sign in sign up
<<
Home , Central neurocytoma, Fibrillary astrocytoma, Ganglioglioma

Copyright © 2009, Barrow Neurological Institute

Dysembryoplastic Neuroepithelial Tumor: A Review n 1988 Dumas-Duport et al. first used Mark Garrett, MD the term dysembryoplastic neuroepi- † I Jennifer Eschbacher, MD thelial tumor to describe low-grade tu- Peter Nakaji, MD mors found in young patients with in- tractable partial .4 In 1993 the Most DNETs are benign, low-grade lesions. However, a small number appear to distinct pathological entity known as have the potential for malignant transformation. We report a patient with a biopsy- DNET was given a place in the WHO proven DNET with features of an ogliodendroglioma and review the clinical fea- classification of brain tumors as a grade I tures of DNETs and their potential for malignant transformation. tumor of neuroepithelial origin.3,10,11 Key Words: dysembryoplastic neuroepithelial tumor, malignant transfor- Many studies have reported successful mation surgical management of this low-grade tumor in the treatment of refractory ep- ilepsy. We report the case of a young man who experienced possible activ- ity and was found to have a biopsy- proven DNET.

Case Report A 30-year-old man with no significant medical history experienced the sudden onset of right facial numbness, which re- solved completely within hours. When questioned he stated that he had experi- enced occasional sensory abnormalities in his right arm and leg throughout the previous year. Computed tomographic scans showed a nonhemorrhagic hypo- dense lesion in the mesial temporal lobe, thalamus, and posterior limb of the inter- nal capsule. The lesion was hyperintense on T2-weighted MR images, hypoin- tense on T1-weighted images, and non- enhancing (Fig. 1). Based on the imag- ing studies, the diagnosis was unclear and we recommended that the patient un- dergo a needle biopsy to guide further treatment. Abbreviations Used: DNET, dysembryoplastic neuroepithelial tumor; An intraoperative frozen specimen was MR, magnetic resonance; SGNE, specific glial neuronal element; WHO, World Health Organization interpreted as either an oligodendroglio- ma or a DNET. The final pathological Divisions of Neurological Surgery and †Neuropathology, Barrow Neurological Institute, St. evaluation described nodular, neoplastic, Joseph’s Hospital and Medical Center, Phoenix, Arizona glioneuronal elements with oligoden-

BARROW QUARTERLY • Vol. 24, No. 1 • 2008 9 Garrett et al: Dysembryoplastic Neuroepithelial Tumor: A Review

droglial-like features and areas of micro- spite being seizure free, one patient com- presence of cortical dysplasia implies that cystic change and hyalinization. On im- mitted suicide 3 months after surgery. these lesions occur during cortical for- mediate postoperative MR imaging, a The second patient received whole brain mation and are not that arise small hemorrhage was visible in the radiation and polychemotherapy and was within normally developed cortex. The tumor bed. The patient suffered no ad- found to have extensive radionecrosis at actual origins of these indolent tumors verse events and was discharged home autopsy. and whether they are truly neoplastic are neurologically intact after a brief period of Although the report by Dumas-Du- still debated. observation. Interestingly, on follow-up port et al. is considered the first to de- imaging the lesion had partially regressed. scribe these tumors and their specific his- Classification We hypothesized that the compressive tology,4 they did credit Cavanagh of The original paper describing DNETs forces of the intraoperative hemorrhage London who published an article in focused on the theory that these tumors had partially obliterated the tumor. 1958 called, On Certain SmallTumors En- had embryonal origins. However, it was countered in the Temporal Lobe.1 The mul- clear that their clinical course differed tinodular lesions that Cavanagh de- from that of tumors classified as embry- Discussion scribed were found while he performed onal tumors of neuroepithelial origin. In 1988 Dumas-Duport and col- temporal lobectomies for temporal lobe Tumors listed in the WHO classification leagues first characterized DNETs when . Cavanagh described the lesions scheme as embryonal are all considered they described neuroepithelial tumors in as hamartomas but opined that areas of WHO grade IV lesions (Table 1).12 Thus 39 patients with medically intractable “early neoplastic change” were suscep- the term dysembryoplastic was coined to partial complex seizures.4 Their cohort tible to malignant transformation into indicate both the origin of these tumors was a combination of epilepsy patients . Dumas-Duport et al.4 consid- and the observation that they share fea- undergoing surgery at St. Anne Hospi- ered the tumor to be at least partially tures with less aggressive, dysplastic le- tal in France and at the Mayo Clinic in neoplastic and argued that these lesions sions. However, the authors did not think Rochester, Minnesota. They noted a dis- formed during embryonic development. that the term was an entirely accurate de- tinct cortical tumor with multinodular Dumas-Duport’s argument that scription of these tumors, which share architecture, associated cortical dysplasia, DNETs had embryonal origins was some similar histologic features with neo- and both neuronal and glial elements. four-fold. First, these tumors exhibited plastic lesions. Nonetheless, the term dys- After resection their patients were fol- multiple cell lineages that could arise embryoplastic still served to denote the lowed a mean of 9 years. Their outcomes from multipotent cells present during predominantly benign clinical course of were excellent. Of the 39 patients, 30 early development. Second, these tu- these tumors. were seizure free, 4 experienced only mors manifest early in life. Third, there In 1993 DNETs were placed in the rare seizures, and the number of seizures is often an adjacent bone deformity, WHO classification scheme was reduced significantly in the remain- which suggests that the tumors are long as a neuronal/mixed glial-neuronal tumor ing3 patients. Two patients died. De- standing with an early onset. Finally, the of neuroepithelial origin.3,10,11 They are

