Childs Nerv Syst DOI 10.1007/s00381-014-2532-2
CASE REPORT
Intracerebellar malignant nerve sheath tumor in a child: case report and review of literature Krishna Chaitanya Joshi & Hariprakash Chakravarthy & Nirmala Subramanian
Received: 31 July 2014 / Accepted: 13 August 2014 # Springer-Verlag Berlin Heidelberg 2014
Abstract Purpose Intracerebellar malignant nerve sheath tumor (ICMNST) is an extremely rare entity, only two cases have been reported previously, and this is the first case to be reported in a child. The histogenesis, diagnosis, and management of this entity are very ambiguous, and natural history in a child is unknown. Methods The authors report a 7-year-old girl who presented with ataxia and signs of raised intracranial pressure and discuss the challenges in diagnosis, surgical strategy, and treatment. Results Following gross total resection and radiation to tumor bed, the patient had unremarkable recovery and is recurrence free at 1-year follow-up. Conclusion ICMNSTs are extremely rare tumors of the cerebellum. Preoperative radiological diagnosis is not possible due to its close radiological resemblance to other common posterior fossa tumors. Immunohistochemistry plays a pivotal role in clinching the diagnosis. Though the reported adult counterparts have shown dismal prognosis, the pediatric counterparts may fare better with good surgical resection followed by radiotherapy.
Keywords Malignant peripheral nerve sheath tumors . Intracerebellar schwannoma . Immunohistochemistry
K. C. Joshi (*) : H. Chakravarthy : N. Subramanian Department of Neurosurgery, M. S. Ramaiah Medical College, MSRIT Post, New BEL Road, Bangalore 560055, India e-mail: [email protected] H. Chakravarthy e-mail: [email protected] N. Subramanian e-mail: [email protected]
Introduction Malignant peripheral nerve sheath tumors (MPNSTs) are rare soft tissue sarcomas of ectomesenchymal origin. Intracranial intraparenchymal schwannomas represent 0.6 % of all central and peripheral nervous system tumors [1], and only two cases of intracerebellar malignant nerve sheath tumor have ever been reported so far. Both the cases were adult females, and this is the first case reported an intracerebellar malignant nerve sheath tumor (ICMNST) in a child. The natural history of these tumors has been uniformly dismal. The behavior of these tumors in children is largely unknown. Clinical presentation of these tumors is nonspecific, and imaging alone is usually not enough to identify and diagnose these lesions. Radiologically ICMNST should be differentiated from other cerebellar lesions like medulloblastoma, pilocytic astrocytoma, and hemangioblastoma. A definitive diagnosis requires histopathological examination, and immunohistochemical markers play a vital role in confirmation of diagnosis. Complete surgical removal of the tumor or element of origin remains to be the most effective treatment for these tumors. The role of adjuvant radiotherapy and chemotherapy in ICMNST is yet to be fully elucidated.
Case report A 7-year-old girl was admitted to the department of neurosurgery with a history of headache and vomiting from the past week. She also complained of dizziness and imbalance of gait. On examination, the child was dull and irritable. Neurological examination revealed nystagmus, impaired finger-nose test, dysdiadochokinesia on the right side, and bilateral papilledema. There were no cranial nerve deficits, and sensory motor examination was unremarkable. Physical examination did not reveal any stigmata of neurocutaneous disorders.
