- Email: [email protected]
Cervical myelopathy caused by bilateral C1–2 dumbbell ganglioneuromas and C2–3 and C3–4 neurofibromas associated with neurofibromatosis type 1
J Orthop Sci DOI 10.1007/s00776-012-0315-8
CASE REPORT
Cervical myelopathy caused by bilateral C1–2 dumbbell ganglioneuromas and C2–3 and C3–4 neurofibromas associated with neurofibromatosis type 1 Kei Ando • Shiro Imagama • Zenya Ito • Kenichi Hirano Ryoji Tauchi • Akio Muramoto • Hiroki Matsui • Tomohiro Matsumoto • Naoki Ishiguro
•
Received: 6 July 2012 / Accepted: 10 September 2012 Ó The Japanese Orthopaedic Association 2012
Introduction Neurofibromatosis type 1 (NF-1) is one of the most common autosomal dominant disorders in humans [1], affecting 1 in 3,000 individuals, although about 50 % of these cases arise sporadically as new mutations [2]. To diagnose the disease, two or more of these major criteria must be present: six or more cafe´ au lait spots or axillary or inguinal freckling; two or more cutaneous neurofibromas; one plexiform neurofibroma; characteristic bony lesions (pseudarthrosis, sphenoid wing hypoplasia, severe kyphoscoliosis); an optic glioma; two or more iris Lisch nodules; or a first-degree relative with NF-1 [3]. Patients with spinal neurofibromatosis have been reported to comprise a subgroup of NF-1 patients in whom all spinal tumors removed or biopsied were neurofibromas [4, 5]. Ganglioneuromas are rare, slow-growing, benign tumors. They usually arise from pluripotent neural crest cells and are closely related to the embryological development of the sympathetic nervous system [6]. Generally, ganglioneuromas are unilateral and solitary; multiple occurrences and an association with NF-1 are very unusual features. To the best of our knowledge, only five cases of cervical ganglioneuromas causing myelopathy associated with NF-1 have been reported in the English literature [7–10], with only three of those cases having a bilateral, symmetrical dumbbell appearance [7–9]. Moreover, there have been no reports on the co-existence of
K. Ando S. Imagama (&) Z. Ito K. Hirano R. Tauchi A. Muramoto H. Matsui T. Matsumoto N. Ishiguro Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai Showa-ward, Nagoya, Aichi 466-8550, Japan e-mail: [email protected]
ganglioneuromas and neurofibromas in the cervical spine. We present a patient with bilateral, symmetrical cervical dumbbell ganglioneuromas and intradural neurofibromas causing myelopathy.
Case report A 20-year-old man presented with difficulty walking, numbness in both hands, alternating constipation and urinary retention for two years, and a gradually progressive gait disturbance and weakness of both arms. He was admitted to our hospital after he stumbled over a rock and fell. Preoperative examination revealed mild tetraplegia and hyperesthesia under the C3 area. He could perform the one leg standing test on each leg, but only for 2 s. He was hyperreflexive in both upper and lower limbs with a bilateral Babinski response. His preoperative Japanese Orthopaedic Association score was 10 (2, 2, 1, 1, 1, 3) [11]. The patient had multiple cafe´ au lait spots and cutaneous and subcutaneous neurofibromas. Moreover, his mother, uncle, and grandmother were diagnosed as having NF-1. His uncle had a cervical fusion due to cervical myelopathy and deformity. Therefore, the patient was diagnosed as having NF-1. Plain X-rays and reconstructed computed tomography of the cervical spine showed enlargement of the foramen at all levels (Fig. 1). Coronal and sagittal cervical magnetic resonance images showed multiple tumors involving several nerve roots (Fig. 2a). The extensive distribution of the tumors produced an MRI picture resembling a Christmas tree [12]. An axial view MRI revealed bilateral extradural tumors at the C1–C2 level and dumbbell-shaped (intraextradural) tumors at the C2–C3 and C3–C4 levels that were severely compressing the spinal cord (Fig. 2b). All tumors had high signal intensity in the T2-weighted image,
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low signal intensity in the T1-weighted image, and moderately heterogeneous increased signal in the gadoliniumenhanced T1-weighted image. MRI at the thoracic and lumbar spine also showed a Christmas tree sign [12]. The patient underwent decompression surgery following resection of the C1 posterior arch and double open-door laminoplasty of C2, C3, and C4. We resected the tumors
