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April2013 Vol.50 Issue:      2 Table of Contents
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A Study of Radio-Pathological Diagnosis in 20 Egyptian Children with Brain Tumors

Hadeer AbdelGhaffar1, Ashraf Azmy2, Hossam Hussein3, Omar Moawia4

Departments of Pediatrics, Fayoum University1, National Research Center2;

Pathology3, Radiodiagnosis4, Cairo University; Egypt



Background: Intracranial tumors are the most common solid tumors in children and the therapeutic modality based on the tumor type, grade. Objective: The objective of the study was to determine if quantitative diffusion imaging improved the MR imaging of pediatric CNS malignancies by comparing the apparent diffusion coefficient to the histo-pathological tumor grading. Methods: This study included twenty patients (twelve boys, eight girls) with neuroglial solid tumors underwent diffusion-weighted MR imaging. The mean age of the patients was 10 years. All patients were submitted to histo-pathological diagnosis and immunohistochemical study. Their pathological diagnosis and tumor grading was carried out according to the World Health Organization classification of brain tumors. Mean apparent diffusion coefficient values obtained from the solid components of each tumor type were compared with the tumor grade. Results: The pilocytic astrocyoma, ependymoma and medulloblastoma were the most common type of brain tumors that represented in this studied group as 30% for each. The mean apparent diffusion coefficient (ADC) values for low-grade gliomas; grade I was 1.7±0.3 ´ 10-3 mm2/sec grade II tumors was 1.4±0.2 ´ 10-3 mm2/sec, while for grade IV medulloblastoma was 0.7±0.20 ´ 10-3 mm2/sec. Conclusion: The histopathological diagnosis remains the gold standard method for pediatric brain tumors assessment. However the apparent diffusion coefficient added more information to MR imaging in differentiating the embryonal tumors (medulloblastoma) from low grade gliomas. [Egypt J Neurol Psychiat Neurosurg.  2013; 50(2): 101-108]

 Key Word: Pediatric, brain tumors, histopathology, MR imaging, diffusion coefficient.

Correspondence to Hadeer Mahmoud Abdel Ghaffar, Pediatric Department, Fayoum University, Egypt. Tel.: +201001787209          email:



Pediatric central nervous system (CNS) tumors are a heterogeneous group of diseases that are, collectively, the second most frequent malignancy in childhood.1 The overall mortality among this group approaches 45%.2 Several technological advancements have increased our knowledge of the cell biology of pediatric brain tumors, facilitated earlier diagnosis, and improved neurosurgical resections while minimizing neurological deficits.         

These in turn have not only improved the survival of children with brain tumors but also their quality of life. Current management strategies in most cases rely on surgery coupled with adjuvant therapies, including radiation therapy and chemotherapy.3 Clinical treatment and prognosis varies with tumor type, histological grade, and stage. WHO grade is one component of a combination of criteria used to predict a response to therapy and outcome. Other criteria include clinical findings such as age of the patient, tumor location; radiological findings; extent of surgical resection; and genetic changes. For each tumor entity, combination of these parameters contributes to an overall estimate of prognosis.4

Conventional MR imaging incorporating contrast-enhanced T1-weighted and T2-weighted sequences helps to characterize the location and extent of these tumors, but MR imaging provides limited information regarding tumor type and grade, that role is reserved for histopathologic evaluation after biopsy.5 Introduction of diffusion-weighted (DW) magnetic resonance (MR)  imaging has enabled us to obtain additional information derived from microscopic motion of the water proton, which is not available by using conventional MR imaging.6 DW imaging has been applied for assignment of tumor grades or differentiation of tumors. Several investigators found correlation between the apparent diffusion coefficient (ADC) calculated from DW images and tumor cellularity.7 Some studies involving the assignment of grades to gliomas by using ADC showed the usefulness of ADC for such assignment8, but others did not.9


Aim of the Work

The purpose of this study was to determine the role of quantitative diffusion imaging that improves the MR imaging of pediatric brain tumors by comparing the tumor apparent diffusion coefficient to the histo-pathological tumor grading, and so determining preoperative tumor grade, to get planning for initial treatment strategy in pediatric brain tumors.



