The Neuroradiology Journal 19: 672-678, 2006
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Primary Neurocytoma in the Spinal Cord A Case Report
CHINCHUN WU, YU-SHU YEN, DONALD M HO, WANYUO GUO School of Medicine, National Yang-Ming University, Taipei Veterans General Hospital; Taipei, Taiwan
Key words: neurocytoma, spinal cord, magnetic resonance imaging
SUMMARY – Central neurocytoma is defined as an intraventricular benign brain tumor. Extraventricular location of central neurocytoma is rare: only nine cases of spinal neurocytoma had been reported in the English literature. We hereby present a case of atypical neurocytoma involving unusual long segments (8-segment) of cervico-thoracic spinal cord in a 29-year-old woman with emphasis on pre- and post-surgical neuroimaging, pathological correlation, and review the pertinent literature.
Introduction
Case Report
Central neurocytoma (CN) is a rare tumor of central nervous system, accounting for only 0.25-0.5% of brain tumors 1. Hassoun et al first described two intraventricular CN in 1982 2. In the current clinical practice, CN is a well-established category of brain tumor. According to the World Health Organization (WHO) classification of brain tumor CN is defined as a tumor composed of small round cells with neuronal differentiation that is typically located in the supratentorial ventricular system near the foramen of Monro. Nevertheless, variants of CN with extraventricular location and clinically or histologically aggressive behavior had been occasionally described in several single case reports. The histopathological appearance of a neurocytoma can be similar to that of an oligodendroglioma. It remains a diagnostic challenge to differentiate oligodendroglioma from extraventricular CN despite advances in neuroradiology, molecular diagnostic tools, immunohistochemical and ultrastructural study by electron microscopy 3. We present a case of primary neurocytoma of cervico-thoracic spinal cord with microscopically high proliferation index in a young female.
A 29-year-old female presented sudden onset of paraplegia of lower limbs and weakness of right upper limb after a nap. One month before the ictus, she had posterior neck pain that was made worse in the night, accompanied by progressive weakness and numbness of bilateral lower limbs. Her health was otherwise good without history of trauma and there was no contributory family history. On neurological examination, she had reduction in sensory below the T4 dermatome, and symmetric proximal weakness of bilateral lower limbs with muscle power grading 0-1/5. Laboratory data, including lumbar puncture, were all within normal limits. CT scan of cervical spine without contrast media administration showed negative findings. MR imaging of cervico-thoracic spine showed an expanded spinal cord with an intramedullary mass lesion extending from C56 to T5 and associated a syrinx extending to the whole spinal cord (figure 1). The tumor was isointense on both T1- (T1W) and T2-weighted (T2W) MR images, and enhanced strongly and heterogeneously. It had an irregular margin and eccentrically located more to left side in the cord. Another cystic tumor with mural nodular enhancement at T11 and T12 was depicted in
672
Primary Neurocytoma in the Spinal Cord. A Case Report
ChinChun Wu
A
B
C
Figure 1 MR images show the long segment neurocytoma extending from C5-6 to T5 (thick arrow) and the associated syrinx involving the whole spinal cord (long and short arrows). a: A sagittal T1W image of cervico-thoracic spine shows the tumor and syrinx. b: A post-contrast enhanced sagittal T1W image of cervico-thoracic spine shows intense enhancement of the tumor. c: A sagittal T2W image of cervico-thoracic spine shows the tumor and syrinx.
A
B
Figure 2 A: A sagittal T1W image of lumbar spine shows another intramedullary cystic lesion (arrow) at T11 to T12. B: A sagittal post-contrast enhanced T1W image of lumbar spine shows the cystic tumor with mural nodular enhancement (arrow).
673
Primary Neurocytoma in the Spinal Cord. A Case Report
ChinChun Wu
Figure 3 Intra-operative photograph of the cervico-thoracic region (left=cephalo, right=caudal) after durotomy and myelotomy: The asterisks indicate dural matter. The neurocytoma is in dark red color and well demarcated (arrowheads). Its interfaces with the spinal cord (arrows) are distinct.
