Atypical Extraventricular Neurocytoma

Article · October 2011with40 Reads
DOI: 10.3340/jkns.2011.50.4.381 · Source: PubMed
The authors report a case of atypical extraventricular neurocytoma (EVN) transformed from EVN which had been initially diagnosed as an oligodendroglioma 15 years ago. An 8-year-old boy underwent a surgical resection for a right frontal mass which was initially diagnosed as oligodendroglioma. When the tumor recurred 15 years later, a secondary operation was performed, followed by salvage gamma knife treatment. The recurrent tumor was diagnosed as an atypical EVN. The initial specimen was reviewed and immunohistochemistry revealed a strong positivity for synaptophysin. The diagnosis of the initial tumor was revised as an EVN. The patient maintained a stable disease state for 15 years after the first operation, and was followed up for one year without any complications or disease progression after the second operation. We diagnosed an atypical extraventricular neurocytoma transformed from EVN which had been initially diagnosed as an oligodendroglioma 15 years earlier. We emphasize that EVN should be included in the differential diagnosis of oligodendroglioma.
ted to our hospital in 1993. At that time, he had one year histo-
ry of headache. No focal neurologic decit was found on ad-
mission. Brain computed tomography scans revealed a high-
density mass in the frontal lobe with midline shiing. Magnetic
resonance (MR) images showed a heterogeneous enhancing
mass in the frontal lobe apart from the lateral ventricle. The
mass was yellow and friable. It was neither hemorrhagic nor
necrotic. The tumor margin was ill-defined. Immumohisto-
chemistry for neurone specic enolase and chromogranin was
negative. e initial diagnosis of the tumor was oligodendrogli-
oma. He was discharged from the hospital without neurologic
decits or additional treatment. e patient was followed yearly
with brain MR imaging. During the follow up periods, the mass
had showed no specic changes and the patient had done well
without any neurologic deterioration.
e MR images taken 15 years aer the initial surgery showed
a solid enhancing lesion of high signal intensity on T2-weight-
ed MR images and low signal intensity on T1-weighted MR im-
ages in the right frontal area. e new lesion was thought to be
a recurrent tumor with malignant transformation (Fig. 1) because
MR spectroscopy image of the lesion showed the elevation of
choline and lactate peaks, the inversion of a lactate peak at long
TE sequence and a decrease in N-acetyl aspartate. 18F-FDG
positron emission tomography images showed that the mass
was hypermetabolic in its inferior portion. A second operation
was performed and a hard calcied mass with a yellow and fria-
ble cystic portion was found. e mass was subtotally removed
as the attachment sites to the internal capsule and basal ganglia
Parenchymal neurocytoma remote from the ventricle, called
extraventricular neurocytoma (EVN),” was reported in 199219).
It shares similar biological behaviors and histopathological
characteristics with central neurocytoma. The World Health
Organization (WHO) classication of brain tumors revised in
2007 includes EVN as a single pathological diagnosis and pro-
poses an ICD-O code identical to that of central neurocytoma8).
e neurocytoma, which exhibited a MIb-1 labeling index of
>2%, or atypical histological features, increased mitosis, focal
necrosis and vascular proliferation, was classied as atypical2, 18)
Some of these cases could have been misdiagnosed as oligoden-
drogliomas due to similarities of clinical and histological fea-
tures and the relative imprecision of neuroradiological diagnostic
tools available at that time. Here, we report a case of atypical EVN
that was diagnosed and treated as oligodendroglioma in 1993.