Childs Nerv Syst Fig. 1 a Axial T1-weighted MRI showing the isointense intra-axial mass in the right cerebellar hemisphere. b Axial T2-weighted MRI showing isointense mass with areas of surrounding hyperintensity representing the CSF caps. c Single-voxel MR spectroscopy showing a choline peak and drop in NAA. d, e, f Axial, sagittal, and coronal contrast images showing the heterogeneously enhancing intraaxial lesion with internal septations
Computed tomographic scan demonstrated a well-defined hyperdense lesion measuring 3.5×5.3 cm in the right cerebellar hemisphere with mild perilesional edema. The lesion showed areas of calcification and necrosis. The fourth ventricle was compressed due to the mass effect, resulting in obstructive hydrocephalus. Contrast-enhanced magnetic resonance imaging showed an intra-axial irregular well-defined mass, which was isointense to hypointense on T1-weighted images, isointense on T2-weighted images with areas of hyperintensities on the periphery, suggesting a CSF cap. The
Fig. 2 Intraoperative image showing the grayish tumor (within the white circle), with ill-defined borders. Areas of hemorrhage are seen on the surface
lesion was heterogeneously enhancing. Single-voxel MR spectroscopy revealed a choline peak with absent Nacetylaspartate (NAA) peak (Fig. 1). Right suboccipital craniotomy was performed. Tumor was soft at the center, with firm areas in the periphery. Tumor appeared grayish, myxoid in consistency, and moderately vascular (Fig. 2). There was a large draining vein in the periphery. External ventricular drain was placed through the right occipital burr hole. Patient was immediately extubated. Postoperative CT scan (Fig. 3) did not show any significant residue, and hydrocephalus was resolved. Her postoperative recovery was unremarkable. Histopathological examination revealed a high-grade tumor composed of predominantly spindle to polygonal cells in sheets, infiltrating the cerebellar folia. Cells were compactly arranged with nuclear hyperchromasia and increased mitosis. Cytoplasm was scanty and eosinophilic. No rosettes were seen. There were focal calcifications. Immunohistochemical examination revealed focal but definite positivity for S-100 and vimentin. Glial fibrillary acidic protein (GFAP),
Fig. 3 a Preoperative CT scan showing the hyperdense intra-axial mass. b Postoperative CT scan showing complete excision of the mass
Childs Nerv Syst
Fig. 4 Histopathology slides. a Hematoxylin and eosin (H and E) stain showing spindle-shaped cells arranged in sheaths with prominent nuclei. b S-100 staining shows patchy cytoplasmic and nuclear positivity in the tumor cells suggestive of nerve sheath tumor. c CD34 stain showing no uptake in the tumor cells with capillary pericytes showing positivity,
which rules out hemangiopericytoma. d Uptake for INI-1 in tumor cells was negative which rules out atypical teratoid rhabdoid tumor. e MIB staining showed uptake in tumor cells with an MIB index of 8 %. f Synaptophysin stain in the normal cerebellar tissue with no uptake by the tumor cells rules out a tumor of neuronal origin
synaptophysin, CD34, epithelial membrane antigen (EMA), Integrase interactor 1 (INI-1), and desmin were negative, and MIB-1 index was 8 %; on the basis of these findings, a histopathological and immunohistochemical diagnosis of a highly malignant nerve sheath tumor was made (Fig. 4). Postoperatively, the child received 6,000-cGy radiation in 30 fractions to the tumor bed from a 6-mV LINAC, with IMRT technique. She is currently doing well at 1 year after surgery; follow-up contrast MRI does not show any
recurrence. She is attending school and is able to perform her daily activities without any assistance.
