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Central nervous system primitive neuroectodermal tumor
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<h2 id="classification">Classification</h2> <p>The <a href="/facts/World_Health_Organization/YNN3bgug">World Health Organization</a> has classified the central nervous system primitive neuroectodermal tumors into five subtypes: <a href="/facts/Neuroblastoma/nzCww7nE">neuroblastoma</a>, <a href="/facts/Ganglioneuroblastoma/ebKFGHSB">ganglioneuroblastoma</a>, <a href="/facts/Medulloepithelioma/v1jNxCf9">medulloepithelioma</a>, ependymoblastoma, and not otherwise specified PNET.<a class="footnote-ref" id="fnref:23" href="#fn:23"><sup>23</sup></a> The last one encompasses the PNETs with varying characteristics that hasn't been well defined yet.<a class="footnote-ref" id="fnref:24" href="#fn:24"><sup>24</sup></a> <a href="/facts/Neuroblastoma/nzCww7nE">Neuroblastomas</a> are PNETS that involve the process of cell differentiation into neurons,<a class="footnote-ref" id="fnref:25" href="#fn:25"><sup>25</sup></a><a class="footnote-ref" id="fnref:26" href="#fn:26"><sup>26</sup></a> while <a href="/facts/Ganglioneuroblastoma/ebKFGHSB">ganglioneuroblastomas</a> are PNETs that involve <a href="/facts/Ganglion_cell/dzKg8jq1">ganglion cells</a>.<a class="footnote-ref" id="fnref:27" href="#fn:27"><sup>27</sup></a> </p><p><a href="/facts/Medulloepithelioma/v1jNxCf9">Medulloepithelioma</a>, on the other hand, are tumors involving the constant cell division on the <a href="/facts/Epithelium/ecKHcHC3">epithelium</a> tissue where bundle of neuron endings are located.<a class="footnote-ref" id="fnref:28" href="#fn:28"><sup>28</sup></a> Such tissue will differentiate into a similar form as the embryonic neural tube, also known as the starting structure of the <a href="/facts/Central_nervous_system/k8I6To97">central nervous system</a>.<a class="footnote-ref" id="fnref:29" href="#fn:29"><sup>29</sup></a><a class="footnote-ref" id="fnref:30" href="#fn:30"><sup>30</sup></a><a class="footnote-ref" id="fnref:31" href="#fn:31"><sup>31</sup></a> Medulloepitheliomas also present a pattern known as rosettes, characterized by the arrangement of a bundle of cells into circular shapes and around a center or a neuropil.<a class="footnote-ref" id="fnref:32" href="#fn:32"><sup>32</sup></a> Ependymoblastoma also present rosettes as well as a higher density of cells.<a class="footnote-ref" id="fnref:33" href="#fn:33"><sup>33</sup></a><a class="footnote-ref" id="fnref:34" href="#fn:34"><sup>34</sup></a> It involves the process of differentiation into ependymal cells.<a class="footnote-ref" id="fnref:35" href="#fn:35"><sup>35</sup></a><a class="footnote-ref" id="fnref:36" href="#fn:36"><sup>36</sup></a> </p> <p>Further classification types have come up but not yet approved by the <a href="/facts/World_Health_Organization/YNN3bgug">World Health Organization</a>.<a class="footnote-ref" id="fnref:37" href="#fn:37"><sup>37</sup></a> The term "embryonal tumor with abundant neuropil and true rosettes", or ETANTR, has been proposed as a sixth subtype of PNET.<a class="footnote-ref" id="fnref:38" href="#fn:38"><sup>38</sup></a> However, the still unofficial term "embryonal tumor with multilayered rosettes" (ETMR) has been more frequently used and encompasses ETANTRs, <a href="/facts/Medulloepithelioma/v1jNxCf9">medulloepitheliomas</a>, ependymoblastomas, and variants of PNETs with presence of rosettes and with no well defined classification.<a class="footnote-ref" id="fnref:39" href="#fn:39"><sup>39</sup></a> </p> <h2 id="risk-factors">Risk factors</h2> <p>The rate of PNETs in not correlated with sex, but it shows a correlation with age.<a class="footnote-ref" id="fnref:40" href="#fn:40"><sup>40</sup></a> Most cases occur in children around 5 years of age, having a very low frequency in adults.<a class="footnote-ref" id="fnref:41" href="#fn:41"><sup>41</sup></a> Regarding genetic mutations, a specific type of gene alteration that directly leads to this tumor hasn't been defined yet.<a class="footnote-ref" id="fnref:42" href="#fn:42"><sup>42</sup></a> However, a positive correlation between individuals with <a href="/facts/Li%E2%80%93Fraumeni_syndrome/BbXVuES9">Li-Fraumeni syndrome</a> with a mutation in the <a href="/facts/P53/YEGULLgM">gene <i>p53</i></a> and PNET has been reported.<a class="footnote-ref" id="fnref:43" href="#fn:43"><sup>43</sup></a> A significant number of individuals with mutations on the <a href="/facts/Retinoblastoma_protein/qc2WKTc4"><i>rb</i> tumor suppressor gene</a> have also developed the tumor.