Low-grade Rhabdoid Meningioma: Morphological Characteristics

Low-grade Rhabdoid Meningioma Morphological CharacteristicsArvids Jakovlevs, Andrejs Vanags, Janis Gardovskis, Ilze StrumfaSUMMARYRhabdoid meningioma (RM) is a r ar type of meningioma. It is classified as a grade III tumour (anaplastic meningioma) in the recent World Health Organization (WHO) motley of the tumours of the central nervous system (CNS). Here we advert a unique case of RM missing any features of malignancy. Few cases of inferior RMs are set forth in the literature in contrast with the grading of this entity in WHO classification.Key words meningioma, rhabdoid, inferiorAIM OF THE DEMONSTRATIONThe aim of our article is to report a case of unusual RM lacking malignant features in project to the issue about the prognostic significance of rhabdoid morphology in meningiomas.CASE REPORTA 37-year-old woman was admitted to the hospital due to progressive headaches over foregoing 1.5 years. The magnetic resonance imaging of head and brain revealed a hygienic-demarcated in tracranial lesion measuring 3.53.63.6 cm (Figure 1A). The mass was located adjacent to the frontal bone and was machine-accessible to the dura mater. The patient underwent a craniotomy and total tumour resection. Histological examination of the neoplasm revealed cells consistent with rhabdoid morphology. The tumour was almost entirely composed of polygonal, rather whopping cells that possessed eccentric nuclei, strongly eosinophilic cytoplasm with abundant pale globular inclusions and prominent cytoplasmic granularity (Figure 1B). The nuclei of neoplastic cells were slightly pleomorphic. Mitoses were absent in the whole specimen. In addition, the tumour had well-developed fibrous capsule that demarcated it from normal brain tissues. Psammoma bodies were found in some areas of the tumour. Immunohistochemical visualization (IHC) showed intense cytoplasmic manifestation of vimentin and epithelial membrane antigen (Figure 1C-D) as well as strong nuclear expression of progesterone rec eptors in the tumour cells. The neoplastic cells did not express beam muscle actin, desmin, HMB-45, S-100 protein, kappa and lambda light chains. Ki-67 proliferation index was as low as 1.5 %.Thus, the morphological appearance and immunohistochemical features were consistent with RM and low-grade cellular characteristics.DISCUSSIONTumours with rhabdoid morphology were first described in 1978 in relation to malignant renal tumours of children (1). Nowadays, many tumours with rhabdoid morphology are known in distinguishable localizations including CNS and meninges. Rhabdoid cells confine no take the stand of myogenic origin. The term rhabdoid is utilise to denote close histological resemblance of tumour cells to rhabdomyoblasts. Rhabdoid cells are characterized by typical light microscopic morphology round cells with eccentric, vesicular nuclei, prominent nucleoli and eosinophilic cytoplasm with paranuclear globular inclusions (3).Meningiomas developing from the meninges are amon g the most common intracranial tumours. Regarding these tumours, surgery is the mainstay of treatment, and neurosurgeon also is complicated in the planning of further observation and treatment in accordance to the tumour grade (5). Meningiomas show wide telescope of histopathological appearances. While the majority of meningiomas are benign tumours (WHO grade I meningiomas), some meningiomas fix increased risk of local recurrences (WHO grade II meningiomas) and the minority are truly malignant and rescue a risk of metastatic dissemination these are classified as WHO grade III meningiomas (2). RM is an uncommon type of meningioma which was described for the first time in 1998 (3). It was found that rhabdoid morphology in meningiomas was associated with a worse prognosis (3). Soon after this finding RM was separated as a distinct entity in WHO classification of CNS tumours published in 2000. RM has been classified as a grade III neoplasm by WHO (2). Consistent with the malignant b ehaviour, significant mitotic military action, anaplasia and other