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Clinical and histopathological profile of dysembryoplastic neuroepithelial tumor: An experience from a tertiary care center


1 Department of Pathology, ICMR- National Institute of Pathology, Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi, India
2 Department of Neurosurgery, Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi, India

Date of Submission21-Aug-2019
Date of Acceptance12-Apr-2020
Date of Web Publication19-Oct-2020

Correspondence Address:
Fouzia Siraj,
Department of Pathology, ICMR- National Institute of Pathology, New Delhi - 110 029
India
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jcrt.JCRT_632_19

 > Abstract 


Introduction: Dysembryoplastic neuroepithelial tumor (DNT) is a rare benign brain tumor predominantly involving children and young adults. Histologically, it corresponds to WHO Grade I tumors; however, it may masquerade aggressive neural tumors such as oligodendroglioma, oligoastrocytoma, pilocytic astrocytoma, and ganglioglioma. The literature on clinical, radiological, and pathological spectrum of DNT is described mostly in the form of case reports, with only a few case series reported till date.
Methods: A retrospective review of files with diagnosis of DNT (2016 to 2018) was made in the Department of Pathology, National Institute of Pathology, New Delhi. A total of ten cases were retrieved, and their clinical, radiological, and histopathological features were reviewed and studied. Special stains and immunohistochemistry were done, wherever required.
Results: The mean age was 14.8 (±7.9) years, with a male-to-female ratio of 1.5:1. The most common mode of presentation was recurrent, intractable seizures. The most common site of lesion was parietal lobe followed by temporal and frontal lobes of the brain. On histology, mucoid matrix admixed with floating neurons and oligodendrocyte-like cells was a consistent feature; however, the presence of specific glioneuronal elements was observed in only a few cases.
Conclusions: DNT is a benign, low-grade, nonrecurrent neuroepithelial neoplasm. It is important to differentiate this rare entity from other mimickers, as it is surgically curable and carries an excellent prognosis without the need for adjuvant chemotherapy and radiotherapy. The study helps to enrich the clinicopathological aspects of this rare but important entity.

Keywords: Childhood brain tumors, dysembryoplastic neuroepithelial tumor, epilepsy, partial seizures, oligodendroglioma



How to cite this URL:
Gupta P, Siraj F, Malik A, Shankar K B. Clinical and histopathological profile of dysembryoplastic neuroepithelial tumor: An experience from a tertiary care center. J Can Res Ther [Epub ahead of print] [cited 2020 Dec 3]. Available from: https://www.cancerjournal.net/preprintarticle.asp?id=298617




 > Introduction Top


Dysembryoplastic neuroepithelial tumor (DNT) is a rare, slow-growing benign brain neoplasm. As per the WHO 2016 classification, it is placed in the category of neuronal and mixed neuronal-glial tumors.[1] It predominantly affects children and young adults with slight male predilection and is most commonly seen in the temporal lobe followed by frontal lobe of the brain. Exact histogenetic profile of this entity is not clearly understood. The clinical and radiological profile is overlapping and not specific. Complete surgical excision is the treatment of choice with very good prognosis. There is no to very little risk of malignant transformation, metastasis, or tumor recurrence, and in most cases, complete resolution of seizures is seen after the surgical removal of tumor. It needs to be differentiated from mimickers such as oligodendroglioma, ganglioglioma, and other gliomas, all of which have different prognosis and treatment.[2],[3] Histopathology remains the gold standard for the diagnosis of DNT.

Aims and objectives

The objective of this study was to evaluate the clinical and histopathological profile of DNT at a tertiary care center in North India.


 > Methods Top


A retrospective review of files (2016–2018) with diagnosis of DNT was made in the Department of Pathology, National Institute of Pathology, New Delhi, India. All patients were operated in the Department of Neurosurgery, Safdarjung Hospital, New Delhi. The clinical, radiological, and histopathological features were studied. The specimens were fixed in neutral-buffered formalin and embedded in paraffin. Four to six micron thick sections were cut and stained with hematoxylin and eosin. Immunohistochemistry for glial fibrillary acidic protein (GFAP dil 1:100), synaptophysin (dil 1:100), S-100 protein (dil 1:100), CD-34 (dil 1:100), IDH1 (dil 1:100), and Ki-67 (dil 1:100) was done, wherever needed.