An 8-year-old boy with convulsive seizure attack was admit-
J Korean Neurosurg Soc 50 :
381-384, 2011
Copyright © 2011 The Korean Neurosurgical Society
Print ISSN 2005-3711 On-line ISSN 1598-7876
Atypical Extraventricular Neurocytoma
Hyunho Choi, M.D.,1 Sung-Hye Park, M.D.,2 Dong Gyu Kim, M.D.,1 Sun Ha Paek, M.D., Ph.D.1
Departments of Neurosurgery,
Cancer Research Institute, Ischemic/Hypoxic Disease Institute,
Seoul National University College of Medicine, Seoul, Korea
The authors report a case of atypical extraventricular neurocytoma (EVN) transformed from EVN which had been initially diagnosed as an oligoden-
droglioma 15 years ago. An 8-year-old boy underwent a surgical resection for a right frontal mass which was initially diagnosed as oligodendroglio-
ma. When the tumor recurred 15 years later, a secondary operation was performed, followed by salvage gamma knife treatment. The recurrent tu-
mor was diagnosed as an atypical EVN. The initial specimen was reviewed and immunohistochemistry revealed a strong positivity for
synaptophysin. The diagnosis of the initial tumor was revised as an EVN. The patient maintained a stable disease state for 15 years after the first
operation, and was followed up for one year without any complications or disease progression after the second operation. We diagnosed an atypical
extraventricular neurocytoma transformed from EVN which had been initially diagnosed as an oligodendroglioma 15 years earlier. We emphasize
that EVN should be included in the differential diagnosis of oligodendroglioma.
Key Words : Atypical extraventricular neurocytoma ∙ Differential diagnosis ∙ Oligodendroglioma ∙ Recurrence.
Case Report
Received : June 21, 2011
Revised : August 24, 2011
Accepted : October 10, 2011
Address for reprints : Sun Ha Paek, M.D., Ph.D.
Department of Neurosurgery, Cancer Research Institute, Ischemic/Hypoxic
Disease Institute, Seoul National University College of Medicine,
101 Daehak-ro, Jongno-gu, Seoul 110-744, Korea
Tel : +82-2-2072-3993, Fax : +82-2-744-8459
E-mail :
J Korean Neurosurg Soc 50 | October 2011
ulum cisternae, dense bodies and glycogen particles. ere were
abundant cell processes containing neurosecretory-type dense
granules, microtubules and glycogen particles with well devel-
oped synapses with accompanying synaptic vesicles (Fig. 2). Fluo-
rescence in situ hybridization showed that chromosomes 1p and
19q were intact. Immunohistochemistry revealed a high Ki-67
labeling index of 16.8%. e pathologic
result was consistent with atypical extra-
ventricular neurocytoma. To confirm
the previous pathologic diagnosis, we re-
examined the specimen taken from the
first operation. Immunohistochemistry
revealed a strong immunoreactivity for
synaptophysin which was consistent
with EVN.
The patient recovered without any
neurologic deficits after surgery. Fol-
lowed-up MR images showed residual
tumor in the right frontal lobe, which
was treated with gamma knife. Follow-
up brain MR images taken at 12 months
aer gamma knife radiosurgery showed
no further growth of the residual tumor
and the patient lived well without any
adverse eect.
EVN is a tumor of the central ner-
vous system that rarely occurs in young
were le alone.
Pathologic examination revealed mitosis in 2 of 10 high power
elds and electron microscopy of the ultrathin sections showed
round to oval neoplastic cells. Tumor cell nuclei were relatively
uniform with marginated chromatin, and cytoplasmic organelles
were sparse and include a few strands of rough endoplasmic retic-
Fig. 1. A : Preoperative T2-weighted image from the surgical specimen at the first operation dem-
onstrates heterogeneous signal intensity in a right frontal mass. B : Contrast-enhanced T1-weighted
image shows subtle peripheral enhancement 13 years after the first operation. C : T2-weighted im-
age taken 15 years after the first operation demonstrates high signal intensity mass lesion in the
right frontal lobe. D : Contrast-enhanced T1-weighted image taken 15 years after the first operation
shows marked enhancement. E : 18F-FDG brain positron emission tomography shows a hypermet-
abolic lesion in the right inferior frontal lobe.