A BC

Figure 1. (A) Axial T2-weighted MR image shows a hyperintense lesion in the mesial temporal lobe. Axial T1-weighted MR images (B) with and (C) without contrast show a hypointense lesion that does not enhance.

10 BARROW QUARTERLY • Vol. 24, No. 1 • 2008 Garrett et al: Dysembryoplastic Neuroepithelial Tumor: A Review

Table 1. Tumors classified as embryonal Table 2. Tumors classified as neuronal within category of tumors with neuroepi- and mixed neuronal-glial tumors within thelial origins.† 12 category of tumors with neuroepithelial origins12 Desmoplastic/nodular medulloblastoma Dysplastic gangliocytoma of cerebellum (Lhermitte-Duclos) Medulloblastoma with extensive nodularity Desmoplastic infantile / Anaplastic medulloblastoma Dysembryoplastic neuroepithelial tumor Large cell medulloblastoma Gangliocytoma Ganglioglioma CNS primitive neuroectodermal tumor Anaplastic ganglioglioma CNS Central CNS Extraventricular neurocytoma Cerebellar liponeurocytoma Ependymoblastoma Papillary glioneuronal tumor Atypical teratoid/rhabdoid tumor Rosette-forming glioneuronal tumor of fourth ventricle †According to the 2007 WHO classification of brain tumors.

classified as Grade I tumors along with Imaging Features treatment of epilepsy was 10.8 years. the other low-grade neuronal tumors On neuroimaging DNETs are corti- They found that 66.7% of their patients such as and gangliocy- cal lesions with little mass effect and a achieved Engel Class I outcomes, indi- tomas (Table 2).12 Although still debat- predilection for the temporal lobes. On cating that they were free of disabling sei- ed, most contemporary neurosurgeons computed tomography DNETs are typ- zures. In the reviewed series of surgical consider these tumors to be frankly neo- ically well-demarcated, hypodense, cor- outcomes for DNETs, 52.4 to 90% of plastic. tical lesions that can be associated with the patients achieved Engel Class I. In- deformation of the overlying skull. In a terestingly, the results that they had pre- Histology radiological study, fewer than 20% con- viously reported for the same group of Three histologic forms of DNET have tained calcifications in contrast to gangli- patients at a mean of 2.7 years of follow- been described: complex, simple, and ogliomas, which had a much higher up were predictive of their long-term nonspecific.2 The complex form (Fig. 2), rate.16 MR images often show a solid and outcomes. Their results, combined with which is the type originally described by cystic mass with the cystic portions ap- those of other studies, led them to con- Dumas-Duport et al.,4 consists of SGNE pearing slightly more intense than cere- clude that a patient who is seizure free 3 (Fig. 3), glial multinodular architecture, brospinal fluid. A cystic signal pattern is years after resection of a DNET can be and associated cortical dysplasia. The not specific to DNET; the pattern is also considered cured. nodular component of a DNET contains found in other tumors frequently associ- Nonetheless, DNETs can recur as both glial and neuronal components and ated with epilepsy such as ganglioglio- Nolan et al. reported in 2004.13 Of 26 can resemble both gliomas and ganglio- mas and gliomas. The solid components children who underwent surgical resec- gliomas. The neuronal component often often appear multinodular, hypointense tion of their tumor for seizure control, 3 consists of “floating” in a ba- on T1-weighted MR images, hyperin- demonstrated a recurrence within 1 to 5 sophilic mucinous matrix (Fig. 4). The tense on T2-weighted MR images, and years. In this series, the rate of incomplete axons are surrounded by “tumoral” oli- occasionally weakly enhancing.6,17 resection was high (63%), and all patients godendrocyte-like cells. These cells ex- who experienced a recurrence showed hibit oligodendroglial features, including Clinical Course some degree of residual tumor on post- prominent perinuclear halos (Fig. 5). The Consistent with their original de- operative imaging. simple form, which was also described by scription, DNETs are tumors associated Dumas-Duport et al.,4 consists only of the with epilepsy in young adults. In 2006 Potential for Malignant Transforma- SGNE. The nonspecific form is more Chan et al. reported the outcomes of pa- tion controversial: It has neither the SGNE tients who underwent surgical removal of In published series the clinical course nor the multinodular architecture. It re- a DNET for seizure control and reviewed of DNETs has been stable. Only rarely sembles a low-grade astrocytoma but has the published series of DNETs.2 The does diagnostic imaging reveal a post- clinical and radiological features more mean long-term outcome of 18 patients operative recurrence. Recent case re- consistent with a DNET.5 with DNETs surgically resected for the ports, however, have shown that these