This cross-sectional, descriptive study included 20 Egyptian children (twelve boys, eight girls) with intra-cranial neoplastic solid mass based on conventional MR imaging as well as diffusion-weighted MR imaging collected from the pediatrics department of Cairo and Fayoum Universities in association with the pathology department of Cairo University. Their age ranged from 1.5 to 17 years. The exclusion criteria were patients with entirely cystic tumors or other previous or concurrent brain diseases. All patients were submitted to full general and neurological examination and were further evaluated by ophthalmological and funduscopic examination. All were subjected to digital EEG under standard conditions to detect the presence of either epileptogenic activities or background abnormalities.

Conventional MR imaging was performed on a 1.0 Tesla Panorama open MR imaging unit (Gyroscan Intera; Philips, The Netherlands), with SENSE head coil using (a) Sagittal and axial  non-contrast images with imaging parameters of 600/15 (TR/TE), (b) Axial fast spin-echo T2-weighted, T2-weighted spin-echo images with imaging parameters of 4000/100 (TR/TE), and (c) Axial fluid-attenuated inversion recovery (FLAIR) with imaging parameters of 6000/90 (TR/TE), Diffusion-weighted images (DWIs) were acquired with imaging parameters of 3000/89 (TR/TE). The apparent diffusion coefficient (ADC) values were calculated from DW images by using standard software.

Routine histo-pathological studies using multiple sections from all paraffin blocks cut at 4 micron thickness and stained by H&E stain were performed together with additional un-stained slides for immuno-histo-chemical studies when needed.

The pathologic classification used was the WHO classification of brain tumors. The glial tumors and embryonal tumors were classified as follow; Grade I pilocytic astrocytomas, giant cell astrocytomas, choroid plexus papilloma. Grade II ependymomas. Grade IV medulloblastoma.


Statistical Analysis

Data analysis was carried out with the statistical package for social science (version 10.0, 1999; SPSS Inc. Chicago, IL, USA). We used descriptive statistics to measure the mean, number and percentages. 




This study included 20 Egyptian children with neuroglial tumors. The studied group comprised of twelve boys and eight girls with male to female ratio 3:2. Their age ranged from 1.5 to 17 years with a mean age of 10 years. The main clinical manifestations of included patients were summarized in Table (1) and showed that nausea with vomiting, headache and papilledema were present in 60-65% of all cases respectively, while ataxic gait and gaze palsy were present in 40-45% of all studied population respectively.           

In Table (2), although three patients only presented by seizures, fifteen patients out of all showed abnormal EEG findings in the form of either focal abnormalities or generalized slowing. Table (3) showed that the pilocytic astrocyoma, ependymoma and medulloblastoma were the most common types of brain tumors that represented in this studied group (30%), while Choroid plexus papilloma and subependymal giant cell astrocytoma in case of tubers sclerosis complex represented the least percentage (5%). The apparent diffusion coefficient values for grade I (pilocytic astrocytoma, subependymal giant cell astrocytoma and Choroid plexus papilloma) were 1.7±0.3 ´ 10-3 mm2/sec (range, 1.32-1.90 ´ 10-3 mm2/sec). The values for grade II ependymoma were 1.4±0.2 ´ 10-3 mm2/sec (range, 1.2-1.60 ´ 10-3 mm2/sec), while for grade IV high-grade tumor embryonal tumors (medulloblastoma) were 0.7±0.20 ´ 10-3 mm2/sec (range, 0.5-0.9 ´ 10-3 mm2/sec).


Table 1. The main clinical characteristics of the study population.


Number of Patients (%)

Clinical Presentations

13 (65%)


12 (60%)

Nausea and vomiting

3 (15%)


3 (15%)


8 (40%)


9 (45%)

Gaze palsy

5 (25%)

Sun set eyes

13 (65%)


3 (15%)


1 (5%)

Hypopigmented patches

Table 2. Types of EEG abnormalities in studied population.