temporary features are usually found in RMs (2, 4). However, there are some isolated reports of RMs with no evidence of cellular atypia (6). In our case diagnosis of RM was accomplished due to pure rhabdoid morphology along with meningothelial origin that was clearly demonstrated by IHC. Absence of atypia in the tumour cells and low Ki-67 proliferation index was consistent with low-grade meningioma in the present case.In conclusion, rhabdoid meningioma occasionally lacks histological features of malignancy that can lead to confusion if the rhabdoid morphology is always associated with malignant behaviour. Increased awareness of low-grade rhabdoid meningiomas is necessary to estimate the prognosis and to plan the treatment appropriately.REFERENCESBeckwith JB, Palmer NF. Histopathology and prognosis of Wilms tumors results from the First National Wilms Tumor Study // Cancer, 1978 411937 1948Cooper WA, Shingde M, L ee VK, Allan RS, Wills EJ, Harper C. Rhabdoid meningioma lacking malignant features. Report of dickens cases // Clin Neuropathol, 2004 23(1)16 20Louis DN, Ohgaki H, Wiestler OD, Cavenee WK. Meningeal tumors // In Bosman FT, Jaffe ES, Lakhani RS, Ohgaki H. WHO Classification of tumours of the central nervous system. 4th edition. Lyon IARC 2007 164-180Perry A, Scheithauer BW, Stafford SL, Abell-Aleff PC, Meyer FB. Rhabdoid meningioma an aggressive variant // Am J Surg Pathol, 1998 221482 1490Walcott BP, Nahed BV, Brastianos PK, Loeffler JS. Radiation treatment for WHO grade II and III meningiomas // Front Oncol, 2013 3227, doi10.3389/fonc.2013.00227Zhou Y, Xie Q, Gong Y, Mao Y, Zhong P, Che X, Jiang C, Huang F, Zheng K, Li S, Gu Y, Bao W, Yang B, Wu J, Wang Y, subgenus Chen H, Xie L, Zheng M, Tang H. Clinicopathological analysis of rhabdoid meningiomas Report of 12 cases and a systematic review of the literature // World Neurosurg, 2013 79(5-6)724 7323t-Alkyl-2r,6c-diarylpiperidin -4-ones Synthesis3t-Alkyl-2r,6c-diarylpiperidin-4-ones Synthesis3t-Alkyl-2r,6c-diarylpiperidin-4-onesSynthesisA very favorable and non-laborious one-pot synthesis method developed by Noller and Baliah 50 has been used successfully for the synthesis of 3t-alkyl-2r, 6c-diarylpiperidin-4-ones 32 by the condensation of methyl radical ketones, aromatic aldehydes and ammonium acetate in 121 molar ratio (Scheme 13). Its a non-laborious one-pot synthesis of 3t-alkyl-2r, 6c-diarylpiperidin-4-ones 32. Various substituted piperidin-4-ones were also synthesized by adapting the above method 53-,57. Often used typical procedure reported by Baliah and Jeyaraman was adapted to synthesis several substituted 3t-alkyl-2r,6c-difuranylpiperidin-4-ones 33 and 3t-benzyl-2r,6c-diarylpiperidin-4-ones 34 with convenient modification 58,59.Seven r(2),c(4)-bis(isopropoxycarbonyl)-t(3)-aryl-c(5)-hydroxy-t(5)-methylcyclohexano-nes (aryl = C6H5, p-ClC6H4, p-FC6H4, p-OMeC6H4, p-Me2NC6H4, m-O2NC6H4 and m-C6H5OC6H 4) shoot been synthesized by abridgment isopropyl acetoacetate with aromatic aldehydes in the presence of methylamine 53. Aridoss et al have synthesized an array of novel N-morpholinoacetyl-2,6-diarylpiperidin-4-ones as well as imidazo(4,5-b) pyridinylethoxypiperidones and Structure and stereochemistry of all the N-morpholinoacetyl-2,6-diarylpiperidin-4-ones have been analyzed utilize 1H and 13C proton magnetic resonance spectroscopic techniques 54,55. 1H and 13C NMR spectra have been recorded for 2r,6c-diarylpiperidin-4-one (3_-hydroxy-2_naphthoyl)hydrazones and 3,3-dimethyl-2r,6c-bis(p-methoxyphenyl)piperidin-4-one 56-57.Conversion to other derivativesOther derivatives from piperidin-4-ones have been obtained which includes oximes 35 60-73, hydrazones 36 57,74, semicarbazones 37 75, thiosemicarbazones 38 69, and phenylhydrazones 39 76 by the reaction of the carbonyl crowd with suitable reagents. 