<a class="footnote-ref" id="fnref:44" href="#fn:44"><sup>44</sup></a> Such gene encodes for the protein Rb responsible for stopping the cell cycle at the <a href="/facts/G1_phase/92lq1LdT">G1 phase</a>.<a class="footnote-ref" id="fnref:45" href="#fn:45"><sup>45</sup></a> Another possible contributing factor are mutations in the <a href="/facts/CREB-binding_protein/F4p9VIV7">CREB-binding protein</a>, whose function includes activating transcription,<a class="footnote-ref" id="fnref:46" href="#fn:46"><sup>46</sup></a> but this interaction still need to be studied further.<a class="footnote-ref" id="fnref:47" href="#fn:47"><sup>47</sup></a> It has also been presumed that the tumor can arise from cranial irradiation.<a class="footnote-ref" id="fnref:48" href="#fn:48"><sup>48</sup></a> </p> <h2 id="diagnosis">Diagnosis</h2> <p>Most children that develop primitive neuroectodermal tumors are diagnosed early in life, usually at around 3–6.8 years of age.<a class="footnote-ref" id="fnref:49" href="#fn:49"><sup>49</sup></a> Symptoms patients present at time of diagnosis include irritable mood, visual difficulties, <a href="/facts/Lethargy/wJFlYuB7">lethargy</a>, and <a href="/facts/Ataxia/suENWGS6">ataxia</a>.<a class="footnote-ref" id="fnref:50" href="#fn:50"><sup>50</sup></a> The circumference of the patient's head might also become enlarged and they might be subject to seizures, especially if they have less than one year of life.<a class="footnote-ref" id="fnref:51" href="#fn:51"><sup>51</sup></a> </p><p>Several analysis can be used to determine the presence of the disease. Physical examinations showing <a href="/facts/Papilledema/WKK6AIsT">papilledema</a>, visual field defects, cranial nerves <a href="/facts/Cerebral_palsy/WTs1Ge0p">palsy</a>, dysphasia, and focal neurological deficits are evidences for possible tumor.<a class="footnote-ref" id="fnref:52" href="#fn:52"><sup>52</sup></a> PNETs can also be spotted through <a href="/facts/CT_scan/NusPJ2S8">computed tomography</a> (CT) and <a href="/facts/Magnetic_resonance_imaging/Vh9yG9qq">magnetic resonance imaging</a> (MRI).<a class="footnote-ref" id="fnref:53" href="#fn:53"><sup>53</sup></a> In images produced by <a href="/facts/Magnetic_resonance_imaging/Vh9yG9qq">MRIs</a>, an irregular augmentation among a solid mass will indicated the presence of tumor.<a class="footnote-ref" id="fnref:54" href="#fn:54"><sup>54</sup></a> However, the results of MRIs are usually ambiguous in defining the presence for this specific tumor.<a class="footnote-ref" id="fnref:55" href="#fn:55"><sup>55</sup></a> In <a href="/facts/CT_scan/NusPJ2S8">CT scans</a>, the presence of PNETs will be indicated by an elevated density and an increase in volume of the brain.<a class="footnote-ref" id="fnref:56" href="#fn:56"><sup>56</sup></a> The <a href="/facts/CT_scan/NusPJ2S8">CT scan</a> can also show <a href="/facts/Calcification/NRSv3tMS">calcification</a>,<a class="footnote-ref" id="fnref:57" href="#fn:57"><sup>57</sup></a> which is present in 41-44% of PNET cases.<a class="footnote-ref" id="fnref:58" href="#fn:58"><sup>58</sup></a> Since the tumor can be replicated in other parts of the nervous system through the <a href="/facts/Cerebrospinal_fluid/tcWG7hhv">cerebrospinal fluid</a> (CSF), a CSF analysis can also be conducted.<a class="footnote-ref" id="fnref:59" href="#fn:59"><sup>59</sup></a> A spinal MRI is a fourth type of analysis that is useful in investigating the level of tumor propagation to the <a href="/facts/Spinal_cord/XbWLr917">spinal cord</a>.<a class="footnote-ref" id="fnref:60" href="#fn:60"><sup>60</sup></a> </p> <h2 id="treatment">Treatment</h2> <p>There is not a standardized procedure to treat primitive neuroectodermal tumors.<a class="footnote-ref" id="fnref:61" href="#fn:61"><sup>61</sup></a> Common strategies involve risk-adapted <a href="/facts/Radiation_therapy/j60q5EC6">radiotherapy</a> combined with <a href="/facts/Chemotherapy/fWTLbaUT">chemotherapy</a> and stem cell rescue.<a class="footnote-ref" id="fnref:62" href="#fn:62"><sup>62</sup></a> For patients younger than 2–3 years of age, treatment with radiation is not used, once they are in a more vulnerable phase and, thus, more prone to risks in development.<a class="footnote-ref" id="fnref:63" href="#fn:63"><sup>63</sup></a> Examinations such as CSF analysis and spinal MRIs are used to investigate the effectiveness of treatment in preventing <a href="/facts/Metastasis/4dadbm6z">metastasis</a>.<a class="footnote-ref" id="fnref:64" href="#fn:64"><sup>64</sup></a> </p><p>A method for eliminating tumorous mass is surgery, where the best outcome would be total resection, meaning the complete removal of the tumor.