Approximate location and number of primary ectopic meningiomas in the head and neck from 2008 to present.
\r\n\tUsually, the most popular alternative to RWG is the printed circuit technology: microstrip or coplanar lines, for instance. Despite the benefits of reduced cost, volume, and manufacturing easiness, these technologies present quite high power losses.
\r\n\r\n\t
\r\n\tNew planar and substrate integrated waveguides are being developed since 2001 to achieve the desired performance of an RWG but synthesized on one or more printed circuit boards. The first one of its kind was the substrate-integrated waveguide (SIW), which emulates a dielectric-filled RWG in a single circuit board where side walls are made of metallic via holes. Although SIW is a good alternative to classic planar technologies, the presence of lossy dielectric makes it impossible to get a performance similar to an RWG. In 2014 the empty substrate-integrated waveguide (ESIW) was introduced as a composite of three soldered metalized circuit board layers where the middle layer had been emptied to emulate an RWG. By now, ESIW is the best approach to an RWG in terms of performance but retains the characteristics of planar circuits: easiness, compactness, mass production, low volume, low weight, and low cost. Newer hybrid planar – 3D waveguiding structures have also arisen since then, both implementing waveguides of just one conductor (no TEM mode) or two conductors (pure TEM mode).
\r\n\t
\r\n\tThese novel hybrid technologies are receiving much research efforts and continuous advances are being published. The maturity of these technologies and their use by the communication industry may come with an increase in the performance of the communication devices and a major economic impact on the high-frequency communication sectors.
\r\n\tThe goals of this book are to present the basis of these new hybrid structures and to show the advances in the design of devices and systems, manufacturing processes and tests, as well as applications where these technologies can be used.
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Ananias, Laurent Chrusciel, André Zoulalian, Carlos Salinas-Lira and Eric Mougel",authors:[{id:"17265",title:"Prof.",name:"Ruben",middleName:"A.",surname:"Ananias",fullName:"Ruben Ananias",slug:"ruben-ananias"},{id:"20049",title:"Dr.",name:"Laurent",middleName:null,surname:"Chrusciel",fullName:"Laurent Chrusciel",slug:"laurent-chrusciel"},{id:"20050",title:"Dr.",name:"André",middleName:null,surname:"Zoulalian",fullName:"André Zoulalian",slug:"andre-zoulalian"},{id:"20051",title:"Dr.",name:"Carlos",middleName:null,surname:"Salinas-Lira",fullName:"Carlos Salinas-Lira",slug:"carlos-salinas-lira"},{id:"20052",title:"Dr.",name:"Eric",middleName:null,surname:"Mougel",fullName:"Eric Mougel",slug:"eric-mougel"}]},{id:"13540",title:"Transport Phenomena in Paper and Wood-Based Panels Production",slug:"transport-phenomena-in-paper-and-wood-based-panels-production",signatures:"Helena Aguilar Ribeiro, Luisa Carvalho, Jorge Martins and Carlos Costa",authors:[{id:"17903",title:"Dr.",name:"Helena",middleName:null,surname:"Aguilar Ribeiro",fullName:"Helena Aguilar Ribeiro",slug:"helena-aguilar-ribeiro"},{id:"20710",title:"Dr.",name:"Luisa",middleName:null,surname:"Carvalho",fullName:"Luisa Carvalho",slug:"luisa-carvalho"},{id:"20711",title:"Prof.",name:"Jorge",middleName:null,surname:"Martins",fullName:"Jorge Martins",slug:"jorge-martins"},{id:"20712",title:"Prof.",name:"Carlos",middleName:null,surname:"Costa",fullName:"Carlos Costa",slug:"carlos-costa"}]},{id:"13541",title:"Control of Polymorphism and Mass-Transfer in Al2O3 Scale Formed by Oxidation of Alumina-Forming Alloys",slug:"control-of-polymorphism-and-mass-transfer-in-al2o3-scale-formed-by-oxidation-of-alumina-forming-allo",signatures:"Satoshi Kitaoka, Tsuneaki Matsudaira and Masashi Wada",authors:[{id:"17072",title:"Dr.",name:"Satoshi",middleName:null,surname:"Kitaoka",fullName:"Satoshi Kitaoka",slug:"satoshi-kitaoka"},{id:"17080",title:"Dr.",name:"Tsuneaki",middleName:null,surname:"Matsudaira",fullName:"Tsuneaki Matsudaira",slug:"tsuneaki-matsudaira"},{id:"17081",title:"Dr.",name:"Masashi",middleName:null,surname:"Wada",fullName:"Masashi Wada",slug:"masashi-wada"}]},{id:"13542",title:"Mass Transfer Investigation of Organic Acid Exatraction with Trioctylamine and Aliquat 336 Dissolved in Various Solvents",slug:"mass-transfer-investigation-of-organic-acid-exatraction-with-trioctylamine-and-aliquat-336-dissolved",signatures:"Monwar Hossain",authors:[{id:"18207",title:"Prof.",name:"Md Monwar",middleName:null,surname:"Hossain",fullName:"Md Monwar Hossain",slug:"md-monwar-hossain"}]},{id:"13543",title:"New Approaches for Theoretical Estimation of Mass Transfer Parameters in Both Gas-Liquid and Slurry Bubble Columns",slug:"new-approaches-for-theoretical-estimation-of-mass-transfer-parameters-in-both-gas-liquid-and-slurry-",signatures:"Stoyan Nedeltchev and Adrian Schumpe",authors:[{id:"18592",title:"Dr.",name:"Stoyan",middleName:null,surname:"Nedeltchev",fullName:"Stoyan Nedeltchev",slug:"stoyan-nedeltchev"},{id:"21442",title:"Dr.",name:"Adrian",middleName:null,surname:"Schumpe",fullName:"Adrian Schumpe",slug:"adrian-schumpe"}]},{id:"13544",title:"Influence of Mass Transfer and Kinetics on Biodiesel Production Process",slug:"influence-of-mass-transfer-and-kinetics-on-biodiesel-production-process",signatures:"Ida Poljanšek and Blaž Likozar",authors:[{id:"21672",title:"Prof.",name:"Ida",middleName:null,surname:"Poljansek",fullName:"Ida Poljansek",slug:"ida-poljansek"},{id:"22218",title:"Prof.",name:"Janvit",middleName:null,surname:"Golob",fullName:"Janvit Golob",slug:"janvit-golob"},{id:"22219",title:"Prof.",name:"Blaž",middleName:null,surname:"Likozar",fullName:"Blaž Likozar",slug:"blaz-likozar"}]},{id:"13545",title:"Condensation Capture of Fine Dust in Jet Scrubbers",slug:"condensation-capture-of-fine-dust-in-jet-scrubbers",signatures:"M.I. Shilyaev and E.M. Khromova",authors:[{id:"18168",title:"Prof.",name:"Michail Ivanovich",middleName:null,surname:"Shilyaev",fullName:"Michail Ivanovich Shilyaev",slug:"michail-ivanovich-shilyaev"}]},{id:"13546",title:"Mass Transfer in Filtration Combustion Processes",slug:"mass-transfer-in-filtration-combustion-processes",signatures:"David Lempert, Sergei Glazov and Georgy Manelis",authors:[{id:"18042",title:"Dr.",name:"David",middleName:null,surname:"Lempert",fullName:"David Lempert",slug:"david-lempert"}]},{id:"13547",title:"Mass Transfer in Hollow Fiber Supported Liquid Membrane for As and Hg Removal from Produced Water in Upstream Petroleum Operation in the Gulf of Thailand",slug:"mass-transfer-in-hollow-fiber-supported-liquid-membrane-for-as-and-hg-removal-from-produced-water-in",signatures:"U. Pancharoen, A.W. Lothongkum and S. Chaturabul",authors:[{id:"16502",title:"Prof.",name:"Ura",middleName:null,surname:"Pancharoen",fullName:"Ura Pancharoen",slug:"ura-pancharoen"}]},{id:"13548",title:"Mass Transfer in Fluidized Bed Drying of Moist Particulate",slug:"mass-transfer-in-fluidized-bed-drying-of-moist-particulate",signatures:"Yassir T. Makkawi and Raffaella Ocone",authors:[{id:"16956",title:"Dr.",name:"Yassir",middleName:"Taha",surname:"Makkawi",fullName:"Yassir Makkawi",slug:"yassir-makkawi"},{id:"20080",title:"Prof.",name:"Raffaella",middleName:null,surname:"Ocone",fullName:"Raffaella Ocone",slug:"raffaella-ocone"}]},{id:"13549",title:"Simulation Studies on the Coupling Process of Heat/Mass Transfer in a Metal Hydride Reactor",slug:"simulation-studies-on-the-coupling-process-of-heat-mass-transfer-in-a-metal-hydride-reactor",signatures:"Fusheng Yang and Zaoxiao Zhang",authors:[{id:"17936",title:"Prof.",name:"Zaoxiao",middleName:null,surname:"Zhang",fullName:"Zaoxiao Zhang",slug:"zaoxiao-zhang"},{id:"20005",title:"Dr.",name:"Fusheng",middleName:null,surname:"Yang",fullName:"Fusheng Yang",slug:"fusheng-yang"}]},{id:"13550",title:"Mass Transfer around Active Particles in Fluidized Beds",slug:"mass-transfer-around-active-particles-in-fluidized-beds",signatures:"Fabrizio Scala",authors:[{id:"17940",title:"Dr.",name:"Fabrizio",middleName:null,surname:"Scala",fullName:"Fabrizio Scala",slug:"fabrizio-scala"}]},{id:"13551",title:"Mass Transfer Phenomena and Biological Membranes",slug:"mass-transfer-phenomena-and-biological-membranes",signatures:"Parvin Zakeri-Milani and Hadi Valizadeh",authors:[{id:"17166",title:"Prof.",name:"Parvin",middleName:null,surname:"Zakeri-Milani",fullName:"Parvin Zakeri-Milani",slug:"parvin-zakeri-milani"},{id:"19860",title:"Dr.",name:"Hadi",middleName:null,surname:"Valizadeh",fullName:"Hadi Valizadeh",slug:"hadi-valizadeh"}]},{id:"13552",title:"Heat and Mass Transfer in Packed Bed Drying of Shrinking Particles",slug:"heat-and-mass-transfer-in-packed-bed-drying-of-shrinking-particles",signatures:"Manoel Marcelo do Prado and Dermeval José Mazzini Sartori",authors:[{id:"19095",title:"Dr.",name:"Dermeval",middleName:null,surname:"Sartori",fullName:"Dermeval Sartori",slug:"dermeval-sartori"},{id:"19105",title:"Dr.",name:"Manoel Marcelo",middleName:null,surname:"Do Prado",fullName:"Manoel Marcelo Do Prado",slug:"manoel-marcelo-do-prado"}]},{id:"13553",title:"Impact of Mass Transfer on Modelling and Simulation of Reactive Distillation Columns",slug:"impact-of-mass-transfer-on-modelling-and-simulation-of-reactive-distillation-columns",signatures:"Zuzana Švandová, Jozef Markoš and Ľudovít Jelemenský",authors:[{id:"12119",title:"Dr.",name:"Jozef",middleName:null,surname:"Markoš",fullName:"Jozef Markoš",slug:"jozef-markos"}]},{id:"13554",title:"Mass Transfer through Catalytic Membrane Reactor",slug:"mass-transfer-through-catalytic-membrane-reactor",signatures:"Nagy Endre",authors:[{id:"19732",title:"Dr.",name:"Endre",middleName:null,surname:"Nagy",fullName:"Endre Nagy",slug:"endre-nagy"}]},{id:"13555",title:"Mass Transfer in Bioreactors",slug:"mass-transfer-in-bioreactors",signatures:"Ma. del Carmen Chávez, Linda V. 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Meningothlelial Proliferations",doi:"10.5772/intechopen.100206",slug:"meninges-outside-the-meninges-ectopic-meningiomas-and-meningothlelial-proliferations",body:'This chapter will cover, in brief, clinical and pathological characteristics of what are known as primary ectopic meningiomas (PEM) and the presence of tissue histomorphologically and immunophenotypically consistent with meningeal tissue (meningothelial) occurring in other organs or as part of teratomas or hamartomas/choristomas. PEMs, that is, those that occur outside of the central nervous system (CNS) can occur as a result of direct extension of a primary CNS meningioma (through calvarial bone into adjacent soft tissue), as a metastatic lesion, or as a primary ectopic meningioma [1]. Cutaneous meningiomas or primary cutaneous meningiomas describe a subset of PEMs mostly found in the scalp and have a classification system delineated by whether lesions are congenital or acquired and whether they have connection to a primary intracranial meningioma. Type I are congenital and may present as midline scalp cystic lesions (rudimentary meningoceles, acoelic meningeal hamartomas). Rarely sinus tracts have been found connecting these to the CNS. Type II are soft tissue meningiomas that have predilection for the nose, mouth, eyes, and ears and have no connection to an intracranial meningioma. Type III are soft tissue extensions of a primary intracranial meningioma [2]. Meningothelial tissue (not meningioma) can be seen most notably described in the lungs and rarely in hamartomas/choristomas (lesions composed of tissue types arranged haphazardly but indigenous to the location; hamartoma or not indigenous to location; choristoma) particularly in the head and neck location. PEM have been described in teratomas and meningothelial tissue is not an infrequent component of mature neuroglial tissues in teratomas (tumors composed of tissues derived from all three primordial germ layers). This review will focus on those some aspects of meningiomas that occur outside the CNS; the primary ectopic meningiomas and lesions where meningothelial tissue has been found with particular focus on pulmonary and gonadal (in the context of gonadal mature teratomas) meningiomas and meningothelial proliferations and separately hamartomas/choristomas particularly of the head and neck. It is these latter lesions that the author has the most familiarity from practicing in the discipline of pediatric pathology.
