An unusual case of a grade I meningioma with perineural spread.

A 39-year-old lady with worsening intermittent diplopia and headaches was diagnosed with a WHO Grade I Meningothelial Meningioma with highly unusual perineural spread on imaging, making this the first reported case of this behaviour. Complete surgical resection was deemed too great a risk and the patient remains under observation. The process of perineural spread is not restricted to more aggressive brain tumours.

Clearance of neurotoxic peptides and proteins by meningothelial cells.

Meningothelial cells (MECs) are the cellular component of the meninges that provide physical protection to the central nervous system (CNS). Their main function is the formation of a barrier enclosing the brain including the cerebrospinal fluid (CSF). Further, MECs are involved in maintaining CSF homeostasis by clearing CSF from bacteria and apoptotic cells. Furthermore, secretion of pro- and anti-inflammatory cytokines and chemokines involves MECs in immunological processes in the CNS. We demonstrated that meningothelial Ben-Men-1 cells ingest neurotoxic peptides amyloid-ß (Aß1-40) and protein α-synuclein up to about 10-fold more efficiently compared to neuronal-like SH-SY5Y cells. Aß1-40 and α-synuclein are mainly taken up via macropinocytosis. Caveolar endocytosis in addition contributes to α-synuclein ingestion. Upon uptake, both are trafficked towards lysosomal degradation. While production of reactive oxygen species (ROS) following exposure to Aß25-35 and α-synuclein was similar between Ben-Men-1 and SH-SY5Y cells, mitochondrial function in Ben-Men-1 was significantly more robust to Aß25-35 treatment compared to neuronal-like SHSY5Y cells. Similarly, Ben-Men-1 were significantly less susceptible to Aß25-35-induced cell death than neuronal-like cells. Furthermore, co-culture with Ben-Men-1 offered significant protection to neuronal-like cells against Aß25-35-induced apoptosis. This study reveals for the first time the function of MECs as scavengers of neurotoxic Aß and α-synuclein, thereby connecting these cells to neuroprotective processes and suggesting a new mechanism and pathway for clearing neurotoxic substances from the CSF.

[Minute Pulmonary Meningothelial-like Nodule:A Case Report and Literature Review].

Minute pulmonary meningothelial-like nodule(MPMN)is a rare respiratory disease with no specific clinical manifestations and requires bronchial or percutaneous lung biopsy for diagnosis.Here we report a case of an old male patient with recurrent cough and sputum as the main manifestations,which failed to be cured by antibiotic.His chest computed tomography showed a mass-like tumorous lesion located in the posterior segment of the right upper lobe,and the pathological diagnosis by percutaneous lung biopsy confirmed MPMN with lung infection.At the same time,we reviewed 34 cases to summarize the clinical data,pathological manifestation,diagnosis,treatment,and prognosis of MPMN.

The extracellular matrix composition of the optic nerve subarachnoid space.

The meninges not only surround the brain and the spinal cord but also the optic nerve. Meningeal-derived extracellular matrix (ECM) is a crucial component of the pial basement membrane, glia limitans and important for maintenance of optic nerve axon integrity, homeostasis and retinal ganglion cell health. To get closer insight into optic nerve meningeal-derived ECM composition, we performed proteomic analysis of the sheep optic nerve subarachnoid space (SAS). Candidate components were confirmed in cultures of primary human meningothelial cells (phMECs) and human optic nerve samples. Sheep optic nerve SAS samples were analysed by LC-MS, identified proteins were matched to their human orthologs and filtered using gene lists representing all major ECM components. To validate these findings digital droplet PCR (ddPCR) to evaluate mRNA expression of all candidate components identified was performed on cultures of phMECs. In addition, one protein per major ECM group was stained on human optic nerve sections and on phMEC cultures. Employing LC-MS, 1273 proteins were identified and subjected to bioinformatic analysis. Gene ontology analysis revealed six out of forty-four collagen types (1A1, 1A2, 3A1, 6A2, 6A3 and 14A1), three out of eleven laminin subunits (A4, B2, C1) and six out of twenty-seven hyaluronan binding proteins (CD44, versican (VCAN), C1q binding protein, neurocan (NCAN), brevican (BCAN) and hyalaluronan proteoglycan link protein 2 (HAPLN2)) were present in our cohort. DdPCR in phMEC cell culture confirmed presence of all candidate components except NCAN, BCAN and HAPLN2. Immunohistochemistry (IHC) staining on human optic nerve sections and immunofluorescence (IF) staining on in vitro cultured phMECs showed strong immunopositivity for collagen-typeI-α1 (COL1A1), lamininγ1 (LAMC1), and VCAN. Fibronectin (FN1) was exclusively present in cultures of phMECs. Using a combined bioinformatics and immunohistological approach, we describe the ECM composition of the optic nerve subarachnoid space. As this space plays an important role in maintaining optic nerve function, a better understanding of ECM composition in this delicate environment might be key to further pathophysiological insight into optic nerve degeneration and associated disorders.