<a class="footnote-ref" id="fnref:65" href="#fn:65"><sup>65</sup></a> Along with the surgery, several measures that contribute to a safe procedure can be taken: urine exams, transfusion, and the constant supervision of arterial pressure.<a class="footnote-ref" id="fnref:66" href="#fn:66"><sup>66</sup></a> Possible problems that arise from the surgery include <a href="/facts/Bleeding/CGyFMU0F">hemorrhage</a>, <a href="/facts/Cerebral_edema/UDlqKHrV">brain edema</a>, and <a href="/facts/Hemiparesis/W44QM11N">hemiparesis</a>.<a class="footnote-ref" id="fnref:67" href="#fn:67"><sup>67</sup></a> <a href="/facts/Magnetic_resonance_imaging/Vh9yG9qq">MRIs</a> are typically done after 1 or 2 days of postoperative in order to inspect the amount of tumor remaining.<a class="footnote-ref" id="fnref:68" href="#fn:68"><sup>68</sup></a> </p> <h2 id="prognosis">Prognosis</h2> <p>The probability of primitive neuroectodermal tumors to have recurrence and <a href="/facts/Metastasis/4dadbm6z">metastasize</a> through <a href="/facts/Cerebrospinal_fluid/tcWG7hhv">cerebrospinal fluid</a> is relatively high.<a class="footnote-ref" id="fnref:69" href="#fn:69"><sup>69</sup></a> The outcome of PNET is more positive when the individual is an adult, independent of age subgroups, or an older child.<a class="footnote-ref" id="fnref:70" href="#fn:70"><sup>70</sup></a> Less than 50% of children survive more than 5 years,<a class="footnote-ref" id="fnref:71" href="#fn:71"><sup>71</sup></a> while the majority of adults live to 7 years.<a class="footnote-ref" id="fnref:72" href="#fn:72"><sup>72</sup></a> The reason the prognosis for such tumor is worst in children is due to the higher probability of the tumor spreading to the rest of the <a href="/facts/Nervous_system/CDxRKU2U">nervous system</a> through the <a href="/facts/Cerebrospinal_fluid/tcWG7hhv">cerebrospinal fluid</a> and growing again.<a class="footnote-ref" id="fnref:73" href="#fn:73"><sup>73</sup></a> Moreover, children have the probability of developing deficiencies in cognitive processes, problems in the <a href="/facts/Endocrine_system/PDvN5cpj">endocrine system</a>, and psychological obstacles after the disease.<a class="footnote-ref" id="fnref:74" href="#fn:74"><sup>74</sup></a> Adults, on the other hand, don't show such propensity.<a class="footnote-ref" id="fnref:75" href="#fn:75"><sup>75</sup></a> As a consequence, 37.7% of children affected by the tumor live to 4 years.<a class="footnote-ref" id="fnref:76" href="#fn:76"><sup>76</sup></a> </p><p>The effect of treatment strategies such as <a href="/facts/Chemotherapy/fWTLbaUT">chemotherapy</a> and <a href="/facts/Radiation_therapy/j60q5EC6">radiation therapy</a> on the prognosis of the disease is still controversial, with studies claiming either their benefits or their ineffectiveness.<a class="footnote-ref" id="fnref:77" href="#fn:77"><sup>77</sup></a> The same holds true for the relationship between volume of tumor removed by surgery and survival.<a class="footnote-ref" id="fnref:78" href="#fn:78"><sup>78</sup></a> Furthermore, factors such as tumor size, location of origin, race, and sex of individual don't show any influence on the outcome of the disease.<a class="footnote-ref" id="fnref:79" href="#fn:79"><sup>79</sup></a> However, interactions of some factors such as tumor site, age, and treatment strategy can affect one's prognosis.<a class="footnote-ref" id="fnref:80" href="#fn:80"><sup>80</sup></a> For instance, when younger children below the age of three develop tumors originating in places other than the <a href="/facts/Pineal_gland/eN9EBq5Q">pineal gland</a> are treated with <a href="/facts/Chemotherapy/fWTLbaUT">chemotherapy</a>, they present better outcomes than those with <a href="/facts/Pineal_gland/eN9EBq5Q">pineal</a> tumors and treated with <a href="/facts/Chemotherapy/fWTLbaUT">chemotherapy</a>.<a class="footnote-ref" id="fnref:81" href="#fn:81"><sup>81</sup></a> </p> <h2 id="references">References</h2> <ol> <li id="fn:1"><p>Karajannis, Matthias A.; Zagzag, David, eds. (2015). Molecular Pathology of Nervous System Tumors. Molecular Pathology Library. Vol. 8. doi:10.1007/978-1-4939-1830-0. ISBN 978-1-4939-1829-4. ISSN 1935-987X. <a href="978-1-4939-1829-4" target="_blank">978-1-4939-1829-4</a> <a href="#fnref:1" class="footnote-back-ref">↩</a></p></li> <li id="fn:2"><p>Hayat, M.A., ed. (2014). Tumors of the Central Nervous System, Volume 13. Vol. 13. doi:10.1007/978-94-007-7602-9. ISBN 978-94-007-7601-2. ISSN 2215-096X. <a href="978-94-007-7601-2" target="_blank">978-94-007-7601-2</a> <a href="#fnref:2" class="footnote-back-ref">↩</a></p></li> <li id="fn:3"><p>Karajannis, Matthias A.; Zagzag, David, eds. (2015). Molecular Pathology of Nervous System Tumors. Molecular Pathology Library. Vol. 8. doi:10.1007/978-1-4939-1830-0. ISBN 