BARROW QUARTERLY • Vol. 24, No. 1 • 2008 11 Garrett et al: Dysembryoplastic Neuroepithelial Tumor: A Review

Figure 2. Schematic representation of the complex form of Figure 3. Schematic representation of the SGNE of a DNET show- DNET. ing the neuronal elements that form the columnar structures per- pendicular to the cortical surface.

lesions may undergo malignant change. a . After this procedure the mediotemporal lobe.8 The patient In 2000 Hammond et al. reported the patient underwent a 6-week course of opted for conservative management first malignant transformation of a . Three years later, his sei- until the tumor developed contrast en- DNET that had been surgically resect- zure activity resumed and a tumor re- hancement after 15 years. Surgical pa- ed.7 The patient, a 29-year-old man currence was found. The patient un- thology revealed a DNET without who suffered from partial seizures, had a derwent a third surgery, and the atypical changes. These findings sug- nonenhancing lesion in his left frontal pathologic diagnosis of the lesion was gest that on imaging these tumors can cortex. He first underwent surgery in consistent with progression to an show progression that does not neces- 1984, when his tumor was labeled as a . sarily imply malignant transformation. “.” The surgeons Three other studies also suggest the Because DNETs have only been dis- reported subtotal resection. The patient potential for transformation or progres- covered within the last 20 years, their received no radiation or chemotherapy, sion of a DNET. Josan et al. reported a natural history is not yet completely de- but 11 years later his seizures recurred. 3-year-old girl with seizures who was fined. The literature, however, suggests MR imaging showed a partially enhanc- found to have a DNET. She was man- that these lesions hold the potential for ing cystic lesion. After repeat resection aged conservatively.9 At the age of 14 malignant change. It is possible that the the pathology was confirmed as a grade years, follow-up MR imaging showed discovery of a higher-grade lesion with- IV astrocytoma. Retrospective histolog- a large cystic lesion, which was resected. in a histologically proven DNET is sim- ical review of the initial tumor found it to The lesion was diagnosed as a pilocytic ply coincidental. Given that some be a DNET with SGNEs, glial nodules, astrocytoma within a surrounding DNETs display high mitotic activity and associated cortical dysplasia. DNET. In a 9-year-old with seizures, based on the Ki-67 proliferation label- In 1974 Rushing et al. described a Sampetrean et al. described a DNET ing index, it seems likely that these tu- 14-year-old boy who underwent sub- with a small ring-enhancing core; the mors arise from neoplastic cells within total resection of a tempoparietal mass size of the lesion tripled in 3 months.15 the DNET itself.2 These findings sup- for the treatment of epilepsy.14 The pa- Surgical resection confirmed the diag- port the argument that a DNET is at thology, which was originally diagnosed nosis of DNET. Five years after surgery, least partially a neoplastic lesion, al- as a “mixed ,” was later the patient remained seizure free with- though its nature is still debated. Al- shown to be a DNET. The patient re- out a recurrence. Jensen et al. reported though some of these tumors progress, ceived postoperative . a 46-year-old patient who had med- most are stable and rarely recur after sur- One year later MR imaging showed the ically refractory seizures with a nonen- gery. Possibly, a subset of these tumors formation of a cyst that was drained via hancing, low-intensity lesion in the yet to be identified has the propensity

