Primary central nervous system lymphoma in immunocompetent patients: Spectrum of findings and differential characteristics

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Gómez Roselló, A.M. Quiles Granado, G. Laguillo Sala, S. Pedraza Gutiérrez" "autores" => array:4 [ 0 => array:4 [ "nombre" => "E." "apellidos" => "Gómez Roselló" "email" => array:1 [ 0 => "evagrosello@hotmail.com" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 1 => array:2 [ "nombre" => "A.M." "apellidos" => "Quiles Granado" ] 2 => array:2 [ "nombre" => "G." "apellidos" => "Laguillo Sala" ] 3 => array:2 [ "nombre" => "S." "apellidos" => "Pedraza Gutiérrez" ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Sección de Neurorradiología, Servicio de Radiología (IDI), Hospital Universitario Dr. Josep Trueta, Girona, Spain" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Linfoma cerebral primario en pacientes inmunocompetentes: espectro de hallazgos y características diferenciales" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 973 "Ancho" => 1667 "Tamanyo" => 118277 ] ] "descripcion" => array:1 [ "en" => "Appearance of one PCNSL on the CT scan, hyperdense without contrast (a) and with uniform enhancement after the administration of contrast (b)." ] ] ] "textoCompleto" => "IntroductionLymphomas can affect the central nervous system (CNS) as a primary tumor or, more commonly, in a secondary way, as the spread of systemic lymphomas in up to 15% of the cases.<a class="elsevierStyleCrossRef" href="#bib0295">1</a>The primary central nervous system lymphoma (PCNSL) is a lymphoma that is restricted to the brain, the leptomeninges, the spine cord, or the eyes without evidence outside the CNS.<a class="elsevierStyleCrossRefs" href="#bib0300">2–4</a>The PCNSL is a rare type of tumor of poor prognosis that is usually found in up to 3–5% of primary brain tumors<a class="elsevierStyleCrossRefs" href="#bib0315">5–7</a> and in 1% of non-Hodgkin lymphomas,<a class="elsevierStyleCrossRefs" href="#bib0315">5,8</a> whose incidence has been growing during the last few years among immunocompetent patients.<a class="elsevierStyleCrossRefs" href="#bib0315">5,9</a> Immunodepressed patients have a higher risk of PCNSLs, which is also higher in the following cases: post-transplant immuosuppressive therapy; congenital immunodeficiencies<a class="elsevierStyleCrossRef" href="#bib0295">1</a> and infections due to human immunodeficiency virus (HIV)<a class="elsevierStyleCrossRefs" href="#bib0295">1,10</a>; the latter not so much since the arrival of antiretroviral therapies.Epidemiologically we say that PCNSLs occur more predominantly in males, with a wide age range, and an average age at diagnosis of 66 years old.<a class="elsevierStyleCrossRef" href="#bib0320">6</a>This paper describes the histological characteristics of the PCNSL in immunocompetent patients, its diagnostic and therapeutic management, and imaging findings – these ones being the most specific findings of all. The magnetic resonance imaging (MRI) is the imaging modality of choice and provides crucial information through morphological and advanced sequences.Pathological anatomyMost tumors are aggressive diffuse large B-cell lymphomas.<a class="elsevierStyleCrossRefs" href="#bib0295">1,3,11</a> The way these neoplasms develop within the CNS is still a mystery since these lymphocytes do not have a known function in the normal parenchyma.Other histological types such as dural lymphomas, a low-grade subtype of marginal zone lymphoma (MALT type), are rarer and have better prognosis.<a class="elsevierStyleCrossRef" href="#bib0330">8</a>Although positivity to Epstein-Barr virus (EBV) in immunocompetent patients is low (compared to what happens in patients with HIV), this association has been described in the classification established by the World Health Organization back in 2008. Age-related EBV+ diffuse large B-cell lymphomas are usually diagnosed in patients over 55 and they have certain neuroradiological particularities that make them different from other PCNSLs in immunocompetent patients. Hemorrhages, necrosis, and ring enhancement after the administration of contrast are characteristic of this type of lymphomas–very similar to the ones described in patients with HIV.<a class="elsevierStyleCrossRef" href="#bib0345">11</a>Diagnosis and treatmentAn early diagnosis is essential since the treatment varies from that of other tumors of the CNS.<a class="elsevierStyleCrossRef" href="#bib0295">1</a> Preferred methods for diagnosis are the cerebrospinal fluid (CSF) cytology and the image-guided stereotactic biopsy.<a class="elsevierStyleCrossRef" href="#bib0325">7</a> The sensitivity of the CSF cytology is low, but when it tests positive and there is clinical and radiological suspicion, it is useful for diagnostic purposes even without a biopsy, thus reducing the rate of complications.<a class="elsevierStyleCrossRefs" href="#bib0300">2,7</a> According to the European Association of Neuro-oncology (EANO), once the PCNSL has been diagnosed, we should figure out what the systemic staging is using the computed tomography (CT) scan and positron emission tomography (PET).<a class="elsevierStyleCrossRef" href="#bib0300">2</a>Corticoids can interfere in the biopsy and the definitive pathological findings, which is why they should only be used when there is a significant mass effect or herniation. The PCNSL is highly sensitive to corticoids, that induce cytolysis or apoptosis, and that can cause the tumor regression and clinical improvement. Also, we can have a complete disappearance of the lesion enhancement on the CT scan and MRI. Unfortunately, these effects are just transient, with the corresponding resistance after long-term courses of treatment. Also, other processes such as multiple sclerosis, sarcoidosis, and occasionally, gliomas, can have a similar response to this kind of treatment.Traditionally, surgery has not been recommended because it does not improve survival, and it is just used to reduce intracranial pressure in cases of herniation.<a class="elsevierStyleCrossRefs" href="#bib0295">1,12</a> This lack of effectiveness has been attributed to microscopic multifocal damage and the infiltrative nature of the tumor well beyond the visible edge of the lesion. Recent studies question this theory and suggest a possible role for surgery.<a class="elsevierStyleCrossRef" href="#bib0300">2</a>The PCNSL is both chemo- and radiosensitive, and the early administration of treatment can affect its prognosis.<a class="elsevierStyleCrossRefs" href="#bib0295">1,7,12</a> It has been confirmed that high doses of methotrexate penetrate the blood–brain barrier and improve survival, which is why it is the drug recommended by the EANO.<a class="elsevierStyleCrossRefs" href="#bib0300">2,12–14</a> More aggressive protocols of chemotherapy do not increase survival and there is a higher risk of severe infections and toxicity.<a class="elsevierStyleCrossRef" href="#bib0355">13</a> Today, the use of radiotherapy has been reduced due to its neurotoxic effects.<a class="elsevierStyleCrossRef" href="#bib0300">2</a> In cases where it is indicated it should be whole brain radiotherapy since, as we have already said, it is one diffuse disease that is usually underestimated by the images.<a class="elsevierStyleCrossRef" href="#bib0350">12</a>Treatment has confirmed remissions of up to 80%, although accompanied by a high risk of recurrence – even distant recurrence, especially during the first few years.<a class="elsevierStyleCrossRef" href="#bib0295">1</a> The medical literature says that the overall survival is between 33 and 60 months.<a class="elsevierStyleCrossRef" href="#bib0325">7</a>Radiological findingsAlthough the PCNSL can have characteristic radiological findings, none of these are totally specific<a class="elsevierStyleCrossRefs" href="#bib0325">7,15,16</a> (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>). Given the varied possible expressions of PCNSLs, it may happen that in its earliest stage, the PCNSL does not look like a tumor in the imaging studies, thus delaying its diagnosis.<a class="elsevierStyleCrossRefs" href="#bib0325">7,17,18</a><elsevierMultimedia ident="tbl0005"></elsevierMultimedia>Location and numberIn the PCNSL, the lesions are typically parenchymatous compared to secondary affectation due to lymphoma, which usually manifests itself in two thirds of the cases with meningeal damage, and in one third of the cases with parenchymatous damage.<a class="elsevierStyleCrossRefs" href="#bib0385">19–22</a>Most are central periventricular lesions,<a class="elsevierStyleCrossRefs" href="#bib0325">7,23,24</a> although the surface-hemisphere location in contact with the meninges is also common. Overall, its proximity to the surfaces of CSF is a common finding.<a class="elsevierStyleCrossRef" href="#bib0415">25</a>The most common location is supratentorial location (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>a), especially the frontal lobe (20–43%) and the basal nodes (13–20%).<a class="elsevierStyleCrossRefs" href="#bib0325">7,26–28</a> The brainstem and the cerebellum are rare locations (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>b), and amount to 9–13% of the cases.<a class="elsevierStyleCrossRefs" href="#bib0425">27–29</a> The spinal cord is affected in 1–2% of the cases.<a class="elsevierStyleCrossRefs" href="#bib0310">4,8,29</a><elsevierMultimedia ident="fig0005"></elsevierMultimedia>In the case of tumor damage to the corpus callosum, the differential diagnosis is limited to the aggressive primary tumors of the CNS: the PCNSL (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>c), and high-grade glial tumors<a class="elsevierStyleCrossRef" href="#bib0440">30</a> (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>d). Metastasic damage or tumefactive demyelinating damage are less common than the lymphoma affectation of the corpus callosum, although the overall incidence of these conditions is much higher.<a class="elsevierStyleCrossRef" href="#bib0295">1</a>Mansour et al.<a class="elsevierStyleCrossRef" href="#bib0445">31</a> claim that the PCNSL of subcortical location usually spares the morphology of the cortex. Although ocular primary damage is extremely rare, the asymptomatic secondary spread from the cerebral parenchymal lesion toward the eye can be detected on the cytology in 25% of the cases of PCNSL.<a class="elsevierStyleCrossRef" href="#bib0450">32</a>As it occurs in other lymphomas, in the PCNSL we can see a great variety of rare atypical patterns. PCNSLs rarely manifest themselves with a pattern of diffuse leukoencephalopathy without contrast enhancement – called brain lymphomatosis, that is considered a diagnostic challenge.<a class="elsevierStyleCrossRef" href="#bib0455">33</a> Primary dural lymphoma is a rare subtype that is biologically different from other PCNSLs and has a better prognosis.<a class="elsevierStyleCrossRef" href="#bib0460">34</a> It has been described that in up to 5% of the cases the initial imaging study can look normal.<a class="elsevierStyleCrossRef" href="#bib0465">35</a>It usually presents itself as one solitary mass,<a class="elsevierStyleCrossRef" href="#bib0385">19</a> although in 20–40% of the cases in immunocompetent patients, multiple lesions are found<a class="elsevierStyleCrossRefs" href="#bib0310">4,7,36</a> (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>e and f). Monofocal lesions are bigger than multifocal lesions, and one hypothesis that may explain this is that multiple lesions have a greater repercussion than solitary lesions, which is why they become symptomatic earlier and, therefore, have a smaller size.