978-1-4939-1829-4. ISSN 1935-987X. <a href="978-1-4939-1829-4" target="_blank">978-1-4939-1829-4</a> <a href="#fnref:3" class="footnote-back-ref">↩</a></p></li> <li id="fn:4"><p>Karajannis, Matthias A.; Zagzag, David, eds. (2015). Molecular Pathology of Nervous System Tumors. Molecular Pathology Library. Vol. 8. doi:10.1007/978-1-4939-1830-0. ISBN 978-1-4939-1829-4. ISSN 1935-987X. <a href="978-1-4939-1829-4" target="_blank">978-1-4939-1829-4</a> <a href="#fnref:4" class="footnote-back-ref">↩</a></p></li> <li id="fn:5"><p>Hayat, M.A., ed. (2014). Tumors of the Central Nervous System, Volume 13. Vol. 13. doi:10.1007/978-94-007-7602-9. ISBN 978-94-007-7601-2. ISSN 2215-096X. <a href="978-94-007-7601-2" target="_blank">978-94-007-7601-2</a> <a href="#fnref:5" class="footnote-back-ref">↩</a></p></li> <li id="fn:6"><p>Fuller, Christine E. (2009-10-23), "Oligodendroglial Tumors", Atlas of Pediatric Brain Tumors, Springer New York, pp. 39–46, doi:10.1007/978-1-4419-1062-2_4, ISBN 9781441910615 <a href="9781441910615" target="_blank">9781441910615</a> <a href="#fnref:6" class="footnote-back-ref">↩</a></p></li> <li id="fn:7"><p>Nelesen, Richard A (March 2000). "Biological Psychology: An Introduction to Behavioral, Cognitive, and Clinical Neuroscience, 2nd edition. Mark R. Rosenweig, Arnold L. Leiman, and S. Marc Breedlove, Sinauer Associates, Inc., Sunderland MA, 1999. 561+92 pp. ISBN 0-87893-791-9". Biological Psychology. 52 (2): 185–186. doi:10.1016/s0301-0511(99)00025-3. ISSN 0301-0511. S2CID 54349873. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:7" class="footnote-back-ref">↩</a></p></li> <li id="fn:8"><p>Karajannis, Matthias A.; Zagzag, David, eds. (2015). Molecular Pathology of Nervous System Tumors. Molecular Pathology Library. Vol. 8. doi:10.1007/978-1-4939-1830-0. ISBN 978-1-4939-1829-4. ISSN 1935-987X. <a href="978-1-4939-1829-4" target="_blank">978-1-4939-1829-4</a> <a href="#fnref:8" class="footnote-back-ref">↩</a></p></li> <li id="fn:9"><p>Hayat, M.A., ed. (2014). Tumors of the Central Nervous System, Volume 13. Vol. 13. doi:10.1007/978-94-007-7602-9. ISBN 978-94-007-7601-2. ISSN 2215-096X. <a href="978-94-007-7601-2" target="_blank">978-94-007-7601-2</a> <a href="#fnref:9" class="footnote-back-ref">↩</a></p></li> <li id="fn:10"><p>Karajannis, Matthias A.; Zagzag, David, eds. (2015). Molecular Pathology of Nervous System Tumors. Molecular Pathology Library. Vol. 8. doi:10.1007/978-1-4939-1830-0. ISBN 978-1-4939-1829-4. ISSN 1935-987X. <a href="978-1-4939-1829-4" target="_blank">978-1-4939-1829-4</a> <a href="#fnref:10" class="footnote-back-ref">↩</a></p></li> <li id="fn:11"><p>Karajannis, Matthias A.; Zagzag, David, eds. (2015). Molecular Pathology of Nervous System Tumors. Molecular Pathology Library. Vol. 8. doi:10.1007/978-1-4939-1830-0. ISBN 978-1-4939-1829-4. ISSN 1935-987X. <a href="978-1-4939-1829-4" target="_blank">978-1-4939-1829-4</a> <a href="#fnref:11" class="footnote-back-ref">↩</a></p></li> <li id="fn:12"><p>Hayat, M.A., ed. (2014). Tumors of the Central Nervous System, Volume 13. Vol. 13. doi:10.1007/978-94-007-7602-9. ISBN 978-94-007-7601-2. ISSN 2215-096X. <a href="978-94-007-7601-2" target="_blank">978-94-007-7601-2</a> <a href="#fnref:12" class="footnote-back-ref">↩</a></p></li> <li id="fn:13"><p>Hayat, M.A., ed. (2014). Tumors of the Central Nervous System, Volume 13. Vol. 13. doi:10.1007/978-94-007-7602-9. ISBN 978-94-007-7601-2. ISSN 2215-096X. <a href="978-94-007-7601-2" target="_blank">978-94-007-7601-2</a> <a href="#fnref:13" class="footnote-back-ref">↩</a></p></li> <li id="fn:14"><p>Hayat, M.A., ed. (2014). Tumors of the Central Nervous System, Volume 13. Vol. 13. doi:10.1007/978-94-007-7602-9. ISBN 978-94-007-7601-2. ISSN 2215-096X. <a href="978-94-007-7601-2" target="_blank">978-94-007-7601-2</a> <a href="#fnref:14" class="footnote-back-ref">↩</a></p></li> <li id="fn:15"><p>Hayat, M.A., ed. (2014). Tumors of the Central Nervous System, Volume 13. Vol. 13. doi:10.1007/978-94-007-7602-9. ISBN 978-94-007-7601-2. ISSN 2215-096X. <a href="978-94-007-7601-2" target="_blank">978-94-007-7601-2</a> <a href="#fnref:15" class="footnote-back-ref">↩</a></p></li> <li id="fn:16"><p>Karajannis, Matthias A.; Zagzag, David, eds. (2015). Molecular Pathology of Nervous System Tumors. Molecular Pathology Library. Vol. 8. doi:10.1007/978-1-4939-1830-0. ISBN 978-1-4939-1829-4. ISSN 1935-987X. <a href="978-1-4939-1829-4" target="_blank">978-1-4939-1829-4</a> <a href="#fnref:16" class="footnote-back-ref">↩</a></p></li> <li id="fn:17"><p>Hayat, M.A., ed. (2014). Tumors of the Central Nervous System, Volume 13. Vol. 13. doi:10.1007/978-94-007-7602-9. ISBN 978-94-007-7601-2. ISSN 2215-096X. <a