This will be a brief section and by no means an exhaustive treatment of the embryological, morphological and molecular genetics aspects of meninges development. For a more thorough review of meninges development, the reader is directed to the excellent reviews by Dasgupta and Jeong [3] and Lopes [4]. However, here, we will attempt to highlight elements of what is known about the embryological and particularly molecular pathways involved in meninges development as it may relate to the development of meningiomas and the presence of meningothelial tissues in other anatomical locations outside of the central nervous system (CNS) proper.
In contrast to other areas of CNS development, relatively little is known about the molecular characteristics of meninges development. In a broad sense, however, the meninges increasingly are being shown to be critical to proper calvarial and underlying brain development. It is noted that the cranial meninges are derived from two cellular pools; the neural crest (ectoderm) and mesoderm. Neural crest derived cells can be found in the three layers of meninges covering the forebrain cerebral hemispheres but not in the meninges covering midbrain or hindbrain. Calvarial development closely parallels meninges development in that the frontal bones are primarily neural crest derived while the parietal bones are of mesodermal origin. Foxc1 is a key and ubiquitously expressed transcription factor in meninges development with noted early upregulation in the primary meninx. Its prominent role is demonstrated by lack of apical arachnoid and dura mater formation as well as lack of apical calvarial development in Foxc1 mutant mice. Parietal bone development appears to depend on the underlying meninges (derived from neural crest) expressing transforming growth factor beta 2 receptor (Tgfbr2) as Tgfbr2 mutant mice show severe defects in both parietal bone and underlying meninges development. The dura or outer dense layer of the meninges becomes closely apposed to the underside of the bony calvarium and is the de facto periosteal layer. The mesenchyme around the developing brain is divided into layers that include a dermal layer (dermis of scalp), skeletogenic layer (skull), and then the meningeal primordium. By extension, it can be plausible that ectopic meningiomas can arise (and indeed do) in the bones of the calvarium and scalp. It has been proposed that arachnoid cells or precursors can migrate with cranial nerves as they exit their foramina during development and be the forerunners of primary ectopic meningiomas in anatomic regions such as the orbit, ear, and neck [1]. Meninges appear to play crucial roles in brain development including providing trophic factors for neuronal survival, migration/positioning of neurons, neuronal generation from neuronal progenitors, blood vessel development, corpus callosum development, and may provide a niche for neural stem cells [5]. Again, by extension, it is not implausible to think that since much of the structures comprising the head and neck are derived from neural crest (and mesenchymal) cells, cells with multipotent capabilities, that some of these cells could be dormant and later directed down a path of meningeal differentiation in aberrant locations.
To begin this section with an aside, the designation of ectopic meningiomas as “primary” necessarily implies that there may be other categories of meningiomas as “secondary”, “tertiary” and so on. The terminology “primary ectopic meningioma” (PEM for brevity sake) then designates those meningiomas that are outside of the CNS that develop presumably from separate meningeal precursor cells; either ectopic arachnoid cells or perhaps cells that are multipotent (e.g. neural crest) as we have briefly noted. In some sense, this terminology is redundant since if the meningioma (or any lesion) is designated as “ectopic” that lesion is not indigenous to its normal anatomic location and would therefore be “primary”. So called “secondary extracranial meningiomas” are defined as those lesions that are an extension of an intracranial meningioma. The author has not seen further designations of meningiomas beyond secondary and it is difficult to conjure a scenario where the designation of “tertiary extracranial meningioma” would be applicable. In addition, in perusing this literature, the terminology is a bit confusing because different names have been applied descriptively to lesions that probably ultimately fall under an umbrella category (see above description of Type I cutaneous meningioma). Some have described extracranial meningothelial proliferations in four categories: 1) extracranial extension of intracranial meningioma, 2) extracranial meningioma, 3) the aforementioned primary cutaneous meningioma, and 4) metastatic meningioma [6]. We already see that category 1 is what has been referenced as a Type III cutaneous meningioma and 3 presumably encompasses the spectrum of cutaneous meningiomas that include Type III. In this author’s simplistic way of thinking and since this is a review, primary ectopic meningioma is not an unreasonable designation because the terms denote a meningioma that is outside the CNS as a “stand alone” or primary tumor in that location. If the designation were only “ectopic meningioma” then extracranial extensions of intracranial meningiomas could technically be under that rubric. Additionally, and similarly, the term “meningothelial” seems to imply tissue that is by all standards meningeal but not a tumor (more later). Meningothelial tissue or proliferations would seem by definition to be primary and ectopic since intracranial meningothelial proliferations are really not a diagnostic category of CNS lesions except for the possibility of meningeal tissue as part of another tumor.
That aside, it is interesting when trying to quell cases of PEM from the searchable medical literature, the variety of names given to these lesions as hinted at, and the ensuing difficulty that arises in attempting to exactly define the numbers and types of PEM reported. As Gibson and Prayson aptly alert the reader in their excellent chapter on this subject [7], a variety of designations have been used when reporting these lesions including ectopic, extracranial, extraneuraxial, extradural, cutaneous, intraosseous, calvarial etc. In addition, case reports may designate one of these categories to describe the lesion, but indeed the lesion may actually represent a secondary extracranial meningioma, or the patient may have had a previous remote intracranial meningioma.
Combined with a previous review of 178 reported cases from the English language medical literature by Lang et al. [8], Gibson cited an additional 100 cases of PEM at the time of publication of their chapter (2009). In this author’s brief survey of the entire medical literature not restricted to the English language from 1/1/2008 to the present, approximately 184 cases of PEM are noted after using search terms that Gibson identified as descriptors for PEMs such as “ectopic”, “extracranial”, “extraneuraxial”, “extradural”, “cutaneous”, “calvarial”, “intraosseous” and “meningioma”. By far, the most cases are reported from the head/neck anatomic location with intraosseous PEM by far exceeding any other location in the head and neck or elsewhere outside of the head and neck (Table 1). The most common site/location for PEM outside the head and neck was interestingly pulmonary followed by spinal/mediastinal/thoracic (Table 2).
Site | N |
---|---|
Intraosseous (skull) | 62 |
Intraosseous (mandible) | 5 |
Intraosseous (maxilla) | 1 |
Scalp | 13 |
Lacrimal/orbital | 11 |
Sinonasal | 10 |
Parapharyngeal/neck | 9 |
Middle ear | 2 |
Soft tissue | 2 |
Cheek | 1 |
N = 117 |
Approximate location and number of primary ectopic meningiomas in the head and neck from 2008 to present.
Site | N |
---|---|
Pulmonary | 34 |
Spinal/mediastinal/thoracic | 21 |
Cutaneous | 5 |
Intraosseous (hip/pelvis) | 3 |
Adrenal gland | 1 |
Brachial plexus | 1 |
Kidney (hilum) | 1 |
Soft tissue (thigh) | 1 |
N = 67 |
Approximate location and number of primary ectopic meningiomas outside the head and neck from 2008 to present.
It should not be terribly surprising that from a teleological perspective and given the developmental biology of meninges that the most commonly cited location of PEM is in the head and neck location and more specifically in the calvarial/skull bones. The intimate association of mesenchymal and/or neural crest cells in the development of the calvarial bones and meninges, particularly the dura which is directly apposed to the bone, makes this causative possibility very plausible. Likewise could be said for the greater number of cases of PEM found in the spinal/mediastinal/thoracic location. In children, certain tumors particularly neuroblastoma and its variants, can be found in this paraxial location along the sympathetic chain where neuroblasts are migrating during development.
PEM are quite uncommon as might be expected and the multiple reviews all cite basically the same incidence of approximately 1–2% of all meningiomas. Several excellent reviews have been published identifying the clinical and pathological characteristics of PEM in general and in specific locations including intraosseous (calvarial) [9], ear and temporal bone [10], sinonasal tract [11], and pulmonary [12, 13, 14, 15]. In addition, PEMs have been reported in skin, kidney, retroperitoneum, mediastinum, extremities, adrenal gland, ovary (mature cystic teratoma) [7], In general, for PEM, in contrast to CNS meningiomas, there is only a slight female predominance in incidence with the exception of perhaps those presenting in the ear and temporal bone where at least in the series by Rushing et al., the M:F ratio (1,2) more closely approximated the M:F ratio for CNS meningiomas in adults [16]. PEM arising in the ear and temporal bone are particularly troublesome for the pathologist as they can have a broad differential diagnosis in a location that is not the genesis of a comparatively large number of specimens that might traverse a general pathologist’s microscope. This differential diagnosis includes entities such as paraganglioma, schwannoma, melanoma, middle ear adenoma or carcinoid, and carcinoma. The middle ear was the most common location for these PEMs with a relatively high association with cholesteatoma (9/36 cases). A smattering of histological subtypes were identified in these PEM and this is the case for PEM in general. The most common histological subtype identified by far is meningothelial (range 47% to over 90% depending on site) followed at a significant distance by atypical or psammomatous [16]. As an aside, in searching our pathology archives for cases of meningioma, we found approximately 730 cases of meningioma over 20 years, with less than 5 PEMs found that were either intraosseous (calvarial) or middle ear (mastoid) (Figure 1) and no cases of extracranial soft tissue, visceral, or pulmonary PEMs.
Meningothelial meningioma of the mastoid presenting with tinnitus in a 46-year-old woman. No connection to the CNS was seen by imaging or intraoperatively. A: Low magnification view of meningioma composed of spindled and epitheliod cells in a whirling pattern with areas of more concentrated fibrous tissue. Scattered psammoma bodies were seen throughout the biopsy pieces (arrow, HE 40X). B: High magnification view of the relatively bland appearing nuclei with numerous pseudoinclusions, a hallmark nuclear feature of meningiomas (arrow, HE 600X). C: Diffuse staining of the meningeal lesional cells with epithelial membrane antigen (EMA 100X).
A few reviews have been published specifically addressing primary pulmonary meningiomas (PPM), that is, meningiomas that occur in the lung parenchyma as cited. Three of the four reviews included part of the time span included in the review here [12, 14, 15]. Our review provides perhaps more emphasis on the pathological phenotypes and concurrence with other tumors than other reviews.