Discussion Intracerebellar schwannomas are extremely rare entities; a MEDLINE search revealed that only 15 cases have been reported in English literature so far, of which only two cases were
Table 1 Data of the reported cases of intracerebellar malignant nerve sheath tumors Reference
Year
Patient age (in years), sex
Tumor site
Surgery
RT
Recurrence (in months)
Follow-up (in months)
Singh et al. [2] Maiuri et al. [3] Current patient
1993 2004 2014
61, F 29, F 8, F
Right cerebellar Vermian Right cerebellar
TR TR TR
RT – RT
8 8 –
18, dead 8, dead 12, alive
TR total resection, RT radiotherapy
Childs Nerv Syst
ICMNST. Up until now, there has been no report of a case of malignant nerve sheath tumor in a child, and to the best of our knowledge, this has been the first case. The age of the patients in the 15 cases ranged from 8 to 79 years (average 45 years). Singh et al. [2] first described a case of malignant schwannoma of the right cerebellar hemisphere in a 61-year-old female who had presented with signs of raised intracranial tension (ICT) and ataxia. Patient underwent a suboccipital craniotomy and tumor excision but died after 18 months with a tumor recurrence. Maiuri et al. [3] described a 29year-old female, with a vermian mass, who also presented with signs of raised ICT and ataxia, and the patient survived only 8 months after surgery. Similar to the two patients reported, our patient is also a female and presented with signs of raised ICT and ataxia. Table 1 summarizes all reported cases of ICMNST to date. Malignant intracerebellar nerve sheath tumor is an enigmatic entity. Theories about the origin of these tumors are filled with ambiguity. Arthur Purdy Stout (1885–1967) was a pioneering pathologist and has played a pivotal role in understanding the origin of nerve sheath tumors. He demonstrated that these tumors arise from Schwann cells [4]. Though this might be true for the benign counterparts arising from peripheral nerves, the origin of malignant intracerebral nerve sheath tumors is elusive. Histogenesis of these tumors is thought to occur from the perivascular nerve plexus of the brain [5] and the spinal cord [1]. Prakash et al. [6] stated that myelinated fibers with Schwann cells can be found in the brain substance as hamartomatous malformations. Considering the young age of the patient, a developmental origin has also been suggested. The possibility of these tumors originating from displaced neural crest cells [7] or differentiation of multipotent mesenchymal elements [8] cannot be ruled out. Immunohistochemistry plays a pivotal role in diagnosing these lesions. In our case, the absence of GFAP rules out gliomas and desmoplastic infantile ganglioglioma, and the absence of EMA, desmin, and CD34 excludes hemangiopericytoma and melanoma. As per Gupta and Maniker [9], malignant intracerebral nerve sheath tumors express S-100; interestingly, others [10] have found a loss of S-100 protein positivity in recurrent undifferentiated malignant schwannoma. A greater than 5 % cellular sharing with
MIB-1 proliferative markers indicates the presence of a highgrade tumor as in our case.
Conclusion ICMNST is an extremely rare tumor in childhood. The clinical course and the natural history of these tumors are largely unknown in childhood. Though their counterparts in adults have shown a dismal prognosis, children might have a better prognosis, as in our case. Awareness of this tumor, extensive surgical excision, thorough histological examination, and immunohistochemistry serve as essential components in diagnosis and management. Postoperative radiotherapy might help in preventing recurrences and increasing the disease-free interval. Further studies in this entity might shed some light into the histogenesis of intracerebral schwannomas.