EEG findings

Number (%)

   Focal discharges


   Focal slowing

4 (20%)

  Generalized slowing




Table 3. MRI and pathological findings with WHO classification among the populated group study.



Tumor histology

WHO classification

Number (%)

Cerebellar hemisphere

Pilocytic astrocyoma

Grade I

6 (30%)

4th ventricle


Grade II

6 (30%)

4th ventricle


Grade IV

6 (30%)

Foramen of Monro

Subependymal giant cell astrocytoma

Grade I

1 (5%)

Lateral ventricle

Choroid plexus papilloma

Grade I

1 (5%)



Figure 1. Eight years old male patient with pilocytic astrocytoma. (a) is axial T2-WI showing left cerebellar well defined cystic lesion with  small enhanced solid nodule at its medial aspect on post contrast series. The calculated ADC value in ADC image (b) was 1.32 ´ 10–3 mm2/sec.




Figure 2. Histo-pathology of the same case showing Pilocytic astrocytoma, WHO Grade I (H & E ´ 100)


Figure 3. One and a half years old female infant with ependymoma. (a) Axial T2WI showing heterogeneous hyperintense posterior fossa neoplastic lesion. The average calculated ADC value in ADC image (b) was 1.2 ´ 10–3 mm2/sec.



Figure 4. Ependymoma WHO Grade II   (H & E ´ 200)



Figure 5. Nine years old  male child with pathologically proven choroid plexus papilloma forming  right lateral intra-ventricular space occupying lesion of hyperintense signal on  T2WI (a) and FLAIR (b), and the average calculated ADC value in ADC image (c) is 1.626 ´ 10–3 mm2/sec. 



Figure 6. Choroid plexus papilloma WHO Grade I (H & E ´ 200) and immunostain



Figure 7. Two years old male patient with desomoplastic medulloblastoma displaying hypointense signal on T1WI (a) hyperintense signal on T2WI (b) The average calculated ADC value in ADC image (c) was 0.605 ´ 10–3 mm2/sec.




Figure 8. Medulloblastoma WHO Grade IV (H & E ´ 200) and immunostain







Approximately 3700 primary brain tumors are diagnosed each year in children and adolescents, with an overall annual incidence of approximately 45 cases/million children <20 years of age. The incidence of CNS tumors is highest in infants and children  ≤ 5 years of age (approximately 52 cases/million children).10 A male predominance was noted in the current study with male to female ratio 3-2 which was in agreement with Packer and colleagues in 2000.11  Headache, nausea with vomiting, and papilledema were present in 60-65%, while ataxic gait and gaze palsy represented in 40-45% as reported by Packer in1999.12  Choroid plexus papilloma  is an unusual tumors, representing less than 2%  of childhood brain tumors, and the onset is usually during infancy.13 Two histological types of tumors exist; choroid plexus papilloma, a low grade variant, and choroid plexus carcinoma, a malignant variant.14 According to the current study, choroid plexus papilloma was represented 5% of all studied group, it was contradictory to other studies regarding the age of onset, it occurred in a male patient aged 9 years while it is more common to occur in infancy.13 The average calculated ADC value in ADC image was 1.626 ´ 10-3 mm2/sec, and according to WHO classification it was grade 1 a low grade variant tumor (figures 5 and 6). According to the routine methodology of management, the gross total resection is curative for papilloma while in choroid plexus carcinoma, the adjuvant therapy either chemotherapy in patients less than 3 years or radiotherapy in patients older than 3 years is often necessary.14 

So the preoperative MR study with calculated ADC was very useful to predict the grade of the tumor as a grade I; low-grade variant, that had been confirmed by the tissue pathology.