<a class="elsevierStyleCrossRef" href="#bib0475">37</a>CT scan and MRI in morphological sequencesThe CT scan reveals hyper- or isodense lesions with contrast uptake<a class="elsevierStyleCrossRefs" href="#bib0385">19,23,26,35</a> (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>a and b). On the MRI, the signal of the T1-weighted sequences is typically iso- or hyperintense,<a class="elsevierStyleCrossRefs" href="#bib0325">7,23,26</a> and the signal of the T2-weighted sequences is usually hypointense. Hemorrhages and calcification are rare,<a class="elsevierStyleCrossRefs" href="#bib0385">19,23</a> and are not associated with cysts.<a class="elsevierStyleCrossRef" href="#bib0445">31</a><elsevierMultimedia ident="fig0010"></elsevierMultimedia>In most cases, the enhancement of the sample goes from moderate to intense degree.<a class="elsevierStyleCrossRefs" href="#bib0310">4,7,15,22,23,26</a> The pattern most predominantly described in immunocompetent patients is homogenous,<a class="elsevierStyleCrossRef" href="#bib0385">19</a> although a ring pattern whose central area does not uptake and is usually isodense or isointense is also possible, distinguishing it from necrotic tumor lesions and abscesses.<a class="elsevierStyleCrossRef" href="#bib0480">38</a> At times, the uptake pattern is radial linear due to the perivascular affinity of the tumor.<a class="elsevierStyleCrossRefs" href="#bib0470">36,37</a>Zhang et al.<a class="elsevierStyleCrossRef" href="#bib0475">37</a> described as specific signs useful for differential diagnostic purposes the thick open not uniform ring (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>a), unlike the ring described in multiple sclerosis–thin and uniform (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>b), and the presence of notch sign, that describes an abnormally deep depression on the tumor edge<a class="elsevierStyleCrossRef" href="#bib0475">37</a> (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>c). In our own experience, the presence of these patterns can be useful, but it is necessary to study the specificity of this finding in longer series of patients (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).<elsevierMultimedia ident="fig0015"></elsevierMultimedia>As an exceptional pattern of PCNSL presentation, the T2-weighted hypersignal and the absence of enhancement have been described.<a class="elsevierStyleCrossRef" href="#bib0470">36</a> It is important to bear in mind that corticoids can modify and overshadow the enhancement of contrast, and eventually determine the regression of the tumor.<a class="elsevierStyleCrossRef" href="#bib0470">36</a> Also, isolated cases of spontaneous regression of lesions with no treatment have been reported.<a class="elsevierStyleCrossRef" href="#bib0485">39</a>The perilesional edema is present, but not as much as in malignant gliomas and metastases,<a class="elsevierStyleCrossRefs" href="#bib0325">7,19</a> and mass effect is described as scarce for the size of the lesion.MRI in advanced sequencesThe classical image can show the typical characteristics on the CT scan and MRI, but still none of these are totally specific to distinguish the PCNSL from other neoplasms or non-neoplastic conditions. Advanced sequences (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>), such as diffusion,<a class="elsevierStyleCrossRefs" href="#bib0325">7,19,39</a> perfusion,<a class="elsevierStyleCrossRefs" href="#bib0485">39,40</a> and spectroscopy,<a class="elsevierStyleCrossRefs" href="#bib0495">41,42</a> are used in the daily practice to distinguish PCNSLs from other lesions.<a class="elsevierStyleCrossRef" href="#bib0385">19</a><elsevierMultimedia ident="tbl0010"></elsevierMultimedia>DiffusionThe isotropic diffusion-weighted MRI measures the diffusion of water molecules inside biological tissues, and acts as a surrogate marker of tumor cellularity since intact cells make up a barrier to water diffusion.<a class="elsevierStyleCrossRef" href="#bib0385">19</a>In the PCNSL, the volume of extracellular space is reduced<a class="elsevierStyleCrossRef" href="#bib0510">44</a>; also, here we are dealing with highly cellular tumors, which is why the diffusion of water is limited, making them look hyperintense on the DWI (<a class="elsevierStyleCrossRef" href="#fig0020">Fig. 4</a>a) and with relatively lower values in the apparent diffusion coefficient (ADC)<a class="elsevierStyleCrossRefs" href="#bib0370">16,39,43</a> (<a class="elsevierStyleCrossRef" href="#fig0020">Fig. 4</a>b). These values are useful to distinguish PCNSLs from high-grade astrocytomas. According to most studies, these values are lower in the PCNSL (<a class="elsevierStyleCrossRef" href="#fig0020">Fig. 4</a>c and d), although other studies describe overlapping values and cannot find any significant differences.<a class="elsevierStyleCrossRefs" href="#bib0490">40,44–46</a><elsevierMultimedia ident="fig0020"></elsevierMultimedia>Calli et al.<a class="elsevierStyleCrossRef" href="#bib0490">40</a> found minimal ADC values in glioblastomas multiformes (GBM); anaplastic astrocytomas; PCNSLs and metastases, of 0.79±0.21 (×10−3mm2/s), 0.75±0.21 (×10−3mm2/s), 0.51±0.09 (×10−3mm2/s), and 0.68±0.11 (×10−3mm2/s), respectively, with statistically significant differences between PCNSLs and GBMs, and also between PCNSLs and anaplastic astrocytomas. Kickingereder et al.<a class="elsevierStyleCrossRef" href="#bib0520">46</a> found significantly lower ADC values in patients with PCNSLs compared to patients with GBMs (minimum ADC values, maximum ADC values, and average ADC values of 0.56±0.12, 0.75±0.18 and 0.65±0.13 for PCNSLs, and 0.79±0.20, 1.21±0.32 and 0.97±0.25 for GBMs, respectively).Pre-treatment ADC in the contrast-enhanced area has also proven a prognostic factor<a class="elsevierStyleCrossRef" href="#bib0525">47</a>: lower ADC values determine faster progression of the disease, and lower survival–both disease-free survival and overall survival. Similarly, the ADC can be used as a biomarker to monitor the response. Thus, higher ADV values are indicative of a favorable response to treatment.<a class="elsevierStyleCrossRefs" href="#bib0385">19,47</a>Doskaliyev et al.<a class="elsevierStyleCrossRef" href="#bib0530">48</a> studied the utility of higher b values to distinguish PCNSLs from GBMs and found the lowest overlapping degree with b values of 4000s/mm2, establishing the cut-off point between the two tumors in ADC values of 0.5×10(−3)mm2.Imaging studies using diffusion tensor imaging (DTI) require measuring diffusion in, at least, six (6) directions, and it is a sensitive tool for the detection of alterations in the structure of white matter.<a class="elsevierStyleCrossRef" href="#bib0515">45</a> Same as it happens with the ADC, the quantitative mapping of fractional anisotropy shows low values in many conditions, including tumors.<a class="elsevierStyleCrossRef" href="#bib0525">47</a> In PCNSLs they are significantly lower than in GBMs, which allows us to distinguish between the two. Determining fractional anisotropy in tumor tissues is complex, which makes it a less adequate marker than the ADC to be able to distinguish between PCNSLs and GBMs.<a class="elsevierStyleCrossRef" href="#bib0515">45</a>PerfusionWhile contrast enhancement expresses the extravasation of contrast due to the disruption of the brain-blood barrier, both perfusion-weighted CT scans and perfusion-weighted MRIs study the tumor vascularization, that is, the arterial blood supply toward the capillary bed in the biological tissue.The dynamic susceptibility contrast perfusion MRI (DSC-PMRI) is based on the first-pass contrast bolus with the measurement of the corresponding loss of signal on the T2-weighted sequences*. Post-processing later provides data such as the cerebral blood volume (CBV), the cerebral blood flow (CBF), the average transit time, and the time to the maximum peak.<a class="elsevierStyleCrossRefs" href="#bib0540">50,51</a>The relative value of the CBV (rCBV) of the PCNSL, only slightly increased compared to normal white matter (<a class="elsevierStyleCrossRef" href="#fig0025">Fig. 5</a>a and b), could be attributed to the pattern of angiocentric growth. Perivascular infiltration leads to the massive extravasation of contrast toward the interstitial space, determining one characteristic intensity-time curve after the first-pass<a class="elsevierStyleCrossRefs" href="#bib0490">40,41</a> (<a class="elsevierStyleCrossRef" href="#fig0025">Fig. 5</a>c).<elsevierMultimedia ident="fig0025"></elsevierMultimedia>The relatively low CBV and the intensity-time curve play an important role when it comes to differentiating PCNSLs from other tumors of the CNS, such as CBMs and metastases, both with increased angiogenesis, and significantly higher CBV values<a class="elsevierStyleCrossRefs" href="#bib0385">19,31,40,52</a> (<a class="elsevierStyleCrossRef" href="#fig0025">Fig. 5</a>e, f and g).Calli et al.<a class="elsevierStyleCrossRef" href="#bib0490">40</a> found values of relative maximum perfusion values (rCBVmax) of 6.33±2.03 in GBMs, 3.66±1.79 in anaplastic astrocytomas, 2.33±0.68 in PCNSLs and 4.45±1.87 in metastases, with statistically significant differences in GBMs and lymphomas. Also, for Kickingereder et al.<a class="elsevierStyleCrossRef" href="#bib0520">46</a> the ratios of CBVmax and average CBV were significantly lower in patients with PCNSLs compared to patients with GBMs with respect to the normal contralateral area; the rCBVmax and average rCBV were 4.16±1.65 and 2.04±0.72 for the PCNSL, and 8.75±4.75 and 5.09±2.57 for the GBM, respectively, obtaining higher accuracy with the average rCBV parameter.These differences suggest lower tumor vascularization and higher vascular patency in PCNSLs.<a class="elsevierStyleCrossRefs" href="#bib0490">40,46</a>Contrast enhanced perfusion is a sequence that provides information on the microvasculature of intracranial tumors. It consists of one T1-weighted 3D dynamic sequence whose processing provides perfusion values such as the volume transfer constant (Ktrans), the flux rate constant (Kep) and the volume of extravascular extracellular space. It is of no use in clinical practice, but it has been studied experimentally. Kickingereder et al.<a class="elsevierStyleCrossRef" href="#bib0535">49</a> looked into the differences between the PCNSL and the GBM, and found that, in the PCNSL, both the Ktrans and the Kep (0.145±0.057 and 0.396±0.088) are significantly higher than in the GBM (0.064±0.021 and 0.230±0.058).Also, experimentally, Suh et al.<a class="elsevierStyleCrossRef" href="#bib0540">50</a> studied the value of the intravoxel incoherent motion (IVIM) image that provides parameters of diffusion and perfusion to distinguish GBMs from PCNSLs of atypical appearance. They estimated the IVIM (f) fraction of maximum perfusion and the IVIM (D) minimum diffusion parameter and found an f value that was significantly higher in GBMs than in PCNSLs.MR spectroscopyThe MR spectroscopy (MRS) provides non-invasive biochemical information on tissues. In a given volume of interest the signal of chemical nuclei is recorded; the most common ones are hydrogen protons.<a class="elsevierStyleCrossRef" href="#bib0385">19</a> Hydrogen is the most abundant element in the human body, has a universal distribution, being protons the dominant elements in its structure.In patients with PCNSL, the MRS with long echo time showed increased choline (Cho) levels, reduced N-acetyl-aspartate (Naa) levels and the presence of lipid peaks.<a class="elsevierStyleCrossRefs" href="#bib0310">4,42,43</a> These findings do not allow us to distinguish PCNSLs from GBMs or metastases (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>), but they can be useful to distinguish PCNSLs from other lesions.<a class="elsevierStyleCrossRefs" href="#bib0385">19,42</a> For example, Lu et al.