Fig. 1 Reconstructed computed tomography of the cervical spine showed enlargement of the foramen at all levels
Fig. 2 Coronal cervical magnetic resonance images showed multiple tumors involving several nerve roots (a). An axial view revealed bilateral extradural tumors at the C1–C2 level and dumbbell-shaped
123
during a microscopic procedure while compound muscle action potential monitoring (biceps, triceps, hypothenar, quadriceps femoris, hamstring, tibialis anterior, gastrocnemius, and anal sphincter muscles, depending on the spinal cord level at which surgery was performed and the somatosensory evoked potential). The bilateral tumors at the C1–C2 level (Fig. 3a), which were solid, encapsulated, smooth, elastic, and partially invading intradurally on the left side, were carefully enucleated without sacrificing the C2 roots. The intradural tumors at the C2–C3 and C3–C4 levels (Fig. 3b, c), which were located ventrally and mainly compressed the spinal cord, extended to the bilateral extradural portion (Fig. 3d, e). Removal of the intradural tumors was performed by amputating the C3 and C4 roots at their rootlets (Fig. 4a, b). We did not attempt to remove the extradural portion because that did not compress the dura. Duraplasty was performed using Gore-Tex dura substitute and fibrin glue bonded for indirect decompression (Fig. 4c). Ultrasound examination confirmed that the spinal cord was decompressed (Fig. 4d–f). Histological examination revealed that the tumors at C1–C2 consisted of bundles of longitudinally and transversely oriented Schwann cells crisscrossing each other in an irregular fashion and large ganglion cells with large vesicular nuclei, which we diagnosed as ganglioneuroma (Fig. 5a). Tumors at C2–C3 and C3–C4 showed the same crisscrossing bundles of Schwann cells as the C1–C2 tumors but without the ganglion cells; we diagnosed these as neurofibromas (Fig. 5b). None of the tumors had
(intra-extradural) tumors at the C2–C3 and C3–C4 levels severely compressing the spinal cord (b)
Cervical myelopathy caused by two different tumors with NF-1
A
C
B
E
D
Fig. 3 Ultrasound examination of the bilateral tumors at the C1–C2 (a), the C2–C3 (b), and C3–C4 (c) levels. The tumors, which were located ventrally and mainly compressed the spinal cord, extended to the bilateral extradural portion (d, e)
A
B
C
D
E
Fig. 4 Removal of the intradural tumors was performed by amputating the C3 and C4 roots at their rootlets (a, b). Duraplasty was performed using Gore-Tex dura substitute and fibrin glue bonded for
F
indirect decompression (c). Ultrasound examination confirmed that the spinal cord was decompressed (d–f)
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K. Ando et al.
Fig. 5 Histological examination revealed that the tumors at C1–C2 consisted of bundles of longitudinally and transversely oriented Schwann cells crisscrossing each other in an irregular fashion and large ganglion cells with large vesicular nuclei, which we diagnosed
as ganglioneuroma (a). Tumors at C2–C3 and C3–C4 showed the same crisscrossing bundles of Schwann cells as the C1–C2 tumors but without the ganglion cells; we diagnosed these as neurofibromas (b)
significant mitotic activity, and the tumors’ MIB-1 indices were less than 1 %. There was no change in the amplitude and latency of spinal cord monitoring during surgery. The postoperative course was uneventful. The patient was immobilized for four days to prevent a cerebrospinal fluid fistula, and subsequent mobilization was well tolerated. Motor weakness and sensory disturbance improved within three weeks, except for the C3–C4 dermatome. The patient returned to his work two months after surgery. Follow-up MRI (two years after surgery) showed a highintensity lesion at the C1–C2 level and residual bilateral extradural tumors with moderate cord compression but without significant enlargement of residual tumors (Fig. 6a, b), and his Japanese Orthopaedics Association score had improved to 15 (3, 4, 1, 2, 2, 3). The patient and his parents gave informed consent to submit this case study for publication.