href="978-94-007-7601-2" target="_blank">978-94-007-7601-2</a> <a href="#fnref:17" class="footnote-back-ref">↩</a></p></li> <li id="fn:18"><p>Hayat, M.A., ed. (2014). Tumors of the Central Nervous System, Volume 13. Vol. 13. doi:10.1007/978-94-007-7602-9. ISBN 978-94-007-7601-2. ISSN 2215-096X. <a href="978-94-007-7601-2" target="_blank">978-94-007-7601-2</a> <a href="#fnref:18" class="footnote-back-ref">↩</a></p></li> <li id="fn:19"><p>Hayat, M.A., ed. (2014). Tumors of the Central Nervous System, Volume 13. Vol. 13. doi:10.1007/978-94-007-7602-9. ISBN 978-94-007-7601-2. ISSN 2215-096X. <a href="978-94-007-7601-2" target="_blank">978-94-007-7601-2</a> <a href="#fnref:19" class="footnote-back-ref">↩</a></p></li> <li id="fn:20"><p>Karajannis, Matthias A.; Zagzag, David, eds. (2015). Molecular Pathology of Nervous System Tumors. Molecular Pathology Library. Vol. 8. doi:10.1007/978-1-4939-1830-0. ISBN 978-1-4939-1829-4. ISSN 1935-987X. <a href="978-1-4939-1829-4" target="_blank">978-1-4939-1829-4</a> <a href="#fnref:20" class="footnote-back-ref">↩</a></p></li> <li id="fn:21"><p>Hayat, M.A., ed. (2014). Tumors of the Central Nervous System, Volume 13. Vol. 13. doi:10.1007/978-94-007-7602-9. ISBN 978-94-007-7601-2. ISSN 2215-096X. <a href="978-94-007-7601-2" target="_blank">978-94-007-7601-2</a> <a href="#fnref:21" class="footnote-back-ref">↩</a></p></li> <li id="fn:22"><p>Louis DN, Ohgaki H, Wiestler OD, Cavenee WK "WHO Classification of Tumours of the Central Nervous System. 4th Edition Revised" <a href="#fnref:22" class="footnote-back-ref">↩</a></p></li> <li id="fn:23"><p>Karajannis, Matthias A.; Zagzag, David, eds. (2015). Molecular Pathology of Nervous System Tumors. Molecular Pathology Library. Vol. 8. doi:10.1007/978-1-4939-1830-0. ISBN 978-1-4939-1829-4. ISSN 1935-987X. <a href="978-1-4939-1829-4" target="_blank">978-1-4939-1829-4</a> <a href="#fnref:23" class="footnote-back-ref">↩</a></p></li> <li id="fn:24"><p>Karajannis, Matthias A.; Zagzag, David, eds. (2015). Molecular Pathology of Nervous System Tumors. Molecular Pathology Library. Vol. 8. doi:10.1007/978-1-4939-1830-0. ISBN 978-1-4939-1829-4. ISSN 1935-987X. <a href="978-1-4939-1829-4" target="_blank">978-1-4939-1829-4</a> <a href="#fnref:24" class="footnote-back-ref">↩</a></p></li> <li id="fn:25"><p>Karajannis, Matthias A.; Zagzag, David, eds. (2015). Molecular Pathology of Nervous System Tumors. Molecular Pathology Library. Vol. 8. doi:10.1007/978-1-4939-1830-0. ISBN 978-1-4939-1829-4. ISSN 1935-987X. <a href="978-1-4939-1829-4" target="_blank">978-1-4939-1829-4</a> <a href="#fnref:25" class="footnote-back-ref">↩</a></p></li> <li id="fn:26"><p>Hayat, M.A., ed. (2014). Tumors of the Central Nervous System, Volume 13. Vol. 13. doi:10.1007/978-94-007-7602-9. ISBN 978-94-007-7601-2. ISSN 2215-096X. <a href="978-94-007-7601-2" target="_blank">978-94-007-7601-2</a> <a href="#fnref:26" class="footnote-back-ref">↩</a></p></li> <li id="fn:27"><p>Karajannis, Matthias A.; Zagzag, David, eds. (2015). Molecular Pathology of Nervous System Tumors. Molecular Pathology Library. Vol. 8. doi:10.1007/978-1-4939-1830-0. ISBN 978-1-4939-1829-4. ISSN 1935-987X. <a href="978-1-4939-1829-4" target="_blank">978-1-4939-1829-4</a> <a href="#fnref:27" class="footnote-back-ref">↩</a></p></li> <li id="fn:28"><p>Karajannis, Matthias A.; Zagzag, David, eds. (2015). Molecular Pathology of Nervous System Tumors. Molecular Pathology Library. Vol. 8. doi:10.1007/978-1-4939-1830-0. ISBN 978-1-4939-1829-4. ISSN 1935-987X. <a href="978-1-4939-1829-4" target="_blank">978-1-4939-1829-4</a> <a href="#fnref:28" class="footnote-back-ref">↩</a></p></li> <li id="fn:29"><p>Karajannis, Matthias A.; Zagzag, David, eds. (2015). Molecular Pathology of Nervous System Tumors. Molecular Pathology Library. Vol. 8. doi:10.1007/978-1-4939-1830-0. ISBN 978-1-4939-1829-4. ISSN 1935-987X. <a href="978-1-4939-1829-4" target="_blank">978-1-4939-1829-4</a> <a href="#fnref:29" class="footnote-back-ref">↩</a></p></li> <li id="fn:30"><p>Hayat, M.A., ed. (2014). Tumors of the Central Nervous System, Volume 13. Vol. 13. doi:10.1007/978-94-007-7602-9. ISBN 978-94-007-7601-2. ISSN 2215-096X. <a href="978-94-007-7601-2" target="_blank">978-94-007-7601-2</a> <a href="#fnref:30" class="footnote-back-ref">↩</a></p></li> <li id="fn:31"><p>Fuller, Christine E. (2009-10-23), "Oligodendroglial Tumors", Atlas of Pediatric Brain Tumors, Springer New York, pp. 39–46, doi:10.1007/978-1-4419-1062-2_4, ISBN 9781441910615 <a href="9781441910615" target="_blank">9781441910615</a> <a href="#fnref:31" class="footnote-back-ref">↩</a></p></li> <li id="fn:32"><p>Karajannis, Matthias A.; Zagzag, David, eds. (2015). Molecular Pathology of Nervous