemical techniques must be used in parallel, and a correlation among their findings should be further performed. In this work, we describe a new histochemical method for myelin and collagen fibers based on luxol fast blue and picrosirius methods, for the evaluation of the morphology, the myelin sheath and the collagen fiber reorganization using a model of peripheral nerve regeneration. Whole brain, normal sciatic nerve and regenerating peripheral nerve samples were fixed in 10% neutral buffered formalin and paraffin-embedded, for the performance of the hematoxylin-eosin stain, the Luxol fast blue method and the new histochemical method for myelin and collagen. The results of this technique revealed that this new histochemical method allowed us to properly evaluate histological patterns, and simultaneously observe the histochemical reaction for myelin sheath and collagen fibers in normal tissue, and during the regeneration process. In conclusion, this new method combines morphological and histochemical properties that allowed us to determine with high accuracy the degree of remyelination and collagen fibers reorganization. For all these reasons, we hypothesize that this new histochemical method could be useful in pathology and tissue engineering.     

人脑对不同频率穴位电刺激反应的功能性磁共振成像

利用功能性磁共振方法研究人脑对不同频率穴位体表电刺激（transcutaneous electric nerve stimulation,TENS)的反应。实验对11名志愿得进行了22次脑部功能性磁共振成像。成像过程中,每名志愿者分别接受了2和100HzTENS刺激,刺激部位为左腿足三里和三阴交穴,结果为不同频率TENS都激活了初级和次级躯体感觉区,频率特异性的激活信号出现在与运动相关的区域、丘脑、边缘系统和联络皮层。结果显示,在相同穴位给予不同频率的TENS要以在大脑引起不同的反应,提示2和100HzTENS可能激活了不同的神经通路,这些神经通路分别在中枢神经系统起着不同的作用。     

Epithelial myoepithelial carcinoma of the parotid gland with malignant ductal and myoepithelial components arising in a pleomorphic adenoma: a case report with cytologic, histologic and immunohistochemical correlation

BACKGROUND: To describe the cytologic, histologic and immunohistochemical findings of a case of epithelial myoepithelial carcinoma (EMC) arising from a pleomorphic adenoma (PA) of the parotid with both malignant epithelial and myoepithelial components. CASE: A 29-year-old female presented with a 1.5 x 1.5-cm, palpable mass of the left parotid of 7-8 months' duration with recent enlargement and pain. Fine needle aspiration biopsy (FNAB) revealed biphasic epithelial (small cell) and myoepithelial (large/clear cell) clusters arranged in a pseudopapillary and trabecular pattern with abundant hyaline material with many naked nuclei, together with areas typical of pleomorphic adenoma (PA) was noted. The cytology was reported as salivary gland neoplasm, "suggestive of adenoid cystic carcinoma, less likely pleomorphic adenoma." The mass was excised and histologically reported as "pleomorphic adenoma, with focal invasion of one resected margin." Four months later the tumor recurred, and FNAB showed almost the same cytologic features as did the previous aspirate. Due to early recurrence, previous histologic sections were reviewed, and typical areas of a biphasic pattern of EMC with atypicality and mitosis of both components was found. The final diagnosis was EMC ex PA. CONCLUSION: Although previous reports mention the difficulties in diagnosing EMC and differentiation from the more common salivary gland neoplasms such as PA, we like to emphasize the cytologic confusion that results when the tumors coexist.     

Identification of miRNA-103 in the cellular fraction of human peripheral blood as a potential biomarker for malignant mesothelioma--a pilot study

Background

To date, no biomarkers with reasonable sensitivity and specificity for the early detection of malignant mesothelioma have been described. The use of microRNAs (miRNAs) as minimally-invasive biomarkers has opened new opportunities for the diagnosis of cancer, primarily because they exhibit tumor-specific expression profiles and have been commonly observed in blood of both cancer patients and healthy controls. The aim of this pilot study was to identify miRNAs in the cellular fraction of human peripheral blood as potential novel biomarkers for the detection of malignant mesothelioma.

Methodology/Principal Findings

Using oligonucleotide microarrays for biomarker identification the miRNA levels in the cellular fraction of human peripheral blood of mesothelioma patients and asbestos-exposed controls were analyzed. Using a threefold expression change in combination with a significance level of p<0.05, miR-103 was identified as a potential biomarker for malignant mesothelioma. Quantitative real-time PCR (qRT-PCR) was used for validation of miR-103 in 23 malignant mesothelioma patients, 17 asbestos-exposed controls, and 25 controls from the general population. For discrimination of mesothelioma patients from asbestos-exposed controls a sensitivity of 83% and a specificity of 71% were calculated, and for discrimination of mesothelioma patients from the general population a sensitivity of 78% and a specificity of 76%.

Conclusions/Significance

The results of this pilot study show that miR-103 is characterized by a promising sensitivity and specificity and might be a potential minimally-invasive biomarker for the diagnosis of mesothelioma. In addition, our results support the concept of using the cellular fraction of human blood for biomarker discovery. However, for early detection of malignant mesothelioma the feasibility of miR-103 alone or in combination with other biomarkers needs to be analyzed in a prospective study.     

Retraction Note to: Silibinin ameliorates arsenic induced nephrotoxicity by abrogation of oxidative stress,inflammation and apoptosis in rats

Molecular Biology Reports -     

Patho- and immunobiology of malignant mesothelioma: characterisation of tumour infiltrating leucocytes and cytokine production in a murine model

Malignant mesothelioma (MM) is an aggressive, uniformly fatal serosal tumour, usually associated with asbestos exposure, for which there currently is no effective treatment. In order to gain insight into the mechanism(s) whereby MM might escape immune surveillance, a murine model for MM was used (a) to characterise the tumour-infiltrating lymphocytes (TIL) and macrophages (TIM) phenotypically, (b) to examine systemic immune recognition of MM, and (c) to examine the possible influence of tumour-derived cytokines on systemic and local pathobiological manifestations of MM. A profound down-regulation of lymphocyte surface markers, known to be infolved in T cell activation, was found in TIL. Likewise, although TIM were present in large numbers, their expression of MHC class II antigen and integrins was weak or absent, suggestive of altered functional activity. Significant amounts of cytokines, in particular transforming growth factor , interleukin-6 (IL-6), IL-1 and tumour necrosis factor were produced during the course of MM tumour development-directly by the MM cells and/or indirectly in response to tumour growth. These factors may contribute both to derangement of antitumour effector mechanisms and to the clinical and pathological manifestations of the disease.