the same MR examination of spine (figure 2). It showed low signal intensity on T1W and high signal intensity on T2W. The initial differential diagnoses based on the imaging findings were ependymoma and astrocytoma with atypical imaging presentations. Her brain MR imaging appeared to be normal. With the working diagnosis of spinal cord tumor, the patient underwent lower cervical to upper thoracic (C5 to T6) and lower thoracic (T10-T12) spine surgery. The C5 to T6 long segment and T10 to T12 mural nodular enhancing tumors were identified and resected (Figure 3). Microscopically, the tumor was mainly composed of small and uniform cells with round nuclei, perinuclear halo and finely stippled chromatin in a fine neuropil like stroma (figure 4). Hypercellularity and vascular proliferation were seen in places. Occasional mitoses were noted. The tumor cells were immunoreactive for synaptophysin, and non-reactive for glial fibrillary acidic protein (GFAP). The MIB-1 labeling index was 18 (figure 4E). The above findings were compatible with those of an atypical CN. The lesion at the lower thoracic spinal cord showed focal vascular proliferation and fibrin material deposition, while no tumor tissue was identified. Post-surgical follow up MR imaging at one month showed almost total removal of the tumor with a tiny enhancing spot in the spinal cord at the level of T2. The syrinx was regressing (figure 5). The patient recovered well postsurgically. Owing to the tumor atypia and high MIB-1 of 18, post-surgical adjuvant radiotherapy was recommended to the patient. However, her family members rejected the proposal. 674
She underwent rehabilitation program after operation. Five months after operation, she could stand and walk with the help of walker. Discussion Intramedullary spinal cord neoplasms are rare, accounting for about 4%-10% of tumors in the central nervous system 4. Most spinal cord neoplasms are malignant, and 90%-95% are classified as glial tumors. Nonglial tumors are much less common. Primary neurocytoma of the spinal cord is extreme rare, and to our best acknowledgment, only nine case reports had been described with details in the English literature, excluding three cases mentioned without available details 5-16. Neurocytoma is typically located in the supratentorial ventricular system. Extraventricular location of the tumor had been reported including cerebral hemisphere (all four lobes), thalamus, cerebellum, pons, amygdala, pineal gland, retina, and spinal cord 3. In the reported cases of spinal neurocytoma (SN), male predominance was noted with only two female patients in total ten cases (including the current one). It showed a wide age distribution ranged from 8 to 67 years. Most SN occurred in the cervical or cervico-thoracic region (six in ten cases). Average segment involved is 4.2 segments with less than or equal to 5 segments in most patients (six in ten cases). The current case involved up to 8 segments of spinal cord, which was unusual in either neurocytoma or other spinal cord tumors. It presented
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The Neuroradiology Journal 19: 672-678, 2006
A
B
D
E
C
Figure 4 Pathological features of the spinal neurocytomas: (A) The tumor is composed of small and uniform cells with round nuclei and perinuclear halo (H&E, ×75). (B) Hypercellularity is noted (H&E, ×75). (C) Vascular proliferation is seen in places (H&E, ×75). (D) The tumor cells are immunoreactive for synaptophysin (anti-synaptophysin, ×75). (E) The MIB-1 labeling index is 18 (anti-MIB-1, ×150).
A
B
Figure 5 Post-surgical follow up MR imaging at one month: A) A sagittal post-contrast enhanced T1W image shows almost total removal of the tumor with a tiny enhancing spot (short arrow) in the spinal cord at the level of T2. B) A sagittal T2W image shows the regressing syrinx (long arrow).
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Primary Neurocytoma in the Spinal Cord. A Case Report
ChinChun Wu
Table 1 Clinical and imaging data on the reported spinal cord neurocytomas
Segment Age Gender involved
Case
Location
T1W
T2W
T1+C
Syrinx
Wall
Reference
11
C6-T1
3
12
M
*
*
*
*
*
13
12
C5-T1
4
24
M
iso
hyper
homogeneously enhanced
no
well-defined
15
13
C4-T1
5
12
M
*
*
partially enhanced
no
partially cystic
11
14
C2-6
5
65
M
iso
*
*
no
*
18
15
C3-4
2
49
M
iso
iso
*
no
*
18
16
T2-T5
4
50
M
iso
iso
intensely enhanced
yes
irregular
14
17
T10-T11
2
67
M
*
*
*
*
*
17
18
T12-L1
2
46
F
*
*
*
*
*
12
19
T2-T8
7
18
M
hypo
hyper
heterogeneously enhanced
yes
*
16
10
C5/6-T5
8
29
F
iso
Iso
heterogeneously enhanced
whole spine
irregular
current case
Note: M: male; F: female; T1W: T1-weighted MR imaging; T2W: T2-weighted MR imaging; T1+C: T1W with contrast agent; iso: isointense on MR images; hyper: hyperintense on MR images; hypo: hypointense on MR images; *: no available data.