<a class="elsevierStyleCrossRef" href="#bib0555">53</a> showed the utility of the MRS to distinguish PCNSLs from demyelinating pseudotumor lesions showing higher Cho/Cr and Cho/Naa ratios, and elevated Lip/Lac peaks. They propose the Cho/Naa ratio as the most useful one.Susceptibility weighted-imaging (SWI)High-resolution susceptibility weighted-imaging (SWI) is much more sensitive than conventional imaging for the detection of small blood vessels, blood remains and calcifications that appear as low-signal structures called intratumoral susceptibility signals (ITSS). This is an important piece of information in order to distinguish PCNSLs from GBMs, since, according to Kim et al.,<a class="elsevierStyleCrossRef" href="#bib0560">54</a> the number of blood vessels detected by the SWI is significantly higher in GBMs and metastases compared to PCNSLs, while hemorrhages–common in GBMs,<a class="elsevierStyleCrossRefs" href="#bib0520">46,54</a> are rare in PCNSLs. There is an exception that we should take into account here–the possibility of microhemorrhages in cases of rare histological variants such as T-cell lymphomas.<a class="elsevierStyleCrossRef" href="#bib0565">55</a>Nuclear medicine: positron emission tomography (PET)Nuclear medicine techniques with radioisotopes produce images that show biological process and their metabolism. In practice they are not used routinely for the diagnosis and management of PCNSLs, although some studies claim that they may be useful.The fluorodeoxyglucose positron emission tomography (FDG PET) shows lesions that are typically hypermetabolic with enhanced FDG uptake in PCNSLs,<a class="elsevierStyleCrossRef" href="#bib0410">24</a> and whose progression can be used for the early assessment of the response to therapy. Some authors say that the FDG PET can even help distinguish PCNSLs from malignant gliomas and metastases.<a class="elsevierStyleCrossRef" href="#bib0570">56</a>Although the methionine uptake in the PCNSL is significantly lower than the FDG uptake, there is no significant difference in the sensitivity of detection of PCNSL between the PET with methionine and the PET with FDG–in both being close to 100%.<a class="elsevierStyleCrossRef" href="#bib0575">57</a>When it comes to PCNSLs of atypical appearance, Kawai et al.<a class="elsevierStyleCrossRef" href="#bib0580">58</a> found that both the visual analysis and the pseudoquantitative and quantitative values were not very useful to distinguish them from other lesions. However, certain specific values (such as quantitative values assessed using the kinetic analysis) were similar in both the typical and atypical PCNSLs, meaning that these parameters may provide valuable information for the diagnosis of PCNSLs.ConclusionsThe PCNSL is a rare type of tumor whose management significantly varies from that of other malignant tumors of the CNS, which is why it is important to suggest the correct imaging diagnosis. The RMI is the diagnostic imaging modality of choice.The PCNSL damages the cerebral parenchyma and its most common manifestation is being one single lesion with homogeneous enhancement, although it may show other patterns such as multifocality and ring enhancement. Its imaging characteristics have to do with its hypercellular nature, and with phenomena of contrast effusion with scarce angiogenesis. Although it has typical findings, none of them is specific, and multiple atypical patterns have been described. MRI advanced sequences, mainly perfusion-weighted MRIs, provide useful information to be able to distinguish this lesion from other conditions, basically other malignant tumors of the CNS, and they can be used as one prognostic marker.Ethical disclosuresProtection of human and animal subjectsThe authors declare that no experiments with human beings or animals have been performed while conducting this investigation.Confidentiality of dataThe authors confirm that in this article there are no data from patients.Right to privacy and informed consentThe authors confirm that in this article there are no data from patients.Authors<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005">1.Manager of the integrity of the study: EGR.</li><li class="elsevierStyleListItem" id="lsti0010">2.Study idea: EGR.</li><li class="elsevierStyleListItem" id="lsti0015">3.Study design: EGR.</li><li class="elsevierStyleListItem" id="lsti0020">4.Data mining: EGR, AMQG, GLS and SPG.</li><li class="elsevierStyleListItem" id="lsti0025">5.Data analysis and interpretation: EGR.</li><li class="elsevierStyleListItem" id="lsti0030">6.Statistical analyses: N/A.</li><li class="elsevierStyleListItem" id="lsti0035">7.Reference: EGR.</li><li class="elsevierStyleListItem" id="lsti0040">8.Writing: EGR.</li><li class="elsevierStyleListItem" id="lsti0045">9.Critical review of the manuscript with intellectually relevant remarks: EGR, AMQG, GLS and SPG.</li><li class="elsevierStyleListItem" id="lsti0050">10.Approval of final version: EGR, AMQG and GLS.</li></ul>Conflicts of interestsThe authors declare no conflict of interests associated with this article whatsoever." "textoCompletoSecciones" => array:1 [ "secciones" => array:13 [ 0 => array:3 [ "identificador" => "xres1060291" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1009151" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1060292" "titulo" => "Resumen" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0010" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1009152" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Pathological anatomy" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Diagnosis and treatment" ] 7 => array:3 [ "identificador" => "sec0020" "titulo" => "Radiological findings" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0025" "titulo" => "Location and number" ] 1 => array:2 [ "identificador" => "sec0030" "titulo" => "CT scan and MRI in morphological sequences" ] 2 => array:3 [ "identificador" => "sec0035" "titulo" => "MRI in advanced sequences" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0040" "titulo" => "Diffusion" ] 1 => array:2 [ "identificador" => "sec0045" "titulo" => "Perfusion" ] 2 => array:2 [ "identificador" => "sec0050" "titulo" => "MR spectroscopy" ] 3 => array:2 [ "identificador" => "sec0055" "titulo" => "Susceptibility weighted-imaging (SWI)" ] ] ] 3 => array:2 [ "identificador" => "sec0060" "titulo" => "Nuclear medicine: positron emission tomography (PET)" ] ] ] 8 => array:2 [ "identificador" => "sec0065" "titulo" => "Conclusions" ] 9 => array:3 [ "identificador" => "sec0070" "titulo" => "Ethical disclosures" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0075" "titulo" => "Protection of human and animal subjects" ] 1 => array:2 [ "identificador" => "sec0080" "titulo" => "Confidentiality of data" ] 2 => array:2 [ "identificador" => "sec0085" "titulo" => "Right to privacy and informed consent" ] ] ] 10 => array:2 [ "identificador" => "sec0090" "titulo" => "Authors" ] 11 => array:2 [ "identificador" => "sec0095" "titulo" => "Conflicts of interests" ] 12 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2016-06-03" "fechaAceptado" => "2017-12-27" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1009151" "palabras" => array:7 [ 0 => "Lymphoma" 1 => "Central nervous system" 2 => "Brain" 3 => "Brain tumor" 4 => "Magnetic resonance imaging" 5 => "Perfusion" 6 => "Diffusion" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1009152" "palabras" => array:7 [ 0 => "Linfoma" 1 => "Sistema nervioso central" 2 => "Cerebro" 3 => "Tumor cerebral" 4 => "Resonancia magnética" 5 => "Perfusión" 6 => "Difusión" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "Primary central nervous system lymphomas (PCNSL) are rare and their management varies significantly from that of other malignant tumors involving the CNS. This article discusses how the imaging findings often suggest the diagnosis early in time. The typical findings in immunocompetent patients consist of one supratentorial intra-axial mass of homogeneous enhancement. Other findings that should be assessed include multifocality and incomplete ring enhancement. The differential diagnosis of PCNSL should mainly consider other malignant tumors of the CNS such as glioblastomas or metastases. PCNSLs tend to have less edema and less mass effect; they also tend to spare the adjacent cortex. Necrosis, hemorrhage, and calcification are rare in PCNSLs. Although the findings in the morphologic sequences are characteristic, they are not completely specific and atypical types can sometimes be found. Advanced imaging techniques such as diffusion-weighted images and, above all, perfusion-weighted images provide qualitative and quantitative data that play an important role in the differentiation of PCNSLs from other brain tumors." ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "El linfoma primario del sistema nervioso central (LPSNC) es infrecuente y su manejo difiere significativamente del resto de los tumores malignos de esta localización. El texto desarrolla cómo los hallazgos radiológicos a menudo sugieren el diagnóstico precozmente. La imagen típica en los pacientes inmunocompetentes es una masa intraaxial supratentorial con realce homogéneo. Otros hallazgos que deben valorarse son la multifocalidad y el realce en anillo incompleto. En el diagnóstico diferencial del LPSNC deben considerarse principalmente otros tumores malignos del SNC, como el glioblastoma y las metástasis. El LPSNC suele tener menor edema y efecto masa, y respeta el córtex adyacente, siendo infrecuentes la necrosis, la hemorragia y la calcificación. Aunque los hallazgos en secuencias morfológicas son típicos, no son por completo específicos y pueden encontrarse formas atípicas. Las técnicas avanzadas, como la difusión y sobre todo la perfusión, muestran valores cualitativos y cuantitativos que desempeñan un papel importante al diferenciar el LPSNC de otros tumores cerebrales." ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: Gómez Roselló E, Quiles Granado AM, Laguillo Sala G, Pedraza Gutiérrez S. Linfoma cerebral primario en pacientes inmunocompetentes: espectro de hallazgos y características diferenciales. Radiología. 2018;60:280–289." ] ] "multimedia" => array:7 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1316 "Ancho" => 2000 "Tamanyo" => 198853 ] ] "descripcion" => array:1 [ "en" => "Location and number of lesions. It shows the most common pattern of the primary central nervous system lymphoma (PCNSL) of deep intra-axial supratentorial location (a). It appears as one infratentorial lesion in 10% of the cases; the image shows it is damaging the left cerebellar hemisphere (b) and, contralaterally, we can see capillary telangiectasias, almost incidentally. There is damage due to two tumors of the interhemispheric connection fibers, in this case, in the anterior commissure – a finding that is consistent with PCNSLs (c) and glial tumors only (d). The solitary mass is the most common presentation, yet multiple lesions with satellite nodes (e), and diffuse bilateral damage (f) are not rare (20–40% of the cases)." ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 973 "Ancho" => 1667 "Tamanyo" => 118277 ] ] "descripcion" => array:1 [ "en" => "Appearance of one PCNSL on the CT scan, hyperdense without contrast (a) and with uniform enhancement after the administration of contrast (b)." ] ] 2 => array:7 [ "identificador" => "fig0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 601 "Ancho" => 1733 "Tamanyo" => 84709 ] ] "descripcion" => array:1 [ "en" => "Enhancement patterns and specific signs. The most typical one is homogeneous enhancement. Ring enhancement is even rarer, but it is still possible. In the PCNSL, the thick and not uniform “open ring” has been described (a), unlike multiple sclerosis, where the ring is thin and uniform (b). One notch can be present in lesions with homogeneous enhancement, and it has been suggested as a specific finding (arrow in c)." ] ] 3 => array:7 [ "identificador" => "fig0020" "etiqueta" => "Figure 4" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr4.jpeg" "Alto" => 2303 "Ancho" => 2000 "Tamanyo" => 320972 ] ] "descripcion" => array:1 [ "en" => "Diffusion. The PCNSL shows diffusion restriction (a) that translates into low values of the apparent diffusion coefficient (ADC) (b) that are consistent with the enhancement region in relation to its hypercellularity, among other factors. Here we can see ADC values that are significantly lower in the PCNSL (c) compared to the glioblastoma (d)." ] ] 4 => array:7 [ "identificador" => "fig0025" "etiqueta" => "Figure 5" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr5.jpeg" "Alto" => 1343 "Ancho" => 2000 "Tamanyo" => 337870 ] ] "descripcion" => array:1 [ "en" => "Perfusion. The PCNSL shows a mild increase both in the color maps and the quantitative levels of cerebral blood volume (CBV) (ROI 1 in a and b), and one characteristic curve with a scarce peak after the first-pass shows contrast effusion above the baseline following the T1 phenomenon (c). Post-contrast T1-weighted images of the reference PCNSL (d). In glioblastomas, however, perfusion is really high (c and d) and its typical curve shows (g) one elevated peak, and normalization after the first-pass (f). Post-contrast T1-weighted image of the reference glioblastoma included (h)." ] ] 5 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Number \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Single 20–40% are multiple lesions \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Location \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Supratentorial (90%): periventricular, hemispheric, subcortical. Possibility of damage to interhemispheric fibers. They spare the cortex Infratentorial (10%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Signal \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Iso/hipersignal on T1-weighted images Tendency to hyposignal on T2-weighted images \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Enhancement pattern \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Clear predominance of homogeneous enhancement Possible ring enhancement without internal necrosis Specific signs described: - Open ring - Notch sign \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Mass effect \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Scarce for its size \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1804542.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Findings in conventional sequences." ] ] 6 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at2" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "GBM: glioblastomas multiforme; PCNSL: primary central nervous system lymphoma; Naa: N-acetyl-aspartate." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">GBM/metastasis \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">PCNSL \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " colspan="3" align="left" valign="top">Diffusion (ADC/FA)</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="3" align="left" valign="top">Perfusion (CBV)</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Inverted peak 1 pass and return to baseline \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Curve: Peak after 1 pass: return to baseline \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Typical curve: Peak after 1 pass: above baseline due to phenomenon of contrast effusion \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="3" align="left" valign="top"></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="3" align="left" valign="top">SWI (microhemorrhages)</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Spectrum \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Choline Naa Lipid peaks \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">The same, does not distinguish between the two \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1804543.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Findings in advanced sequences: differences among high-grade glial tumor, metastasis, and primary lymphoma of the central nervous system." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:58 [ 0 => array:3 [ "identificador" => "bib0295" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Imaging of lymphoma of the central nervous system, spine and orbit" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "S. 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Update in Radiology

Linfoma cerebral primario en pacientes inmunocompetentes: espectro de hallazgos y características diferenciales

E. Gómez Roselló

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evagrosello@hotmail.com

Corresponding author.

, A.M. Quiles Granado, G. Laguillo Sala, S. Pedraza Gutiérrez

Sección de Neurorradiología, Servicio de Radiología (IDI), Hospital Universitario Dr. Josep Trueta, Girona, Spain

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          "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Appearance of one PCNSL on the CT scan&#44; hyperdense without contrast &#40;a&#41; and with uniform enhancement after the administration of contrast &#40;b&#41;&#46;</p>"
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Lymphomas can affect the central nervous system &#40;CNS&#41; as a primary tumor or&#44; more commonly&#44; in a secondary way&#44; as the spread of systemic lymphomas in up to 15&#37; of the cases&#46;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">1</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">The primary central nervous system lymphoma &#40;PCNSL&#41; is a lymphoma that is restricted to the brain&#44; the leptomeninges&#44; the spine cord&#44; or the eyes without evidence outside the CNS&#46;<a class="elsevierStyleCrossRefs" href="#bib0300"><span class="elsevierStyleSup">2&#8211;4</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">The PCNSL is a rare type of tumor of poor prognosis that is usually found in up to 3&#8211;5&#37; of primary brain tumors<a class="elsevierStyleCrossRefs" href="#bib0315"><span class="elsevierStyleSup">5&#8211;7</span></a> and in 1&#37; of non-Hodgkin lymphomas&#44;<a class="elsevierStyleCrossRefs" href="#bib0315"><span class="elsevierStyleSup">5&#44;8</span></a> whose incidence has been growing during the last few years among immunocompetent patients&#46;<a class="elsevierStyleCrossRefs" href="#bib0315"><span class="elsevierStyleSup">5&#44;9</span></a> Immunodepressed patients have a higher risk of PCNSLs&#44; which is also higher in the following cases&#58; post-transplant immuosuppressive therapy&#59; congenital immunodeficiencies<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">1</span></a> and infections due to human immunodeficiency virus &#40;HIV&#41;<a class="elsevierStyleCrossRefs" href="#bib0295"><span class="elsevierStyleSup">1&#44;10</span></a>&#59; the latter not so much since the arrival of antiretroviral therapies&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">Epidemiologically we say that PCNSLs occur more predominantly in males&#44; with a wide age range&#44; and an average age at diagnosis of 66 years old&#46;<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">6</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">This paper describes the histological characteristics of the PCNSL in immunocompetent patients&#44; its diagnostic and therapeutic management&#44; and imaging findings &#8211; these ones being the most specific findings of all&#46; The magnetic resonance imaging &#40;MRI&#41; is the imaging modality of choice and provides crucial information through morphological and advanced sequences&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Pathological anatomy</span><p id="par0030" class="elsevierStylePara elsevierViewall">Most tumors are <span class="elsevierStyleItalic">aggressive diffuse large B</span>-<span class="elsevierStyleItalic">cell</span> lymphomas&#46;<a class="elsevierStyleCrossRefs" href="#bib0295"><span class="elsevierStyleSup">1&#44;3&#44;11</span></a> The way these neoplasms develop within the CNS is still a mystery since these lymphocytes do not have a known function in the normal parenchyma&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Other histological types such as dural lymphomas&#44; a low-grade subtype of marginal zone lymphoma &#40;MALT type&#41;&#44; are rarer and have better prognosis&#46;<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">8</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">Although positivity to Epstein-Barr virus &#40;EBV&#41; in immunocompetent patients is low &#40;compared to what happens in patients with HIV&#41;&#44; this association has been described in the classification established by the World Health Organization back in 2008&#46; Age-related EBV&#43; <span class="elsevierStyleItalic">diffuse large B</span>-<span class="elsevierStyleItalic">cell</span> lymphomas are usually diagnosed in patients over 55 and they have certain neuroradiological particularities that make them different from other PCNSLs in immunocompetent patients&#46; Hemorrhages&#44; necrosis&#44; and ring enhancement after the administration of contrast are characteristic of this type of lymphomas&#8211;very similar to the ones described in patients with HIV&#46;<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">11</span></a></p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Diagnosis and treatment</span><p id="par0045" class="elsevierStylePara elsevierViewall">An early diagnosis is essential since the treatment varies from that of other tumors of the CNS&#46;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">1</span></a> Preferred methods for diagnosis are the cerebrospinal fluid &#40;CSF&#41; cytology and the image-guided stereotactic biopsy&#46;<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">7</span></a> The sensitivity of the CSF cytology is low&#44; but when it tests positive and there is clinical and radiological suspicion&#44; it is useful for diagnostic purposes even without a biopsy&#44; thus reducing the rate of complications&#46;<a class="elsevierStyleCrossRefs" href="#bib0300"><span class="elsevierStyleSup">2&#44;7</span></a> According to the European Association of Neuro-oncology &#40;EANO&#41;&#44; once the PCNSL has been diagnosed&#44; we should figure out what the systemic staging is using the computed tomography &#40;CT&#41; scan and positron emission tomography &#40;PET&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">2</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">Corticoids can interfere in the biopsy and the definitive pathological findings&#44; which is why they should only be used when there is a significant mass effect or herniation&#46; The PCNSL is highly sensitive to corticoids&#44; that induce cytolysis or apoptosis&#44; and that can cause the tumor regression and clinical improvement&#46; Also&#44; we can have a complete disappearance of the lesion enhancement on the CT scan and MRI&#46; Unfortunately&#44; these effects are just transient&#44; with the corresponding resistance after long-term courses of treatment&#46; Also&#44; other processes such as multiple sclerosis&#44; sarcoidosis&#44; and occasionally&#44; gliomas&#44; can have a similar response to this kind of treatment&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">Traditionally&#44; surgery has not been recommended because it does not improve survival&#44; and it is just used to reduce intracranial pressure in cases of herniation&#46;<a class="elsevierStyleCrossRefs" href="#bib0295"><span class="elsevierStyleSup">1&#44;12</span></a> This lack of effectiveness has been attributed to