System Tumors. Molecular Pathology Library. Vol. 8. doi:10.1007/978-1-4939-1830-0. ISBN 978-1-4939-1829-4. ISSN 1935-987X. <a href="978-1-4939-1829-4" target="_blank">978-1-4939-1829-4</a> <a href="#fnref:32" class="footnote-back-ref">↩</a></p></li> <li id="fn:33"><p>Karajannis, Matthias A.; Zagzag, David, eds. (2015). Molecular Pathology of Nervous System Tumors. Molecular Pathology Library. Vol. 8. doi:10.1007/978-1-4939-1830-0. ISBN 978-1-4939-1829-4. ISSN 1935-987X. <a href="978-1-4939-1829-4" target="_blank">978-1-4939-1829-4</a> <a href="#fnref:33" class="footnote-back-ref">↩</a></p></li> <li id="fn:34"><p>Fuller, Christine E. (2009-10-23), "Oligodendroglial Tumors", Atlas of Pediatric Brain Tumors, Springer New York, pp. 39–46, doi:10.1007/978-1-4419-1062-2_4, ISBN 9781441910615 <a href="9781441910615" target="_blank">9781441910615</a> <a href="#fnref:34" class="footnote-back-ref">↩</a></p></li> <li id="fn:35"><p>Hayat, M.A., ed. (2014). Tumors of the Central Nervous System, Volume 13. Vol. 13. doi:10.1007/978-94-007-7602-9. ISBN 978-94-007-7601-2. ISSN 2215-096X. <a href="978-94-007-7601-2" target="_blank">978-94-007-7601-2</a> <a href="#fnref:35" class="footnote-back-ref">↩</a></p></li> <li id="fn:36"><p>Fuller, Christine E. (2009-10-23), "Oligodendroglial Tumors", Atlas of Pediatric Brain Tumors, Springer New York, pp. 39–46, doi:10.1007/978-1-4419-1062-2_4, ISBN 9781441910615 <a href="9781441910615" target="_blank">9781441910615</a> <a href="#fnref:36" class="footnote-back-ref">↩</a></p></li> <li id="fn:37"><p>Karajannis, Matthias A.; Zagzag, David, eds. (2015). Molecular Pathology of Nervous System Tumors. Molecular Pathology Library. Vol. 8. doi:10.1007/978-1-4939-1830-0. ISBN 978-1-4939-1829-4. ISSN 1935-987X. <a href="978-1-4939-1829-4" target="_blank">978-1-4939-1829-4</a> <a href="#fnref:37" class="footnote-back-ref">↩</a></p></li> <li id="fn:38"><p>Karajannis, Matthias A.; Zagzag, David, eds. (2015). Molecular Pathology of Nervous System Tumors. Molecular Pathology Library. Vol. 8. doi:10.1007/978-1-4939-1830-0. ISBN 978-1-4939-1829-4. 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ISSN 2215-096X. <a href="978-94-007-7601-2" target="_blank">978-94-007-7601-2</a> <a href="#fnref:44" class="footnote-back-ref">↩</a></p></li> <li id="fn:45"><p>Baker, Henry V (June 2003). "Essential Genetics: A Genomics Perspective . Third Edition. By Daniel L Hartl and , Elizabeth W Jones. Sudbury (Massachusetts): Jones and Bartlett Publishers . $78.95 (Paper). Xxvi + 613 p; ill.; index. ISBN: 0–7637–1852–1. 2002". The Quarterly Review of Biology. 78 (2): 225–226. doi:10.1086/377959. ISSN 0033-5770. <a href="https://archive.org/details/essentialgenetic0000hart/page/225" target="_blank">https://archive.org/details/essentialgenetic0000hart/page/225</a> <a href="#fnref:45" class="footnote-back-ref">↩</a></p></li> <li id="fn:46"><p>Baker, Henry V (June 2003). "Essential Genetics: A Genomics Perspective . Third Edition. By Daniel L Hartl and , Elizabeth W Jones. Sudbury (Massachusetts): Jones and Bartlett Publishers . $78.95 (Paper). Xxvi + 613 p; ill.; index. ISBN: 0–7637–1852–1. 2002". The Quarterly Review of Biology. 78 (2): 225–226. doi:10.1086/377959. ISSN 0033-5770. <a href="https://archive.org/details/essentialgenetic0000hart/page/225" target="_blank">https://archive.org/details/essentialgenetic0000hart/page/225</a> <a href="#fnref:46" class="footnote-back-ref">↩</a></p></li> <li id="fn:47"><p>Hayat, M.A., ed. (2014). Tumors of the Central Nervous System, Volume 13. Vol. 13. doi:10.1007/978-94-007-7602-9. ISBN 978-94-007-7601-2. ISSN 2215-096X. <a href="978-94-007-7601-2" target="_blank">978-94-007-7601-2</a> <a href="#fnref:47" class="footnote-back-ref">↩</a></p></li> <li id="fn:48"><p>Hayat, M.A., ed. (2014). Tumors of the Central Nervous System, Volume 13. Vol. 13. doi:10.1007/978-94-007-7602-9. ISBN 978-94-007-7601-2. ISSN 2215-096X. <a href="978-94-007-7601-2" target="_blank">978-94-007-7601-2</a> <a href="#fnref:48" class="footnote-back-ref">↩</a></p></li> <li id="fn:49"><p>Hayat, M.A., ed. (2014). Tumors of the Central Nervous System, Volume 13. Vol. 13. doi:10.1007/978-94-007-7602-9. ISBN 978-94-007-7601-2. ISSN 2215-096X. <a href="978-94-007-7601-2" target="_blank">978-94-007-7601-2</a> <a href="#fnref:49" class="footnote-back-ref">↩</a></p></li> <li id="fn:50"><p>Hayat, M.A., ed. (2014). Tumors of the Central Nervous System, Volume 13. Vol. 13. doi:10.1007/978-94-007-7602-9. ISBN 978-94-007-7601-2. ISSN 2215-096X. <a href="978-94-007-7601-2" target="_blank">978-94-007-7601-2</a> <a href="#fnref:50" class="footnote-back-ref">↩</a></p></li> <li id="fn:51"><p>Hayat, M.A., ed. (2014). Tumors of the Central