Unusual subcutaneous dedifferentiated liposarcoma exhibiting coexistence of meningothelial-like whorls and inflammatory myofibroblastic tumor-like structures.

To explore the clinicopathological features of a rare dedifferentiated liposarcoma (DDLPS) with meningothelial-like whorls, we retrospectively analyzed 46 reported cases and 1 case that we encountered. Fluorescence in situ hybridization (FISH) analysis of the MDM2 amplification status of our case was also performed. Our case involved a 73-year-old male patient who had a mass in the upper part of his left arm for 10 years and was treated by surgical ablation of the tumor because of the mass' recent rapid enlargement. Microscopically, the tumor tissues showed coexistence of well-differentiated and dedifferentiated components, the latter of which included meningothelial-like whorls and inflammatory myofibroblastic tumor-like structures. The dedifferentiated components diffusely expressed vimentin, MDM2, CDK4, p16, and smooth muscle actin. They were also focally positive for desmin but negative for S-100, CD117, CD34, ALK, EMA, SOX-10, p53, and ß-catenin. FISH detection showed MDM2 amplification. In conclusion, subcutaneous DDLPS with meningothelial-like whorls and inflammatory myofibroblastic tumor-like features is rare. This case broadens the histopathological lineage of DDLPS, and confirms DDLPS with myogenic differentiation. The use of the combination of MDM2, CDK4, p16, and FISH to detect MDM2 amplification is a reliable basis for the diagnosis of DDLPS with meningothelial-like whorls.

MUC4 expression in meningiomas: under-recognized immunophenotype particularly in meningothelial and angiomatous subtypes.

AIMS: MUC4 is a transmembrane glycoprotein that plays a role in cell growth signalling and is expressed in various epithelial tissues. Gene expression profiling and immunohistochemical analyses revealed that MUC4 is also constantly and specifically expressed in low-grade fibromyxoid sarcomas and sclerosing epithelioid fibrosarcomas among the mesenchymal tumours, and immunohistochemical detection of MUC4 is extremely useful for their diagnoses. In our routine pathological practice, we noticed that meningiomas are also often positive for MUC4, which has not yet been reported previously, despite the extensive scrutiny of its expression in soft tissue tumours. METHODS AND RESULTS: We examined immunohistochemically the expression of MUC4, progesterone receptor (PgR) and somatostatin receptor 2A (SSTR2A) in 140 meningiomas of various histological subtypes and 123 other mesenchymal tumours, including intracranial or sinonasal tumours and peripheral nerve sheath tumours. MUC4 was expressed in 130 meningiomas (92.9%). MUC4 expression was constant and almost diffuse in meningothelial and angiomatous subtypes, whereas it was limited in 5% or fewer tumour cells or absent in 26 of 28 fibrous meningiomas. All other mesenchymal tumours examined were negative for MUC4. PgR and SSTR2A were expressed in 94 (67.1%) and 134 (95.7%) meningiomas, respectively. Five of six SSTR2A-negative meningiomas focally expressed MUC4. CONCLUSIONS: MUC4 is expressed variably but almost consistently in meningiomas, particularly in meningothelial or angiomatous subtypes. Its immunohistochemical detection is useful to distinguish meningiomas from other intracranial or head and neck mesenchymal tumours, particularly those with epithelioid features. Our study could expand a variety of MUC4-positive mesenchymal tumours.

[Diffuse pulmonary meningotheliomatosis: a case report and literature review].