two separated intramedullary lesions (one in cervico-thoracic and the other one in low thoracic spinal cord). Synchronous intramedullary metastasis was considered initially, although no tumor cell in the low thoracic one was identified on histopathological examination. The etiology and the clinical significance of such lesion are uncertain. Histologically, extraventricular neurocytomas are similar to intraventricular neurocytomas although the former display a wider morphological spectrum. The diagnostic criteria of histopathological features include monotonous neoplastic cells with delicate fibrillary matrix similar to neuropil, and evidence of neuronal differentiation demonstrated by positive immunohistochemical staining for synaptophysin or electron microscopy. On light microscopy, neurocytomas can be similar to oligodendrogliomas or clear cell ependymomas, which should be considered in the differential diagnoses. Oligodendrogliomas do not have features suggesting neurocytomas such as presence of fibrillary background similar to neuropil, fine granular nuclei with nucleoli, and diffuse or focal ganglion cell differentiation Ependymomas are lack of immunoreactivity for synaptophysin. The 676
perivascular pseudorosette and true rosette, commonly observed in ependymomas, are not seen in neurocytomas. Further confirmation of neurocytoma can be achieved by observing dense core granules and microtubules on electron microscopy, lack of p53 immunostaining, and absence of chromosome 1p/19q loss 3. The morphological and immunohistochemical features of the current case are consistent with SN although ultrastructural study by electron microscopy is not available. The majority of reports on SN focused on pathological features while radiological features were only sparsely described (table 1). Spinal neurocytomas are different from intraventricular CN on neuroimaging although they are similar in histological characteristics. Unlike the typical “bubbly” appearance (intramural cysts) of intraventricular CN, most SN appears as intramedullary solid masses. Most SN are isointense on T1W and isointense or hyperintense on T2W to spinal cord. Besides, calcification is common in intraventricular CN but was not seen in all the reported SN. After administration of gadolinium-based contrast agent, moderate to intense enhancement, either homogenous or heterogeneous, of SN was reported. Associated synrix
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The Neuroradiology Journal 19: 672-678, 2006
Table 2 Clinical, neurosurgical and pathological data on reported spinal cord neurocytomas
Case
Histopathological diagnosis
MIB-1
Surgery
Radiation
Follow up (month)
Reference
1
typical
*
incomplete
–
133 NR
13
2
atypical
19
incomplete
–
118 RN
15
3
typical
*
complete
–
133 NR
11
4
typical
*
incomplete (Biopsy)
+
120 NR
18
5
atypical
*
incomplete
+
72 R and mortality
18
6
typical
*
incomplete
–
124 NR
14
7
typical
*
complete
–
130 NR
17
8
typical
*
complete
–
112 NR
12
9
atypical
13
incomplete
–
10
atypical
18
incomplete
–
16 116 NR
Current case
Note: *: no available data; +: procedure performed; –: procedure not performed; R: recurrence; NR: no recurrence
was noted only in three cases, and two of them involved long segment of the spinal cord. Based on the limited reported neuroimaging data, it is suggested that SN is generally presented as an intramedullary solid tumor, which shows isointense on T1W, iso- or hyperintense on T2W and is enhanced heterogeneously on MR images. Spinal ependymomas and astrocytomas may have MR features similar to that of SN. However, ependymomas are more often seen in adults whereas astrocytomas are the most common intramedullary tumor in children. These two tumor categories constitute up to 70% of intramedullary spinal cord tumors 4. Both ependymomas and SN tend to involve cervical region, while astrocytomas tend to involve thoracic level. Myxopapillary ependymomas have a distinct predilection for the conus medullaris or filum terminale and cord astrocytomas may involve the entire cord (holocord presentation) in children. A central location, well-circumscribed mass within the spinal cord, presence of a cleavage tissue plane, and intense homogenous enhancement are the typical imaging features that favor an ependymoma. Besides, hemorrhage is common in ependymoma, and about