As regard the astrocytoma, the low-grade histological type is more common than the high grade in children. The cerebellar astrocytomas are the benign tumors of childhood known to be associated with excellent long-term survival in patients in whom complete surgical resection is possible. However, the roles of other factors (clinical, radiological, histological, and therapeutic) in the survival of the patient, tumor recurrence, and long-term patient outcome remain imprecise.15 In the current study; all cases of astrocytoma were of low grade histological appearance. Seizures are the most common initial feature of low-grade gliomas when are close to cortical structure as reported by pecker 1999.  Three cases out of six with pilocytic astrocyoma in this study were manifested with focal seizures with focal epileptogenic activity in their EEG, while all six cases had headache with generalized slowing in EEG. The apparent diffusion coefficient values for grade I pilocytic astrocytoma were 1.7±0.3 ´ 10-3 mm2/sec (range, 1.32–1.90 ´ 10-3 mm2/sec) as shown in figures 1 and 2, so it was very useful to detect the cellularity grading before the tissue sample.

Ependymomas are tumors derived from cells that line the ventricular system and may be either supratentorial or infratentorial in location. All six cases with ependymomas in the current study derived from 4th ventricles, and all of them represented with papilledema as a common feature, 4/6 cases (66%) of them manifested with ataxia which was different to what reported by Paulino (2002) who found that ataxia was present in 90% of infratentorial ependymoma and papilledema in 75% at the time of initial examination.16

All cases of ependymoma were of grade II in histo-pathological classification in the current study with mean apparent diffusion coefficient values 1.4±0.2 ´ 10-3 mm2/sec as shown in figures 3 and 4 which were lower than those of grade 1. McLaughlin 1998 reported that the survival related directly to the effectiveness of surgical removal followed by either radiation therapy or chemotherapy, and the radiation therapy is reserved for children in whom a gross total resection is not possible.17 Medulloblastoma is an infratentorial primitive neuroectodermal tumors (PNET), it is highly malignant and the progression of symptoms is rapid so, the time to diagnose should be less than 3 months.18   Brasme in 2012 reported that the median interval from symptom onset until diagnosis for 166 patients was 65 days. The most frequent manifestations were; vomiting (88%), headaches (79%), and psychomotor regression (60%) of children under 3 years. A meticulous neurological examination and cerebral imaging for such patients facilitated the earlier diagnosis.19 In the current study 4/6 cases (66%) manifested initially with ataxia with periodic attacks of headache while all 6 cases of medulloblastomas were presented with vomiting and nausea. According to what reported by Eberhart 2002 vomiting was the initial symptom in 58% of children, headache in 40% and the unsteady gait in 20%.18 In this study, Medulloblastoma were histologically grade IV, and the mean apparent diffusion coefficient values were 0.7±0.20 ´ 10-3 mm2/sec as shown in figures 7 and 8 which was significantly lower than in grade I and grade II.  The combination of surgical removal, radiation therapy and chemotherapy greatly improve the prognosis for children with medulloblastoma. The overall 5-years survival rate is approximately 40%, and the survival can be improved to 60%-70% in children who have gross total tumor resection.18-19 The presence of dissemination is the most important factor that correlates with poor outcome.20 Tumor grading is a key factor influencing the choice of therapies particularly determining the use of adjuvant radiation and specific chemotherapy protocols. Since its first publication in 1979, the WHO classification of tumors of the nervous system has included a grading scheme that is a “malignancy scale” ranging across a wide variety of neoplasms rather than a strict histological grading system.21

WHO Grade I lesions generally include tumors of low proliferative potential and the possibility of cure following surgical resection alone. Lesions designated as grade II are generally infiltrative in nature and despite low-level proliferative activity, they often recur.22 The designation grade IV which assigned to cytologically malignant, mitotically active, necrosis-prone neoplasms is often associated with rapid pre-and post-operative disease evolution and a fatal outcome.23 Studies had shown that the apparent diffusion coefficient values of abscess fluid are markedly lower than those of cystic or necrotic portions of tumor.24 Murakami and colleagues in 2008 suggested that the minimum ADC reflected the sits of highest cellularity within heterogeneous tumors, and therefore be of diagnostic value in identification high grade tumor components.25 Tumors in pediatric patients have a wide range of cellularity: Malignant embryonal tumors typically have high cell counts, and stroma-rich while benign lesions typically have low cell counts. Moreover, tissues with high cellularity and those with low cellularity differ in terms of water distribution in the intra and extracellular compartments.26  