Objective: To analyze the clinical features, diagnosis and differential diagnosis of diffuse pulmonary meningotheliomatosis (DPM), a rare subtype of minute pulmonary meningothelial-like nodules (MPMN), so as to improve the understanding of this disorder. Methods: The clinical data of a patient diagnosed as DPM admitted in department of Respiratory Medicine, Peking University Third Hospital in August 2016 were reported and the related literatures were reviewed. With "pulmonary meningothelial-like nodules" , "minute pulmonary meningothelial-like nodules" or "diffuse pulmonary meningotheliomatosis" as the search terms, and the search time before November 1st 2017 for Wanfangdata, China National Knowledge Infrastructure (CNKI), and PubMed.Twenty-five articles were retrieved, among which 6 English (all case reports) articles were found with the search term "diffuse pulmonary meningotheliomatosis" involving 10 cases, and the other 19 articles (1 Chinese, 18 English) about MPMN mainly discussed non-DPM cases,including 13 case reports and 6 pathological/genetic studies. Results: A 68-year old female was admitted to the hospital because of intermittent cough and expectoration for more than 3 years and aggravation for 3 weeks. Her pulmonary CT showed diffuse minute nodules distributed randomly throughout both lungs, and did not improve after treatment with oral Moxifloxacin for 2 weeks. A video-assisted thoracoscopic biopsy was performed. The specimens showed MPMN and no other lesions, which confirmed the final diagnosis of DPM. She was followed without any medication therapy and her pulmonary CT showed stabilization of the lesions one year later. DPM was considered as a rare type of MPMN. A total of 11 cases were analyzed, including 10 cases reported in the literature. The patients included 1man and 10 women, aged 51 to 75 years, with an average age of (64±8) years. Among the 11 patients, 8 denied a history of smoking or of occupational exposure, 7 presented with dyspnea, shortness of breath, or fatigue, and 8 had mild abnormalities of pulmonary function test. The pulmonary CT of all the patients showed randomly distributed, diffuse bilateral small solid or ground-glass nodules, with the diameters less than 5 millimeters, some of which were cavitated. Only 1 patient had pulmonary thromboembolism, while the other 10 did not have any other lung diseases. All the patients were histologically diagnosed, 8 by open lung biopsies, 2 by transbronchial lung biopsy, and 1 by CT-guided fine needle aspiration. Three patients were followed for 12-92 months and the lung lesions were all stable. Conclusions: As a rare subtype of MPMN, DPM lacks specificity of clinical manifestations, and presents with diffuse bilateral small solid or ground-glass nodules, distributed randomly throughout both lungs. An early correct diagnosis depends on biopsy.

Rare congenital meningothelial hamartoma of the scalp with progressive growth.

Scalp lesions are common pediatric findings that present for neurosurgical evaluation and management. The majority will be benign. Meningothelial hamartomas represent a rare subset of congenital cutaneous lesions with the potential for intracranial extension and microscopic infiltration of the surrounding tissues. The authors report in this paper a case of meningothelial hamartoma of the scalp that demonstrated serial growth and invasion of the scalp. The degree of microscopic involvement and growth necessitated close follow-up and repeat excision.

Anaplastic and meningothelial meningiomas in a single tumor: A "dedifferentiated meningioma"?

The patient was a 74-year-old man, who developed progressive cognitive impairment and gait instability. Neuroradiological examination demonstrated a large and predominantly extra-axial tumor spreading over the bilateral frontal base, indicative of olfactory groove meningioma. The greater part of the resected tumor consisted of a dense, patternless proliferation of large, round or polygonal cells, and compactly fascicular growth of spindle cells. Tumor cells showed markedly anaplastic cytological features. In small areas of the tumor, a typical meningothelial meningioma showing no cellular atypism was found. Both tumor components were closely juxtaposed and no pathological features of an intermediate grade (atypical meningioma) were noted. Shortly after the operation, the patient developed a local recurrence of the tumor and multiple metastases to the cerebrum, bone and skin. Anaplastic meningioma is a rare, highly malignant neoplasm which arises de novo or as a result of the progressive transformation of a low-grade meningioma. The coexistence of anaplastic and low-grade components in a single meningeal tumor has been rarely reported. This dimorphic appearance is reminiscent of "dedifferentiation", a phenomenon infrequently seen in various mesenchymal and salivary gland neoplasms. We think that the term "dedifferentiated meningioma" can be appropriately applied to tumors such as that reported herein.

[Meningothelial hamartoma of the scalp. A case report]. / Meningoteliální hamartom mekkých tkání hlavy.

We report the case of a 34-year - old male with meningothelial hamartoma. The patient had a subcutaneous tumor of the scalp, clinically diagnosed as a lipoma. Histologically, the tumor consisted of mature connective tissue elements, adipose tissue, blood vessels and clusters of cuboidal or polygonal cells with scant eosinophilic or amphophilic cytoplasm and regular nuclei. Mitoses were absent. Immunohistochemically, these cells showed diffuse positivity for vimentin, epithelial membrane antigen (EMA) and progesterone receptors. Other markers examined, including α-smooth muscle actin, CD34, desmin, cytokeratin AE1/AE3, cytokeratin CAM 5.2, α-inhibin, estrogen receptors, synaptophysin, chromogranin A and S100 protein, were negative. Meningothelial hamartoma is a rare benign lesion known under many synonyms and the exact number of reported cases is difficult to establish.