Fig. 2. A : H&E staining shows round to oval, small uniform cells from the specimen taken at the first operation (Magnification; ×200, H&E stain). B :
Immunostaining for synaptophysin demonstrates a strong positivity in the specimen taken at the first operation (Magnification; ×400, synaptophysin
immunochemical stain). C : Small round cells with large clear cytoplasms and round nuclei (Magnification; ×400, H&E stain). D : A strong positivity for
synaptophysin is seen (Magnification; ×400, synaptophysin immunochemical stain). E : Electron microscope shows that the cytoplasmic organelles
are sparse and include a few strands of RER cisternae, dense bodies and glycogen particles (Magnification; ×7,000, electron microscopy).
Recurrent Extraventricular Neurocytoma | H Choi, et al.
e initial diagnosis of oligodendroglioma was made without
immunochemistry which may have been helpful in dierentiat-
ing between oligodendroglioma and EVN. erefore, immuno-
histochemisty should be performed in cases which require dif-
ferential diagnosis of these two entities.
e treatment of atypical neurocytoma is not well established.
Rades et al.14) have documented that complete resection would
provide better local control and survival rates than incomplete
resection and that local control and survival rates are improved
with postoperative radiation therapy in cases of incomplete re-
section. Since there have been only a few reports on the out-
comes of chemotherapy in patients with atypical neurocytoma1),
the therapeutic effect of chemotherapy remains uncertain. In
our case, complete resection was not performed because of the
possibility of injury to the basal ganglia and internal capsule. To
obtain a better local control and a higher survival rate, addition-
al gamma knife (GK) stereotactic radiosurgery (SRS) was per-
formed. Although central neurocytoma (CN) has benign bio-
logical behavior, conventional radiotherapy has been eective to
control residual CN after surgery7,11). However, Some authors
criticized conventional radiotherapy could induce delayed com-
plication5,9,10). Rades and Schild15) reported the outcome of CN
aer incomplete resection followed by conventional radiothera-
py or GK SRS. ey concluded that the GK SRS could be the al-
ternative treatment option for the residual CN. Kim et al.6) re-
ported the long-term outcome of GK SRS with CN. ey treated
CN with GK SRS as a primary or a secondary postoperative thera-
py. e GK SRS could be a primary or secondary postoperative
treatment, and especially, it could be a initial treatment for the
CN in a small size mass that the longitudinal diameter was be-
low 3 cm. EVN has the same pathologic feature with CN, so GK
SRS could be a attractive treatment option of EVN in a small size.
EVN is a benign tumor that is dicult to diagnose because it
shares common clinical and histologic features with oligoden-
droglioma. ere is the possibility that EVN was misdiagnosed
in the past as oligodendroglioma because diagnostic tools were
underdeveloped and the disease entity of EVN was not clearly es-
tablished. Since these two tumors have dierent prognoses and
treatment outcomes, their dierential diagnosis is very important
to establish an appropriate treatment plan. Immunochemisty
plays an important role in the differential diagnosis between
EVN and oligodendroglioma.
1. Brandes AA, Amistà P, Gardiman M, Volpin L, Danieli D, Guglielmi B,
et al. : Chemotherapy in patients with recurrent and progressive central
neurocytoma. Cancer 88 : 169-174, 2000
2. Brat DJ, Scheithauer BW, Eberhart CG, Burger PC : Extraventricular
neurocytomas : pathologic features and clinical outcome. Am J Surg
Pathol 25 : 1252-1260, 2001
3. Choi YS, Song YJ, Huh KY, Kim KU : Malignant variant of the central
people. is tumor is usually located in the periventricular pa-
renchyma with benign nature. In 1997, Giangaspero et al.2) re-
ported the rst case of a tumor that mimicked central neurocy-
toma but was located in the extraventricular area. The 2007
WHO classication included EVN as a brain tumor entity to
distinguish it from intraventricular neurocytoma8). It is a diag-
nostic challenge to dierentiate oligodendroglioma from EVN
because of its similarities in clinical and histological ndings2,3).