neurofibromas. Ganglioneuromas of the cervical spine are rare tumors associated with NF-1, with only five of these tumors confirmed pathologically and reported in the literature [7–10, 13] (Table 1). Ganglioneuromas reside within a class of neuronal tumor in which the neoplastic cells express a mature neuronal phenotype [14]. This type of tumor is slow-growing, benign, and characterized by a firm, round or oval, well-encapsulated mass with occasional lobulations [15]. They are mostly found in the posterior mediastinum and abdomen because they arise from the sympathetic nervous system [9]. The intraspinal portion of these tumors extended intradurally in 3 of 6 (50 %) reported cases, although it is believed that these tumors tended to extend extradurally, as in the present case. Ganglioneuromas associated with NF-1 may be another unusual feature. Neurofibromas are commonly associated with NF-1; they typically arise from the extradural portion of the spine, although they may be intradural in NF-2 patients [4]. In the present case, neurofibromas at C2–C3 and C3–C4 severely compressed the spinal cord intradurally. To our knowledge, this is the first report on the co-existence of ganglioneuromas and neurofibromas of the cervical spine. Only 1.6 %
Discussion We have presented a case of NF-1 with cervical myelopathy caused by dumbbell-shaped ganglioneuromas and
123
Cervical myelopathy caused by two different tumors with NF-1
Fig. 6 Follow-up MRI showed a high-intensity lesion at the C1–C2 level but there was no significant enlargement of residual tumors (a). An axial view revealed residual bilateral extradural tumors with moderate cord compression (b)
Table 1 Summary of previously published case reports with cervical ganglioneuroma in neurofibromatosis type 1 patients Patient number
Authors
Age/sex
Affected levels
Bilateral
Intraspinal extension
Multiplicity
Other tumors resected during surgery
1
Miyakoshi et al. [8]
15/male
C1–2, 3–4
?
Extradural
?
-
2
Bacci et al. [7]
32/female
C1, C4–7
?
n.s.
?
-
3
Shephard et al. [10]
35/male
C2–7
-
Intradural
?
-
4
Sinclair and Yang [13]
44/female
C2–5
-
Intradural
?
-
5
Kyoshima et al. [9]
35/male
C2–3
?
Intradural
?
-
6
This study
20/male
C1–2, 2–3, 3–4
?
Extradural
?
? (neurofibroma)
of NF-1 patients have symptoms, and these patients seldom need surgery [4]. Histological examination has been performed in a minority of NF-1-associated spinal tumors; therefore, we may speculate that the probability of finding both ganglioneuroma and neurofibroma in NF-1 patients might be higher than expected [7], although genetic associations between NF-1 and ganglioneuroma remain unclear [9]. For the tumors at C1–C2, we enucleated them for removal because the axial view MRI revealed bilateral extradural tumors. The intradural tumors at C2–C3 and C3–C4 were removed because they were located ventrally and mainly compressed spinal cord. Ganglioneuromas have well-differentiated cellular features and grow slowly. Serebrin and Robertson [16] described a 20-year follow-up of a very slow growing ganglioneuroma in the pituitary fossa. Coupled with an often well-circumscribed appearance,
total surgical excision remains the treatment of choice with large tumors [14]. Although surgical decompression must be undertaken as soon as possible when spinal cord compression is present [17], it may be impossible to completely excise multiple tumors at all sites, as in the present case. Subtotal or partial resection might be the goal for cases with multiple spinal tumors [8], but such patients should be carefully monitored for the rest of their lives, especially regarding spinal cord compression, due to the residual tumor.
Conclusions We reported on the case of a 20-year-old man with NF-1 who presented with cervical myelopathy caused by ganglioneuroma and neurofibroma. Although his neurological
123
K. Ando et al.
status improved after surgery, he will be followed carefully to watch for neurological symptoms resulting from growth of the residual tumors. Conflict of interest of interest.