12 BARROW QUARTERLY • Vol. 24, No. 1 • 2008 Garrett et al: Dysembryoplastic Neuroepithelial Tumor: A Review

Figure 4. Low-power view of -like cells with promi- Figure 5. High-power view of a floating (hematoxylin and nent perinuclear halos embedded in a background of abundant ba- eosin, original magnification x400). sophilic mucin (hematoxylin and eosin, original magnification x200). for malignant transformation. When 11. Louis DN, Ohgaki H, Wiestler OD, et al: The 2007 References WHO classification of tumours of the central ner- the natural history of these tumors is vous system. Acta Neuropathol 114:97-109, 1. Cavanagh JB: On certain small tumours en- better defined with longer follow-up, 2007 countered in the temporal lobe. Brain 81:389- we also may find that a greater percent- 405, 1958 12. Louis DN, Ohgaki H, Wiestler OD, et al: WHO classification of tumours of the central nervous age progress to more aggressive lesions 2. Chan CH, Bittar RG, Davis GA, et al: Long-term system. IARC: Lyon, France, 2007 than previously thought. For now these seizure outcome following surgery for dysem- bryoplastic neuroepithelial tumor. J Neurosurg 13. Nolan MA, Sakuta R, Chuang N, et al: Dysem- reports demonstrate the importance of 104:62-69, 2006 bryoplastic neuroepithelial tumors in childhood: Long-term outcome and prognostic features. regular follow-up, both clinical and ra- 3. Dumas-Duport C: Dysembryoplastic neuroepi- Neurology 62:2270-2276, 2004 diographic, for patients who harbor thelial tumours. Brain Pathol 3:283-295, 1993 14. Rushing EJ, Thompson LD, Mena H: Malignant 4. Dumas-Duport C, Scheithauer BW, Chodkiewicz DNETs. transformation of a dysembryoplastic neuroepi- JP, et al: Dysembryoplastic neuroepithelial thelial tumor after radiation and chemotherapy. tumor: a surgically curable tumor of young pa- Ann Diagn Pathol 7:240-244, 2003 tients with intractable partial seizures. Report of Conclusion thirty-nine cases. 23:545-556, 15. Sampetrean O, Maehara T, Arai N, et al: Rapidly 1988 growing dysembryoplastic neuroepithelial tumor: Since their discovery in 1988, much Case report. Neurosurgery 59:E1337-E1338, 5. Dumas-Duport C, Varlet P, Bacha S, et al: Dys- 2006 has been learned about the characteristics embryoplastic neuroepithelial tumors: Nonspe- and clinical course of DNETs. It is wide- cific histological forms—a study of 40 cases. J 16. Shin JH, Lee HK, Khang SK, et al: Neuronal tu- ly accepted that patients with seizures at- Neurooncol 41:267-280, 1999 mors of the : Radiologic findings and pathologic correlation. Radio- 6. Fernandez C, Girard N, Paz PA, et al: The use- tributable to these lesions are excellent graphics 22:1177-1189, 2002 fulness of MR imaging in the diagnosis of dys- surgical candidates who achieve good embryoplastic neuroepithelial tumor in children: 17. Stanescu CR, Varlet P, Beuvon F, et al: Dysem- outcomes and low recurrence rates with- A study of 14 cases. AJNR Am J Neuroradiol bryoplastic neuroepithelial tumors: CT, MR find- 24:829-834, 2003 ings and imaging follow-up: A study of 53 cases. out the use of adjunct therapies. Al- J Neuroradiol 28:230-240, 2001 though most DNETs are benign, low- 7. Hammond RR, Duggal N, Woulfe JM, et al: Ma- lignant transformation of a dysembryoplastic grade lesions, it is becoming increasingly neuroepithelial tumor. Case report. J Neurosurg apparent that a small number will progress 92:722-725, 2000 to more aggressive lesions. Consequent- 8. Jensen RL, Caamano E, Jensen EM, et al: De- velopment of contrast enhancement after long- ly, we recommend that these patients term observation of a dysembryoplastic neuro- have regular follow-up examinations to epithelial tumor. J Neurooncol 78:59-62, 2006 identify progression at its early stages. As 9. Josan V, Smith P, Kornberg A, et al: Development the natural history of DNETs is better of a in a dysembryoplastic neuroepithelial tumor. Case report. J Neurosurg defined, it should become increasingly 106:509-512, 2007 possible to tailor treatments and follow- 10. Kleihues P, Burger PC, Scheithauer BW: The new up regimens to individual patients. WHO classification of brain tumours. Brain Pathol 3:255-268, 1993

BARROW QUARTERLY • Vol. 24, No. 1 • 2008 13