PPMs are interesting entities for several reasons. One, their pathogenesis might not be as teleologically obvious compared to PEMs that occur say in the head and neck. Two, pulmonary meningothelial proliferations/nodules are not a terribly uncommon finding incidentally in lung resections and will be the subject of the latter part of this review as part of the spectrum of extracranial/extraneuraxial lesions of meningothelial lineage. Three, there are multiple case reports of concurrent CNS and pulmonary meningiomas [17] as well as reports of concurrent PEMs in lung and bone [18], metastases from CNS meningiomas to the lung [19] in particular, and metastases from other tumors into CNS meningiomas [20] and even metastases from PEMs to the lung [21]. Four, PPM can be mimickers of a primary lung cancer, now the second most common cancer in both men and women in the United States and therefore should be considered (albeit somewhat down the differential diagnostic list) by every pathologist who looks at lung biopsies and resections [22]. Five, pulmonary meningothelial proliferations, either sporadic or diffuse, may even be more troublesome for the pathologist. These interesting categories in the spectrum of meningiomas cannot, unfortunately, be further elucidated in this brief review.
Table 3 represents a review of the medical literature (English and non-English) searched in PubMed using the search terms “pulmonary” or “lung” and “meningioma” contained in the title/abstract from January 1, 2008 to August 16, 2021 (roughly corresponding to the last cases of PEM reported by Gibson et al. as noted). This search yielded 407 results of which 34 case reports were included reporting PPM [12, 13, 14, 15, 18, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50]. One patient had two case reports approximately 10 years apart and one article published in a Spanish journal could not be obtained. The clinical characteristics (age, gender, location, size, recurrence rate) are in keeping with other reviews of PPM [12, 13, 14, 15]. The immunohistochemical profiles were also in line with other reviews with most PPMs demonstrating staining with epithelial membrane antigen (EMA), progesterone receptor (PR), and vimentin. This review demonstrated perhaps higher numbers of both WHO grades II and III tumors (if presuming the remainder of the undesignated cases were WHO grade I which is a reasonably safe assumption).
Characteristic | N = 34 cases |
---|---|
Age at presentation (years) (n = 34) | |
Mean (SD) | 57.1 (17.8) |
Range | 18–108 |
Median | 60 |
Gender (M:F) | 9:25 (1:2.8) |
Symptoms at presentation | 11 (23- no designation) |
Follow-up (n = 17) | |
Disease free/no recurrence | 17 |
Mean (years) (SD) | 3.2 (4.5) |
Range | 0.17–20 |
Patients with history of other malignancies | 10/34 |
Multiple PPM | 3/34 |
Site (R/L) | 19:15 |
Size (cm) (n = 31) | |
Mean (SD) | 2.4 (2.6) |
Range | 0.45–15 |
Histological type (n = 29) | |
Malignant | 3 |
Atypical | 1 |
WHO I | 2 |
Transitional | 5 |
Chordoid | 2 |
Fibrous | 1 |
Meningothelial | 1 |
Psammomatous | 1 |
Rhabdoid | 1 |
Intrapulmonary metastases | 1 |
No designation | 17 |
WHO grade (I, II, III) | 28/3/4* |
Psammoma bodies | 11/15 |
No designation | 20 |
Epithelial membrane antigen/EMA + | 30/30 (5-no designation) |
Progesterone receptor (PR) + | 17/18 (17-no designation) |
Vimentin + | 20/20 (15-no designation) |
S100 + | 6/14 (21-no designation) |
Cytokeratins + | 0/16 (19-no designation) |
Ki-67 (≥ 10%) | 3/14 (15-no designation) |
≥ 10% | 3 |
< 10% | 13 |
No designation | 19 |
Review of clinical and pathological characteristics of primary pulmonary meningioma 2008–2021.
- One patient had two asynchronous tumors.
An interesting aspect in the review of these cases and not overly emphasized in other reviews is the seemingly high number of patients with a history of other malignancies; almost one-third of the patients (10/34) with one patient having multiple (3) other tumors (osteosarcoma, fibrous dysplasia, and giant cell tumor of bone). This patient had a somatic mutation in the giant cell tumor of H3.3A and a germline mutation of BRCA2. Of course, one must be careful in drawing conclusions from a small dataset and in this case the patients with other malignancies were all in the age range where other malignancies are not uncommon (mean age 65 years, range 52–80). The malignancies in this group included buccal (1) (presumably squamous cell carcinoma), breast (2), gastric adenocarcinoma (1), papillary thyroid carcinoma (1), thymoma (1)/renal cell carcinoma (1)(same patient), rectal adenocarcinoma (1), concurrent lung adenocarcinoma (1) and teratoma (1) (immature and mature teratoma of the ovary and retroperitoneum, respectively). With the exception of the teratomas and thymoma, the other tumors are not uncommonly seen in this age group. As an aside, the PPM in the patient with teratomas does raise the remote possibility of a meningothelial/meningioma metastases from one of the teratomas particularly since one teratoma was designated as immature.
A 21-year-old female with Diamond-Blackfan anemia was included in this cohort who presented with a chordoid histology PPM [39]. Diamond-Blackfan anemia (DBA) is an inherited bone marrow failure syndrome that has approximately 20 known genetic aberrations in genes encoding small/large subunit associated ribosomal proteins (RPS and RPL genes) [51]. A cursory review shows no definitive RPS or RPL genes to be associated with any of the non-neurofibromatosis, type 2 (NF2) associated genes known to be mutated in meningiomas [52, 53, 54]. While DBA is associated with higher rates of other cancers including osteosarcoma, vaginal squamous cell carcinomas, esophageal cancer, colon adenocarcinoma, and myeloid leukemias, increased risk for meningiomas have not been seen in patients with DBA to date [51]. However, subsequent to the publication of this young patient with DBA and chordoid meningioma, she was found to have a mutation of the RSP19 gene [51].
As noted, one patient in this cohort had papillary thyroid carcinoma (PTC). An interesting epidemiological study by Sughrue et al. [55] showed that compared to the expected prevalence for a similar population, patients with meningioma had a statistically higher incidence of papillary thyroid cancer and acute leukemia. From a pathology perspective, it is also interesting that both tumors share at least one characteristic histopathological feature; psammoma bodies. Psammoma bodies can be seen characteristically in several tumors including PTC, meningiomas, serous cystadenocarcinoma of the ovary, and melanotic schwannoma (one of the tumors with high prevalence in Carney syndrome). The pathogenesis of psammoma bodies is still controversial with theories involving vascular thrombosis of papillae, followed by calcification and endothelial necrosis. More recently, osteopontin (OPN), a calcium-binding glycophosphotein has been implicated in the formation of psammoma bodies being expressed in CD68 positive macrophages along with other factors that include alkaline phosphatase, osteocalcin, metalloproteinases, bone sialoprotein, and others [56]. OPN expression has been shown to be increased in meningiomas compared to normal meninges, correlates with histological grade, and is a predictor of recurrence in WHO grade I tumors [57, 58].
The pathogenesis of PPM and PEM particularly those outside of the head and neck, of course, remains speculative as do many aspects of normal meninges development as noted earlier. Hypotheses regarding the origin of PEMs have included ectopic arachnoid cells that are present in cranial and peripheral nerve sheaths and in cranial sutures, misplacement of arachnoid cells during development, pluripotent mesenchymal cells, perineurial cells of peripheral nerves, and entrapped meninges at sites of trauma [7, 16]. Meningiomas, arachnoid cap cells (cells making up the outer layer of the arachnoid mater and villi), and spindle cells within perineurium express EMA that is detected immunohistochemically. While nearly all meningiomas and perineuriomas express EMA, only about one-third of meningiomas express glucose transporter-1 (GLUT-1) while most perineuriomas express GLUT-1. Similarly, SSTR2 and PR are expressed in a high percentage of meningiomas compared to perineuriomas while the reverse is true for claudin-1 [59]. Indirect support for pluripotent mesenchymal cells as the cell of origin for PEMs derives from the fact that meningiomas can exhibit histologically other tissue types including bone, cartilage, muscle, vascular, and other tissues. With regards to PPM specifically, two theories have arisen regarding their pathogenesis. The first is similar to what has been proposed for PEMs elsewhere; pluripotent mesenchymal cells that reside in the subpleural region or from “precursor” lesions known as minute pulmonary meningothelial nodules (MPMN, more on these later) [12]. Both PPM and MPMN share some similar phenotypes particularly the expression of similar immunohistochemical markers (EMA, PR, vimentin) but it is certainly unclear if MPMNs are truly precursors of PPM. Indeed, there seems to be some discrepancy in incidence of MPMN and meningiomas in autopsy series leading some to conclude that MPMN cannot be a precursor lesion [12]. Some have argued that MPMN are not precursor lesions based on genotyping studies demonstrating higher frequencies of loss of heterozygosity (LOH) and LOH affecting different loci in meningiomas compared to MPMN [60]. It is interesting that a progression of increasing frequency of LOH was noted from solitary MPMN to meningotheliomatosis to meningioma. Weissferdt et al. demonstrated that MPMN do share some genotypic alterations with PPM and CNS meningioma particularly deletion of the NF2 gene and gains of chromosome 22q [61]. The distinction between the two has mostly been by somewhat arbitrary size criteria (≤ 3 mm for MPMN). PPMs also tend to form a “mass” displacing lung.
From the pathology perspective, PEMs present specific and diverse diagnostic challenges. This is largely due to the variable histomorphologies that have been described not only in CNS meningiomas but also in PEMs and the various locations that PEMs can occur which raise different differential diagnoses. The differential diagnoses for PEM in the middle ear and temporal bone has already been discussed. For all PEMs in the head and neck location, Rushing et al. found paraganglioma, schwannoma, and metastatic carcinomas to be the most frequent misdiagnoses for ear and temporal bone PEM; Carcinoma, melanoma, olfactory neuroblastoma, and aggressive psammomatoid ossifying fibroma for sinonasal tract PEM, and dermatofibroma, melanoma, fibrosarcoma, leimyosarcoma, and synovial sarcoma for soft tissue and skin PEM [16]. The differential diagnosis for PPMs brings a variety of entities that can occur in the lung and mediastinum. These include sarcomatoid mesothelioma, solitary fibrous tumor, spindle cell thymoma, spindle cell carcinomas, inflammatory myofibroblastic tumor, synovial sarcoma, epithelioid hemangioendothelioma, and of course metastases [12]. As noted, meningiomas can present with a wide range of histological features including meningothelial, fibrous, microcystic, transitional (spindle cell component) psammomatous, angiomatous, secretory, metaplastic (lipidized cells), lymphoplasmacytic rich (all WHO grade I), clear cell (mimicking clear cell renal cell carcinoma), chordoid, atypical (WHO grade II), and rhabdoid (cells with eccentric nuclei and abundant eosinophilic cytoplasm), papillary, and anaplastic (WHO grade III). There are several excellent reviews of the histopathology of meningiomas along with the criteria for atypical and anaplastic variants [52, 54, 62]. And as mentioned before, other tissue types can be seen occasionally within meningiomas (i.e. bone, cartilage/chondroid, muscle). The variety of tissue types and potential to produce other tissues speaks highly for a pluripotent cell of origin (neural crest, mesenchymal) and are reminiscent of some other tumors that have such potentially variable histological appearances (e.g. yolk sac/endodermal sinus tumor which is derived from a pluripotent cell). Suffice it to say that given these variations, the differential diagnoses become expanded and criteria for narrowing the diagnoses are critical. Most of the identified histological subtypes have been identified in PEMs. In the review by Rushing et al. of extracranial head and neck PEMs, meningothelial, psammomatous, clear cell, atypical, and anaplastic were noted [16]. In sinonasal tract meningiomas, meningothelial is the most common subtype and transitional, metaplastic, and psammomatous types have been identified [11]. In PPMs, as noted in this review and others, meningothelial, transitional, fibrous, chordoid, rhabdoid, psammomatous, atypical, and anaplastic have been reported. Transitional histology is reported as the most common histological subtype in PPMs [12]. As seen in our review and noted in many publications, the immunohistochemical trio of EMA, vimentin, and progesterone receptor is present in the majority of cases of meningioma including PPMs. A smattering of cases will show staining with CD34, S100, and CD68 but are almost always negative for cytokeratins. In cases where these stains and morphology still leave doubt, other markers should be included in the work-up panel. A cytokeratin stain (both high and low molecular weight or pankeratin) is very important in the exclusion of entities such as metastases from carcinoma, mesothelioma, and thymoma. Neural markers (chromogranin, synaptophysin) are usually negative in meningiomas and positive in paragangliomas for instance. CD56 has been shown to mark some meningiomas (4 positive cases in our series although most cases in the series did not perform or report this marker) but is also strongly positive in most paragangliomas. Since melanoma can be a great mimicker of many tumors, markers such as HMB-45, melan-A, MART1, and MITF are helpful in this distinction since these are almost always negative in meningiomas. S100 may be useful also in the distinction of melanocytic tumors and peripheral nerve sheath tumors (schwannoma) with usual strong diffuse staining of these entities. However, as seen, 6/14 cases that reported results of S100 staining in PPMs were positive in our series. While most did not report the extent or intensity of staining for S100, in general, it is probably not to the degree seen in melanocytic or peripheral nerve sheath tumors. Vascular markers, CD31 and CD34, can be helpful since most meningiomas are negative for these markers. These vascular markers should be positive in hemangioendothelioma. CD34 is usually positive in solitary fibrous tumor along with bcl-2 and is almost always negative for EMA. Bcl-2 is also useful for distinguishing synovial sarcoma. Muscle markers (smooth muscle actin, muscle specific actin, calponin and others) can helpful in the distinction of smooth muscle neoplasms and inflammatory myofibroblastic tumors along with ALK-1.