The authors declare that they have no conflict
References 1. Huson SM, Harper PS, Compston DA. Von Recklinghausen neurofibromatosis. A clinical and population study in south-east Wales. Brain. 1988;111(Pt 6):1355–81. 2. Cawthon RM, Weiss R, Xu GF, Viskochil D, Culver M, Stevens J, Robertson M, Dunn D, Gesteland R, O’Connell P. A major segment of the neurofibromatosis type 1 gene: cDNA sequence, genomic structure, and point mutations. Cell. 1990;62(1): 193–201. 3. Mulvihill JJ, Parry DM, Sherman JL, Pikus A, Kaiser-Kupfer MI, Eldridge R. NIH conference. Neurofibromatosis 1 (Recklinghausen disease) and neurofibromatosis 2 (bilateral acoustic neurofibromatosis). An update. Ann Intern Med. 1990;113(1):39–52. 4. Thakkar SD, Feigen U, Mautner VF. Spinal tumours in neurofibromatosis type 1: an MRI study of frequency, multiplicity and variety. Neuroradiology. 1999;41(9):625–9. 5. Kluwe L, Tatagiba M, Funsterer C, Mautner VF. NF1 mutations and clinical spectrum in patients with spinal neurofibromas. J Med Genet. 2003;40(5):368–71. 6. Lonergan GJ, Schwab CM, Suarez ES, Carlson CL. Neuroblastoma, ganglioneuroblastoma, and ganglioneuroma: radiologic– pathologic correlation. Radiographics. 2002;22(4):911–34.
123
7. Bacci C, Sestini R, Ammannati F, Bianchini E, Palladino T, Carella M, Melchionda S, Zelante L, Papi L. Multiple spinal ganglioneuromas in a patient harboring a pathogenic NF1 mutation. Clin Genet. 2010;77(3):293–7. 8. Miyakoshi N, Hongo M, Kasukawa Y, Misawa A, Shimada Y. Bilateral and symmetric C1–C2 dumbbell ganglioneuromas associated with neurofibromatosis type 1 causing severe spinal cord compression. Spine J. 2010;10(4):e11–5. 9. Kyoshima K, Sakai K, Kanaji M, Oikawa S, Kobayashi S, Sato A, Nakayama J. Symmetric dumbbell ganglioneuromas of bilateral C2 and C3 roots with intradural extension associated with von Recklinghausen’s disease: case report. Surg Neurol. 2004;61 (5):468–73 (discussion 73). 10. Shephard RH, Sutton D. Dumb-bell ganglioneuromata of the spine with a report of four cases. Br J Surg. 1958;45(192): 305–17. 11. Japanese Orthopaedic Association scoring system for cervical myelopathy. J Jpn Orthop Assoc. 1994;68:134–47. 12. Ashkan K, Casey AT. Christmas tree sign. J Neurol Neurosurg Psychiatry. 1999;67(6):824. 13. Sinclair JE, Yang YH. Ganglioneuroma of the spine associated with von Recklinghausen’s disease. J Neurosurg. 1961;18:115–9. 14. Pang BC, Tchoyoson Lim CC, Tan KK. Giant spinal ganglioneuroma. J Clin Neurosci. 2005;12(8):967–72. 15. Carpenter WB, Kernohan JW. Retroperitoneal ganglioneuromas and neurofibromas. A clinicopathological study. Cancer. 1963;16: 788–97. 16. Serebrin R, Robertson DM. Ganglioneuroma arising in the pituitary fossa: a twenty year follow-up. J Neurol Neurosurg Psychiatry. 1984;47(1):97–8. 17. Maggi G, Dorato P, Trischitta V, Varone A, Civetta F. Cervical dumbbell ganglioneuroma in an eighteen month old child. A case report. J Neurosurg Sci. 1995;39(4):257–60.