2r,6c-diarylpiperidin-4-ones have been reduced to obtain 4t-Hydroxy-2r, 6c-dipheny lpiperidines 40a and 4c-hydroxy-2r,6c-diphenylpiperidines 40b. N-substituted 2r,6c-diarylpiperidin-4-ones 41-51 was obtained by the reaction of the NH function with suitable reagents have been reported (Scheme 13) 77-84.Physico-chemical studiesSeveral physico-chemical studies have been performed for 3t-Alkyl-2r,6c-diarylpiperidin-4-ones and their derivatives 64-91. Several studies have documented the conformations of various substituted 2,6-diarylpiperidin-4-ones 78,86. Pandiarajan et al. 88 have elaborately discussed the conformations of 32 and suggested chair conformation to these compounds with equatorial disposition of the aryl and alkyl substituents based on their NMR spectral data. Substitution of alkyl group at C-3 position of the piperidine ring causes the ring to flatten slightly about C(2)-C(3) bond probably to decrease graceless interaction between aryl and alkyl groups at C(2) and C(3). Stereochemistry of N-acetyl and N-benzoyl-2r,6c-diphenylpiperidin-4-one oximes 5256 h as been already reported 89. Synthesis and conformation of 3t-chloro-2r,6c-diarylpiperidin-4-ones 57 also been reported 90,91. Manimekalai et al. 92 demonstrated the conformation of benzyl group in 4-benzyl-4-hydroxypiperidines 58.Pharmacological studiesMany piperidine derivatives possess pharmacological activities including disinfectant, antioxidant and anticancer activities and to form an essential part of the molecular structure of classic drugs 9, 93-97. Piperidin-4-ones have been used for outgrowth of compounds with selective biological activities include antiviral 98, antitumor 99, analgesic 100, local anesthetic 101,102, bactericidal 103, fungicidal 103, herbicidal 103, insecticidal 104, antihistaminic 104, anti-inflammatory 104, anticancer 105, CNS stimulant 105, antitubercular and soporific 106 activities. Earlier reports have clearly established that the biological activitiesR1 of piperidin-4-ones were improved by incorporation of the substituents at C-2, C-3 and C-6 1 06,107. Ferguson documented that N-nitrosopiperidines are carcinogenic in nature and stop of one of the position by an alkyl group significantly reduces the carcinogenic activity 108. Lijinsky and Taylor have also supports that blocking of positions to the N-nitroso group by methyl groups reduces the carcinogenic activity 109.3t,5t-Dimethyl-2r,6c-diarylpiperidin-4-one hydrochlorides 59-61 have shown anti-histaminic activity 110. Furthermore, 3t,5t-dimethyl-2r,6c-bis(4-hydroxyphenyl)piperidin-4-one 62 and 3t-methyl-5-substitutedphenyl-2r,6c-diarylpiperidin-4-ones 63 showed antimicrobial, insecticidal and antihistaminic activities 111. 2,3,6-Triarylpiperidin-4-ones 64 and their oximes exhibits marked bactericidal, fungicidal and herbicidal activities 104. N-Substituted piperidin-4-one 65 and its derivatives 66 and 67 exhibited potential Juvenile hormone activity on Bombyx mori 112. N-methyl-3E,5E-bis(arylidine)piperidin- 4-ones 68, possessing a variety of aryl and heteroaryl groups, showed antiviral and antitumor activities 98. 3E,5E-Bis(benzylidene)piperidin-4-one 69, 1-acryloyl derivatives of 69, and 70 the adduct of 2-mercaptoethanesulfonic acid 71 as well as 3E,5E-Bis(thienylidene)-piperidin-4-ones 72 have shown antitumor activity towards human carcinoma cell lines Caov3, Scov3 and A549 113. Furthermore, modification of position 3 of the piperidin-4-one nucleus as well as a substitution of certain serviceable groups in the para position of phenyl ring habituated to C-2 and C-6 carbons of the piperidine moiety would result in compounds of potent biological activities.HydrazonesHydrazones are a class of organic compounds with azomethine -NHN=CH- proton that constitutes an definitive class of compounds for new drug development 10,97,98. Hydrazone are formed usually by the action of hydrazine on ketones or aldehydes. Hydrazide-hydrazone derivatives receive the attention of various medicative chemists as a result of their takingsual biological potencies vi z., antimicrobial, anti-tubercular, and also anticonvulsant actions 10,114-116. Some hydrazones is known to act as herbicides, insecticides, nematocides, rodenticides and plant growth regulators. Several studies have documented the spasmolytic activity, hypotensive action and activity against leukaemia, sarcomas and other