Nervous System, Volume 13. Vol. 13. doi:10.1007/978-94-007-7602-9. ISBN 978-94-007-7601-2. ISSN 2215-096X. <a href="978-94-007-7601-2" target="_blank">978-94-007-7601-2</a> <a href="#fnref:51" class="footnote-back-ref">↩</a></p></li> <li id="fn:52"><p>Hayat, M.A., ed. (2014). Tumors of the Central Nervous System, Volume 13. Vol. 13. doi:10.1007/978-94-007-7602-9. ISBN 978-94-007-7601-2. ISSN 2215-096X. <a href="978-94-007-7601-2" target="_blank">978-94-007-7601-2</a> <a href="#fnref:52" class="footnote-back-ref">↩</a></p></li> <li id="fn:53"><p>Hayat, M.A., ed. (2014). Tumors of the Central Nervous System, Volume 13. Vol. 13. doi:10.1007/978-94-007-7602-9. ISBN 978-94-007-7601-2. ISSN 2215-096X. <a href="978-94-007-7601-2" target="_blank">978-94-007-7601-2</a> <a href="#fnref:53" class="footnote-back-ref">↩</a></p></li> <li id="fn:54"><p>Fuller, Christine E. (2009-10-23), "Oligodendroglial Tumors", Atlas of Pediatric Brain Tumors, Springer New York, pp. 39–46, doi:10.1007/978-1-4419-1062-2_4, ISBN 9781441910615 <a href="9781441910615" target="_blank">9781441910615</a> <a href="#fnref:54" class="footnote-back-ref">↩</a></p></li> <li id="fn:55"><p>Hayat, M.A., ed. (2014). Tumors of the Central Nervous System, Volume 13. Vol. 13. doi:10.1007/978-94-007-7602-9. ISBN 978-94-007-7601-2. ISSN 2215-096X. <a href="978-94-007-7601-2" target="_blank">978-94-007-7601-2</a> <a href="#fnref:55" class="footnote-back-ref">↩</a></p></li> <li id="fn:56"><p>Hayat, M.A., ed. (2014). Tumors of the Central Nervous System, Volume 13. Vol. 13. doi:10.1007/978-94-007-7602-9. ISBN 978-94-007-7601-2. ISSN 2215-096X. <a href="978-94-007-7601-2" target="_blank">978-94-007-7601-2</a> <a href="#fnref:56" class="footnote-back-ref">↩</a></p></li> <li id="fn:57"><p>Fuller, Christine E. (2009-10-23), "Oligodendroglial Tumors", Atlas of Pediatric Brain Tumors, Springer New York, pp. 39–46, doi:10.1007/978-1-4419-1062-2_4, ISBN 9781441910615 <a href="9781441910615" target="_blank">9781441910615</a> <a href="#fnref:57" class="footnote-back-ref">↩</a></p></li> <li id="fn:58"><p>Hayat, M.A., ed. (2014). Tumors of the Central Nervous System, Volume 13. Vol. 13. doi:10.1007/978-94-007-7602-9. ISBN 978-94-007-7601-2. ISSN 2215-096X. <a href="978-94-007-7601-2" target="_blank">978-94-007-7601-2</a> <a href="#fnref:58" class="footnote-back-ref">↩</a></p></li> <li id="fn:59"><p>Hayat, M.A., ed. (2014). Tumors of the Central Nervous System, Volume 13. Vol. 13. doi:10.1007/978-94-007-7602-9. ISBN 978-94-007-7601-2. ISSN 2215-096X. <a href="978-94-007-7601-2" target="_blank">978-94-007-7601-2</a> <a href="#fnref:59" class="footnote-back-ref">↩</a></p></li> <li id="fn:60"><p>Hayat, M.A., ed. (2014). Tumors of the Central Nervous System, Volume 13. Vol. 13. doi:10.1007/978-94-007-7602-9. ISBN 978-94-007-7601-2. ISSN 2215-096X. <a href="978-94-007-7601-2" target="_blank">978-94-007-7601-2</a> <a href="#fnref:60" class="footnote-back-ref">↩</a></p></li> <li id="fn:61"><p>Hayat, M.A., ed. (2014). Tumors of the Central Nervous System, Volume 13. Vol. 13. doi:10.1007/978-94-007-7602-9. ISBN 978-94-007-7601-2. ISSN 2215-096X. <a href="978-94-007-7601-2" target="_blank">978-94-007-7601-2</a> <a href="#fnref:61" class="footnote-back-ref">↩</a></p></li> <li id="fn:62"><p>Karajannis, Matthias A.; Zagzag, David, eds. (2015). Molecular Pathology of Nervous System Tumors. Molecular Pathology Library. Vol. 8. doi:10.1007/978-1-4939-1830-0. ISBN 978-1-4939-1829-4. ISSN 1935-987X. <a href="978-1-4939-1829-4" target="_blank">978-1-4939-1829-4</a> <a href="#fnref:62" class="footnote-back-ref">↩</a></p></li> <li id="fn:63"><p>Karajannis, Matthias A.; Zagzag, David, eds. (2015). Molecular Pathology of Nervous System Tumors. Molecular Pathology Library. Vol. 8. doi:10.1007/978-1-4939-1830-0. ISBN 978-1-4939-1829-4. ISSN 1935-987X. <a href="978-1-4939-1829-4" target="_blank">978-1-4939-1829-4</a> <a href="#fnref:63" class="footnote-back-ref">↩</a></p></li> <li id="fn:64"><p>Hayat, M.A., ed. (2014). Tumors of the Central Nervous System, Volume 13. Vol. 13. doi:10.1007/978-94-007-7602-9. ISBN 978-94-007-7601-2. ISSN 2215-096X. <a href="978-94-007-7601-2" target="_blank">978-94-007-7601-2</a> <a href="#fnref:64" class="footnote-back-ref">↩</a></p></li> <li id="fn:65"><p>Hayat, M.A., ed. (2014). Tumors of the Central Nervous System, Volume 13. Vol. 13. doi:10.1007/978-94-007-7602-9. ISBN 978-94-007-7601-2. ISSN 2215-096X. <a href="978-94-007-7601-2" target="_blank">978-94-007-7601-2</a> <a href="#fnref:65" class="footnote-back-ref">↩</a></p></li> <li id="fn:66"><p>Hayat, M.A., ed. (2014). Tumors of the Central Nervous System, Volume 13. Vol. 13. doi:10.1007/978-94-007-7602-9. ISBN 978-94-007-7601-2. ISSN 