According to the mean ACD values comparing to WHO tumor grading results we found the higher the tumor grade, the lower the ADC in brain tumors as reported by Ji and colleagues in 2011.27  



Although, the current study was limited by many factors (including the small number of patients and pediatric age group), the apparent diffusion coefficient may be helpful in predicting the grades of tumors, and may be a useful tool in characterizing tumor cellularity. So the quantitative diffusion imaging may determine the preoperative tumor grade either low or high, thus opening the way for a possible planning of initial treatment strategy in pediatric brain tumors to improve the survival and reduce the possibilities of neurological deficits.

Further studies should be followed to assess the possible role of neo-adjuvant therapy in pediatric brain tumors.


[Disclosure: Authors report no conflict of interest]




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الملخص العربى


دراسة للأهمية التشخيصية الباثولوجية والإشعاعية على عشرين طفل مصاب بأورام المخ


تعتبر أورام المخ عند الأطفال أكثر الأورام انتشارا إلا انه قد بدأ حديثا تحسن فى نتائج العلاج عن طريق جراحات المخ والعلاج الاشعاعى والعلاج الكيمائي لكل نوع ومرحلة ودرجة لنوع الورم.

والهدف من هذه الدراسة هو التعرف على علاقة التغيير فى كم ومعدل الانتشار(الارتواء) بالرنين المغناطيسى وتحديد نوع ودرجة الورم مقارنة بنتائج الفحص الباثولوجى لإيجاد وسيلة لتشخيص مبكر.

تم إجراء هذا البحث على عشرين طفل مصاب بأورام المخ بعد عمل الفحص الاكلينيكى الشامل وفحص للجهاز العصبى وتحديد الأعراض وعمل رسومات مخ  وفحص رنين مغناطيسى روتينى بالإضافة الى عمل أشعة رنين ذات مرجع انتشار وإرسال العينات النسيجية لإجراء فحص باثولوجى بعد استئصال الورم جراحيا مع عمل شرائح ميكروسكوبية وصباغتها بواسطة الهيماتوكسيلين لجميع الحالات وعمل الصبغة المناعية إذا لزم ذلك.

النتائج : وضعت درجة الورم بالفحص الباثولوجى وفق تصنيف منظمة الصحة العالمية لأورام المخ الصادر عام 2007 أما بالنسبة لمعامل الانتشار الظاهرى المكافئ فقد تم تحديده على الأورام الصلبة أو على الأجزاء الصلبة من الورم. وقد وجد أن مكافئ الانشار الظاهرى فى الرنين المغناطيسى كان أكثر ارتفاعا فى الأورام الدبقية ذات الدرجة الورمية والمحتويات الخلوية والكثافة الانوية المنخفضة أما فى حالات الأورام ذات الدرجة عالية الورمية وكذلك المحتويات الخلوية العالية فان مكافئ الانتشار الظاهرى كان ذو معدل منخفض

ومن هنا نستنتج انه على الرغم من أن التشخيص النسيجى الباثولوجى هو المعيار فى تقييم حالات أورام الأطفال من حيث النوع ودرجة الورمية الا انه يمكن اتخاذ قياس مكافئ الانتشار الظاهري من خلال الرنين المغناطيسى وسيلة مبكرة لتحديد درجة الورم والتفريق بين أنواع الأورام ذات الدرجات المختلفة قبل التدخل الجراحى حيث سيكون له أهمية كبرى فى وضع خطة علاج مبكرة مستقبلية والوصول الى أعلى درجات الشفاء وتقليل احتمالية المضعفات التاية للمرض.

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