 > Results Top


A total of ten cases were studied [Table 1]. The mean age of patients was 14.8 (±7.9) years, with a male-to-female ratio of 1.5:1. Eight (80%) patients were diagnosed in the second decade of life, whereas the other two (20%) were detected in the fourth decade of life. Sudden onset of partial seizures with secondary generalization was the most frequent mode of presentation. The seizures were recurrent, partial complex, and refractory to conventional antiepileptic drugs. On neuroimaging, all the tumors were cortical in location; the most common site was parietal lobe followed by temporal and frontal lobes of the brain [Figure 1]. On gross pathological examination, most tumors were multinodular with soft-to-gelatinous consistency. On histopathology, the tumor showed a large number of oligodendrocyte-like cells admixed with floating neurons on a background of mucoid matrix and few scattered astrocytes. Features of dysplasia were not seen in the neuronal component which was confirmed by immunohistochemistry. There was no significant increase in mitotic figures, endothelial proliferation, or necrosis [Figure 2]. Based on the number of nodules, these were classified into three categories: six (60%) were multinodular and two (20%) cases showed a single cortical nodule. However, in two cases (20%), the composition of nodules and internodular areas was similar, exhibiting diffuse morphology. Foci of microcalcification were noted in only one (10%) case. To confirm the diagnosis, a panel comprising immunohistochemical stains including S-100, synaptophysin, CD-34, and GFAP was used in selected cases. On immunohistochemical staining, small oligodendrocyte-like cells stained positive for S-100 and negative for GFAP. GFAP was expressed by scattered astrocytes within and around the tumor, whereas floating neurons on mucoid matrix stained positive for synaptophysin and negative for CD-34 (owing to their nondysplastic nature in DNT) [Figure 3].
Table 1: Clinical and histopathological profile of the cases studied

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Figure 1: T2- weighted magnetic resonance image shows a cortex based hyperintense lesion in the right frontal region (arrow)

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Figure 2: Microphotograph showing (a) Subcortical presence of tumor (arrow), ×40, (b) and (c) Tumor cells in the mucoid matrix at ×100 and ×400 respectively, and (d) Foci of calcification (arrow), ×400 (H and E stain)

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Figure 3: Microphotograph showing immunohistochemical staining (a) CD-34-negative neuron (arrow), (b) synaptophysin positivity in neurons (arrow), (c) Ki-67 negativity in tumor cells (arrow), and (d) glial fibrillary acidic protein negativity in tumor cells

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 > Discussion Top


DNT was first described by Daumas-Duport et al. in 1988 as a mixed glial-neuronal neoplasm with a multinodular architecture, cortical supratentorial location, and association with focal cortical dysplasia.[4] The term DNT was proposed for this rare tumor due to the presence of a number of clinicopathological features suggestive of dysembryoplastic origin such as onset of seizures at an early age, presence of focal cortical dysplasia in adjacent brain cortex, and deformity of the overlying skull.[5],[6] DNT is a benign glioneuronal neoplasm classified in the WHO Grade 1 category of central nervous system tumors. Exact histogenesis of this rare tumor is not understood. It is reported at an incidence of 1.2% in patients under the age of 20 years and 0.2% in those aged >20 years.[7] The most common mode of presentation is recurrent, intractable seizures during childhood, which are refractory to conventional antiepileptic drugs. Partial complex seizures are the most frequent type, followed by generalized tonic–clonic, simple partial, and partial seizures with secondary generalization.[8],[9],[10]

DNT is typically described as a cortical and well-circumscribed tumor. The most common location is temporal lobe followed by frontal lobe of the brain. Other less common reported locations include caudate nucleus, septum pellucidum, trigonoseptal region, and cerebellum.[10] On radiology, magnetic resonance imaging shows discrete multicystic heterogeneous cortical lesions with cortical topography. The lesions are hypointense on T1-weighted images and hyperintense on T2-weighted images with typical absence of mass effect and perilesional edema.[11],[12]