malignant neoplasms 114-116.Many of the physiologically active hydrazones have applications in diseases like tuberculosis, leprosy and mental overturn are characterized by the presence of the triatomic group (C=NN73 117. Hydrazones are also useful in detection, determination and isolation of compounds containing the carbonyl group and many other metals 10. Syringaldehyde hydrazones 74 and 6-nitro-3,4-methylene-dioxophenyl-N-acylhydrazone 75 exhibits antioxidant properties 118,119. Hydrazone and its substituted derivatives showed good antibacterial, antifungal, anticonvulsant, antitubercular, anticancer and antitumor activities. 1-4=(2-(4-Substitutedphenyl)methylen ehydrazine carbonyl)phenyl-3-substituted thioureas 76 exhibited good clinically active tuberculostat 120.Some coupling products from 4-aminobenzoic acid hydrazones 77 and (7-Hydroxy-2-oxo-2H-chromen-4-yl)acetic hydrazide 78 showed antimicrobial activity 121,122. A series of 4-fluorobenzoic acid (substituted methylene/ ethylidine) hydrazide derivatives 79 showed the chemotherapeutic antituberculosis activities 123. Hemalatha et al have documented the antibacterial and antifungal activities of N-nitroso-2,6-diarylpiperidin-4-one semicarbazones 124. Some bicyclic semicarbazones and thiosemicarbazones 81 showed a wide variety of biological activities 124.The significance of fusing heterocyclesHeterocycles possess an enormously diverse group of compounds, are widely distributed in nature. Heterocycles can be tardily manipulated and modified by organic synthetic methods to increase or decrease reactivity. They are used extensively as intermediates in various reactions as well as building blocks in organic synthesis. Novel libraries of biologically diverse heterocyclic compounds have been synthesized by incorporation and substitution of a wide range of functional groups (ring activators or deactivators) and their positions around the ring of heterocycles. Several studies provide evidence that combination of two bio-active heterocyclic moieties together leads to the production of novel and biologically important compounds with the anticipation of several promising pharmacological agents 4,125. Based on the above features discussed under 3t-Alkyl-2r,6c-diarylpiperidin-4-ones, 2r,4c-Diaryl-3-azabicyclo3.3.1nonan-9-ones and hydrazones, we have developed the system that fuse 3-azabicyclonones/piperidin-4-one pharmacophore and hydrazide moieties together to produce the gibe hydrazones with the anticipation of several promising antioxidant, anticancer and antimicrobial agents arising.The relevant technique used to elucidate the structure of the newly synthesized compounds Specialized spectroscopic instruments can be used to generate development that enables the determination of the structure of an unknown organic compound. This includes Infrared spectrometry (IR), nuclear magnetic spectrometry (NMR) and elemental analysis. Among all getable spectrometric methods, NMR is the only technique which offers a complete analysis and adaptation of the entire spectrum 126,127. A few of the strategies of NMR experiments that are used in determination of different compounds are described as follows.NUCLEAR MAGNETIC RESONANCE SPECTROSCOPYNuclear magnetic resonance spectroscopy, one of the most assorted techniques for elucidation of structure of organic compounds, has shown a tremendous progress due to improved experimental technology and novel forward motiones. In NMR, the most useful information comes from the interactions between two nuclei, either through the bonds which connect them (J-coupling interaction) or directly through space (NOE interaction) 126- 128.Interpretation of NMR spectra is well understood from the following elemental information gathered from NMR spectra. 