Sgouros et al.17) have shown that tumors previously diagnosed
as oligodendroglioma can be reclassied as central neurocyto-
mas, a new entity. Perry et al.13) have suggested a potential histo-
genic link between oligodendroglioma and EVN. EVN and oli-
godendroglioma share common histological features such as
round, regular nuclei with clear cytoplasms, although ganglion-
ic dierentiation is more common in EVN. Immunochemistry
is needed to dierentiate EVN from oligodendroglioma. EVN
shows a strong immunoreactivity for synaptophysin in the neu-
ropil and perinuclear cytoplasm, whereas oligodendroglioma
usually shows negative reactions. Perry et al.12) reported that
chromosome 1p loss occurs in 40-92% of the tumor, and 19q
loss in 50-80%. Loss of chromosome 1p/19q has not been de-
tected in EVN, which provides a clue to dierentiate it from oli-
godendrogliomas. Fujisawa et al.4) mentioned that allelic loss on
1p and 19q can be useful for making a dierential diagnosis. In
our case, the patient was rst diagnosed with a oligodendrogli-
oma by light microscopic examination and underwent subtotal
resection without additional treatment. He survived for 15
years without neurological decits and maintained a stable dis-
ease state without adjuvant therapy. Follow-up MR imaging
showed a recurrent tumor just beside the pre-existing residual
mass in the right frontal area. Because histological ndings were
consistent with atypical EVN, immunohistochemistry was per-
formed, which revealed a strong immunoreactivity for synapto-
physin, being consistent with EVN. It is thought that the dier-
ential diagnosis between EVN and oligodendroglioma was not
established and the tumor resected in 1993 under a misdiagnosis
of oligodendroglioma. We concluded that the tumor was actually
EVN and the residual mass underwent malignant transforma-
tion to atypical EVN aer 15 years. Sakurada et al.16) reported a
case of EVN that was initially diagnosed as oligodendroglioma
but was later diagnosed as EVN from the surgical specimen tak-
en at the second operation for the tumor which recurred 25 years
later. When the surgical specimen taken at the rst operation was
reexamined, the specimen was consistent with EVN. Although
his patient survived for 25 years, she died 4 months aer the
second operation. In our case, the patient maintained a stable
disease state for 15 years aer the rst operation, and was fol-
lowed up for 1 year without any complications and disease pro-
gression aer the second operation. e neurocytoma, which
exhibited a MIb-1 labeling index of >2%, or atypical histologi-
cal features, increased mitosis, focal necrosis and vascular pro-
liferation, was classied as atypical2,18). is is the rst reported
case of an EVN with malignant transformation into atypical EVN.