Another marker that demonstrates very high positive and negative predictive values for meningiomas is the monoclonal antibody to SSTR2a (somatostatin receptor 2a) [63]. This receptor is highly expressed in meningiomas as are other somatostatin receptors. Somatostatin ligand analogs such as DOTATOC and DOTATATE have been linked to 68Ga and used in PET imaging of meningiomas with great success. 68Ga-DOTATATE uptake correlates with SSTR2 expression and has high sensitivity for detecting active tumor in untreated and recurrent meningiomas [64]. In tissue specimens, the monoclonal antibody to SSTR2a has higher sensitivity than EMA or PR and did not stain with high intensity other lesions in the differential diagnoses including peripheral nerve sheath tumors (malignant and benign) and other carcinomas, mesenchymal tumors, or melanomas [63]. A high percentage of meningiomas also express p40 which is one isoform of p63 (p53 homolog gene) and the intensity of expression correlates with histological grade and recurrence [65].
All meningiomas are not sporadic. Multiple familial syndromes associated with specific genetic aberrations have increased risk for development of meningiomas. Neurofibromatosis 2 (NF2 gene, chromosome 22q12) has the highest lifetime risk for development of meningioma at 50%. Approximately 40% of sporadic meningiomas are driven by other genetic mutations other than NF2 [54]. Table 4 highlights the known familial syndromes associated with varying degrees of increased risk of meningioma. As somewhat of an aside, patients with Werner syndrome (Progeria, premature aging syndrome) as noted have an increased risk of meningioma. In the excellent review by Lauper et al. [66], they noted 27 meningiomas in their cohort of 189 confirmed Werner syndrome patients. Eight of these tumors occurred in patients with multiple tumors and 5/9 patients with meningiomas also had thyroid neoplasia (1 PTC, 1 thyroid carcinoma NOS, 3 adenomas). Four of 5 patients had only meningioma and thyroid neoplasia as manifestation of their multiple tumors. Gardner/Turcot syndrome (APC-associated polyposis), PTEN hamartoma syndrome (Cowden, Bannayan-Riley-Ruvalcaba, Lhermitte-Duclos syndromes), MEN1 (Wermer syndrome), and Werner syndrome are familial inherited syndromes also highly associated with thyroid neoplasia [67]. Carney complex also has a high association of thyroid neoplasia and has as a pathognomonic lesion the melanotic schwannoma, a tumor characterized by schwannian differentiation with the feature of psammoma bodies. Carney complex is known to result from mutations in PRKAR1A (chromosome 17q22–24) and CNC2 (2p16) while WHO grades II and III meningiomas have been shown to be associated with gains and amplification of 17q [53, 54, 67]. In addition, interestingly, Gardner/Turcot syndrome, Carney complex, and Werner syndrome all have various bone tumors as part of the manifestation/diagnostic criteria for their respective syndromes. In the review by Lauper et al. [66], 17/189 Werner syndrome patients had osteosarcoma with 7/19 osteosarcomas occurring in patients with multiple tumors and one of these patients had meningioma/thyroid adenoma/osteosarcoma as the manifestation of multiple neoplasia. Another association is the presence of neoplasia associated with derivatives of the neural crest (retinal epithelial hypertrophy, benign and malignant peripheral nerve sheath tumors, benign and malignant melanocytic lesions). Gardner/Turcot, Carney complex, PTEN hamartoma, Werner syndromes all have melanocytic lesions as part of their neoplasia spectrum.
Familial syndrome | Gene | Chromosome location | Risk % |
---|---|---|---|
Neurofibromatosis 2 | NF2 | 22q12 | >50 |
Multiple spinal meningiomas | SMARCE1 | 17q21.2 | |
BAP1 tumor predisposition | BAP1 | 3p21.1 | 2 |
Familial schwannomatosis | SMARCB1 | 22q11.23 | |
Gorlin syndrome | PTCH1 | 9q22.3 | 5 |
Cowden disease | PTEN | 10q23.31 | 8 |
Familial multiple meningiomas | SUFU | 10q24.32 | |
Li-Fraumeni | TP53/CHEK2 | 17p13.1/22q12.1 | |
Rubinstein-Taybi | CREBBP | 16p13.3 | |
Gardner syndrome/Turcot syndrome | APC | 5q21–22 | |
Multiple endocrine neoplasia I | MEN | 11q13 | |
Werner syndrome | WRN (RECQL) | 8p11.1–21.2 | 14 |
Von Hippel–Lindau | VHL | 3p25.3 | |
Ataxia telangiectasia | ATM | 11q22 |
Familial syndromes associated with increased risk of meningioma.
These are very interesting associations and can and will lead us to further elucidation of unifying mechanisms of molecular and cellular origins of tumors and in this case meningiomas. It is worth noting here that there are very few reports of PEMs associated with a familial inherited syndrome. What was presented above was data for associations with primary CNS meningiomas. Very few reports of PEMs in patients with a familial syndrome can be found. One case report describes an ectopic meningioma of the right parapharyngeal space in a 14-year-old girl with NF2 [68]. A second report describes an intranodal meningothelial proliferation in a 55-year-old woman with confirmed Cowden syndrome [69]. There seems likely a true difference in familial genetic syndromes and association with PEMs since one would think that specific case reports would address this as part of the unique spectrum of individual presentations of PEM.
I suppose a general definition of “meningothelial proliferation” would likely be in order. It was alluded to earlier in this review. I say “general” because as noted in the case of PPMs the distinction between what is a meningothelial nodule/proliferation and what is termed a meningioma may be a bit arbitrary and certainly subjective. In this review of PPM, for instance, 6/31 “meningiomas” were less than 1 cm in greatest dimension. In pathology, the distinction between what determines a proliferation and what determines a “tumor” is sometimes based on size with 1 cm being a threshold size for specific tumor designations. For instance, the distinction of papillary thyroid microcarcinoma and papillary thyroid carcinoma is based on the former being less than 1 cm in greatest dimension. In radiology, the standard threshold for detecting tumors has traditionally (although not as much now with improvements in imaging modalities) been less than or greater than 1 cm. In the practice of pathology, these distinctions are not always clear and other features in addition to size are considered in the diagnostic algorithm. An important feature is what the tumor is doing to the surrounding tissue. Is it “blending” in as in the cases, for example, of dominant hyperplastic nodules in the thyroid or nephroblastomatosis in the spectrum of Wilms tumor or it is replacing/pushing normal tissue.
With regards to meningothelial proliferations that occur outside the CNS, that is the presence of meningothelial or meningeal tissue that is not a tumor of meninges, these have been described in a few general settings (although not an exhaustive list) including heterotopic neuroglial proliferations, pulmonary meningothelial nodules (to include diffuse pulmonary meningotheliomatosis), teratomas, and rarely in choristomatous lesions particularly in the head and neck.
One of the reasons to include a review of PPM as cited above was that meningothelial proliferations are well-described in the lungs. In the older pathological literature, MPMNs were originally termed “minute pulmonary paragangliomas” or “chemodectomas” since their ontogeny was thought to be distal airway chemoreceptors [70]. However, subsequently, these have been shown not only morphologically but immunohistochemically and ultrastructurally to be meningothelial in origin. They present as a nested proliferation of spindled and epithelioid cells with bland nuclei around small veins in the lung and exhibit the characteristic EMA+, vimentin+, and PR+ immunophenotype. The incidence of MPMN is reported up to 5% in autopsy studies and in up to approximately 14% of surgical biopsy specimens and in nearly half of lobectomy specimens [70]. Interestingly, in the large series by Mukhopadhyay that included resections from patients in the pediatric age range and over 90 pediatric autopsies, no MPMN were seen in the pediatric population [71]. Radiographically, by CT, MPMN are round solid or partially solid nodules and can be multiple and have a “ground glass” appearance. They typically show low SUV (benign) values for FDG-avidity on 18F-FDG PET-CT imaging [13]. Depending on the clinical scenarios (concurrent other lung lesions, history or concurrence of other tumors), metastases or synchronous tumors cannot be entirely excluded thus necessitating removal and pathological examination. Rarely, MPMN can occur in the setting of PPM; some of these cases being diagnosed as intrapulmonary metastases [14, 25].
Diffuse pulmonary meningotheliomatosis (DPM) is an interesting if not quite rare entity. These patients can present with symptoms of restrictive pulmonary disease with diffuse bilateral reticulonodular infiltrates that have the differential diagnoses including a variety of interstitial lung diseases, carcinomatosis, neuroendocrine tumorlets, metastatic meningioma, and pulmonary lymphangioleiomyomatosis (PLAM). The separation of these entities is relatively straightforward based on morphology and immunophenotyping. Metastatic meningiomas should be distinguished by clinical grounds (presence of a CNS tumor), involvement of the bronchovascular tree as opposed to DPM which is usually found centered around small veins, and more atypical appearance. Carcinomatosis, neuroendocrine tumorlets, and PLAM are distinguished by positivity for keratins, neuroendocrine markers (typically synaptophysin and chromogranin), and actins while similarly to MPMN and PPM, DPM lesions are EMA, vimentin, and PR positive [61, 71, 72, 73]. Primary pulmonary meningothelial lesions (MPMN, DPM, and PPM) are very interesting from developmental and genetic perspectives as lung meningothelial lesions seem to predominate the epidemiological landscape of meningothelial lesions outside of the CNS and head/neck and seem to have an extremely low prevalence in the pediatric population leading some to speculate that their origins may not be pluripotent mesenchymal cells but more related to environmental and age-related factors. Although, just because they are not found in the pediatric age group, should not totally discount that they arise from resting pluripotent stem cells or other dormant embryological remnants and their recrudescence as meningothelial lesions is stimulated by other factors. The lungs like other organs also have a “stem cell niche” that is triggered when there is bronchial epithelial injury for the purposes of regeneration/repair [74]. As we have also discussed there seems to be a spectrum of increasing mutations in MPMN and DPM raising the possibilities for a mutational spectrum or “hit” hypotheses in their pathogenesis.
Meningothelial tissue can occur as part of other pathological lesions. In this final section we will briefly touch on the presence of meningiomas and meningothelial tissue in teratomas and meningothelial elements as part of heterotopic/choristomatous/hamartomatous lesions. Somewhat surprisingly, very few cases of meningioma or meningothelial tissue in teratomas are described. A search of PubMed for “meningiomas” and “teratomas” yielded 8 results. One case was a posterior fossa tumor mimicking a meningioma and another case was teratoma and meningioma in the temporoparietal region. The remaining 6 cases were all gonadal teratomas with meningioma [75, 76, 77, 78, 79, 80, 81, 82]. The clinical and pathological characteristics of these meningiomas is presented in Table 5. Two cases were in the pediatric age range (5-year-old male and 15-year-old female and all meningiomas were seen on gross examination to be whitish or brown firm nodular areas within the broader context of the mature cystic teratoma (MCT). Chen et al. searched for and characterized meningothelial proliferations in 25 consecutive ovarian MCT [83]. They found that 40% of their tumor had meningothelial proliferations that resembled what has been described in hamartoma of the scalp with ectopic meningothelial elements (more on this later). The meningeal nature of the tissue was confirmed morphologically and by EMA positivity. In all cases the meningothelial tissue was in close association with skin and mature glial tissue (ectodermally derived). Eight of 10 cases had pigmented cells and 3 had psammomatous calcifications. In the author’s anecdotal experience, having microscopically examined numerous teratomas from children and adults and teratomas derived from the harvested embryonic stem cells from several species, the finding of meningeal tissue seems not that uncommon, although I have not encountered a meningioma tumor. A recent case of mine illustrates this from a 13-year-old girl with MCT. The meningeal tissue is intimately associated with mature neuroglial tissue and resembles arachnoid of the meninges (Figure 2).