1) Chemical shift, which identifies the type of proton based on their electronic environment, 2) Spin-Spin splitting patterns, which identifies neighbouring protons, 3) Peak Area, which is proportional to the number of protons giving a feature resonance line, 4) The observation of a triplet and a quartet spin state confirming usually the presence of an ethyl group (CH3CH2) and 5) The observation of value between 7.2-8.0 indicates that the structure contains a benzene ring (benzyl proton) 126-130.Generally, three approaches are used in NMR spectroscopy methods. These include one dimension (1D), two dimensions (2D) and three dimensions (3D). The first approach of 1D-NMR (1H DEPT, 13C, 15N, 19F, 31P, etc.) generates good information about the structure of simple organic compounds. However, it is overcrowded in case e of larger molecules. The second approach of 2D- NMR (COSY, DQFCOSY, MQFCOSY, HETCOR, HSQC, HMQC, HMBC, TOCSY, NOESY, EXSY, etc.) is used for the further larger molecules. A 2D-NMR spectrum also becomes complex and overlapping in case of further very large molecules like proteins. Therefore, multi-Dimensional-NMR (Homonuclear and Heteronuclear) are more often than not used to achieve high resolution and reduced overlapping in spectra of very large molecules 126,128,129. This section further describes the general interpretation of structure of different organic compounds by different NMR techniques.1D NMR SPECTROSCOPY1H-NMR Spin transitions of only hydrogen nuclei are observed in in 1H-NMR spectroscopy. Table 1 represents different values, couplings, coupling constants and chemical shifts of 1H nuclei processing in different chemical environments. Commonly, value scale of 1H-NMR ranges from 0-10 ppm with respect to Tetra methyl Silane (TMS) as internal standard. 1H-NMR spectral interpretation can be best understood from table 4 126,131.1H Chemical shiftsBecause of variations in the electron distribution, the variation of nuclear magnetic resonance frequencies of the same pleasant of nucleus is referred to as chemical shift (symbolized by ). Quantitative chemical shift are measured in frequency (Hertz) relative to a standard, Tetra methyl silane (TMS). Characterization of the structure of a molecule is depending upon the position and number of chemical shifts 111,112,115. The chemical shift range of 1H nuclei can also be understood from a chart given in figure 1 126.The chemical shift values for methyl protons attached to groups of varied electronegativity are given under 127CH3I-2.16CH3Br-2.18CH3Cl-3.05 andCH3F-4.26 ppm,The electron density around the proton affects its chemical shift. Because of the e- density around the H nuclei, the CH3 protons come to resonance at higher values as the electronegativity of a functional group is increased. Electronic charge surrounded to H nuclei shields the nucleus t o some extent from the influence of the applied theater. The magnetic flux overcomes this shielding effect in order to bring a proton to resonance. Thus, the higher the electron density around the proton, the greater the induced diamagnetic effect and the greater the external field required to overcome the shielding effect. Electro-ve groups like fluorine in CH3F withdraws e- density from the CH3 group (-inductive effect). This leads to de-shielding by lower value of an applied magnetic field in order bring the methyl proton to resonance. Fluorine is more electro-ve than Cl, thus the proton in CH3F appears at a higher values than those in CH3Cl. The chemical shift positions for protons attached to C=C in alkenes is higher compared to that of accounted by electronegative effect alone. Alkene and aromatic protons appear at high values while alkyne CC protons appear at a relatively low value 126,127,132.The magnetic field created by pi electrons or rings is referred to as Magnetic anisotropy, which describes an environment where different magnetic fields are found at different points in space. Since Pi electrons are held less strongly than sigma electrons, pi electrons are more able to move in response to the magnetic field. The anisotropic effects of the electrons of C-C bond is low compared to those of the circulating -electrons. The equatorial protons in cyclohexane come across at 0.5 ppm higher than the axial protons. This is due to the anisotropic effect of the -electron in the C-C bonds 127,133 (Figure. 2).R1Specify which biological activity