J Korean Neurosurg Soc 50 | October 2011
term outcome of conventional radiation therapy for central neurocyto-
ma. J Neurooncol 90 : 25-30, 2008
12. Perry A, Fuller CE, Banerjee R, Brat DJ, Scheithauer BW : Ancillary
FISH analysis for 1p and 19q status : preliminary observations in 287
gliomas and oligodendroglioma mimics. Front Biosci 8 : a1-a9, 2003
13. Perry A, Scheithauer BW, Macaulay RJ, Rael C, Roth KA, Kros JM :
Oligodendrogliomas with neurocytic dierentiation. A report of 4 cases
with diagnostic and histogenetic implications. J Neuropathol Exp Neu-
rol 61 : 947-955, 2002
14. Rades D, Fehlauer F, Schild SE : Treatment of atypical neurocytomas.
Cancer 100 : 814-817, 2004
15. Rades D, Schild SE : Value of postoperative stereotactic radiosurgery
and conventional radiotherapy for incompletely resected typical neuro-
cytomas. Cancer 106 : 1140-1143, 2006
16. Sakurada K, Akasaka M, Kuchiki H, Saino M, Mori W, Sato S, et al. : A
rare case of extraventricular neurocytoma. Brain Tumor Pathol 24 : 19-
23, 2007
17. Sgouros S, Carey M, Aluwihare N, Barber P, Jackowski A : Central neu-
rocytoma : a correlative clinicopathologic and radiologic analysis. Surg
Neurol 49 : 197-204, 1998
18. Soylemezoglu F, Scheithauer BW, Esteve J, Kleihues P : Atypical central
neurocytoma. J Neuropathol Exp Neurol 56 : 551-556, 1997
19. Zentner J, Peier J, Roggendorf W, Grote E, Hassler W : Periventricular
neurocytoma : a pathological entity. Surg Neurol 38 : 38-42, 1992
neurocytoma. J Korean Neurosurg Soc 35 : 313-316, 2004
4. Fujisawa H, Marukawa K, Hasegawa M, Tohma Y, Hayashi Y, Uchiyama
N, et al. : Genetic dierences between neurocytoma and dysembryo-
plastic neuroepithelial tumor and oligodendroglial tumors. J Neurosurg
97 : 1350-1355, 2002
5. Hamilton R : Case of the month. August 1996--frontal lobe tumor in 11
year old girl. Brain Pathol 7 : 713-714, 1997
6. Kim CY, Paek SH, Jeong SS, Chung HT, Han JH, Park CK, et al. : Gam-
ma knife radiosurgery for central neurocytoma : primary and second-
ary treatment. Cancer 110 : 2276-2284, 2007
7. Kim DG, Paek SH, Kim IH, Chi JG, Jung HW, Han DH, et al. : Central
neurocytoma : the role of radiation therapy and long term outcome.
Cancer 79 : 1995-2002, 1997
8. Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, Burger PC, Jouvet A,
et al. : e 2007 WHO classication of tumours of the central nervous
system. Acta Neuropathol 114 : 97-109, 2007
9. Maiuri F, Spaziante R, De Caro ML, Cappabianca P, Giamundo A, Ia-
conetta G : Central neurocytoma : clinico-pathological study of 5 cases
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278-282, 1998
11. Paek SH, Han JH, Kim JW, Park CK, Jung HW, Park SH, et al. : Long-
    • Appropriate IHC along with molecular cytogenetics for chromosome 1p/19q (lost in oligodendrogliomas) helps to distinguish both. [3] Presently, there is no consensus if atypical EVN should be considered as WHO grade II or III tumors, and have not been categorized separately although having anaplastic features. The treatment of atypical EVN is also not well established with the extent of resection as a key determinant of recurrence.
    [Show abstract] [Hide abstract] ABSTRACT: Central neurocytomas are tumors with neuronal differentiation, generally arising in the lateral ventricles in the region of foramen of Monro. Whenever these tumors arise in the brain parenchyma they are called 'extraventricular neurocytomas'. We present two unusual cases of extraventricular atypical neurocytomas at uncommon locations with a very high Ki-67 index. The WHO grading of this tumor is yet to be answered. © 2015 Journal of Cancer Research and Therapeutics | Published by Wolters Kluwer - Medknow.
    Article · Jan 2015
  • [Show abstract] [Hide abstract] ABSTRACT: Differentiating oligodendroglioma from extraventricular neurocytoma by conventional light microscopy alone can present a diagnostic challenge. We report pathologic findings of an unusual spinal cord tumor from a 33-year-old male patient which showed hybrid features of oligodendroglioma and extraventricular neurocytoma. Magnetic resonance imaging (MRI) showed an enhancing intramedullary mass in the cervicothoracic region (C7 through T6). Histologic examination revealed a clear cell neoplasm containing ganglion-like cells and calcifications, prompting the differential diagnosis of oligodendroglioma and extraventricular neurocytoma. The immunohistochemical analysis disclosed neural differentiation of the neoplastic cells with strong synaptophysin and neurofilament staining consistent with extraventricular neurocytoma, as well as strong S-100 and glial fibrillary acidic protein (GFAP) expression. Molecular studies with fluorescent in situ hybridization (FISH) revealed chromosome 1p/(partial) 19q deletions, a finding commonly observed in oligodendroglioma. The proliferation index (using antibody MIB1) of the tumor was approximately 30%. The morphologic findings and these results strengthen the hypothesis that these tumors may share a common progenitor cell, which has also been observed by others. Because there are differences in patient management and long-term prognosis, it is important to attempt to distinguish between oligodendroglioma and neurocytoma. This unusual case and similar rare reported cases support the need to reclassify tumors showing pathologic features common to both neurocytoma and oligodendroglioma as a unique entity, while the effort continues to identify the cell of origin.