microscopic multifocal damage and the infiltrative nature of the tumor well beyond the visible edge of the lesion&#46; Recent studies question this theory and suggest a possible role for surgery&#46;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">2</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">The PCNSL is both chemo- and radiosensitive&#44; and the early administration of treatment can affect its prognosis&#46;<a class="elsevierStyleCrossRefs" href="#bib0295"><span class="elsevierStyleSup">1&#44;7&#44;12</span></a> It has been confirmed that high doses of methotrexate penetrate the blood&#8211;brain barrier and improve survival&#44; which is why it is the drug recommended by the EANO&#46;<a class="elsevierStyleCrossRefs" href="#bib0300"><span class="elsevierStyleSup">2&#44;12&#8211;14</span></a> More aggressive protocols of chemotherapy do not increase survival and there is a higher risk of severe infections and toxicity&#46;<a class="elsevierStyleCrossRef" href="#bib0355"><span class="elsevierStyleSup">13</span></a> Today&#44; the use of radiotherapy has been reduced due to its neurotoxic effects&#46;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">2</span></a> In cases where it is indicated it should be whole brain radiotherapy since&#44; as we have already said&#44; it is one diffuse disease that is usually underestimated by the images&#46;<a class="elsevierStyleCrossRef" href="#bib0350"><span class="elsevierStyleSup">12</span></a></p><p id="par0065" class="elsevierStylePara elsevierViewall">Treatment has confirmed remissions of up to 80&#37;&#44; although accompanied by a high risk of recurrence &#8211; even distant recurrence&#44; especially during the first few years&#46;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">1</span></a> The medical literature says that the overall survival is between 33 and 60 months&#46;<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">7</span></a></p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Radiological findings</span><p id="par0070" class="elsevierStylePara elsevierViewall">Although the PCNSL can have characteristic radiological findings&#44; none of these are totally specific<a class="elsevierStyleCrossRefs" href="#bib0325"><span class="elsevierStyleSup">7&#44;15&#44;16</span></a> &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46; Given the varied possible expressions of PCNSLs&#44; it may happen that in its earliest stage&#44; the PCNSL does not look like a tumor in the imaging studies&#44; thus delaying its diagnosis&#46;<a class="elsevierStyleCrossRefs" href="#bib0325"><span class="elsevierStyleSup">7&#44;17&#44;18</span></a></p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Location and number</span><p id="par0075" class="elsevierStylePara elsevierViewall">In the PCNSL&#44; the lesions are typically parenchymatous compared to secondary affectation due to lymphoma&#44; which usually manifests itself in two thirds of the cases with meningeal damage&#44; and in one third of the cases with parenchymatous damage&#46;<a class="elsevierStyleCrossRefs" href="#bib0385"><span class="elsevierStyleSup">19&#8211;22</span></a></p><p id="par0080" class="elsevierStylePara elsevierViewall">Most are central periventricular lesions&#44;<a class="elsevierStyleCrossRefs" href="#bib0325"><span class="elsevierStyleSup">7&#44;23&#44;24</span></a> although the surface-hemisphere location in contact with the meninges is also common&#46; Overall&#44; its proximity to the surfaces of CSF is a common finding&#46;<a class="elsevierStyleCrossRef" href="#bib0415"><span class="elsevierStyleSup">25</span></a></p><p id="par0085" class="elsevierStylePara elsevierViewall">The most common location is supratentorial location &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>a&#41;&#44; especially the frontal lobe &#40;20&#8211;43&#37;&#41; and the basal nodes &#40;13&#8211;20&#37;&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0325"><span class="elsevierStyleSup">7&#44;26&#8211;28</span></a> The brainstem and the cerebellum are rare locations &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>b&#41;&#44; and amount to 9&#8211;13&#37; of the cases&#46;<a class="elsevierStyleCrossRefs" href="#bib0425"><span class="elsevierStyleSup">27&#8211;29</span></a> The spinal cord is affected in 1&#8211;2&#37; of the cases&#46;<a class="elsevierStyleCrossRefs" href="#bib0310"><span class="elsevierStyleSup">4&#44;8&#44;29</span></a></p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0090" class="elsevierStylePara elsevierViewall">In the case of tumor damage to the corpus callosum&#44; the differential diagnosis is limited to the aggressive primary tumors of the CNS&#58; the PCNSL &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>c&#41;&#44; and high-grade glial tumors<a class="elsevierStyleCrossRef" href="#bib0440"><span class="elsevierStyleSup">30</span></a> &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>d&#41;&#46; Metastasic damage or <span class="elsevierStyleItalic">tumefactive demyelinating</span> damage are less common than the lymphoma affectation of the corpus callosum&#44; although the overall incidence of these conditions is much higher&#46;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">1</span></a></p><p id="par0095" class="elsevierStylePara elsevierViewall">Mansour et al&#46;<a class="elsevierStyleCrossRef" href="#bib0445"><span class="elsevierStyleSup">31</span></a> claim that the PCNSL of subcortical location usually spares the morphology of the cortex&#46; Although ocular primary damage is extremely rare&#44; the asymptomatic secondary spread from the cerebral parenchymal lesion toward the eye can be detected on the cytology in 25&#37; of the cases of PCNSL&#46;<a class="elsevierStyleCrossRef" href="#bib0450"><span class="elsevierStyleSup">32</span></a></p><p id="par0100" class="elsevierStylePara elsevierViewall">As it occurs in other lymphomas&#44; in the PCNSL we can see a great variety of rare atypical patterns&#46; PCNSLs rarely manifest themselves with a pattern of diffuse leukoencephalopathy without contrast enhancement &#8211; called brain lymphomatosis&#44; that is considered a diagnostic challenge&#46;<a class="elsevierStyleCrossRef" href="#bib0455"><span class="elsevierStyleSup">33</span></a> Primary dural lymphoma is a rare subtype that is biologically different from other PCNSLs and has a better prognosis&#46;<a class="elsevierStyleCrossRef" href="#bib0460"><span class="elsevierStyleSup">34</span></a> It has been described that in up to 5&#37; of the cases the initial imaging study can look normal&#46;<a class="elsevierStyleCrossRef" href="#bib0465"><span class="elsevierStyleSup">35</span></a></p><p id="par0105" class="elsevierStylePara elsevierViewall">It usually presents itself as one solitary mass&#44;<a class="elsevierStyleCrossRef" href="#bib0385"><span class="elsevierStyleSup">19</span></a> although in 20&#8211;40&#37; of the cases in immunocompetent patients&#44; multiple lesions are found<a class="elsevierStyleCrossRefs" href="#bib0310"><span class="elsevierStyleSup">4&#44;7&#44;36</span></a> &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>e and f&#41;&#46; Monofocal lesions are bigger than multifocal lesions&#44; and one hypothesis that may explain this is that multiple lesions have a greater repercussion than solitary lesions&#44; which is why they become symptomatic earlier and&#44; therefore&#44; have a smaller size&#46;<a class="elsevierStyleCrossRef" href="#bib0475"><span class="elsevierStyleSup">37</span></a></p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">CT scan and MRI in morphological sequences</span><p id="par0110" class="elsevierStylePara elsevierViewall">The CT scan reveals hyper- or isodense lesions with contrast uptake<a class="elsevierStyleCrossRefs" href="#bib0385"><span class="elsevierStyleSup">19&#44;23&#44;26&#44;35</span></a> &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>a and b&#41;&#46; On the MRI&#44; the signal of the T1-weighted sequences is typically iso- or hyperintense&#44;<a class="elsevierStyleCrossRefs" href="#bib0325"><span class="elsevierStyleSup">7&#44;23&#44;26</span></a> and the signal of the T2-weighted sequences is usually hypointense&#46; Hemorrhages and calcification are rare&#44;<a class="elsevierStyleCrossRefs" href="#bib0385"><span class="elsevierStyleSup">19&#44;23</span></a> and are not associated with cysts&#46;<a class="elsevierStyleCrossRef" href="#bib0445"><span class="elsevierStyleSup">31</span></a></p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0115" class="elsevierStylePara elsevierViewall">In most cases&#44; the enhancement of the sample goes from moderate to intense degree&#46;<a class="elsevierStyleCrossRefs" href="#bib0310"><span class="elsevierStyleSup">4&#44;7&#44;15&#44;22&#44;23&#44;26</span></a> The pattern most predominantly described in immunocompetent patients is homogenous&#44;<a class="elsevierStyleCrossRef" href="#bib0385"><span class="elsevierStyleSup">19</span></a> although a ring pattern whose central area does not uptake and is usually isodense or isointense is also possible&#44; distinguishing it from necrotic tumor lesions and abscesses&#46;<a class="elsevierStyleCrossRef" href="#bib0480"><span class="elsevierStyleSup">38</span></a> At times&#44; the uptake pattern is radial linear due to the perivascular affinity of the tumor&#46;<a class="elsevierStyleCrossRefs" href="#bib0470"><span class="elsevierStyleSup">36&#44;37</span></a></p><p id="par0120" class="elsevierStylePara elsevierViewall">Zhang et al&#46;<a class="elsevierStyleCrossRef" href="#bib0475"><span class="elsevierStyleSup">37</span></a> described as specific signs useful for differential diagnostic purposes the thick open not uniform ring &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>a&#41;&#44; unlike the ring described in multiple sclerosis&#8211;thin and uniform &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>b&#41;&#44; and the presence of notch sign&#44; that describes an abnormally deep depression on the tumor edge<a class="elsevierStyleCrossRef" href="#bib0475"><span class="elsevierStyleSup">37</span></a> &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>c&#41;&#46; In our own experience&#44; the presence of these patterns can be useful&#44; but it is necessary to study the specificity of this finding in longer series of patients &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0125" class="elsevierStylePara elsevierViewall">As an exceptional pattern of PCNSL presentation&#44; the T2-weighted hypersignal and the absence of enhancement have been described&#46;<a class="elsevierStyleCrossRef" href="#bib0470"><span class="elsevierStyleSup">36</span></a> It is important to bear in mind that corticoids can modify and overshadow the enhancement of contrast&#44; and eventually determine the regression of the tumor&#46;<a class="elsevierStyleCrossRef" href="#bib0470"><span class="elsevierStyleSup">36</span></a> Also&#44; isolated cases of spontaneous regression of lesions with no treatment have been reported&#46;<a class="elsevierStyleCrossRef" href="#bib0485"><span class="elsevierStyleSup">39</span></a></p><p id="par0130" class="elsevierStylePara elsevierViewall">The perilesional edema is present&#44; but not as much as in malignant gliomas and metastases&#44;<a class="elsevierStyleCrossRefs" href="#bib0325"><span class="elsevierStyleSup">7&#44;19</span></a> and mass effect is described as scarce for the size of the lesion&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">MRI in advanced sequences</span><p id="par0135" class="elsevierStylePara elsevierViewall">The classical image can show the typical characteristics on the CT scan and MRI&#44; but still none of these are totally specific to distinguish