20%-30% of ependymomas demonstrate the “cap sign” on T2W due to hemosiderin deposition at the poles of the tumor. Intramedullary astrocytomas are usually ill defined, patchy enhanced and eccentrically located within the cord. Associated osseous changes such as scoliosis, widened interpedicular distance and bone erosion may be seen in ependymomas and astrocytomas, but not in SN. Hemangioblastomas are the third most common intramedullary spinal cored tumor. Nevertheless, there are no pathognomonic imaging findings that allow definitive differentiation of intramedullary spinal tumors in all cases. Clinically, in addition to the aforementioned spinal cord tumors, ganglioglioma and spinal CN should be also included in the list of differential diagnosis for a long-segment cervico-thoracic intramedullary heterogeneous enhanced tumor when a syrinx is associated 4. Paragangliomas and primitive neuroectodermal tumors, which have the affinity for filum terminale and cauda equina, are the other tumors to be differentiated. The benigncy of CN is questioned after atypical CN with “malignant” or aggressive clinical, radiological, and histological features have been described. The histological diagnosis of atypical 677
Primary Neurocytoma in the Spinal Cord. A Case Report
CN is based upon the presence of atypical histological features, such as focal necrosis, vascular proliferation, and increased mitotic activity, or Ki-67 (MIB-1) labeling index of more than 2% 17. Atypical histological features constitute about one third (4 in 10 patients) of SN (table 2), which is higher than that of CN (25%). The case reported by Sharma et al had high MIB1. The tumor was recurrent with poor clinical outcome 15. The current case presented mitotic index higher than the case reported by Sharma et al. Although a correlation between histological hallmarks of malignancy and a poor clinical outcome is not yet established in spinal CN, we propose that the current spinal CN may
ChinChun Wu
deserve post-surgical adjuvant treatment and close follow-up. In conclusion, we describe a case of primary SN with unusual long segments involvement and high mitotic index. Based on the observations, we suggest that the histopathological features and immunoprofile of SN are similar to that of intraventricular CN, but their biological potential, radiological features and clinical behavior may be variable. Spinal neurocytoma may have a well-demarcated margin and make a total or almost total surgical excision feasible. In selecting patient with high mitotic index, SN may deserve close follow-up and postoperative adjuvant therapy.
References 1 Hassoun J, S¨oylemezoglu F, Gambarelli D et Al: Central neurocytoma: a synopsis of clinical and histologic features. Brain Pathol 3: 297-306, 1993. 2 Hassoun J, Gambarelli, Grisoli F et Al: Central neurocytoma: an electronmicroscopic study of two cases. Acta Neuropathol 56: 151-156, 1982. 3 Sharma MC, Deb P, Sharma S et Al: Neurocytoma: a comprehensive review. Neurosurg Rev 29:251-352, 2006. 4 Koeller KK, Rosenblum RS, Morrison AL: Neoplasms of the spinal cord and filum terminale: radiologic-pathologic correlation. Radiographics 20:1721-1749, 2000. 5 Louis DN, Swearingen B, Linggood RM et Al: Central nervous system neurocytoma and neuroblastoma in adults--report of eight cases. J Neurooncol 9: 231-238, 1990. 6 Miller DC, Kim R, Zagzag D: Neurocytomas. Non-classical sites and mixed elements. J Neuropathol Exp Neurol 51: 364, 1992. 7 Coca S, Moreno M, Martos JA et Al: Neurocytoma of spinal cord. Acta Neuropathol 87: 537-540, 19947. Tatter SB BL, Louis DN. Central neurocytomas of the cervical spinal cord: report of two cases. J Neurosurg 81: 288-293, 1994. 8 Tatter SB, Borges LF, Louis DN: Central neurocytomas of the cervical spinal cord: report of two cases. J Neurosurg 81:288-293, 1994. 9 Tatter SB, Borges LF, Louis DN. Correction: central neurocytomas of the cervical spinal cord. J Neurosurg 82: 706, 1994. 10 Stapleton SR, David KM, Harkness WF et Al: Central neurocytoma of the cervical spinal cord. J Neurol Neurosurg Psychiatr 63:119, 1997. 11 Giangaspero F, Cenacchi G, Losi L et Al: Extraventricular neoplasms with neurocytoma features. A clinicopathological study of 11 cases. Am J Surg Pathol 21:206-212, 1997. 12 Stephan CL, Kepes JJ, Arnold P et Al: Neurocytoma of the cauda equina case report. J Neurosurg 90: 247-251, 1999. 13 Ashkan K, Casey AT, D’Arrigo C et Al: Benign Central Neurocytoma: A Double Misnomer. Cancer 89: 11111120, 2000.