    Article · May 2007
  • [Show abstract] [Hide abstract] ABSTRACT: Neurocytoma, a rare brain tumor, is characterized by a mass located mainly in cerebral ventricles. It is prone to be misdiagnosed as oligodendroglioma or ependymoma due to their similar histopathological features in clinical practice. This study aimed to examine the clinicopathological features and differential diagnosis of central and extraventricular neurocytoma. The clinical and histopathological data of 17 patients (male: female=7:10; age: 4-41 years; mean age: 27.4 years) with central or extraventricular neurocytoma were retrospectively analyzed. These patients showed typical radiological, histopathological and immunohistochemical features of neurocytoma. The tumor tissue was found to be composed of small uniform cells with round nuclei and clear cytoplasm resembling that of oligodendroglioma and ependymoma. Immunohistochemistry revealed the tumor tissues were positive for neuronal markers such as synaptophysin (SYN) and neuronal nuclear antigen (NeuN). It was concluded histopathological features of neurocytoma overlaps with some tumors in the central neural system. Immunopositivity for SYN and NeuN can help differentially diagnose neurocytoma.
    Article · Dec 2010
  • [Show abstract] [Hide abstract] ABSTRACT: A 42-year-old woman had suffered from headaches since April 2009. Computed tomography revealed a tumor with marked calcification in the left frontal lobe adjacent to the left anterior horn of the lateral ventricle. T1-weighted gadolinium-enhanced magnetic resonance imaging showed a well-enhanced tumor at the lesion. Dynamic methionine positron emission tomography showed no delayed methionine attenuation. Initial preoperative diagnosis was extraventricular neurocytoma (EVN). However, oligodendroglioma was determined upon a second diagnosis. The patient underwent total tumor removal. Hematoxylin and eosin staining showed the characteristic fried egg-like cells, round nuclei, and immunohistochemically, the tumor cells were positive for glial fibrillary acidic protein, synaptophysin, neuronal nuclear antigen, microtubule-associated protein 2 and Olig2. The MIB-1 labeling index was 20%, which suggested malignancy. Although these findings demonstrated that the tumor had glioneuronal character, it was difficult to differentiate between EVN and oligodendroglioma. There have been reports that Olig2 immunohistochemistry is generally positive in cases of oligodendroglioma, but not in cases of neurocytoma. We completed the diagnosis as oligodendroglioma. Subsequent electron microscopy results presented oligodendroglial but not neuronal characteristics. We concluded that Olig2 is useful in the differential diagnosis of oligodendrogliomas and EVNs.
    Full-text · Article · Feb 2011
  • [Show abstract] [Hide abstract] ABSTRACT: Gamma-knife surgery may be an effective alternative for treatment of central neurocytomas owing to its relative safety compared with conventional radiotherapy. In this paper we present results of gamma-knife treatment (GKS) of residual or recurrent neurocytomas. Twenty-two patients (14 female, 8 male) with recurrent or residual neurocytomas who underwent GKS were included. Diagnosis was based on histological findings. The proliferative potential of the tumors was examined by immunostaining with MIB-1 antibody, which is specific for detection of Ki-67 antigen. Tumor volume was determined by using post-gadolinium magnetic resonance images. After GKS treatment, MR imaging was scheduled at three-month intervals in the first year, at six months intervals in the second year, and yearly thereafter. Histopathological diagnoses were: 18 cases of central neurocytomas, two liponeurocytomas, one cerebral neurocytoma and one cerebellar neurocytoma. The MIB1 labeling index (LI) varied from 0 to 5.7%. Marked reduction in tumor volume was seen in 15 patients. In six patients, the tumor volume remained unchanged, and progression was observed for one patient. No complications because of GKS were noted. Shrinking effect on tumor volume increased with increasing duration of follow-up. On the other hand, high MIB labeling index did not seem to have an effect on tumor response to GKS treatment. Findings of this study suggest that GKS is an effective and safe treatment alternative for residual or recurrent neurocytomas. However, its effectiveness should be confirmed with larger studies.
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