the PCNSL from other neoplasms or non-neoplastic conditions&#46; Advanced sequences &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#44; such as diffusion&#44;<a class="elsevierStyleCrossRefs" href="#bib0325"><span class="elsevierStyleSup">7&#44;19&#44;39</span></a> perfusion&#44;<a class="elsevierStyleCrossRefs" href="#bib0485"><span class="elsevierStyleSup">39&#44;40</span></a> and spectroscopy&#44;<a class="elsevierStyleCrossRefs" href="#bib0495"><span class="elsevierStyleSup">41&#44;42</span></a> are used in the daily practice to distinguish PCNSLs from other lesions&#46;<a class="elsevierStyleCrossRef" href="#bib0385"><span class="elsevierStyleSup">19</span></a></p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Diffusion</span><p id="par0140" class="elsevierStylePara elsevierViewall">The isotropic diffusion-weighted MRI measures the diffusion of water molecules inside biological tissues&#44; and acts as a surrogate marker of tumor cellularity since intact cells make up a barrier to water diffusion&#46;<a class="elsevierStyleCrossRef" href="#bib0385"><span class="elsevierStyleSup">19</span></a></p><p id="par0145" class="elsevierStylePara elsevierViewall">In the PCNSL&#44; the volume of extracellular space is reduced<a class="elsevierStyleCrossRef" href="#bib0510"><span class="elsevierStyleSup">44</span></a>&#59; also&#44; here we are dealing with highly cellular tumors&#44; which is why the diffusion of water is limited&#44; making them look hyperintense on the DWI &#40;<a class="elsevierStyleCrossRef" href="#fig0020">Fig&#46; 4</a>a&#41; and with relatively lower values in the apparent diffusion coefficient &#40;ADC&#41;<a class="elsevierStyleCrossRefs" href="#bib0370"><span class="elsevierStyleSup">16&#44;39&#44;43</span></a> &#40;<a class="elsevierStyleCrossRef" href="#fig0020">Fig&#46; 4</a>b&#41;&#46; These values are useful to distinguish PCNSLs from high-grade astrocytomas&#46; According to most studies&#44; these values are lower in the PCNSL &#40;<a class="elsevierStyleCrossRef" href="#fig0020">Fig&#46; 4</a>c and d&#41;&#44; although other studies describe overlapping values and cannot find any significant differences&#46;<a class="elsevierStyleCrossRefs" href="#bib0490"><span class="elsevierStyleSup">40&#44;44&#8211;46</span></a></p><elsevierMultimedia ident="fig0020"></elsevierMultimedia><p id="par0150" class="elsevierStylePara elsevierViewall">Calli et al&#46;<a class="elsevierStyleCrossRef" href="#bib0490"><span class="elsevierStyleSup">40</span></a> found minimal ADC values in glioblastomas multiformes &#40;GBM&#41;&#59; anaplastic astrocytomas&#59; PCNSLs and metastases&#44; of 0&#46;79<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;21 &#40;&#215;10<span class="elsevierStyleSup">&#8722;3</span><span class="elsevierStyleHsp" style=""></span>mm<span class="elsevierStyleSup">2</span>&#47;s&#41;&#44; 0&#46;75<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;21 &#40;&#215;10<span class="elsevierStyleSup">&#8722;3</span><span class="elsevierStyleHsp" style=""></span>mm<span class="elsevierStyleSup">2</span>&#47;s&#41;&#44; 0&#46;51<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;09 &#40;&#215;10<span class="elsevierStyleSup">&#8722;3</span><span class="elsevierStyleHsp" style=""></span>mm<span class="elsevierStyleSup">2</span>&#47;s&#41;&#44; and 0&#46;68<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;11 &#40;&#215;10<span class="elsevierStyleSup">&#8722;3</span><span class="elsevierStyleHsp" style=""></span>mm<span class="elsevierStyleSup">2</span>&#47;s&#41;&#44; respectively&#44; with statistically significant differences between PCNSLs and GBMs&#44; and also between PCNSLs and anaplastic astrocytomas&#46; Kickingereder et al&#46;<a class="elsevierStyleCrossRef" href="#bib0520"><span class="elsevierStyleSup">46</span></a> found significantly lower ADC values in patients with PCNSLs compared to patients with GBMs &#40;minimum ADC values&#44; maximum ADC values&#44; and average ADC values of 0&#46;56<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;12&#44; 0&#46;75<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;18 and 0&#46;65<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;13 for PCNSLs&#44; and 0&#46;79<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;20&#44; 1&#46;21<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;32 and 0&#46;97<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;25 for GBMs&#44; respectively&#41;&#46;</p><p id="par0155" class="elsevierStylePara elsevierViewall">Pre-treatment ADC in the contrast-enhanced area has also proven a prognostic factor<a class="elsevierStyleCrossRef" href="#bib0525"><span class="elsevierStyleSup">47</span></a>&#58; lower ADC values determine faster progression of the disease&#44; and lower survival&#8211;both disease-free survival and overall survival&#46; Similarly&#44; the ADC can be used as a biomarker to monitor the response&#46; Thus&#44; higher ADV values are indicative of a favorable response to treatment&#46;<a class="elsevierStyleCrossRefs" href="#bib0385"><span class="elsevierStyleSup">19&#44;47</span></a></p><p id="par0160" class="elsevierStylePara elsevierViewall">Doskaliyev et al&#46;<a class="elsevierStyleCrossRef" href="#bib0530"><span class="elsevierStyleSup">48</span></a> studied the utility of higher b values to distinguish PCNSLs from GBMs and found the lowest overlapping degree with b values of 4000<span class="elsevierStyleHsp" style=""></span>s&#47;mm<span class="elsevierStyleSup">2</span>&#44; establishing the cut-off point between the two tumors in ADC values of 0&#46;5<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">&#40;&#8722;3&#41;</span><span class="elsevierStyleHsp" style=""></span>mm<span class="elsevierStyleSup">2</span>&#46;</p><p id="par0165" class="elsevierStylePara elsevierViewall">Imaging studies using diffusion tensor imaging &#40;DTI&#41; require measuring diffusion in&#44; at least&#44; six &#40;6&#41; directions&#44; and it is a sensitive tool for the detection of alterations in the structure of white matter&#46;<a class="elsevierStyleCrossRef" href="#bib0515"><span class="elsevierStyleSup">45</span></a> Same as it happens with the ADC&#44; the quantitative mapping of fractional anisotropy shows low values in many conditions&#44; including tumors&#46;<a class="elsevierStyleCrossRef" href="#bib0525"><span class="elsevierStyleSup">47</span></a> In PCNSLs they are significantly lower than in GBMs&#44; which allows us to distinguish between the two&#46; Determining fractional anisotropy in tumor tissues is complex&#44; which makes it a less adequate marker than the ADC to be able to distinguish between PCNSLs and GBMs&#46;<a class="elsevierStyleCrossRef" href="#bib0515"><span class="elsevierStyleSup">45</span></a></p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Perfusion</span><p id="par0170" class="elsevierStylePara elsevierViewall">While contrast enhancement expresses the extravasation of contrast due to the disruption of the brain-blood barrier&#44; both perfusion-weighted CT scans and perfusion-weighted MRIs study the tumor vascularization&#44; that is&#44; the arterial blood supply toward the capillary bed in the biological tissue&#46;</p><p id="par0175" class="elsevierStylePara elsevierViewall">The dynamic susceptibility contrast perfusion MRI &#40;DSC-PMRI&#41; is based on the first-pass contrast bolus with the measurement of the corresponding loss of signal on the T2-weighted sequences&#42;&#46; Post-processing later provides data such as the cerebral blood volume &#40;CBV&#41;&#44; the cerebral blood flow &#40;CBF&#41;&#44; the average transit time&#44; and the time to the maximum peak&#46;<a class="elsevierStyleCrossRefs" href="#bib0540"><span class="elsevierStyleSup">50&#44;51</span></a></p><p id="par0180" class="elsevierStylePara elsevierViewall">The relative value of the CBV &#40;rCBV&#41; of the PCNSL&#44; only slightly increased compared to normal white matter &#40;<a class="elsevierStyleCrossRef" href="#fig0025">Fig&#46; 5</a>a and b&#41;&#44; could be attributed to the pattern of angiocentric growth&#46; Perivascular infiltration leads to the massive extravasation of contrast toward the interstitial space&#44; determining one characteristic intensity-time curve after the first-pass<a class="elsevierStyleCrossRefs" href="#bib0490"><span class="elsevierStyleSup">40&#44;41</span></a> &#40;<a class="elsevierStyleCrossRef" href="#fig0025">Fig&#46; 5</a>c&#41;&#46;</p><elsevierMultimedia ident="fig0025"></elsevierMultimedia><p id="par0185" class="elsevierStylePara elsevierViewall">The relatively low CBV and the intensity-time curve play an important role when it comes to differentiating PCNSLs from other tumors of the CNS&#44; such as CBMs and metastases&#44; both with increased angiogenesis&#44; and significantly higher CBV values<a class="elsevierStyleCrossRefs" href="#bib0385"><span class="elsevierStyleSup">19&#44;31&#44;40&#44;52</span></a> &#40;<a class="elsevierStyleCrossRef" href="#fig0025">Fig&#46; 5</a>e&#44; f and g&#41;&#46;</p><p id="par0190" class="elsevierStylePara elsevierViewall">Calli et al&#46;<a class="elsevierStyleCrossRef" href="#bib0490"><span class="elsevierStyleSup">40</span></a> found values of relative maximum perfusion values &#40;rCBVmax&#41; of 6&#46;33<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#46;03 in GBMs&#44; 3&#46;66<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;79 in anaplastic astrocytomas&#44; 2&#46;33<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;68 in PCNSLs and 4&#46;45<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;87 in metastases&#44; with statistically significant differences in GBMs and lymphomas&#46; Also&#44; for Kickingereder et al&#46;<a class="elsevierStyleCrossRef" href="#bib0520"><span class="elsevierStyleSup">46</span></a> the ratios of CBVmax and average CBV were significantly lower in patients with PCNSLs compared to patients with GBMs with respect to the normal contralateral area&#59; the rCBVmax and average rCBV were 4&#46;16<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;65 and 2&#46;04<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;72 for the PCNSL&#44; and 8&#46;75<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>4&#46;75 and 5&#46;09<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#46;57 for the GBM&#44; respectively&#44; obtaining higher accuracy with the average rCBV parameter&#46;</p><p id="par0195" class="elsevierStylePara elsevierViewall">These differences suggest lower tumor vascularization and higher vascular patency in PCNSLs&#46;<a class="elsevierStyleCrossRefs" href="#bib0490"><span class="elsevierStyleSup">40&#44;46</span></a></p><p id="par0200" class="elsevierStylePara elsevierViewall">Contrast enhanced perfusion is a sequence that provides information on the microvasculature of intracranial tumors&#46; It consists of one T1-weighted 3D dynamic sequence whose processing provides perfusion values such as the volume transfer constant &#40;Ktrans&#41;&#44; the flux rate constant &#40;Kep&#41; and the volume of extravascular extracellular space&#46; It is of no use in clinical practice&#44; but it has been studied experimentally&#46; Kickingereder et al&#46;<a class="elsevierStyleCrossRef" href="#bib0535"><span class="elsevierStyleSup">49</span></a> looked into the differences between the PCNSL and the GBM&#44; and found that&#44; in the PCNSL&#44; both the Ktrans and the Kep &#40;0&#46;145<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;057 and 0&#46;396<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;088&#41; are significantly higher than in the GBM &#40;0&#46;064<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;021 and 0&#46;230<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;058&#41;&#46;</p><p