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14 Martin AJ, Sharr MM, Teddy PJ et Al: Neurocytoma of the thoracic spinal cord. Acta Neurochir 144: 823-828, 2000. 15 Sharma S, Sarkar C, Gaikwad S et Al: Primary neurocytoma of the spinal cord: a case report and review of literature. J Neurooncol 74: 47-52, 2005. 16 Singh A, Chand K, Singh H et Al: Atypical neurocytoma of the spinal cord in a young child. Childs Nerv Syst [Epub ahead of print] July 13, 2006. 17 Brat DJ, Scheithauer BW, Eberhart CG et Al: Extraventricular neurocytomas: pathologic features and clinical outcome. Am J Surg Pathol 25: 1252-1260, 2001.
Professor WanYuo Guo, M.D., Ph.D. Department of Radiology Taipei Veterans General Hospital 201, Sect II, Shih-Pai Road Taipei 11217 TAIWAN Tel.: +886-2-28757481 Fax: +886-2-28757612 E-mail: [email protected]
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Primary Neurocytoma in the Spinal Cord A Case Report
CHINCHUN WU, YU-SHU YEN, DONALD M HO, WANYUO GUO School of Medicine, National Yang-Ming University, Taipei Veterans General Hospital; Taipei, Taiwan
Key words: neurocytoma, spinal cord, magnetic resonance imaging
SUMMARY – Central neurocytoma is defined as an intraventricular benign brain tumor. Extraventricular location of central neurocytoma is rare: only nine cases of spinal neurocytoma had been reported in the English literature. We hereby present a case of atypical neurocytoma involving unusual long segments (8-segment) of cervico-thoracic spinal cord in a 29-year-old woman with emphasis on pre- and post-surgical neuroimaging, pathological correlation, and review the pertinent literature.
Introduction
Case Report
Central neurocytoma (CN) is a rare tumor of central nervous system, accounting for only 0.25-0.5% of brain tumors 1. Hassoun et al first described two intraventricular CN in 1982 2. In the current clinical practice, CN is a well-established category of brain tumor. According to the World Health Organization (WHO) classification of brain tumor CN is defined as a tumor composed of small round cells with neuronal differentiation that is typically located in the supratentorial ventricular system near the foramen of Monro. Nevertheless, variants of CN with extraventricular location and clinically or histologically aggressive behavior had been occasionally described in several single case reports. The histopathological appearance of a neurocytoma can be similar to that of an oligodendroglioma. It remains a diagnostic challenge to differentiate oligodendroglioma from extraventricular CN despite advances in neuroradiology, molecular diagnostic tools, immunohistochemical and ultrastructural study by electron microscopy 3. We present a case of primary neurocytoma of cervico-thoracic spinal cord with microscopically high proliferation index in a young female.
A 29-year-old female presented sudden onset of paraplegia of lower limbs and weakness of right upper limb after a nap. One month before the ictus, she had posterior neck pain that was made worse in the night, accompanied by progressive weakness and numbness of bilateral lower limbs. Her health was otherwise good without history of trauma and there was no contributory family history. On neurological examination, she had reduction in sensory below the T4 dermatome, and symmetric proximal weakness of bilateral lower limbs with muscle power grading 0-1/5. Laboratory data, including lumbar puncture, were all within normal limits. CT scan of cervical spine without contrast media administration showed negative findings. MR imaging of cervico-thoracic spine showed an expanded spinal cord with an intramedullary mass lesion extending from C56 to T5 and associated a syrinx extending to the whole spinal cord (figure 1). The tumor was isointense on both T1- (T1W) and T2-weighted (T2W) MR images, and enhanced strongly and heterogeneously. It had an irregular margin and eccentrically located more to left side in the cord. Another cystic tumor with mural nodular enhancement at T11 and T12 was depicted in
672
Primary Neurocytoma in the Spinal Cord. A Case Report
ChinChun Wu
A
B
C
Figure 1 MR images show the long segment neurocytoma extending from C5-6 to T5 (thick arrow) and the associated syrinx involving the whole spinal cord (long and short arrows). a: A sagittal T1W image of cervico-thoracic spine shows the tumor and syrinx. b: A post-contrast enhanced sagittal T1W image of cervico-thoracic spine shows intense enhancement of the tumor. c: A sagittal T2W image of cervico-thoracic spine shows the tumor and syrinx.