Intracranial cystic meningiomas: A rare type of tumours.

INTRODUCTION: Intracranial cystic meningiomas are rare and preoperative diagnosis is difficult. The present study was performed to assess the clinical and radiological outcome of intracranial cystic meningiomas. METHODS: We performed a retrospective analysis of 13 patients (mean age: 49.9 years) who underwent surgical resection of intracranial cystic meningiomas from January 2006 to February 2014. There were 5 male and 8 female patients. The Glasgow Outcome Scale was used to assess the clinical outcome at 6 months. RESULTS: Headache was the main presenting clinical feature. Most of the tumours were located on the right side. The frontal convexity was the most common site. Gross total resection was performed in 10 patients. The most common histopathological type was meningothelial variety. CONCLUSION: Intracranial cystic meningiomas are usually benign that occur in relatively young patients. Resection of cysts that show contrast enhancement is essential to reduce recurrence.

Meningothelial cells as part of the central nervous system host defence.

BACKGROUND INFORMATION: Meningothelial cells (MECs) are the cellular components of the meninges protecting the brain and as such provide important barrier function for the central nervous system building the interface between neuronal tissue and the cerebrospinal fluid (CSF). MECs were previously shown to be involved in the clearance of waste products from the CSF and in maintaining the optic nerve microenvironment. In addition, MECs are involved in immunological processes in the brain by secretion of pro-inflammatory cytokines in response to various pathologically relevant stress conditions. RESULTS: In this study, we analysed the uptake of latex beads as well as bacteria by human MECs using flow cytometric analyses. We found that MECs are highly active phagocytes able of ingesting large amounts of latex beads, as well as Gram-positive and Gram-negative bacteria. Phagocytic activity of MECs was sensitive to nocodazole and cytochalasin D treatment to a varying degree depending on particle composition. Interestingly, Gram-positive bacteria such as Staphylococcus aureus are more readily taken up compared with Gram-negative Escherichia coli. In addition, pre-treatment of MECs with lipopolysaccharide (LPS) or phorbol-12-myristate-13-acetate (PMA) enhanced S. aureus uptake, whereas PMA but not LPS was effective in enhancing E. coli uptake. CONCLUSIONS: Thus, MECs are highly active facultative phagocytes likely important for the maintenance of CSF homeostasis and host defence in the central nervous system especially against Gram-positive bacteria.

Primary pulmonary meningioma and minute pulmonary meningothelial-like nodules: Rare pulmonary nodular lesions requiring more awareness in clinical practice.

In this editorial, we comment on an article by Ruan et al published in a recent issue of the World Journal of Clinical Case. Pulmonary meningothelial proliferative lesions, including primary pulmonary meningiomas, minute pulmonary meningothelial-like nodules, and metastatic pulmonary meningiomas are rare pulmonary lesions. These lesions are difficult to differentiate from lung cancers based on clinical and imaging manifestations. Herein, we briefly introduce the clinical, imaging, and pathological characteristics of these lesions and discuss their pathogenesis to strengthen the current understanding of pulmonary meningothelial proliferative lesions in clinical diagnosis and therapy.

Optic nerve meningioma and cloacal adenocarcinoma in a Humboldt penguin.

A 26-y-old, male, captive Humboldt penguin (Spheniscus humboldti) was euthanized following a 3.5-mo history of weakened elimination mechanics, recurrent tenesmus, intermittent hemorrhagic droppings, and a cloacal mass. Blepharospasm, of unknown cause, of the right eye was present for ~3 mo before euthanasia. Autopsy revealed a cloacal adenocarcinoma with localized coelomic carcinomatosis and distant metastases to the liver and lungs. On histopathology, a 2.6 × 1.2 × 0.5-mm, well-demarcated mass was found surrounding the right optic nerve, expanding the subdural space and wrapping the leptomeninges. The mass was composed of neoplastic spindle-to-polygonal cells consistent with a meningioma, meningothelial subtype. No evidence of neoplasia was found in the optic chiasm or brain, indicating a primary retrobulbar meningioma. Immunohistochemistry for cytokeratin AE1/AE3, vimentin, and S100 revealed robust and consistent immunoreactivity to vimentin, and weak and variable immunoreactivity to cytokeratin and S100, supporting the diagnosis. Meningiomas have been described only rarely in avian species, and we found no reports of optic nerve meningiomas in any avian species to date. The optic nerve meningioma in this case was considered a clinically incidental finding.