2215-096X. <a href="978-94-007-7601-2" target="_blank">978-94-007-7601-2</a> <a href="#fnref:66" class="footnote-back-ref">↩</a></p></li> <li id="fn:67"><p>Hayat, M.A., ed. (2014). Tumors of the Central Nervous System, Volume 13. Vol. 13. doi:10.1007/978-94-007-7602-9. ISBN 978-94-007-7601-2. ISSN 2215-096X. <a href="978-94-007-7601-2" target="_blank">978-94-007-7601-2</a> <a href="#fnref:67" class="footnote-back-ref">↩</a></p></li> <li id="fn:68"><p>Hayat, M.A., ed. (2014). Tumors of the Central Nervous System, Volume 13. Vol. 13. doi:10.1007/978-94-007-7602-9. ISBN 978-94-007-7601-2. ISSN 2215-096X. <a href="978-94-007-7601-2" target="_blank">978-94-007-7601-2</a> <a href="#fnref:68" class="footnote-back-ref">↩</a></p></li> <li id="fn:69"><p>Fuller, Christine E. (2009-10-23), "Oligodendroglial Tumors", Atlas of Pediatric Brain Tumors, Springer New York, pp. 39–46, doi:10.1007/978-1-4419-1062-2_4, ISBN 9781441910615 <a href="9781441910615" target="_blank">9781441910615</a> <a href="#fnref:69" class="footnote-back-ref">↩</a></p></li> <li id="fn:70"><p>Hayat, M.A., ed. (2014). Tumors of the Central Nervous System, Volume 13. Vol. 13. doi:10.1007/978-94-007-7602-9. ISBN 978-94-007-7601-2. ISSN 2215-096X. <a href="978-94-007-7601-2" target="_blank">978-94-007-7601-2</a> <a href="#fnref:70" class="footnote-back-ref">↩</a></p></li> <li id="fn:71"><p>Karajannis, Matthias A.; Zagzag, David, eds. (2015). Molecular Pathology of Nervous System Tumors. Molecular Pathology Library. Vol. 8. doi:10.1007/978-1-4939-1830-0. ISBN 978-1-4939-1829-4. ISSN 1935-987X. <a href="978-1-4939-1829-4" target="_blank">978-1-4939-1829-4</a> <a href="#fnref:71" class="footnote-back-ref">↩</a></p></li> <li id="fn:72"><p>Hayat, M.A., ed. (2014). Tumors of the Central Nervous System, Volume 13. Vol. 13. doi:10.1007/978-94-007-7602-9. ISBN 978-94-007-7601-2. ISSN 2215-096X. <a href="978-94-007-7601-2" target="_blank">978-94-007-7601-2</a> <a href="#fnref:72" class="footnote-back-ref">↩</a></p></li> <li id="fn:73"><p>Hayat, M.A., ed. (2014). Tumors of the Central Nervous System, Volume 13. Vol. 13. doi:10.1007/978-94-007-7602-9. ISBN 978-94-007-7601-2. ISSN 2215-096X. <a href="978-94-007-7601-2" target="_blank">978-94-007-7601-2</a> <a href="#fnref:73" class="footnote-back-ref">↩</a></p></li> <li id="fn:74"><p>Hayat, M.A., ed. (2014). Tumors of the Central Nervous System, Volume 13. Vol. 13. doi:10.1007/978-94-007-7602-9. ISBN 978-94-007-7601-2. ISSN 2215-096X. <a href="978-94-007-7601-2" target="_blank">978-94-007-7601-2</a> <a href="#fnref:74" class="footnote-back-ref">↩</a></p></li> <li id="fn:75"><p>Hayat, M.A., ed. (2014). Tumors of the Central Nervous System, Volume 13. Vol. 13. doi:10.1007/978-94-007-7602-9. ISBN 978-94-007-7601-2. ISSN 2215-096X. <a href="978-94-007-7601-2" target="_blank">978-94-007-7601-2</a> <a href="#fnref:75" class="footnote-back-ref">↩</a></p></li> <li id="fn:76"><p>Hayat, M.A., ed. (2014). Tumors of the Central Nervous System, Volume 13. Vol. 13. doi:10.1007/978-94-007-7602-9. ISBN 978-94-007-7601-2. ISSN 2215-096X. <a href="978-94-007-7601-2" target="_blank">978-94-007-7601-2</a> <a href="#fnref:76" class="footnote-back-ref">↩</a></p></li> <li id="fn:77"><p>Hayat, M.A., ed. (2014). Tumors of the Central Nervous System, Volume 13. Vol. 13. doi:10.1007/978-94-007-7602-9. ISBN 978-94-007-7601-2. ISSN 2215-096X. <a href="978-94-007-7601-2" target="_blank">978-94-007-7601-2</a> <a href="#fnref:77" class="footnote-back-ref">↩</a></p></li> <li id="fn:78"><p>Hayat, M.A., ed. (2014). Tumors of the Central Nervous System, Volume 13. Vol. 13. doi:10.1007/978-94-007-7602-9. ISBN 978-94-007-7601-2. ISSN 2215-096X. <a href="978-94-007-7601-2" target="_blank">978-94-007-7601-2</a> <a href="#fnref:78" class="footnote-back-ref">↩</a></p></li> <li id="fn:79"><p>Hayat, M.A., ed. (2014). Tumors of the Central Nervous System, Volume 13. Vol. 13. doi:10.1007/978-94-007-7602-9. ISBN 978-94-007-7601-2. ISSN 2215-096X. <a href="978-94-007-7601-2" target="_blank">978-94-007-7601-2</a> <a href="#fnref:79" class="footnote-back-ref">↩</a></p></li> <li id="fn:80"><p>Hayat, M.A., ed. (2014). Tumors of the Central Nervous System, Volume 13. Vol. 13. doi:10.1007/978-94-007-7602-9. ISBN 978-94-007-7601-2. ISSN 2215-096X. <a href="978-94-007-7601-2" target="_blank">978-94-007-7601-2</a> <a href="#fnref:80" class="footnote-back-ref">↩</a></p></li> <li id="fn:81"><p>Hayat, M.A., ed. (2014). Tumors of the Central Nervous System, Volume 13. Vol. 13. doi:10.1007/978-94-007-7602-9. ISBN 978-94-007-7601-2. ISSN 2215-096X. <a href="978-94-007-7601-2" target="_blank">978-94-007-7601-2</a> <a href="#fnref:81" class="footnote-back-ref">↩</a></p></li> </ol>