A
B
Figure 2 A: A sagittal T1W image of lumbar spine shows another intramedullary cystic lesion (arrow) at T11 to T12. B: A sagittal post-contrast enhanced T1W image of lumbar spine shows the cystic tumor with mural nodular enhancement (arrow).
673
Primary Neurocytoma in the Spinal Cord. A Case Report
ChinChun Wu
Figure 3 Intra-operative photograph of the cervico-thoracic region (left=cephalo, right=caudal) after durotomy and myelotomy: The asterisks indicate dural matter. The neurocytoma is in dark red color and well demarcated (arrowheads). Its interfaces with the spinal cord (arrows) are distinct.
the same MR examination of spine (figure 2). It showed low signal intensity on T1W and high signal intensity on T2W. The initial differential diagnoses based on the imaging findings were ependymoma and astrocytoma with atypical imaging presentations. Her brain MR imaging appeared to be normal. With the working diagnosis of spinal cord tumor, the patient underwent lower cervical to upper thoracic (C5 to T6) and lower thoracic (T10-T12) spine surgery. The C5 to T6 long segment and T10 to T12 mural nodular enhancing tumors were identified and resected (Figure 3). Microscopically, the tumor was mainly composed of small and uniform cells with round nuclei, perinuclear halo and finely stippled chromatin in a fine neuropil like stroma (figure 4). Hypercellularity and vascular proliferation were seen in places. Occasional mitoses were noted. The tumor cells were immunoreactive for synaptophysin, and non-reactive for glial fibrillary acidic protein (GFAP). The MIB-1 labeling index was 18 (figure 4E). The above findings were compatible with those of an atypical CN. The lesion at the lower thoracic spinal cord showed focal vascular proliferation and fibrin material deposition, while no tumor tissue was identified. Post-surgical follow up MR imaging at one month showed almost total removal of the tumor with a tiny enhancing spot in the spinal cord at the level of T2. The syrinx was regressing (figure 5). The patient recovered well postsurgically. Owing to the tumor atypia and high MIB-1 of 18, post-surgical adjuvant radiotherapy was recommended to the patient. However, her family members rejected the proposal. 674
She underwent rehabilitation program after operation. Five months after operation, she could stand and walk with the help of walker. Discussion Intramedullary spinal cord neoplasms are rare, accounting for about 4%-10% of tumors in the central nervous system 4. Most spinal cord neoplasms are malignant, and 90%-95% are classified as glial tumors. Nonglial tumors are much less common. Primary neurocytoma of the spinal cord is extreme rare, and to our best acknowledgment, only nine case reports had been described with details in the English literature, excluding three cases mentioned without available details 5-16. Neurocytoma is typically located in the supratentorial ventricular system. Extraventricular location of the tumor had been reported including cerebral hemisphere (all four lobes), thalamus, cerebellum, pons, amygdala, pineal gland, retina, and spinal cord 3. In the reported cases of spinal neurocytoma (SN), male predominance was noted with only two female patients in total ten cases (including the current one). It showed a wide age distribution ranged from 8 to 67 years. Most SN occurred in the cervical or cervico-thoracic region (six in ten cases). Average segment involved is 4.2 segments with less than or equal to 5 segments in most patients (six in ten cases). The current case involved up to 8 segments of spinal cord, which was unusual in either neurocytoma or other spinal cord tumors. It presented
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The Neuroradiology Journal 19: 672-678, 2006
A
B
D
E
C
Figure 4 Pathological features of the spinal neurocytomas: (A) The tumor is composed of small and uniform cells with round nuclei and perinuclear halo (H&E, ×75). (B) Hypercellularity is noted (H&E, ×75). (C) Vascular proliferation is seen in places (H&E, ×75). (D) The tumor cells are immunoreactive for synaptophysin (anti-synaptophysin, ×75). (E) The MIB-1 labeling index is 18 (anti-MIB-1, ×150).
A
B
Figure 5 Post-surgical follow up MR imaging at one month: A) A sagittal post-contrast enhanced T1W image shows almost total removal of the tumor with a tiny enhancing spot (short arrow) in the spinal cord at the level of T2. B) A sagittal T2W image shows the regressing syrinx (long arrow).