Characteristic | N = 6 cases |
---|---|
Teratoma type (T/O*) | |
MCT** (T) | 2 |
MCT (O) | 4 |
Gender (M:F) | 2:4 |
Age (years) (SD) | 33.8 (20.7) |
Range | 5–60 |
Size (cm) (SD) | 2.7 (1.2) |
Psammoma bodies | 5/6 |
Epithelial membrane antigen/EMA + | 5 (1 with no designation) |
Vimentin + | 2 (4 with no designation) |
Progesterone receptor (PR) + | 2 (5 with no designation) |
Clinicopathological characteristics of meningiomas arising in gonadal teratomas.
T-testis, O-ovary.
MCT-mature cystic teratoma.
Meningeal/meningothelial tissue within a mature cystic teratoma of the ovary in a 13-year-old girl. A: Low magnification view showing mature neuroglial tissue (upper left corner) adjacent to a proliferation of rarified, wispy anastomosing cords of fibrous tissue lined by bland small indistinct nuclei. In other areas of the teratoma, this pattern was also seen adjacent to skin and adnexal structures. This segregation of the meningothelial elements near skin and mature neuroglial is common. (HE, 40X). B: Weak by definite staining of the meningeal tissue with epithelial membrane antigen (EMA, 200X). C: Variably intense staining with progesterone receptor (PR, 400X). D: Diffuse strong intensity staining with vimentin (vimentin, 200X).
Meningothelial tissue can be part of lesions described as heterotopias, particularly of the neuroglial flavor, hamartomas, and choristomas (tissues not indigenous to the anatomic location). In 2005, we reported a temporal glioneuronal heterotopia in a 19-month-old child without underlying connection to the CNS or calvarial defect. In our review of similar cases from the medical literature to that time, 11 infants were identified ranging in age from birth to 15-months. Six of 11 cases had no connection to the CNS (true heterotopias) and 2/6 had meningothelial elements as a component histologically [84]. In another review published at approximately the same time by Rogers et al. from Boston Children’s Hospital, they reported 11 patients with 12 tumors of the scalp ranging in age from 1-month to 20-months. Seven of the 12 tumors had no connection to the CNS and 5 of those 7 tumors had meningothelial tissue as a prominent component histologically [85].
Ectopic meningothelial tissues have been described that appear to arise entirely within the skin and often present in the neonate or infant (so called Type I cutaneous meningioma; defined in the beginning of this chapter). These have been previously termed “acoelic meningeal hamartoma” “cutaneous heterotopic meningeal nodules” and “rudimentary meningocele”. In the series published in 1989 by Sibley and Cooper referenced earlier, they described 5 cases of what they termed “primary cutaneous meningioma”. What they describe histologically is what is expected in meninges both morphologically and immunophenotypically including collagenous bodies and psammomatous calcifications. Some areas in the superficial dermis had a more rarified and lacy appearance with meningocytes wrapping around vessels and adnexa in intimate association similar to that described shortly thereafter by Suster and Rosai [86]. Their series described 5 patients who had pseudoinfiltrative lesions of the skin and subcutis by meningothelial elements that were in intimate association with the surrounding tissue elements (vessels, fat, connective tissue). In fact, they designated that the meningothelial elements were an interspersed component between a proliferation of connective tissue elements. Their designation for these lesions was “hamartoma of the scalp with ectopic meningothelial elements” and this has become the diagnostic term for such lesions. More recent reports in some cases have shortened the nomenclature to “meningothelial hamartoma”. Suster and Rosai give the poignant perspective that the designation of these hamartomatous lesions with meningothelial elements are distinguished from primary cutaneous meningiomas by the association with other poorly arranged elements constituting a hamartoma. We have encountered similar tumors in the scalp (Figure 3A and B) and have published two cases in young children of tongue lesions with meningothelial elements (Figure 3C and D). Both tongue lesions were entirely composed of the typical anastomosing slit-like channels lined by bland flat-to-cuboidal cells expressing progesterone receptor and epithelial membrane antigen. Interestingly, but not surprisingly, meningothelial elements have been described occurring in the rare “teratoid” lesion of the palate known as hairy polyp [6]. These are pedunculated growths that can be composed of a variety of tissues derived predominantly from ectodermal and mesodermal (mesenchymal) germ layers. In the reported case, the presence of meningothelial tissue was confirmed by immunohistochemistry and ultrastructural examination demonstrating the characteristic interdigitating cytoplasmic processes connected by cell junctions, desmosomes, intermediate filaments (hence positive expression of vimentin).
Examples of ectopic meningothelial proliferations in the head and neck. A and B represent “hamartoma of the scalp with ectopic meningothelial elements” in a young child. 3A: Low magnification view of loose proliferation of anastomosing wispy fibrous cords lined by bland nuclei interdigitating around adnexal structures (HE, 40X). 3B: High magnification view of the microarchitecture of meningothelial proliferations. This pattern closely resembles vascular proliferations, particularly lymphatic malformations in children and must be excluded in the differential diagnosis (HE, 400X). C and D are from a nearly 2-year-old boy with a tongue mass. 3C: Less obvious than the previous case shown here yet the same microarchitectural pattern is appreciated below the surface epithelium of the tongue. This rarified pattern might be considered a “hemangiopericytomatous” pattern but in any case, is abnormal for the submucosa of the tongue (HE, 40X). 3D: This meningothelial proliferation show strong nuclear staining for progesterone receptor (PR, 400X).
In summary, CNS meningiomas are the most common primary CNS tumor and meningiomas and meningothelial tissue/proliferation occur in a multitude of extra-CNS sites and present in a diverse manner from isolated non-tumor proliferations to part of hamartomatous lesions to diffuse meningotheliomatosis to meningiomas tumors arising in multiple anatomic locations. Morphologically, immunophenotypically, ultrastructurally, and perhaps genetically, the meningeal tumors and proliferations outside the CNS are very similar to their CNS counterparts suggesting a common cellular origin. Because of the possibility of arising in diverse anatomic locations, they join a long list of differential diagnostic considerations for the practicing pathologist and should be entertained as possibilities particularly when the morphology could significantly overlap other tumors. In most cases, the immunohistochemical profile of EMA, vimentin, progesterone receptor, and SSTR2a (if available) is diagnostic in the proper morphological context. This panel should be included in diagnostically challenging cases.
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Among these heavy metals, a few have direct or indirect impact on the human body. Some of these heavy metals such as copper, cobalt, iron, nickel, magnesium, molybdenum, chromium, selenium, manganese and zinc have functional roles which are essential for various diverse physiological and biochemical activities in the body. However, some of these heavy metals in high doses can be harmful to the body while others such as cadmium, mercury, lead, chromium, silver, and arsenic in minute quantities have delirious effects in the body causing acute and chronic toxicities in humans. The focus of this chapter is to describe the various mechanism of intoxication of some selected heavy metals in humans along with their health effects. Therefore it aims to highlight on biochemical mechanisms of heavy metal intoxication which involves binding to proteins and enzymes, altering their activity and causing damage. 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Unachukwu",authors:[{id:"241837",title:"Mr.",name:"Godwill Azeh",middleName:null,surname:"Engwa",slug:"godwill-azeh-engwa",fullName:"Godwill Azeh Engwa"},{id:"274194",title:"BSc.",name:"Paschaline Ferdinand",middleName:null,surname:"Okeke",slug:"paschaline-ferdinand-okeke",fullName:"Paschaline Ferdinand Okeke"},{id:"286975",title:"Dr.",name:"Friday",middleName:null,surname:"Nweke Nwalo",slug:"friday-nweke-nwalo",fullName:"Friday Nweke Nwalo"},{id:"286976",title:"Dr.",name:"Marian",middleName:null,surname:"Unachukwu",slug:"marian-unachukwu",fullName:"Marian Unachukwu"}]},{id:"65467",title:"Anesthesia Management for Large-Volume Liposuction",slug:"anesthesia-management-for-large-volume-liposuction",totalDownloads:5710,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"The apparent easiness with which liposuction is performed favors that patients, young surgeons, and anesthesiologists without experience in this field ignore the many events that occur during this procedure. Liposuction is a procedure to improve the body contour and not a surgery to reduce weight, although recently people who have failed in their plans to lose weight look at liposuction as a means to contour their body figure. Tumescent liposuction of large volumes requires a meticulous selection of each patient; their preoperative evaluation and perioperative management are essential to obtain the expected results. The various techniques of general anesthesia are the most recommended and should be monitored in the usual way, as well as monitoring the total doses of infiltrated local anesthetics to avoid systemic toxicity. The management of intravenous fluids is controversial, but the current trend is the restricted use of hydrosaline solutions. The most feared complications are deep vein thrombosis, pulmonary thromboembolism, fat embolism, lung edema, hypothermia, infections and even death. The adherence to the management guidelines and prophylaxis of venous thrombosis/thromboembolism is mandatory.",book:{id:"6221",slug:"anesthesia-topics-for-plastic-and-reconstructive-surgery",title:"Anesthesia Topics for Plastic and Reconstructive Surgery",fullTitle:"Anesthesia Topics for Plastic and Reconstructive Surgery"},signatures:"Sergio Granados-Tinajero, Carlos Buenrostro-Vásquez, Cecilia\nCárdenas-Maytorena and Marcela Contreras-López",authors:[{id:"273532",title:"Dr.",name:"Sergio Octavio",middleName:null,surname:"Granados Tinajero",slug:"sergio-octavio-granados-tinajero",fullName:"Sergio Octavio Granados Tinajero"}]},{id:"30178",title:"Chest Mobilization Techniques for Improving Ventilation and Gas Exchange in Chronic Lung Disease",slug:"chest-mobilization-techniques-for-improving-ventilation-and-gas-exchange-in-chronic-lung-disease",totalDownloads:30993,totalCrossrefCites:0,totalDimensionsCites:5,abstract:null,book:{id:"648",slug:"chronic-obstructive-pulmonary-disease-current-concepts-and-practice",title:"Chronic Obstructive Pulmonary Disease",fullTitle:"Chronic Obstructive Pulmonary Disease - Current Concepts and Practice"},signatures:"Donrawee Leelarungrayub",authors:[{id:"73709",title:"Associate Prof.",name:"Jirakrit",middleName:null,surname:"Leelarungrayub",slug:"jirakrit-leelarungrayub",fullName:"Jirakrit Leelarungrayub"}]}],onlineFirstChaptersFilter:{topicId:"3",limit:6,offset:0},onlineFirstChaptersCollection:[{id:"81779",title:"Cancer Genes and Breast Cancers",slug:"cancer-genes-and-breast-cancers",totalDownloads:1,totalDimensionsCites:0,doi:"10.5772/intechopen.104801",abstract:"Cancer is the name given to all malignant tumors, the main reason for which is uncontrolled growth, and the tumor, which has become a mass as a result of uncontrolled cell proliferation, also attacks the surrounding cells and envelops the whole body (metastasis) in the later stages of the disease. Although cancer is an important health problem, it is not a common disease in childhood. On the other hand, statistics show that cancer affects one in three adults, causes up to 20% of all deaths, and covers about 10% of treatment costs in developed countries. Although it is known that cancer develops under the influence of genetic and environmental factors, environmental factors are more prominent in the formation of some types of cancer. Breast cancer is one of the cancer types known to have tumor suppressor genes in its etiology. These tumor suppressor genes are BRCA1 and BRCA2 genes. Studies have shown that these two genes are particularly effective in the development of familial breast cancers. These types of cancers occur much earlier than non-familial cancers. The research, two genes; It has shown that it is especially effective in the development of familial breast cancers.",book:{id:"10793",title:"Molecular Mechanisms in Cancer",coverURL:"https://cdn.intechopen.com/books/images_new/10793.jpg"},signatures:"Metin Budak and Hatice Segmen"},{id:"81783",title:"Tumour Angiogenesis in Breast