There are three histological variants of DNT – simple, complex, and nonspecific.[13] Simple form consists of only specific glioneuronal elements, whereas complex form has specific glioneuronal elements in association with glial nodules and/or focal cortical dysplasia. The histological hallmark of DNT “specific glioneuronal element” is characterized by the presence of columnar bundles of axons lined by oligodendrocyte-like cells which are oriented at right angles to the cortical surface. The nonspecific form of DNT lacks characteristic histologic features such as specific glioneuronal elements and multinodularlity, and may, therefore, mimic gliomas such as pilocytic astrocytoma, with which it should be differentiated on the basis of clinicoradiological features. Eight (80%) cases showed complex form and two cases showed histology of simple form, which is the presence of specific glioneuronal elements only (20%). Mitosis, endothelial proliferation, and nuclear atypia are not commonly seen in classical DNT. However, it may be frequently noted in glial nodules of complex and nonspecific forms of DNT.[13] On immunohistochemistry, the small oligodendrocyte-like cells express S-100, OLIG-2, NOGO-A, but generally stain negative for GFAP. GFAP positivity is seen in scattered astrocytes, whereas floating neurons stain positive for synaptophysin, neurofilament, NeuN, neuron-specific enolase, MAP2, and Class III β-tubulin.[14] These groups of tumors are negative for IDH. In general, special stains and immunohistochemistry have little role in the diagnosis of DNT; however, these might be of help in differentiating it from mimickers, the critical ones being oligodendroglioma and ganglioglioma. The clinical, radiological, and pathological features of DNT in comparison to ganglioglioma and oligodendroglioma are summarized in [Table 2].[15]
Table 2: Comparison of clinical, radiological, and pathological features of ganglioglioma, oligodendroglioma, and dysembryoplastic neuroepithelial neoplasm

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Malignant transformation of DNT is extremely rare, with only a few cases described in the literature.[16],[17] The treatment of choice for DNT is complete surgical excision. It is a surgically curable neoplasm and carries an excellent prognosis without any need for adjuvant chemotherapy or radiotherapy. To the best of our knowledge, this is one of the largest studies on DNT from Indian subcontinent after the study by Sharma et al., which described clinicopathological spectrum of 32 DNT cases over a period of 12 years.[18] The mean age of presentation (14.7 years vs. 16.5 years) and male: female ratio (1.5:1 vs. 1.9:1) was comparable in the two studies. While the parietal lobe of the brain was the most frequently affected site in our study, the frontal lobe was reported as the most common site in the other study. The most common mode of presentation was recurrent seizures (complex partial, generalized tonic–clonic, and simple partial seizures) in both the studies. Histopathology showed multinodular appearance in both the series in majority of the cases (60% vs. 81%), with microscopic evidence of calcification in few cases (10% vs. 31%). No significant increase in mitoses and necrosis was seen in both the series; however, one of their cases showed a significant increase in vascular proliferation.


 > Conclusions Top


DNT is a rare, benign, low-grade, nonrecurrent neuroepithelial neoplasm which is classified as WHO Grade I neoplasm. It is important to differentiate this rare tumor from other mimickers (such as ganglioglioma and oligodendroglioma), as it is surgically curable and carries an excellent prognosis without the need for adjuvant chemotherapy and radiotherapy. The present study helps to enrich the existing sparse literature on clinical and pathological profile of DNT.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
 > References Top

1.
Louis DN, Perry A, Reifenberger G, von Deimling A, Figarella-Branger D, Cavenee WK, et al. The 2016 World Health Organization Classification of tumors of the central nervous system: A summary. Acta Neuropathol 2016;131:803-20.  Back to cited text no. 1
    
2.
Huse JT, Snuderl M, Jones DT, Brathwaite CD, Altman N, Lavi E, et al. Polymorphous low-grade neuroepithelial tumor of the young (PLNTY): An epileptogenic neoplasm with oligodendroglioma-like components, aberrant CD34 expression, and genetic alterations involving the MAP kinase pathway. Acta Neuropathol 2017;133:417-29.  Back to cited text no. 2
    
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Rheims S, Rubi S, Bouvard S, Bernard E, Streichenberger N, Guenot M, et al. Accuracy of distinguishing between dysembryoplastic neuroepithelial tumors and other epileptogenic brain neoplasms with [11C] methionine PET. Neuro Oncol 2014;16:1417-26.  Back to cited text no. 3
    