675
Primary Neurocytoma in the Spinal Cord. A Case Report
ChinChun Wu
Table 1 Clinical and imaging data on the reported spinal cord neurocytomas
Segment Age Gender involved
Case
Location
T1W
T2W
T1+C
Syrinx
Wall
Reference
11
C6-T1
3
12
M
*
*
*
*
*
13
12
C5-T1
4
24
M
iso
hyper
homogeneously enhanced
no
well-defined
15
13
C4-T1
5
12
M
*
*
partially enhanced
no
partially cystic
11
14
C2-6
5
65
M
iso
*
*
no
*
18
15
C3-4
2
49
M
iso
iso
*
no
*
18
16
T2-T5
4
50
M
iso
iso
intensely enhanced
yes
irregular
14
17
T10-T11
2
67
M
*
*
*
*
*
17
18
T12-L1
2
46
F
*
*
*
*
*
12
19
T2-T8
7
18
M
hypo
hyper
heterogeneously enhanced
yes
*
16
10
C5/6-T5
8
29
F
iso
Iso
heterogeneously enhanced
whole spine
irregular
current case
Note: M: male; F: female; T1W: T1-weighted MR imaging; T2W: T2-weighted MR imaging; T1+C: T1W with contrast agent; iso: isointense on MR images; hyper: hyperintense on MR images; hypo: hypointense on MR images; *: no available data.
two separated intramedullary lesions (one in cervico-thoracic and the other one in low thoracic spinal cord). Synchronous intramedullary metastasis was considered initially, although no tumor cell in the low thoracic one was identified on histopathological examination. The etiology and the clinical significance of such lesion are uncertain. Histologically, extraventricular neurocytomas are similar to intraventricular neurocytomas although the former display a wider morphological spectrum. The diagnostic criteria of histopathological features include monotonous neoplastic cells with delicate fibrillary matrix similar to neuropil, and evidence of neuronal differentiation demonstrated by positive immunohistochemical staining for synaptophysin or electron microscopy. On light microscopy, neurocytomas can be similar to oligodendrogliomas or clear cell ependymomas, which should be considered in the differential diagnoses. Oligodendrogliomas do not have features suggesting neurocytomas such as presence of fibrillary background similar to neuropil, fine granular nuclei with nucleoli, and diffuse or focal ganglion cell differentiation Ependymomas are lack of immunoreactivity for synaptophysin. The 676
perivascular pseudorosette and true rosette, commonly observed in ependymomas, are not seen in neurocytomas. Further confirmation of neurocytoma can be achieved by observing dense core granules and microtubules on electron microscopy, lack of p53 immunostaining, and absence of chromosome 1p/19q loss 3. The morphological and immunohistochemical features of the current case are consistent with SN although ultrastructural study by electron microscopy is not available. The majority of reports on SN focused on pathological features while radiological features were only sparsely described (table 1). Spinal neurocytomas are different from intraventricular CN on neuroimaging although they are similar in histological characteristics. Unlike the typical “bubbly” appearance (intramural cysts) of intraventricular CN, most SN appears as intramedullary solid masses. Most SN are isointense on T1W and isointense or hyperintense on T2W to spinal cord. Besides, calcification is common in intraventricular CN but was not seen in all the reported SN. After administration of gadolinium-based contrast agent, moderate to intense enhancement, either homogenous or heterogeneous, of SN was reported. Associated synrix
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The Neuroradiology Journal 19: 672-678, 2006
Table 2 Clinical, neurosurgical and pathological data on reported spinal cord neurocytomas
Case
Histopathological diagnosis
MIB-1
Surgery
Radiation
Follow up (month)
Reference
1
typical
*
incomplete
–
133 NR
13
2
atypical
19
incomplete
–
118 RN
15
3
typical
*
complete
–
133 NR
11
4
typical
*
incomplete (Biopsy)
+
120 NR
18
5
atypical
*
incomplete
+
72 R and mortality
18
6
typical
*
incomplete
–
124 NR
14
7
typical
*
complete
–
130 NR
17
8
typical
*
complete
–
112 NR
12
9
atypical
13
incomplete
–
10
atypical
18
incomplete
–
16 116 NR
Current case
Note: *: no available data; +: procedure performed; –: procedure not performed; R: recurrence; NR: no recurrence