id="par0205" class="elsevierStylePara elsevierViewall">Also&#44; experimentally&#44; Suh et al&#46;<a class="elsevierStyleCrossRef" href="#bib0540"><span class="elsevierStyleSup">50</span></a> studied the value of the intravoxel incoherent motion &#40;IVIM&#41; image that provides parameters of diffusion and perfusion to distinguish GBMs from PCNSLs of atypical appearance&#46; They estimated the IVIM &#40;f&#41; fraction of maximum perfusion and the IVIM &#40;D&#41; minimum diffusion parameter and found an f value that was significantly higher in GBMs than in PCNSLs&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">MR spectroscopy</span><p id="par0210" class="elsevierStylePara elsevierViewall">The MR spectroscopy &#40;MRS&#41; provides non-invasive biochemical information on tissues&#46; In a given volume of interest the signal of chemical nuclei is recorded&#59; the most common ones are hydrogen protons&#46;<a class="elsevierStyleCrossRef" href="#bib0385"><span class="elsevierStyleSup">19</span></a> Hydrogen is the most abundant element in the human body&#44; has a universal distribution&#44; being protons the dominant elements in its structure&#46;</p><p id="par0215" class="elsevierStylePara elsevierViewall">In patients with PCNSL&#44; the MRS with long echo time showed increased choline &#40;Cho&#41; levels&#44; reduced N-acetyl-aspartate &#40;Naa&#41; levels and the presence of lipid peaks&#46;<a class="elsevierStyleCrossRefs" href="#bib0310"><span class="elsevierStyleSup">4&#44;42&#44;43</span></a> These findings do not allow us to distinguish PCNSLs from GBMs or metastases &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#44; but they can be useful to distinguish PCNSLs from other lesions&#46;<a class="elsevierStyleCrossRefs" href="#bib0385"><span class="elsevierStyleSup">19&#44;42</span></a> For example&#44; Lu et al&#46;<a class="elsevierStyleCrossRef" href="#bib0555"><span class="elsevierStyleSup">53</span></a> showed the utility of the MRS to distinguish PCNSLs from demyelinating pseudotumor lesions showing higher Cho&#47;Cr and Cho&#47;Naa ratios&#44; and elevated Lip&#47;Lac peaks&#46; They propose the Cho&#47;Naa ratio as the most useful one&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Susceptibility weighted-imaging &#40;SWI&#41;</span><p id="par0220" class="elsevierStylePara elsevierViewall">High-resolution susceptibility weighted-imaging &#40;SWI&#41; is much more sensitive than conventional imaging for the detection of small blood vessels&#44; blood remains and calcifications that appear as low-signal structures called intratumoral susceptibility signals &#40;ITSS&#41;&#46; This is an important piece of information in order to distinguish PCNSLs from GBMs&#44; since&#44; according to Kim et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0560"><span class="elsevierStyleSup">54</span></a> the number of blood vessels detected by the SWI is significantly higher in GBMs and metastases compared to PCNSLs&#44; while hemorrhages&#8211;common in GBMs&#44;<a class="elsevierStyleCrossRefs" href="#bib0520"><span class="elsevierStyleSup">46&#44;54</span></a> are rare in PCNSLs&#46; There is an exception that we should take into account here&#8211;the possibility of microhemorrhages in cases of rare histological variants such as T-cell lymphomas&#46;<a class="elsevierStyleCrossRef" href="#bib0565"><span class="elsevierStyleSup">55</span></a></p></span></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Nuclear medicine&#58; positron emission tomography &#40;PET&#41;</span><p id="par0225" class="elsevierStylePara elsevierViewall">Nuclear medicine techniques with radioisotopes produce images that show biological process and their metabolism&#46; In practice they are not used routinely for the diagnosis and management of PCNSLs&#44; although some studies claim that they may be useful&#46;</p><p id="par0230" class="elsevierStylePara elsevierViewall">The fluorodeoxyglucose positron emission tomography &#40;FDG PET&#41; shows lesions that are typically hypermetabolic with enhanced FDG uptake in PCNSLs&#44;<a class="elsevierStyleCrossRef" href="#bib0410"><span class="elsevierStyleSup">24</span></a> and whose progression can be used for the early assessment of the response to therapy&#46; Some authors say that the FDG PET can even help distinguish PCNSLs from malignant gliomas and metastases&#46;<a class="elsevierStyleCrossRef" href="#bib0570"><span class="elsevierStyleSup">56</span></a></p><p id="par0235" class="elsevierStylePara elsevierViewall">Although the methionine uptake in the PCNSL is significantly lower than the FDG uptake&#44; there is no significant difference in the sensitivity of detection of PCNSL between the PET with methionine and the PET with FDG&#8211;in both being close to 100&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0575"><span class="elsevierStyleSup">57</span></a></p><p id="par0240" class="elsevierStylePara elsevierViewall">When it comes to PCNSLs of atypical appearance&#44; Kawai et al&#46;<a class="elsevierStyleCrossRef" href="#bib0580"><span class="elsevierStyleSup">58</span></a> found that both the visual analysis and the pseudoquantitative and quantitative values were not very useful to distinguish them from other lesions&#46; However&#44; certain specific values &#40;such as quantitative values assessed using the kinetic analysis&#41; were similar in both the typical and atypical PCNSLs&#44; meaning that these parameters may provide valuable information for the diagnosis of PCNSLs&#46;</p></span></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Conclusions</span><p id="par0245" class="elsevierStylePara elsevierViewall">The PCNSL is a rare type of tumor whose management significantly varies from that of other malignant tumors of the CNS&#44; which is why it is important to suggest the correct imaging diagnosis&#46; The RMI is the diagnostic imaging modality of choice&#46;</p><p id="par0250" class="elsevierStylePara elsevierViewall">The PCNSL damages the cerebral parenchyma and its most common manifestation is being one single lesion with homogeneous enhancement&#44; although it may show other patterns such as multifocality and ring enhancement&#46; Its imaging characteristics have to do with its hypercellular nature&#44; and with phenomena of contrast effusion with scarce angiogenesis&#46; Although it has typical findings&#44; none of them is specific&#44; and multiple atypical patterns have been described&#46; MRI advanced sequences&#44; mainly perfusion-weighted MRIs&#44; provide useful information to be able to distinguish this lesion from other conditions&#44; basically other malignant tumors of the CNS&#44; and they can be used as one prognostic marker&#46;</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Ethical disclosures</span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Protection of human and animal subjects</span><p id="par0255" class="elsevierStylePara elsevierViewall">The authors declare that no experiments with human beings or animals have been performed while conducting this investigation&#46;</p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Confidentiality of data</span><p id="par0260" class="elsevierStylePara elsevierViewall">The authors confirm that in this article there are no data from patients&#46;</p></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Right to privacy and informed consent</span><p id="par0265" class="elsevierStylePara elsevierViewall">The authors confirm that in this article there are no data from patients&#46;</p></span></span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Authors</span><p id="par0270" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">1&#46;</span><p id="par0275" class="elsevierStylePara elsevierViewall">Manager of the integrity of the study&#58; EGR&#46;</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">2&#46;</span><p id="par0280" class="elsevierStylePara elsevierViewall">Study idea&#58; EGR&#46;</p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">3&#46;</span><p id="par0285" class="elsevierStylePara elsevierViewall">Study design&#58; EGR&#46;</p></li><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">4&#46;</span><p id="par0290" class="elsevierStylePara elsevierViewall">Data mining&#58; EGR&#44; AMQG&#44; GLS and SPG&#46;</p></li><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel">5&#46;</span><p id="par0295" class="elsevierStylePara elsevierViewall">Data analysis and interpretation&#58; EGR&#46;</p></li><li class="elsevierStyleListItem" id="lsti0030"><span class="elsevierStyleLabel">6&#46;</span><p id="par0300" class="elsevierStylePara elsevierViewall">Statistical analyses&#58; N&#47;A&#46;</p></li><li class="elsevierStyleListItem" id="lsti0035"><span class="elsevierStyleLabel">7&#46;</span><p id="par0305" class="elsevierStylePara elsevierViewall">Reference&#58; EGR&#46;</p></li><li class="elsevierStyleListItem" id="lsti0040"><span class="elsevierStyleLabel">8&#46;</span><p id="par0310" class="elsevierStylePara elsevierViewall">Writing&#58; EGR&#46;</p></li><li class="elsevierStyleListItem" id="lsti0045"><span class="elsevierStyleLabel">9&#46;</span><p id="par0315" class="elsevierStylePara elsevierViewall">Critical review of the manuscript with intellectually relevant remarks&#58; EGR&#44; AMQG&#44; GLS and SPG&#46;</p></li><li class="elsevierStyleListItem" id="lsti0050"><span class="elsevierStyleLabel">10&#46;</span><p id="par0320" class="elsevierStylePara elsevierViewall">Approval of final version&#58; EGR&#44; AMQG and GLS&#46;</p></li></ul></p></span><span id="sec0095" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Conflicts of interests</span><p id="par0325" class="elsevierStylePara elsevierViewall">The authors declare no conflict of interests associated with this article whatsoever&#46;</p></span></span>"
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          "titulo" => "References"
        ]
      ]
    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2016-06-03"
    "fechaAceptado" => "2017-12-27"
    "PalabrasClave" => array:2 [
      "en" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec1009151"
          "palabras" => array:7 [
            0 => "Lymphoma"
            1 => "Central nervous system"
            2 => "Brain"
            3 => "Brain tumor"
            4 => "Magnetic resonance imaging"
            5 => "Perfusion"
            6 => "Diffusion"
          ]
        ]
      ]
      "es" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec1009152"
          "palabras" => array:7 [
            0 => "Linfoma"
            1 => "Sistema nervioso central"
            2 => "Cerebro"
            3 => "Tumor cerebral"
            4 => "Resonancia magn&#233;tica"
            5 => "Perfusi&#243;n"
            6 => "Difusi&#243;n"
          ]
        ]
      ]
    ]
    "tieneResumen" => true
    "resumen" => array:2 [
      "en" => array:2 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Primary central nervous system lymphomas &#40;PCNSL&#41; are rare and their management varies significantly from that of other malignant tumors involving the CNS&#46; This article discusses how the imaging findings often suggest the diagnosis early in time&#46; The typical findings in immunocompetent patients consist of one supratentorial intra-axial mass of homogeneous enhancement&#46; Other findings that should be assessed include multifocality and incomplete ring enhancement&#46; The differential diagnosis of PCNSL should mainly consider other malignant tumors of the CNS such as glioblastomas or metastases&#46; PCNSLs tend to have less edema and less mass effect&#59; they also tend to spare the adjacent cortex&#46; Necrosis&#44; hemorrhage&#44; and calcification are rare in PCNSLs&#46; Although the findings in the morphologic sequences are characteristic&#44; they are not completely specific and atypical types can sometimes be found&#46; Advanced imaging techniques such as diffusion-weighted images and&#44; above all&#44; perfusion-weighted images provide qualitative and quantitative data that play an important role in the differentiation of PCNSLs from other brain tumors&#46;</p></span>"