Multiple pulmonary nodules with diffuse idiopathic pulmonary neuroendocrine cell hyperplasia and minute pulmonary meningothelial-like nodules.

A 78-year-old woman presented with multiple pulmonary nodules, mixed with solid and ground-glass nodules. We pathologically confirmed that the multiple pulmonary nodules were a combination of diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) and multiple pulmonary meningothelial-like nodules (MPMNs). This is the first case report of concurrent DIPNECH and MPMNs.

Meningothelial hamartoma on the forehead of a young cat.

A 1 year and 2-months-old neutered male cat underwent surgical resection of a cutaneous nodule on the midline of the forehead that had been present since approximately 6 months of age. Histopathologically, the nodule was composed of interlacing collagenous fibres interspersed with varying numbers of spindloid cells with round to oval nuclei and moderate to abundant amounts of pale eosinophilic cytoplasm. Similar to meningothelial cells, the spindloid cells were immunopositive for vimentin, neuron-specific enolase, E-cadherin and somatostatin receptor 2. Based on these findings and the absence of nuclear atypia and mitotic figures, the nodule was diagnosed as meningothelial hamartoma. Although cases of cutaneous meningioma have been reported, this is the first report of meningothelial hamartoma in a domestic animal.

Primary extracranial meningioma of maxilla- A case report.

Meningiomas represent one of the commonest benign neural tissue neoplasms, but it is an extremely rare finding in the oral cavity. It tends to arise from the arachnoid cap cells pertaining to dura matter of the Meninges, the choroid plexus, or the brain stem. Herein, we report the case of a 36-year-old male patient, who visited our Department with the chief complaint of facial swelling associated with asymmetry. Based on thorough clinical, radiological, histopathological and immunohistochemical analyses, a diagnosis of Primary Extracranial Meningioma (PEM) of the Maxilla was made. Later, the tumor was surgically removed, and on follow up, the patient is doing well. Our presented case is extremely unique-it represents a PEM involving the oral cavity.

[Recent Advances and Controversies in Minute Pulmonary Meningothelial-like Nodules].

Minute pulmonary meningothelial-like nodules (MPMNs) are benign small lesions in the lungs, with similar pathological characteristics to the meningeal epithelium. MPMNs have similar imaging manifestations to malignant tumors, which can lead to misdiagnosis in clinical practice. There is no consensus on the pathogenesis of MPMNs, with some suggest that MPMNs derive from reactive proliferation, while others suggest that MPMNs share a common origin and molecular mechanism with meningiomas in the central nervous system. Understanding the characteristics of MPMNs and studying their pathogenesis will help improve the understanding and diagnosis of MPMNs. In this article, we reviewed the clinical, pathological, imaging characteristics, differential diagnosis and pathogenesis of MPMNs. We also analyze the existing research advances regarding the pathogenesis and propose prospects for further research.
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Diffuse pulmonary meningotheliomatosis with pan-TRK expression by immunohistochemistry: a novel finding and potential pitfall.

BACKGROUND: Pulmonary meningothelial-like nodules (PMNs) are benign proliferations of unclear clinical significance. They are mainly asymptomatic lesions that are usually discovered during the pathologic evaluation of resected pulmonary specimens or following post-mortem examination. Diffuse pulmonary meningotheliomatosis (DPM), which presents as bilateral multiple PMNs throughout the lungs, has been described less frequently. DPMs are benign lesions associated with both neoplastic and non-neoplastic pulmonary conditions. CASE PRESENTATION: We report the case of a 59-year-old female patient who presented with a history of cough. Computerized tomography (CT) imaging revealed multiple subcentimeter bilateral pulmonary nodules. transbronchial biopsies were obtained which revealed foci of nodular interstitial proliferations composed of epithelioid to spindled cells in a vague whorled pattern. Immunohistochemical stains were diffusely positive for EMA and progesterone receptor. Furthermore, pan-TRK exhibited strong and diffuse membranous expression in the lesional cells. INSM1 was negative for expression. RNA-based next-generation sequencing for the detection of NTRK fusions was performed and was negative for gene rearrangements involving NTRK1, NTRK2, and NTRK3. CONCLUSION: Here, we report a rare case of DPM and report pan-TRK expression in PMNs which has not been described. We provide a brief review of the literature and provide insight into the potential physiologic nature of PMNs. Lastly, we emphasize the recognition of pan-TRK immunoexpression in PMNs to avoid potential diagnostic errors.