Cancer",slug:"tumour-angiogenesis-in-breast-cancer",totalDownloads:1,totalDimensionsCites:0,doi:"10.5772/intechopen.102944",abstract:"Since the last comprehensive assessment of antiangiogenic therapy was published in Breast Cancer Research 3 years ago, clinical trials in a variety of tumour types, including breast cancer, have underscored the key relevance of tumour neovascularization. Bevacizumab, a drug designed to target vascular endothelial cell growth factor, was utilised in many of these studies (VEGF). Clinical trials using antiangiogenic treatment in breast cancer have highlighted the critical role of tumour neovascularization. Personalised medicine will become increasingly important to generate maximum therapeutic benefit to the patient but also to realise the optimal economic advantage from the finite resources available, according to a report by the US Department of Health and Human Services (HHS) and the National Institute for Occupational and Environmental Health (NIH). This overview covers the history of breast tumour neovascularization in both in situ and invasive breast cancer, the processes by which it occurs, and the impact of the microenvironment, with a focus on hypoxia. The regulation of angiogenesis, as well as the antivascular drugs employed in antiangiogenic dosing schedules, both innovative and traditional, are discussed.",book:{id:"10833",title:"Tumor Angiogenesis",coverURL:"https://cdn.intechopen.com/books/images_new/10833.jpg"},signatures:"Pooja G. Singh, Kanthesh M. Basalingappa, T.S. Gopenath and B.V. Sushma"},{id:"81794",title:"Mycobacterium ulcerans Disease and Host Immune Responses",slug:"mycobacterium-ulcerans-disease-and-host-immune-responses",totalDownloads:0,totalDimensionsCites:0,doi:"10.5772/intechopen.103843",abstract:"Mycobacterium ulcerans is the causative agent of the subcutaneous necrotic condition known as Buruli ulcer (BU).BU is Neglected Tropical Disease. The bacillus is the third most common mycobacteria disease-causing agent after Mycobacterium tuberculosis and Mycobacterium leprae. M. ulcerans produces the toxin-Mycolactone, which plays a key role in the pathophysiological features of the disease. Buruli ulcer has been reported in 34 countries, mainly in the tropics and subtropics. Tropical countries include Benin, Cameroon, Ghana, Democratic Republic of Congo and Nigeria. BU is also prevalent in Queensland, a subtropical region, and in Victoria, a temperate area, all within Australia. The exact mode of the transmission remains unclear. However, M. ulcerans is believed to have an aquatic niche. Initial diagnosis of BU is based on the experience of the clinician, but PCR targeting the M. ulcerans DNA, IS2404, isolation and culture of the bacillus and histopathology are used for confirmation. The current, commonly used methods for confirmatory diagnosis have logistic and resource challenges. Novel cell mediated immunity (CMI) and serology-based tests would be beneficial to provide a more accurate assessment of population exposure.",book:{id:"11227",title:"New Advances in Neglected Tropical Diseases",coverURL:"https://cdn.intechopen.com/books/images_new/11227.jpg"},signatures:"Michael S. Avumegah"},{id:"81793",title:"Canine parvovirus-2: An Emerging Threat to Young Pets",slug:"canine-parvovirus-2-an-emerging-threat-to-young-pets",totalDownloads:0,totalDimensionsCites:0,doi:"10.5772/intechopen.104846",abstract:"Canine parvovirus-2 (CPV-2) is a highly contagious and key enteropathogen affecting the canine population around the globe by causing canine parvoviral enteritis (CPVE) and vomition. CPVE is one of the the leading causes of morbidity and mortality in puppies and young dogs. Over the years, five distinct antigenic variants of CPV-2, namely CPV-2a, CPV-2b, new CPV-2a, new CPV-2b, and CPV-2c, have emerged throughout the world. CPV-2 infects a diverse range of wild animals, and the newer variants of CPV-2 have expanded their host range to include felines. Despite the availability of highly specific diagnostics and efficacious vaccines, CPV-2 outbreaks have been reported globally due to the emergence of newer antigenic variants, expansion of the viral host range, and vaccination failures. The present chapter describes the latest information pertaining to virus properties and replication, disease manifestations in animals, and an additional recent updates on diagnostic, prevention and control strategies of CPV-2.",book:{id:"11580",title:"Recent Advances in Canine Medicine",coverURL:"https://cdn.intechopen.com/books/images_new/11580.jpg"},signatures:"Mithilesh Singh, Rajendran Manikandan, Ujjwal Kumar De, Vishal Chander, Babul Rudra Paul, Saravanan Ramakrishnan and Darshini Maramreddy"},{id:"81767",title:"Living and Coping with Spinocerebellar Ataxia: Palliative Care Approach",slug:"living-and-coping-with-spinocerebellar-ataxia-palliative-care-approach",totalDownloads:0,totalDimensionsCites:0,doi:"10.5772/intechopen.104605",abstract:"The discussion about the palliative care approach in spinocerebellar ataxia (SCA) has become extremely relevant. Mainly after considering that most progressive ataxias are incurable, there are few published studies on their palliative and end-of-life care. Although many patients with degenerative neurological diseases have a normal life expectancy, some forms of SCA (e.g., type 1, 2, 3, and 17) can progress rapidly, with a shorter life span. This chapter will discuss current guidelines and recommendations that have been drawn from the broader field of progressive neurological conditions. In addition, we also review aspects of strategic end-of-life care management, the involvement of the multidisciplinary team and the contribution of allied health professionals are essential for excellent patient support care in a palliative approach. More studies on your supportive care and end-of-life care to manage this serious illness to improve quality of life and reduce suffering, addressing complex medical symptoms, psychosocial issues, general well-being, and planning strategies for better living and coping are needed.",book:{id:"9625",title:"Spinocerebellar Ataxia - Concepts, Particularities and Generalities",coverURL:"https://cdn.intechopen.com/books/images_new/9625.jpg"},signatures:"Caroline Bozzetto Ambrosi and Patricia Bozzetto Ambrosi"},{id:"81554",title:"Revascularization Strategies in Liver Transplantation",slug:"revascularization-strategies-in-liver-transplantation",totalDownloads:1,totalDimensionsCites:0,doi:"10.5772/intechopen.104708",abstract:"Vascular complications following liver transplantation chan jeopardize the liver graft and recipient survival. Aggressive strategies to diagnose and treat these complications may avoid patient and graft loss. With the evolving knowledge and novel therapies, less invasive strategies are gaining importance in the treatment of post liver transplant vascular complications. Portal, hepatic, and arterial thrombosis may be managed with systemic therapies, endovascular approaches, surgical and lastly with retransplantation. The timing between the diagnosis and the directed treatment is paramount for the success. Revascularization by means of interventional radiology plays an important role in the resolution and long-term patency of arterial and venous complications. This chapter will lead the reader into the most up-to-date treatments of post liver transplant vascular complications.",book:{id:"10712",title:"Thrombectomy - Recent Advances in Ischaemic Damage Treatment",coverURL:"https://cdn.intechopen.com/books/images_new/10712.jpg"},signatures:"Flavia H. Feier, Melina U. Melere, Alex Horbe and Antonio N. 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The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}},{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}}]},series:{item:{id:"14",title:"Artificial Intelligence",doi:"10.5772/intechopen.79920",issn:"2633-1403",scope:"Artificial Intelligence (AI) is a rapidly developing multidisciplinary research area that aims to solve increasingly complex problems. In today's highly integrated world, AI promises to become a robust and powerful means for obtaining solutions to previously unsolvable problems. This Series is intended for researchers and students alike interested in this fascinating field and its many applications.",coverUrl:"https://cdn.intechopen.com/series/covers/14.jpg",latestPublicationDate:"May 14th, 2022",hasOnlineFirst:!0,numberOfPublishedBooks:8,editor:{id:"218714",title:"Prof.",name:"Andries",middleName:null,surname:"Engelbrecht",slug:"andries-engelbrecht",fullName:"Andries Engelbrecht",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRNR8QAO/Profile_Picture_1622640468300",biography:"Andries Engelbrecht received the Masters and PhD degrees in Computer Science from the University of Stellenbosch, South Africa, in 1994 and 1999 respectively. He is currently appointed as the Voigt Chair in Data Science in the Department of Industrial Engineering, with a joint appointment as Professor in the Computer Science Division, Stellenbosch University. Prior to his appointment at Stellenbosch University, he has been at the University of Pretoria, Department of Computer Science (1998-2018), where he was appointed as South Africa Research Chair in Artifical Intelligence (2007-2018), the head of the Department of Computer Science (2008-2017), and Director of the Institute for Big Data and Data Science (2017-2018). In addition to a number of research articles, he has written two books, Computational Intelligence: An Introduction and Fundamentals of Computational Swarm Intelligence.",institutionString:null,institution:{name:"Stellenbosch University",institutionURL:null,country:{name:"South Africa"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:6,paginationItems:[{id:"22",title:"Applied Intelligence",coverUrl:"https://cdn.intechopen.com/series_topics/covers/22.jpg",isOpenForSubmission:!0,editor:{id:"27170",title:"Prof.",name:"Carlos",middleName:"M.",surname:"Travieso-Gonzalez",slug:"carlos-travieso-gonzalez",fullName:"Carlos Travieso-Gonzalez",profilePictureURL:"https://mts.intechopen.com/storage/users/27170/images/system/27170.jpeg",biography:"Carlos M. Travieso-González received his MSc degree in Telecommunication Engineering at Polytechnic University of Catalonia (UPC), Spain in 1997, and his Ph.D. degree in 2002 at the University of Las Palmas de Gran Canaria (ULPGC-Spain). He is a full professor of signal processing and pattern recognition and is head of the Signals and Communications Department at ULPGC, teaching from 2001 on subjects on signal processing and learning theory. His research lines are biometrics, biomedical signals and images, data mining, classification system, signal and image processing, machine learning, and environmental intelligence. He has researched in 52 international and Spanish research projects, some of them as head researcher. He is co-author of 4 books, co-editor of 27 proceedings books, guest editor for 8 JCR-ISI international journals, and up to 24 book chapters. He has over 450 papers published in international journals and conferences (81 of them indexed on JCR – ISI - Web of Science). He has published seven patents in the Spanish Patent and Trademark Office. He has been a supervisor on 8 Ph.D. theses (11 more are under supervision), and 130 master theses. He is the founder of The IEEE IWOBI conference series and the president of its Steering Committee, as well as the founder of both the InnoEducaTIC and APPIS conference series. He is an evaluator of project proposals for the European Union (H2020), Medical Research Council (MRC, UK), Spanish Government (ANECA, Spain), Research National Agency (ANR, France), DAAD (Germany), Argentinian Government, and the Colombian Institutions. He has been a reviewer in different indexed international journals (<70) and conferences (<250) since 2001. He has been a member of the IASTED Technical Committee on Image Processing from 2007 and a member of the IASTED Technical Committee on Artificial Intelligence and Expert Systems from 2011. \n\nHe has held the general chair position for the following: ACM-APPIS (2020, 2021), IEEE-IWOBI (2019, 2020 and 2020), A PPIS (2018, 2019), IEEE-IWOBI (2014, 2015, 2017, 2018), InnoEducaTIC (2014, 2017), IEEE-INES (2013), NoLISP (2011), JRBP (2012), and IEEE-ICCST (2005)\n\nHe is an associate editor of the Computational Intelligence and Neuroscience Journal (Hindawi – Q2 JCR-ISI). He was vice dean from 2004 to 2010 in the Higher Technical School of Telecommunication Engineers at ULPGC and the vice dean of Graduate and Postgraduate Studies from March 2013 to November 2017. He won the “Catedra Telefonica” Awards in Modality of Knowledge Transfer, 2017, 2018, and 2019 editions, and awards in Modality of COVID Research in 2020.