CASE REPORT
Cervical myelopathy caused by bilateral C1–2 dumbbell ganglioneuromas and C2–3 and C3–4 neurofibromas associated with neurofibromatosis type 1 Kei Ando • Shiro Imagama • Zenya Ito • Kenichi Hirano Ryoji Tauchi • Akio Muramoto • Hiroki Matsui • Tomohiro Matsumoto • Naoki Ishiguro
•
Received: 6 July 2012 / Accepted: 10 September 2012 Ó The Japanese Orthopaedic Association 2012
Introduction Neurofibromatosis type 1 (NF-1) is one of the most common autosomal dominant disorders in humans [1], affecting 1 in 3,000 individuals, although about 50 % of these cases arise sporadically as new mutations [2]. To diagnose the disease, two or more of these major criteria must be present: six or more cafe´ au lait spots or axillary or inguinal freckling; two or more cutaneous neurofibromas; one plexiform neurofibroma; characteristic bony lesions (pseudarthrosis, sphenoid wing hypoplasia, severe kyphoscoliosis); an optic glioma; two or more iris Lisch nodules; or a first-degree relative with NF-1 [3]. Patients with spinal neurofibromatosis have been reported to comprise a subgroup of NF-1 patients in whom all spinal tumors removed or biopsied were neurofibromas [4, 5]. Ganglioneuromas are rare, slow-growing, benign tumors. They usually arise from pluripotent neural crest cells and are closely related to the embryological development of the sympathetic nervous system [6]. Generally, ganglioneuromas are unilateral and solitary; multiple occurrences and an association with NF-1 are very unusual features. To the best of our knowledge, only five cases of cervical ganglioneuromas causing myelopathy associated with NF-1 have been reported in the English literature [7–10], with only three of those cases having a bilateral, symmetrical dumbbell appearance [7–9]. Moreover, there have been no reports on the co-existence of
K. Ando S. Imagama (&) Z. Ito K. Hirano R. Tauchi A. Muramoto H. Matsui T. Matsumoto N. Ishiguro Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai Showa-ward, Nagoya, Aichi 466-8550, Japan e-mail: [email protected]
ganglioneuromas and neurofibromas in the cervical spine. We present a patient with bilateral, symmetrical cervical dumbbell ganglioneuromas and intradural neurofibromas causing myelopathy.
Case report A 20-year-old man presented with difficulty walking, numbness in both hands, alternating constipation and urinary retention for two years, and a gradually progressive gait disturbance and weakness of both arms. He was admitted to our hospital after he stumbled over a rock and fell. Preoperative examination revealed mild tetraplegia and hyperesthesia under the C3 area. He could perform the one leg standing test on each leg, but only for 2 s. He was hyperreflexive in both upper and lower limbs with a bilateral Babinski response. His preoperative Japanese Orthopaedic Association score was 10 (2, 2, 1, 1, 1, 3) [11]. The patient had multiple cafe´ au lait spots and cutaneous and subcutaneous neurofibromas. Moreover, his mother, uncle, and grandmother were diagnosed as having NF-1. His uncle had a cervical fusion due to cervical myelopathy and deformity. Therefore, the patient was diagnosed as having NF-1. Plain X-rays and reconstructed computed tomography of the cervical spine showed enlargement of the foramen at all levels (Fig. 1). Coronal and sagittal cervical magnetic resonance images showed multiple tumors involving several nerve roots (Fig. 2a). The extensive distribution of the tumors produced an MRI picture resembling a Christmas tree [12]. An axial view MRI revealed bilateral extradural tumors at the C1–C2 level and dumbbell-shaped (intraextradural) tumors at the C2–C3 and C3–C4 levels that were severely compressing the spinal cord (Fig. 2b). All tumors had high signal intensity in the T2-weighted image,
123
K. Ando et al.
low signal intensity in the T1-weighted image, and moderately heterogeneous increased signal in the gadoliniumenhanced T1-weighted image. MRI at the thoracic and lumbar spine also showed a Christmas tree sign [12]. The patient underwent decompression surgery following resection of the C1 posterior arch and double open-door laminoplasty of C2, C3, and C4. We resected the tumors
Fig. 1 Reconstructed computed tomography of the cervical spine showed enlargement of the foramen at all levels
Fig. 2 Coronal cervical magnetic resonance images showed multiple tumors involving several nerve roots (a). An axial view revealed bilateral extradural tumors at the C1–C2 level and dumbbell-shaped
123