was noted only in three cases, and two of them involved long segment of the spinal cord. Based on the limited reported neuroimaging data, it is suggested that SN is generally presented as an intramedullary solid tumor, which shows isointense on T1W, iso- or hyperintense on T2W and is enhanced heterogeneously on MR images. Spinal ependymomas and astrocytomas may have MR features similar to that of SN. However, ependymomas are more often seen in adults whereas astrocytomas are the most common intramedullary tumor in children. These two tumor categories constitute up to 70% of intramedullary spinal cord tumors 4. Both ependymomas and SN tend to involve cervical region, while astrocytomas tend to involve thoracic level. Myxopapillary ependymomas have a distinct predilection for the conus medullaris or filum terminale and cord astrocytomas may involve the entire cord (holocord presentation) in children. A central location, well-circumscribed mass within the spinal cord, presence of a cleavage tissue plane, and intense homogenous enhancement are the typical imaging features that favor an ependymoma. Besides, hemorrhage is common in ependymoma, and about
20%-30% of ependymomas demonstrate the “cap sign” on T2W due to hemosiderin deposition at the poles of the tumor. Intramedullary astrocytomas are usually ill defined, patchy enhanced and eccentrically located within the cord. Associated osseous changes such as scoliosis, widened interpedicular distance and bone erosion may be seen in ependymomas and astrocytomas, but not in SN. Hemangioblastomas are the third most common intramedullary spinal cored tumor. Nevertheless, there are no pathognomonic imaging findings that allow definitive differentiation of intramedullary spinal tumors in all cases. Clinically, in addition to the aforementioned spinal cord tumors, ganglioglioma and spinal CN should be also included in the list of differential diagnosis for a long-segment cervico-thoracic intramedullary heterogeneous enhanced tumor when a syrinx is associated 4. Paragangliomas and primitive neuroectodermal tumors, which have the affinity for filum terminale and cauda equina, are the other tumors to be differentiated. The benigncy of CN is questioned after atypical CN with “malignant” or aggressive clinical, radiological, and histological features have been described. The histological diagnosis of atypical 677
Primary Neurocytoma in the Spinal Cord. A Case Report
CN is based upon the presence of atypical histological features, such as focal necrosis, vascular proliferation, and increased mitotic activity, or Ki-67 (MIB-1) labeling index of more than 2% 17. Atypical histological features constitute about one third (4 in 10 patients) of SN (table 2), which is higher than that of CN (25%). The case reported by Sharma et al had high MIB1. The tumor was recurrent with poor clinical outcome 15. The current case presented mitotic index higher than the case reported by Sharma et al. Although a correlation between histological hallmarks of malignancy and a poor clinical outcome is not yet established in spinal CN, we propose that the current spinal CN may
ChinChun Wu
deserve post-surgical adjuvant treatment and close follow-up. In conclusion, we describe a case of primary SN with unusual long segments involvement and high mitotic index. Based on the observations, we suggest that the histopathological features and immunoprofile of SN are similar to that of intraventricular CN, but their biological potential, radiological features and clinical behavior may be variable. Spinal neurocytoma may have a well-demarcated margin and make a total or almost total surgical excision feasible. In selecting patient with high mitotic index, SN may deserve close follow-up and postoperative adjuvant therapy.
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14 Martin AJ, Sharr MM, Teddy PJ et Al: Neurocytoma of the thoracic spinal cord. Acta Neurochir 144: 823-828, 2000. 15 Sharma S, Sarkar C, Gaikwad S et Al: Primary neurocytoma of the spinal cord: a case report and review of literature. J Neurooncol 74: 47-52, 2005. 16 Singh A, Chand K, Singh H et Al: Atypical neurocytoma of the spinal cord in a young child. Childs Nerv Syst [Epub ahead of print] July 13, 2006. 17 Brat DJ, Scheithauer BW, Eberhart CG et Al: Extraventricular neurocytomas: pathologic features and clinical outcome. Am J Surg Pathol 25: 1252-1260, 2001.
Professor WanYuo Guo, M.D., Ph.D. Department of Radiology Taipei Veterans General Hospital 201, Sect II, Shih-Pai Road Taipei 11217 TAIWAN Tel.: +886-2-28757481 Fax: +886-2-28757612 E-mail: [email protected]