\n\nPublic References:\nResearcher ID http://www.researcherid.com/rid/N-5967-2014\nORCID https://orcid.org/0000-0002-4621-2768 \nScopus Author ID https://www.scopus.com/authid/detail.uri?authorId=6602376272\nScholar Google https://scholar.google.es/citations?user=G1ks9nIAAAAJ&hl=en \nResearchGate https://www.researchgate.net/profile/Carlos_Travieso",institutionString:null,institution:{name:"University of Las Palmas de Gran Canaria",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null},{id:"23",title:"Computational Neuroscience",coverUrl:"https://cdn.intechopen.com/series_topics/covers/23.jpg",isOpenForSubmission:!0,editor:{id:"14004",title:"Dr.",name:"Magnus",middleName:null,surname:"Johnsson",slug:"magnus-johnsson",fullName:"Magnus Johnsson",profilePictureURL:"https://mts.intechopen.com/storage/users/14004/images/system/14004.png",biography:"Dr Magnus Johnsson is a cross-disciplinary scientist, lecturer, scientific editor and AI/machine learning consultant from Sweden. \n\nHe is currently at Malmö University in Sweden, but also held positions at Lund University in Sweden and at Moscow Engineering Physics Institute. \nHe holds editorial positions at several international scientific journals and has served as a scientific editor for books and special journal issues. \nHis research interests are wide and include, but are not limited to, autonomous systems, computer modeling, artificial neural networks, artificial intelligence, cognitive neuroscience, cognitive robotics, cognitive architectures, cognitive aids and the philosophy of mind. \n\nDr. Johnsson has experience from working in the industry and he has a keen interest in the application of neural networks and artificial intelligence to fields like industry, finance, and medicine. \n\nWeb page: www.magnusjohnsson.se",institutionString:null,institution:{name:"Malmö University",institutionURL:null,country:{name:"Sweden"}}},editorTwo:null,editorThree:null},{id:"24",title:"Computer Vision",coverUrl:"https://cdn.intechopen.com/series_topics/covers/24.jpg",isOpenForSubmission:!0,editor:{id:"294154",title:"Prof.",name:"George",middleName:null,surname:"Papakostas",slug:"george-papakostas",fullName:"George Papakostas",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002hYaGbQAK/Profile_Picture_1624519712088",biography:"George A. Papakostas has received a diploma in Electrical and Computer Engineering in 1999 and the M.Sc. and Ph.D. degrees in Electrical and Computer Engineering in 2002 and 2007, respectively, from the Democritus University of Thrace (DUTH), Greece. Dr. Papakostas serves as a Tenured Full Professor at the Department of Computer Science, International Hellenic University, Greece. Dr. Papakostas has 10 years of experience in large-scale systems design as a senior software engineer and technical manager, and 20 years of research experience in the field of Artificial Intelligence. Currently, he is the Head of the “Visual Computing” division of HUman-MAchines INteraction Laboratory (HUMAIN-Lab) and the Director of the MPhil program “Advanced Technologies in Informatics and Computers” hosted by the Department of Computer Science, International Hellenic University. He has (co)authored more than 150 publications in indexed journals, international conferences and book chapters, 1 book (in Greek), 3 edited books, and 5 journal special issues. His publications have more than 2100 citations with h-index 27 (GoogleScholar). His research interests include computer/machine vision, machine learning, pattern recognition, computational intelligence. \nDr. Papakostas served as a reviewer in numerous journals, as a program\ncommittee member in international conferences and he is a member of the IAENG, MIR Labs, EUCogIII, INSTICC and the Technical Chamber of Greece (TEE).",institutionString:null,institution:{name:"International Hellenic University",institutionURL:null,country:{name:"Greece"}}},editorTwo:null,editorThree:null},{id:"25",title:"Evolutionary Computation",coverUrl:"https://cdn.intechopen.com/series_topics/covers/25.jpg",isOpenForSubmission:!0,editor:{id:"136112",title:"Dr.",name:"Sebastian",middleName:null,surname:"Ventura Soto",slug:"sebastian-ventura-soto",fullName:"Sebastian Ventura Soto",profilePictureURL:"https://mts.intechopen.com/storage/users/136112/images/system/136112.png",biography:"Sebastian Ventura is a Spanish researcher, a full professor with the Department of Computer Science and Numerical Analysis, University of Córdoba. Dr Ventura also holds the positions of Affiliated Professor at Virginia Commonwealth University (Richmond, USA) and Distinguished Adjunct Professor at King Abdulaziz University (Jeddah, Saudi Arabia). Additionally, he is deputy director of the Andalusian Research Institute in Data Science and Computational Intelligence (DaSCI) and heads the Knowledge Discovery and Intelligent Systems Research Laboratory. He has published more than ten books and over 300 articles in journals and scientific conferences. Currently, his work has received over 18,000 citations according to Google Scholar, including more than 2200 citations in 2020. In the last five years, he has published more than 60 papers in international journals indexed in the JCR (around 70% of them belonging to first quartile journals) and he has edited some Springer books “Supervised Descriptive Pattern Mining” (2018), “Multiple Instance Learning - Foundations and Algorithms” (2016), and “Pattern Mining with Evolutionary Algorithms” (2016). He has also been involved in more than 20 research projects supported by the Spanish and Andalusian governments and the European Union. He currently belongs to the editorial board of PeerJ Computer Science, Information Fusion and Engineering Applications of Artificial Intelligence journals, being also associate editor of Applied Computational Intelligence and Soft Computing and IEEE Transactions on Cybernetics. Finally, he is editor-in-chief of Progress in Artificial Intelligence. He is a Senior Member of the IEEE Computer, the IEEE Computational Intelligence, and the IEEE Systems, Man, and Cybernetics Societies, and the Association of Computing Machinery (ACM). Finally, his main research interests include data science, computational intelligence, and their applications.",institutionString:null,institution:{name:"University of Córdoba",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null},{id:"26",title:"Machine Learning and Data Mining",coverUrl:"https://cdn.intechopen.com/series_topics/covers/26.jpg",isOpenForSubmission:!0,editor:{id:"24555",title:"Dr.",name:"Marco Antonio",middleName:null,surname:"Aceves Fernandez",slug:"marco-antonio-aceves-fernandez",fullName:"Marco Antonio Aceves Fernandez",profilePictureURL:"https://mts.intechopen.com/storage/users/24555/images/system/24555.jpg",biography:"Dr. Marco Antonio Aceves Fernandez obtained his B.Sc. (Eng.) in Telematics from the Universidad de Colima, Mexico. 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Saxena",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRET3QAO/Profile_Picture_2022-05-10T10:10:26.jpeg",institutionString:null,institution:{name:"King George's Medical University",institutionURL:null,country:{name:"India"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null}]},subseriesFiltersForPublishedBooks:[{group:"subseries",caption:"Bacterial Infectious Diseases",value:3,count:2},{group:"subseries",caption:"Parasitic Infectious Diseases",value:5,count:4},{group:"subseries",caption:"Viral Infectious Diseases",value:6,count:7}],publicationYearFilters:[{group:"publicationYear",caption:"2022",value:2022,count:2},{group:"publicationYear",caption:"2021",value:2021,count:4},{group:"publicationYear",caption:"2020",value:2020,count:3},{group:"publicationYear",caption:"2019",value:2019,count:3},{group:"publicationYear",caption:"2018",value:2018,count:1}],authors:{paginationCount:301,paginationItems:[{id:"116250",title:"Dr.",name:"Nima",middleName:null,surname:"Rezaei",slug:"nima-rezaei",fullName:"Nima Rezaei",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/116250/images/system/116250.jpg",biography:"Professor Nima Rezaei obtained an MD from Tehran University of Medical Sciences, Iran. He also obtained an MSc in Molecular and Genetic Medicine, and a Ph.D. in Clinical Immunology and Human Genetics from the University of Sheffield, UK. He also completed a short-term fellowship in Pediatric Clinical Immunology and Bone Marrow Transplantation at Newcastle General Hospital, England. Dr. Rezaei is a Full Professor of Immunology and Vice Dean of International Affairs and Research, at the School of Medicine, Tehran University of Medical Sciences, and the co-founder and head of the Research Center for Immunodeficiencies. He is also the founding president of the Universal Scientific Education and Research Network (USERN). Dr. Rezaei has directed more than 100 research projects and has designed and participated in several international collaborative projects. He is an editor, editorial assistant, or editorial board member of more than forty international journals. He has edited more than 50 international books, presented more than 500 lectures/posters in congresses/meetings, and published more than 1,100 scientific papers in international journals.",institutionString:"Tehran University of Medical Sciences",institution:{name:"Tehran University of Medical Sciences",country:{name:"Iran"}}},{id:"180733",title:"Dr.",name:"Jean",middleName:null,surname:"Engohang-Ndong",slug:"jean-engohang-ndong",fullName:"Jean Engohang-Ndong",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/180733/images/system/180733.png",biography:"Dr. Jean Engohang-Ndong was born and raised in Gabon. After obtaining his Associate Degree of Science at the University of Science and Technology of Masuku, Gabon, he continued his education in France where he obtained his BS, MS, and Ph.D. in Medical Microbiology. He worked as a post-doctoral fellow at the Public Health Research Institute (PHRI), Newark, NJ for four years before accepting a three-year faculty position at Brigham Young University-Hawaii. Dr. Engohang-Ndong is a tenured faculty member with the academic rank of Full Professor at Kent State University, Ohio, where he teaches a wide range of biological science courses and pursues his research in medical and environmental microbiology. Recently, he expanded his research interest to epidemiology and biostatistics of chronic diseases in Gabon.",institutionString:"Kent State University",institution:{name:"Kent State University",country:{name:"United States of America"}}},{id:"188773",title:"Prof.",name:"Emmanuel",middleName:null,surname:"Drouet",slug:"emmanuel-drouet",fullName:"Emmanuel Drouet",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/188773/images/system/188773.png",biography:"Emmanuel Drouet, PharmD, is a Professor of Virology at the Faculty of Pharmacy, the University Grenoble-Alpes, France. As a head scientist at the Institute of Structural Biology in Grenoble, Dr. Drouet’s research investigates persisting viruses in humans (RNA and DNA viruses) and the balance with our host immune system. He focuses on these viruses’ effects on humans (both their impact on pathology and their symbiotic relationships in humans). He has an excellent track record in the herpesvirus field, and his group is engaged in clinical research in the field of Epstein-Barr virus diseases. He is the editor of the online Encyclopedia of Environment and he coordinates the Universal Health Coverage education program for the BioHealth Computing Schools of the European Institute of Science.",institutionString:null,institution:{name:"Grenoble Alpes University",country:{name:"France"}}},{id:"131400",title:"Prof.",name:"Alfonso J.",middleName:null,surname:"Rodriguez-Morales",slug:"alfonso-j.