References 1. Casadei GP, Komori T, Scheithauer BW, Miller GM, Parisi JE, Kelly PJ (1993) Intracranial parenchymal schwannoma. J Neurosurg 79: 217–222 2. Singh RV, Suys S, Campbell DA, Broome JC (1993) Malignant schwannoma of the cerebellum: case report. Surg Neurol 39:128–132 3. Maiuri F, Colella G, D’Acunzi G, De Caro Mdel B (2004) Malignant intracerebellar schwannoma. J Neuro-Oncol 66:191–195 4. Stout AP (1949) tumors of peripheral nervous system. In: Stout AP (ed) Atlas of tumor pathology. Armed Forces Institute of Pathology, Washington D.C. 5. MJ P (1972) The physiology of cerebral circulation. The physiology of cerebral circulation. Cambridge University Press, London, pp 44– 68 6. Prakash B, Roy S, Tandon PN (1980) Schwannoma of the brain stem. J Neurosurg 53:121–123 7. Frim DM, Ogilvy CS, Vonsattal JP, Chapman PH (1992) Is intracerebral schwannoma a developmental tumor of children and young adults? Pediatr Neurosurg 18:190–194 8. FEIGIN I, OGATA J (1971) Schwann cells and peripheral myelin within human central nervous tissues: the mesenchymal character of Schwann cells. J Neuropathol Exp Neurol 30:603–612 9. Gupta G, Maniker A (2007) Malignant peripheral nerve sheath tumors. Neurosurg Focus 22:1–8 10. Akimoto J, Ito H, Kudo M (2000) Primary intracranial malignant schwannoma of trigeminal nerve. A case report with review of the literature. Acta Neurochir 142:591–595
CASE REPORT
Intracerebellar malignant nerve sheath tumor in a child: case report and review of literature Krishna Chaitanya Joshi & Hariprakash Chakravarthy & Nirmala Subramanian
Received: 31 July 2014 / Accepted: 13 August 2014 # Springer-Verlag Berlin Heidelberg 2014
Abstract Purpose Intracerebellar malignant nerve sheath tumor (ICMNST) is an extremely rare entity, only two cases have been reported previously, and this is the first case to be reported in a child. The histogenesis, diagnosis, and management of this entity are very ambiguous, and natural history in a child is unknown. Methods The authors report a 7-year-old girl who presented with ataxia and signs of raised intracranial pressure and discuss the challenges in diagnosis, surgical strategy, and treatment. Results Following gross total resection and radiation to tumor bed, the patient had unremarkable recovery and is recurrence free at 1-year follow-up. Conclusion ICMNSTs are extremely rare tumors of the cerebellum. Preoperative radiological diagnosis is not possible due to its close radiological resemblance to other common posterior fossa tumors. Immunohistochemistry plays a pivotal role in clinching the diagnosis. Though the reported adult counterparts have shown dismal prognosis, the pediatric counterparts may fare better with good surgical resection followed by radiotherapy.
Keywords Malignant peripheral nerve sheath tumors . Intracerebellar schwannoma . Immunohistochemistry
K. C. Joshi (*) : H. Chakravarthy : N. Subramanian Department of Neurosurgery, M. S. Ramaiah Medical College, MSRIT Post, New BEL Road, Bangalore 560055, India e-mail: [email protected] H. Chakravarthy e-mail: [email protected] N. Subramanian e-mail: [email protected]
Introduction Malignant peripheral nerve sheath tumors (MPNSTs) are rare soft tissue sarcomas of ectomesenchymal origin. Intracranial intraparenchymal schwannomas represent 0.6 % of all central and peripheral nervous system tumors [1], and only two cases of intracerebellar malignant nerve sheath tumor have ever been reported so far. Both the cases were adult females, and this is the first case reported an intracerebellar malignant nerve sheath tumor (ICMNST) in a child. The natural history of these tumors has been uniformly dismal. The behavior of these tumors in children is largely unknown. Clinical presentation of these tumors is nonspecific, and imaging alone is usually not enough to identify and diagnose these lesions. Radiologically ICMNST should be differentiated from other cerebellar lesions like medulloblastoma, pilocytic astrocytoma, and hemangioblastoma. A definitive diagnosis requires histopathological examination, and immunohistochemical markers play a vital role in confirmation of diagnosis. Complete surgical removal of the tumor or element of origin remains to be the most effective treatment for these tumors. The role of adjuvant radiotherapy and chemotherapy in ICMNST is yet to be fully elucidated.
Case report A 7-year-old girl was admitted to the department of neurosurgery with a history of headache and vomiting from the past week. She also complained of dizziness and imbalance of gait. On examination, the child was dull and irritable. Neurological examination revealed nystagmus, impaired finger-nose test, dysdiadochokinesia on the right side, and bilateral papilledema. There were no cranial nerve deficits, and sensory motor examination was unremarkable. Physical examination did not reveal any stigmata of neurocutaneous disorders.