during a microscopic procedure while compound muscle action potential monitoring (biceps, triceps, hypothenar, quadriceps femoris, hamstring, tibialis anterior, gastrocnemius, and anal sphincter muscles, depending on the spinal cord level at which surgery was performed and the somatosensory evoked potential). The bilateral tumors at the C1–C2 level (Fig. 3a), which were solid, encapsulated, smooth, elastic, and partially invading intradurally on the left side, were carefully enucleated without sacrificing the C2 roots. The intradural tumors at the C2–C3 and C3–C4 levels (Fig. 3b, c), which were located ventrally and mainly compressed the spinal cord, extended to the bilateral extradural portion (Fig. 3d, e). Removal of the intradural tumors was performed by amputating the C3 and C4 roots at their rootlets (Fig. 4a, b). We did not attempt to remove the extradural portion because that did not compress the dura. Duraplasty was performed using Gore-Tex dura substitute and fibrin glue bonded for indirect decompression (Fig. 4c). Ultrasound examination confirmed that the spinal cord was decompressed (Fig. 4d–f). Histological examination revealed that the tumors at C1–C2 consisted of bundles of longitudinally and transversely oriented Schwann cells crisscrossing each other in an irregular fashion and large ganglion cells with large vesicular nuclei, which we diagnosed as ganglioneuroma (Fig. 5a). Tumors at C2–C3 and C3–C4 showed the same crisscrossing bundles of Schwann cells as the C1–C2 tumors but without the ganglion cells; we diagnosed these as neurofibromas (Fig. 5b). None of the tumors had
(intra-extradural) tumors at the C2–C3 and C3–C4 levels severely compressing the spinal cord (b)
Cervical myelopathy caused by two different tumors with NF-1
A
C
B
E
D
Fig. 3 Ultrasound examination of the bilateral tumors at the C1–C2 (a), the C2–C3 (b), and C3–C4 (c) levels. The tumors, which were located ventrally and mainly compressed the spinal cord, extended to the bilateral extradural portion (d, e)
A
B
C
D
E
Fig. 4 Removal of the intradural tumors was performed by amputating the C3 and C4 roots at their rootlets (a, b). Duraplasty was performed using Gore-Tex dura substitute and fibrin glue bonded for
F
indirect decompression (c). Ultrasound examination confirmed that the spinal cord was decompressed (d–f)
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K. Ando et al.
Fig. 5 Histological examination revealed that the tumors at C1–C2 consisted of bundles of longitudinally and transversely oriented Schwann cells crisscrossing each other in an irregular fashion and large ganglion cells with large vesicular nuclei, which we diagnosed
as ganglioneuroma (a). Tumors at C2–C3 and C3–C4 showed the same crisscrossing bundles of Schwann cells as the C1–C2 tumors but without the ganglion cells; we diagnosed these as neurofibromas (b)
significant mitotic activity, and the tumors’ MIB-1 indices were less than 1 %. There was no change in the amplitude and latency of spinal cord monitoring during surgery. The postoperative course was uneventful. The patient was immobilized for four days to prevent a cerebrospinal fluid fistula, and subsequent mobilization was well tolerated. Motor weakness and sensory disturbance improved within three weeks, except for the C3–C4 dermatome. The patient returned to his work two months after surgery. Follow-up MRI (two years after surgery) showed a highintensity lesion at the C1–C2 level and residual bilateral extradural tumors with moderate cord compression but without significant enlargement of residual tumors (Fig. 6a, b), and his Japanese Orthopaedics Association score had improved to 15 (3, 4, 1, 2, 2, 3). The patient and his parents gave informed consent to submit this case study for publication.
neurofibromas. Ganglioneuromas of the cervical spine are rare tumors associated with NF-1, with only five of these tumors confirmed pathologically and reported in the literature [7–10, 13] (Table 1). Ganglioneuromas reside within a class of neuronal tumor in which the neoplastic cells express a mature neuronal phenotype [14]. This type of tumor is slow-growing, benign, and characterized by a firm, round or oval, well-encapsulated mass with occasional lobulations [15]. They are mostly found in the posterior mediastinum and abdomen because they arise from the sympathetic nervous system [9]. The intraspinal portion of these tumors extended intradurally in 3 of 6 (50 %) reported cases, although it is believed that these tumors tended to extend extradurally, as in the present case. Ganglioneuromas associated with NF-1 may be another unusual feature. Neurofibromas are commonly associated with NF-1; they typically arise from the extradural portion of the spine, although they may be intradural in NF-2 patients [4]. In the present case, neurofibromas at C2–C3 and C3–C4 severely compressed the spinal cord intradurally. To our knowledge, this is the first report on the co-existence of ganglioneuromas and neurofibromas of the cervical spine. Only 1.6 %
Discussion We have presented a case of NF-1 with cervical myelopathy caused by dumbbell-shaped ganglioneuromas and
123
Cervical myelopathy caused by two different tumors with NF-1
Fig. 6 Follow-up MRI showed a high-intensity lesion at the C1–C2 level but there was no significant enlargement of residual tumors (a). An axial view revealed residual bilateral extradural tumors with moderate cord compression (b)
Table 1 Summary of previously published case reports with cervical ganglioneuroma in neurofibromatosis type 1 patients Patient number
Authors
Age/sex
Affected levels
Bilateral
Intraspinal extension
Multiplicity
Other tumors resected during surgery
1
Miyakoshi et al. [8]
15/male
C1–2, 3–4
?