      ]
      "es" => array:2 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">El linfoma primario del sistema nervioso central &#40;LPSNC&#41; es infrecuente y su manejo difiere significativamente del resto de los tumores malignos de esta localizaci&#243;n&#46; El texto desarrolla c&#243;mo los hallazgos radiol&#243;gicos a menudo sugieren el diagn&#243;stico precozmente&#46; La imagen t&#237;pica en los pacientes inmunocompetentes es una masa intraaxial supratentorial con realce homog&#233;neo&#46; Otros hallazgos que deben valorarse son la multifocalidad y el realce en anillo incompleto&#46; En el diagn&#243;stico diferencial del LPSNC deben considerarse principalmente otros tumores malignos del SNC&#44; como el glioblastoma y las met&#225;stasis&#46; El LPSNC suele tener menor edema y efecto masa&#44; y respeta el c&#243;rtex adyacente&#44; siendo infrecuentes la necrosis&#44; la hemorragia y la calcificaci&#243;n&#46; Aunque los hallazgos en secuencias morfol&#243;gicas son t&#237;picos&#44; no son por completo espec&#237;ficos y pueden encontrarse formas at&#237;picas&#46; Las t&#233;cnicas avanzadas&#44; como la difusi&#243;n y sobre todo la perfusi&#243;n&#44; muestran valores cualitativos y cuantitativos que desempe&#241;an un papel importante al diferenciar el LPSNC de otros tumores cerebrales&#46;</p></span>"
      ]
    ]
    "NotaPie" => array:1 [
      0 => array:2 [
        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; G&#243;mez Rosell&#243; E&#44; Quiles Granado AM&#44; Laguillo Sala G&#44; Pedraza Guti&#233;rrez S&#46; Linfoma cerebral primario en pacientes inmunocompetentes&#58; espectro de hallazgos y caracter&#237;sticas diferenciales&#46; Radiolog&#237;a&#46; 2018&#59;60&#58;280&#8211;289&#46;</p>"
      ]
    ]
    "multimedia" => array:7 [
      0 => array:7 [
        "identificador" => "fig0005"
        "etiqueta" => "Figure 1"
        "tipo" => "MULTIMEDIAFIGURA"
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        "figura" => array:1 [
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        "descripcion" => array:1 [
          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Location and number of lesions&#46; It shows the most common pattern of the primary central nervous system lymphoma &#40;PCNSL&#41; of deep intra-axial supratentorial location &#40;a&#41;&#46; It appears as one infratentorial lesion in 10&#37; of the cases&#59; the image shows it is damaging the left cerebellar hemisphere &#40;b&#41; and&#44; contralaterally&#44; we can see capillary telangiectasias&#44; almost incidentally&#46; There is damage due to two tumors of the interhemispheric connection fibers&#44; in this case&#44; in the anterior commissure &#8211; a finding that is consistent with PCNSLs &#40;c&#41; and glial tumors only &#40;d&#41;&#46; The solitary mass is the most common presentation&#44; yet multiple lesions with satellite nodes &#40;e&#41;&#44; and diffuse bilateral damage &#40;f&#41; are not rare &#40;20&#8211;40&#37; of the cases&#41;&#46;</p>"
        ]
      ]
      1 => array:7 [
        "identificador" => "fig0010"
        "etiqueta" => "Figure 2"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
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        "figura" => array:1 [
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          "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Appearance of one PCNSL on the CT scan&#44; hyperdense without contrast &#40;a&#41; and with uniform enhancement after the administration of contrast &#40;b&#41;&#46;</p>"
        ]
      ]
      2 => array:7 [
        "identificador" => "fig0015"
        "etiqueta" => "Figure 3"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
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        "descripcion" => array:1 [
          "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Enhancement patterns and specific signs&#46; The most typical one is homogeneous enhancement&#46; Ring enhancement is even rarer&#44; but it is still possible&#46; In the PCNSL&#44; the thick and not uniform &#8220;open ring&#8221; has been described &#40;a&#41;&#44; unlike multiple sclerosis&#44; where the ring is thin and uniform &#40;b&#41;&#46; One notch can be present in lesions with homogeneous enhancement&#44; and it has been suggested as a specific finding &#40;arrow in c&#41;&#46;</p>"
        ]
      ]
      3 => array:7 [
        "identificador" => "fig0020"
        "etiqueta" => "Figure 4"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr4.jpeg"
            "Alto" => 2303
            "Ancho" => 2000
            "Tamanyo" => 320972
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        "descripcion" => array:1 [
          "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Diffusion&#46; The PCNSL shows diffusion restriction &#40;a&#41; that translates into low values of the apparent diffusion coefficient &#40;ADC&#41; &#40;b&#41; that are consistent with the enhancement region in relation to its hypercellularity&#44; among other factors&#46; Here we can see ADC values that are significantly lower in the PCNSL &#40;c&#41; compared to the glioblastoma &#40;d&#41;&#46;</p>"
        ]
      ]
      4 => array:7 [
        "identificador" => "fig0025"
        "etiqueta" => "Figure 5"
        "tipo" => "MULTIMEDIAFIGURA"
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        "figura" => array:1 [
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        "descripcion" => array:1 [
          "en" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Perfusion&#46; The PCNSL shows a mild increase both in the color maps and the quantitative levels of cerebral blood volume &#40;CBV&#41; &#40;ROI 1 in a and b&#41;&#44; and one characteristic curve with a scarce peak after the first-pass shows contrast effusion above the baseline following the T1 phenomenon &#40;c&#41;&#46; Post-contrast T1-weighted images of the reference PCNSL &#40;d&#41;&#46; In glioblastomas&#44; however&#44; perfusion is really high &#40;c and d&#41; and its typical curve shows &#40;g&#41; one elevated peak&#44; and normalization after the first-pass &#40;f&#41;&#46; Post-contrast T1-weighted image of the reference glioblastoma included &#40;h&#41;&#46;</p>"
        ]
      ]
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        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
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        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at1"
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        "tabla" => array:1 [
          "tablatextoimagen" => array:1 [
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                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Number&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Single<br>20&#8211;40&#37; are multiple lesions&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Location&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Supratentorial &#40;90&#37;&#41;&#58; periventricular&#44; hemispheric&#44; subcortical&#46; Possibility of damage to interhemispheric fibers&#46; They spare the cortex<br>Infratentorial &#40;10&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Signal&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Iso&#47;hipersignal on T1-weighted images<br>Tendency to hyposignal on T2-weighted images&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Enhancement pattern&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Clear predominance of homogeneous enhancement<br>Possible ring enhancement without internal necrosis<br>Specific signs described&#58;<br>- Open ring<br>- Notch sign&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Mass effect&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Scarce for its size&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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                0 => "xTab1804542.png"
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        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Findings in conventional sequences&#46;</p>"
        ]
      ]
      6 => array:8 [
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        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
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          "leyenda" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">GBM&#58; glioblastomas multiforme&#59; PCNSL&#58; primary central nervous system lymphoma&#59; Naa&#58; N-acetyl-aspartate&#46;</p>"
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                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">GBM&#47;metastasis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">PCNSL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " colspan="3" align="left" valign="top"><span class="elsevierStyleBold">Diffusion &#40;ADC&#47;FA&#41;</span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="3" align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Perfusion &#40;CBV&#41;</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Inverted peak 1 pass and return to baseline&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Curve&#58; Peak after 1 pass&#58; return to baseline&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Typical curve&#58; Peak after 1 pass&#58; above baseline due to phenomenon of contrast effusion&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="3" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="3" align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">SWI &#40;microhemorrhages&#41;</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Spectrum&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Choline<br>Naa<br>Lipid peaks&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">The same&#44; does not distinguish between the two&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
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        "descripcion" => array:1 [
          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Findings in advanced sequences&#58; differences among high-grade glial tumor&#44; metastasis&#44; and primary lymphoma of the central nervous system&#46;</p>"
        ]
      ]
    ]
    "bibliografia" => array:2 [
      "titulo" => "References"
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        0 => array:2 [
          "identificador" => "bibs0015"
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                  ]
                  "host" => array:1 [
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                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
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                            2 => "J&#46;A&#46; van Dijck"
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Article information

ISSN: 21735107
Original language: English

DOI:10.1016/j.rxeng.2018.04.003

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2024 August	32	3	35
2024 July	15	1	16
2024 June	15	0	15
2024 May	7	2	9
2024 April	12	2	14
2024 March	40	5	45
2024 February	34	7	41
2024 January	26	0	26
2023 December	40	7	47
2023 November	58	1	59
2023 October	46	5	51
2023 September	34	5	39
2023 August	17	2	19
2023 July	27	2	29
2023 June	12	0	12
2023 May	21	0	21
2023 April	7	1	8
2023 March	7	2	9
2023 February	1	0	1
2023 January	1	0	1
2021 May	4	0	4
2019 May	0	2	2
2018 December	1	2	3

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