4.
Daumas-Duport C, Scheithauer BW, Chodkiewicz JP, Laws ER Jr, Vedrenne C. Dysembryoplastic neuroepithelial tumor: A surgically curable tumor of young patients with intractable partial seizures. Report of thirty-nine cases. Neurosurgery 1988;23:545-56.  Back to cited text no. 4
    
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Whittle IR, Dow GR, Lammie GA, Wardlaw J. Dsyembryoplastic neuroepithelial tumour with discrete bilateral multifocality: Further evidence for a germinal origin. Br J Neurosurg 1999;13:508-11.  Back to cited text no. 5
    
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Takahashi A, Hong SC, Seo DW, Hong SB, Lee M, Suh YL. Frequent association of cortical dysplasia in dysembryoplastic neuroepithelial tumor treated by epilepsy surgery. Surg Neurol 2005;64:419-27.  Back to cited text no. 6
    
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Rosemberg S, Vieira GS. Dysembryoplastic neuroepithelial tumor. An epidemiological study from a single institution. Arq Neuropsiquiatr 1998;56:232-6.  Back to cited text no. 7
    
8.
Chang EF, Christie C, Sullivan JE, Garcia PA, Tihan T, Gupta N, et al. Seizure control outcomes after resection of dysembryoplastic neuroepithelial tumor in 50 patients. J Neurosurg Pediatr 2010;5:123-30.  Back to cited text no. 8
    
9.
Babini M, Giulioni M, Galassi E, Marucci G, Martinoni M, Rubboli G, et al. Seizure outcome of surgical treatment of focal epilepsy associated with low-grade tumors in children. J Neurosurg Pediatr 2013;11:214-23.  Back to cited text no. 9
    
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Fernandez C, Girard N, Paz Paredes A, Bouvier-Labit C, Lena G, Figarella-Branger D. The usefulness of MR imaging in the diagnosis of dysembryoplastic neuroepithelial tumor in children: A study of 14 cases. AJNR Am J Neuroradiol 2003;24:829-34.  Back to cited text no. 10
    
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Stark J, Friedman E, Thompson S, Von Allmen G, Bhattacharjee M, Tandon N. Atypical presentations of dysembryoplastic neuroepithelial tumors. Epilepsia 2018;59:e14-7.  Back to cited text no. 11
    
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Stanescu Cosson R, Varlet P, Beuvon F, Daumas Duport C, Devaux B, Chassoux F, et al. Dysembryoplastic neuroepithelial tumors: CT, MR findings and imaging follow-up: A study of 53 cases. J Neuroradiol 2001;28:230-40.  Back to cited text no. 12
    
13.
Daumas-Duport C, Scheithauer BW, Chodkiewicz JP, Laws ER Jr., Vedrenne C. Dysembryoplastic neuroepithelial tumor: A surgically curable tumor of young patients with intractable partial seizures. Report of thirty-nine cases. Neurosurgery 1988;23:545-56.  Back to cited text no. 13
    
14.
Suh YL. Dysembryoplastic Neuroepithelial Tumors. J Pathol Transl Med 2015;49:438-49.  Back to cited text no. 14
    
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Louis DN, Ohgaki K, Wiestler OD, Cavenee WK, Ellison D, Figarella-Branger D. WHO classification of tumours of the central nervous system. Revised 4th ed. Lyon: IARC. ISBN 978-92-832-4492-9; 2016.  Back to cited text no. 15
    
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Gonzales M, Dale S, Susman M, Nolan P, Ng WH, Maixner W, et al. Dysembryoplastic neuroepithelial tumor (DNT)-like oligodendrogliomas or Dnts evolving into oligodendrogliomas: Two illustrative cases. Neuropathology 2007;27:324-30.  Back to cited text no. 16
    
17.
Rushing EJ, Thompson LD, Mena H. Malignant transformation of a dysembryoplastic neuroepithelial tumor after radiation and chemotherapy. Ann Diagn Pathol 2003;7:240-4.  Back to cited text no. 17
    
18.
Sharma MC, Jain D, Gupta A, Sarkar C, Suri V, Garg A, et al. Dysembryoplastic neuroepithelial tumor: A clinicopathological study of 32 cases. Neurosurg Rev 2009;32:161-9.  Back to cited text no. 18
    


    Figures

  [Figure 1], [Figure 2], [Figure 3]
 
 
    Tables

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