Extradural
?
-
2
Bacci et al. [7]
32/female
C1, C4–7
?
n.s.
?
-
3
Shephard et al. [10]
35/male
C2–7
-
Intradural
?
-
4
Sinclair and Yang [13]
44/female
C2–5
-
Intradural
?
-
5
Kyoshima et al. [9]
35/male
C2–3
?
Intradural
?
-
6
This study
20/male
C1–2, 2–3, 3–4
?
Extradural
?
? (neurofibroma)
of NF-1 patients have symptoms, and these patients seldom need surgery [4]. Histological examination has been performed in a minority of NF-1-associated spinal tumors; therefore, we may speculate that the probability of finding both ganglioneuroma and neurofibroma in NF-1 patients might be higher than expected [7], although genetic associations between NF-1 and ganglioneuroma remain unclear [9]. For the tumors at C1–C2, we enucleated them for removal because the axial view MRI revealed bilateral extradural tumors. The intradural tumors at C2–C3 and C3–C4 were removed because they were located ventrally and mainly compressed spinal cord. Ganglioneuromas have well-differentiated cellular features and grow slowly. Serebrin and Robertson [16] described a 20-year follow-up of a very slow growing ganglioneuroma in the pituitary fossa. Coupled with an often well-circumscribed appearance,
total surgical excision remains the treatment of choice with large tumors [14]. Although surgical decompression must be undertaken as soon as possible when spinal cord compression is present [17], it may be impossible to completely excise multiple tumors at all sites, as in the present case. Subtotal or partial resection might be the goal for cases with multiple spinal tumors [8], but such patients should be carefully monitored for the rest of their lives, especially regarding spinal cord compression, due to the residual tumor.
Conclusions We reported on the case of a 20-year-old man with NF-1 who presented with cervical myelopathy caused by ganglioneuroma and neurofibroma. Although his neurological
123
K. Ando et al.
status improved after surgery, he will be followed carefully to watch for neurological symptoms resulting from growth of the residual tumors. Conflict of interest of interest.
The authors declare that they have no conflict
References 1. Huson SM, Harper PS, Compston DA. Von Recklinghausen neurofibromatosis. A clinical and population study in south-east Wales. Brain. 1988;111(Pt 6):1355–81. 2. Cawthon RM, Weiss R, Xu GF, Viskochil D, Culver M, Stevens J, Robertson M, Dunn D, Gesteland R, O’Connell P. A major segment of the neurofibromatosis type 1 gene: cDNA sequence, genomic structure, and point mutations. Cell. 1990;62(1): 193–201. 3. Mulvihill JJ, Parry DM, Sherman JL, Pikus A, Kaiser-Kupfer MI, Eldridge R. NIH conference. Neurofibromatosis 1 (Recklinghausen disease) and neurofibromatosis 2 (bilateral acoustic neurofibromatosis). An update. Ann Intern Med. 1990;113(1):39–52. 4. Thakkar SD, Feigen U, Mautner VF. Spinal tumours in neurofibromatosis type 1: an MRI study of frequency, multiplicity and variety. Neuroradiology. 1999;41(9):625–9. 5. Kluwe L, Tatagiba M, Funsterer C, Mautner VF. NF1 mutations and clinical spectrum in patients with spinal neurofibromas. J Med Genet. 2003;40(5):368–71. 6. Lonergan GJ, Schwab CM, Suarez ES, Carlson CL. Neuroblastoma, ganglioneuroblastoma, and ganglioneuroma: radiologic– pathologic correlation. Radiographics. 2002;22(4):911–34.
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