-rodriguez-morales",fullName:"Alfonso J. Rodriguez-Morales",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/131400/images/system/131400.png",biography:"Dr. Rodriguez-Morales is an expert in tropical and emerging diseases, particularly zoonotic and vector-borne diseases (especially arboviral diseases). He is the president of the Travel Medicine Committee of the Pan-American Infectious Diseases Association (API), as well as the president of the Colombian Association of Infectious Diseases (ACIN). He is a member of the Committee on Tropical Medicine, Zoonoses, and Travel Medicine of ACIN. He is a vice-president of the Latin American Society for Travel Medicine (SLAMVI) and a Member of the Council of the International Society for Infectious Diseases (ISID). Since 2014, he has been recognized as a Senior Researcher, at the Ministry of Science of Colombia. He is a professor at the Faculty of Medicine of the Fundacion Universitaria Autonoma de las Americas, in Pereira, Risaralda, Colombia. He is an External Professor, Master in Research on Tropical Medicine and International Health, Universitat de Barcelona, Spain. He is also a professor at the Master in Clinical Epidemiology and Biostatistics, Universidad Científica del Sur, Lima, Peru. In 2021 he has been awarded the “Raul Isturiz Award” Medal of the API. Also, in 2021, he was awarded with the “Jose Felix Patiño” Asclepius Staff Medal of the Colombian Medical College, due to his scientific contributions to COVID-19 during the pandemic. He is currently the Editor in Chief of the journal Travel Medicine and Infectious Diseases. His Scopus H index is 47 (Google Scholar H index, 68).",institutionString:"Institución Universitaria Visión de las Américas, Colombia",institution:null},{id:"332819",title:"Dr.",name:"Chukwudi Michael",middleName:"Michael",surname:"Egbuche",slug:"chukwudi-michael-egbuche",fullName:"Chukwudi Michael Egbuche",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/332819/images/14624_n.jpg",biography:"I an Dr. Chukwudi Michael Egbuche. I am a Senior Lecturer in the Department of Parasitology and Entomology, Nnamdi Azikiwe University, Awka.",institutionString:null,institution:{name:"Nnamdi Azikiwe University",country:{name:"Nigeria"}}},{id:"284232",title:"Mr.",name:"Nikunj",middleName:"U",surname:"Tandel",slug:"nikunj-tandel",fullName:"Nikunj Tandel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/284232/images/8275_n.jpg",biography:'Mr. Nikunj Tandel has completed his Master\'s degree in Biotechnology from VIT University, India in the year of 2012. He is having 8 years of research experience especially in the field of malaria epidemiology, immunology, and nanoparticle-based drug delivery system against the infectious diseases, autoimmune disorders and cancer. He has worked for the NIH funded-International Center of Excellence in Malaria Research project "Center for the study of complex malaria in India (CSCMi)" in collaboration with New York University. The preliminary objectives of the study are to understand and develop the evidence-based tools and interventions for the control and prevention of malaria in different sites of the INDIA. Alongside, with the help of next-generation genomics study, the team has studied the antimalarial drug resistance in India. Further, he has extended his research in the development of Humanized mice for the study of liver-stage malaria and identification of molecular marker(s) for the Artemisinin resistance. At present, his research focuses on understanding the role of B cells in the activation of CD8+ T cells in malaria. Received the CSIR-SRF (Senior Research Fellow) award-2018, FIMSA (Federation of Immunological Societies of Asia-Oceania) Travel Bursary award to attend the IUIS-IIS-FIMSA Immunology course-2019',institutionString:"Nirma University",institution:{name:"Nirma University",country:{name:"India"}}},{id:"334383",title:"Ph.D.",name:"Simone",middleName:"Ulrich",surname:"Ulrich Picoli",slug:"simone-ulrich-picoli",fullName:"Simone Ulrich Picoli",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/334383/images/15919_n.jpg",biography:"Graduated in Pharmacy from Universidade Luterana do Brasil (1999), Master in Agricultural and Environmental Microbiology from Federal University of Rio Grande do Sul (2002), Specialization in Clinical Microbiology from Universidade de São Paulo, USP (2007) and PhD in Sciences in Gastroenterology and Hepatology (2012). She is currently an Adjunct Professor at Feevale University in Medicine and Biomedicine courses and a permanent professor of the Academic Master\\'s Degree in Virology. She has experience in the field of Microbiology, with an emphasis on Bacteriology, working mainly on the following topics: bacteriophages, bacterial resistance, clinical microbiology and food microbiology.",institutionString:null,institution:{name:"Universidade Feevale",country:{name:"Brazil"}}},{id:"229220",title:"Dr.",name:"Amjad",middleName:"Islam",surname:"Aqib",slug:"amjad-aqib",fullName:"Amjad Aqib",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/229220/images/system/229220.png",biography:"Dr. Amjad Islam Aqib obtained a DVM and MSc (Hons) from University of Agriculture Faisalabad (UAF), Pakistan, and a PhD from the University of Veterinary and Animal Sciences Lahore, Pakistan. Dr. Aqib joined the Department of Clinical Medicine and Surgery at UAF for one year as an assistant professor where he developed a research laboratory designated for pathogenic bacteria. Since 2018, he has been Assistant Professor/Officer in-charge, Department of Medicine, Manager Research Operations and Development-ORIC, and President One Health Club at Cholistan University of Veterinary and Animal Sciences, Bahawalpur, Pakistan. He has nearly 100 publications to his credit. His research interests include epidemiological patterns and molecular analysis of antimicrobial resistance and modulation and vaccine development against animal pathogens of public health concern.",institutionString:"Cholistan University of Veterinary and Animal Sciences",institution:null},{id:"62900",title:"Prof.",name:"Fethi",middleName:null,surname:"Derbel",slug:"fethi-derbel",fullName:"Fethi Derbel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/62900/images/system/62900.jpeg",biography:"Professor Fethi Derbel was born in 1960 in Tunisia. He received his medical degree from the Sousse Faculty of Medicine at Sousse, University of Sousse, Tunisia. He completed his surgical residency in General Surgery at the University Hospital Farhat Hached of Sousse and was a member of the Unit of Liver Transplantation in the University of Rennes, France. He then worked in the Department of Surgery at the Sahloul University Hospital in Sousse. Professor Derbel is presently working at the Clinique les Oliviers, Sousse, Tunisia. His hospital activities are mostly concerned with laparoscopic, colorectal, pancreatic, hepatobiliary, and gastric surgery. He is also very interested in hernia surgery and performs ventral hernia repairs and inguinal hernia repairs. He has been a member of the GREPA and Tunisian Hernia Society (THS). During his residency, he managed patients suffering from diabetic foot, and he was very interested in this pathology. For this reason, he decided to coordinate a book project dealing with the diabetic foot. Professor Derbel has published many articles in journals and collaborates intensively with IntechOpen Access Publisher as an editor.",institutionString:"Clinique les Oliviers",institution:null},{id:"300144",title:"Dr.",name:"Meriem",middleName:null,surname:"Braiki",slug:"meriem-braiki",fullName:"Meriem Braiki",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/300144/images/system/300144.jpg",biography:"Dr. Meriem Braiki is a specialist in pediatric surgeon from Tunisia. She was born in 1985. She received her medical degree from the University of Medicine at Sousse, Tunisia. She achieved her surgical residency training periods in Pediatric Surgery departments at University Hospitals in Monastir, Tunis and France.\r\nShe is currently working at the Pediatric surgery department, Sidi Bouzid Hospital, Tunisia. Her hospital activities are mostly concerned with laparoscopic, parietal, urological and digestive surgery. She has published several articles in diffrent journals.",institutionString:"Sidi Bouzid Regional Hospital",institution:null},{id:"229481",title:"Dr.",name:"Erika M.",middleName:"Martins",surname:"de Carvalho",slug:"erika-m.-de-carvalho",fullName:"Erika M. de Carvalho",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/229481/images/6397_n.jpg",biography:null,institutionString:null,institution:{name:"Oswaldo Cruz Foundation",country:{name:"Brazil"}}},{id:"186537",title:"Prof.",name:"Tonay",middleName:null,surname:"Inceboz",slug:"tonay-inceboz",fullName:"Tonay Inceboz",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/186537/images/system/186537.jfif",biography:"I was graduated from Ege University of Medical Faculty (Turkey) in 1988 and completed his Med. PhD degree in Medical Parasitology at the same university. I became an Associate Professor in 2008 and Professor in 2014. I am currently working as a Professor at the Department of Medical Parasitology at Dokuz Eylul University, Izmir, Turkey.\n\nI have given many lectures, presentations in different academic meetings. I have more than 60 articles in peer-reviewed journals, 18 book chapters, 1 book editorship.\n\nMy research interests are Echinococcus granulosus, Echinococcus multilocularis (diagnosis, life cycle, in vitro and in vivo cultivation), and Trichomonas vaginalis (diagnosis, PCR, and in vitro cultivation).",institutionString:"Dokuz Eylül University",institution:{name:"Dokuz Eylül University",country:{name:"Turkey"}}},{id:"71812",title:"Prof.",name:"Hanem Fathy",middleName:"Fathy",surname:"Khater",slug:"hanem-fathy-khater",fullName:"Hanem Fathy Khater",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/71812/images/1167_n.jpg",biography:"Prof. Khater is a Professor of Parasitology at Benha University, Egypt. She studied for her doctoral degree, at the Department of Entomology, College of Agriculture, Food and Natural Resources, University of Missouri, Columbia, USA. She has completed her Ph.D. degrees in Parasitology in Egypt, from where she got the award for “the best scientific Ph.D. dissertation”. She worked at the School of Biological Sciences, Bristol, England, the UK in controlling insects of medical and veterinary importance as a grant from Newton Mosharafa, the British Council. Her research is focused on searching of pesticides against mosquitoes, house flies, lice, green bottle fly, camel nasal botfly, soft and hard ticks, mites, and the diamondback moth as well as control of several parasites using safe and natural materials to avoid drug resistances and environmental contamination.",institutionString:null,institution:{name:"Banha University",country:{name:"Egypt"}}},{id:"99780",title:"Prof.",name:"Omolade",middleName:"Olayinka",surname:"Okwa",slug:"omolade-okwa",fullName:"Omolade Okwa",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/99780/images/system/99780.jpg",biography:"Omolade Olayinka Okwa is presently a Professor of Parasitology at Lagos State University, Nigeria. She has a PhD in Parasitology (1997), an MSc in Cellular Parasitology (1992), and a BSc (Hons) Zoology (1990) all from the University of Ibadan, Nigeria. She teaches parasitology at the undergraduate and postgraduate levels. She was a recipient of a Commonwealth fellowship supported by British Council tenable at the Centre for Entomology and Parasitology (CAEP), Keele University, United Kingdom between 2004 and 2005. She was awarded an Honorary Visiting Research Fellow at the same university from 2005 to 2007. \nShe has been an external examiner to the Department of Veterinary Microbiology and Parasitology, University of Ibadan, MSc programme between 2010 and 2012. She is a member of the Nigerian Society of Experimental Biology (NISEB), Parasitology and Public Health Society of Nigeria (PPSN), Science Association of Nigeria (SAN), Zoological Society of Nigeria (ZSN), and is Vice Chairperson of the Organisation of Women in Science (OWSG), LASU chapter. She served as Head of Department of Zoology and Environmental Biology, Lagos State University from 2007 to 2010 and 2014 to 2016. She is a reviewer for several local and international journals such as Unilag Journal of Science, Libyan Journal of Medicine, Journal of Medicine and Medical Sciences, and Annual Research and Review in Science. \nShe has authored 45 scientific research publications in local and international journals, 8 scientific reviews, 4 books, and 3 book chapters, which includes the books “Malaria Parasites” and “Malaria” which are IntechOpen access publications.",institutionString:"Lagos State University",institution:{name:"Lagos State University",country:{name:"Nigeria"}}},{id:"273100",title:"Dr.",name:"Vijay",middleName:null,surname:"Gayam",slug:"vijay-gayam",fullName:"Vijay Gayam",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/273100/images/system/273100.jpeg",biography:"Dr. Vijay Bhaskar Reddy Gayam is currently practicing as an internist at Interfaith Medical Center in Brooklyn, New York, USA. 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Recently, bioinspired systems have been successfully employing biomechanics to develop and improve assistive technology and rehabilitation devices. The research topic "Bioinspired Technology and Biomechanics" welcomes studies reporting recent advances in bioinspired technologies that contribute to individuals\' health, inclusion, and rehabilitation. Possible contributions can address (but are not limited to) the following research topics: Bioinspired design and control of exoskeletons, orthoses, and prostheses; Experimental evaluation of the effect of assistive devices (e.g., influence on gait, balance, and neuromuscular system); Bioinspired technologies for rehabilitation, including clinical studies reporting evaluations; Application of neuromuscular and biomechanical models to the development of bioinspired technology.',coverUrl:"https://cdn.intechopen.com/series_topics/covers/8.jpg",hasOnlineFirst:!1,hasPublishedBooks:!0,annualVolume:11404,editor:{id:"144937",title:"Prof.",name:"Adriano",middleName:"De Oliveira",surname:"Andrade",slug:"adriano-andrade",fullName:"Adriano Andrade",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRC8QQAW/Profile_Picture_1625219101815",biography:"Dr. Adriano de Oliveira Andrade graduated in Electrical Engineering at the Federal University of Goiás (Brazil) in 1997. 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