Childs Nerv Syst Fig. 1 a Axial T1-weighted MRI showing the isointense intra-axial mass in the right cerebellar hemisphere. b Axial T2-weighted MRI showing isointense mass with areas of surrounding hyperintensity representing the CSF caps. c Single-voxel MR spectroscopy showing a choline peak and drop in NAA. d, e, f Axial, sagittal, and coronal contrast images showing the heterogeneously enhancing intraaxial lesion with internal septations
Computed tomographic scan demonstrated a well-defined hyperdense lesion measuring 3.5×5.3 cm in the right cerebellar hemisphere with mild perilesional edema. The lesion showed areas of calcification and necrosis. The fourth ventricle was compressed due to the mass effect, resulting in obstructive hydrocephalus. Contrast-enhanced magnetic resonance imaging showed an intra-axial irregular well-defined mass, which was isointense to hypointense on T1-weighted images, isointense on T2-weighted images with areas of hyperintensities on the periphery, suggesting a CSF cap. The
Fig. 2 Intraoperative image showing the grayish tumor (within the white circle), with ill-defined borders. Areas of hemorrhage are seen on the surface
lesion was heterogeneously enhancing. Single-voxel MR spectroscopy revealed a choline peak with absent Nacetylaspartate (NAA) peak (Fig. 1). Right suboccipital craniotomy was performed. Tumor was soft at the center, with firm areas in the periphery. Tumor appeared grayish, myxoid in consistency, and moderately vascular (Fig. 2). There was a large draining vein in the periphery. External ventricular drain was placed through the right occipital burr hole. Patient was immediately extubated. Postoperative CT scan (Fig. 3) did not show any significant residue, and hydrocephalus was resolved. Her postoperative recovery was unremarkable. Histopathological examination revealed a high-grade tumor composed of predominantly spindle to polygonal cells in sheets, infiltrating the cerebellar folia. Cells were compactly arranged with nuclear hyperchromasia and increased mitosis. Cytoplasm was scanty and eosinophilic. No rosettes were seen. There were focal calcifications. Immunohistochemical examination revealed focal but definite positivity for S-100 and vimentin. Glial fibrillary acidic protein (GFAP),
Fig. 3 a Preoperative CT scan showing the hyperdense intra-axial mass. b Postoperative CT scan showing complete excision of the mass
Childs Nerv Syst
Fig. 4 Histopathology slides. a Hematoxylin and eosin (H and E) stain showing spindle-shaped cells arranged in sheaths with prominent nuclei. b S-100 staining shows patchy cytoplasmic and nuclear positivity in the tumor cells suggestive of nerve sheath tumor. c CD34 stain showing no uptake in the tumor cells with capillary pericytes showing positivity,
which rules out hemangiopericytoma. d Uptake for INI-1 in tumor cells was negative which rules out atypical teratoid rhabdoid tumor. e MIB staining showed uptake in tumor cells with an MIB index of 8 %. f Synaptophysin stain in the normal cerebellar tissue with no uptake by the tumor cells rules out a tumor of neuronal origin
synaptophysin, CD34, epithelial membrane antigen (EMA), Integrase interactor 1 (INI-1), and desmin were negative, and MIB-1 index was 8 %; on the basis of these findings, a histopathological and immunohistochemical diagnosis of a highly malignant nerve sheath tumor was made (Fig. 4). Postoperatively, the child received 6,000-cGy radiation in 30 fractions to the tumor bed from a 6-mV LINAC, with IMRT technique. She is currently doing well at 1 year after surgery; follow-up contrast MRI does not show any
recurrence. She is attending school and is able to perform her daily activities without any assistance.
Discussion Intracerebellar schwannomas are extremely rare entities; a MEDLINE search revealed that only 15 cases have been reported in English literature so far, of which only two cases were
Table 1 Data of the reported cases of intracerebellar malignant nerve sheath tumors Reference
Year
Patient age (in years), sex
Tumor site
Surgery
RT
Recurrence (in months)
Follow-up (in months)
Singh et al. [2] Maiuri et al. [3] Current patient
1993 2004 2014
61, F 29, F 8, F
Right cerebellar Vermian Right cerebellar
TR TR TR
RT – RT
8 8 –
18, dead 8, dead 12, alive
TR total resection, RT radiotherapy
Childs Nerv Syst
ICMNST. Up until now, there has been no report of a case of malignant nerve sheath tumor in a child, and to the best of our knowledge, this has been the first case. The age of the patients in the 15 cases ranged from 8 to 79 years (average 45 years). Singh et al. [2] first described a case of malignant schwannoma of the right cerebellar hemisphere in a 61-year-old female who had presented with signs of raised intracranial tension (ICT) and ataxia. Patient underwent a suboccipital craniotomy and tumor excision but died after 18 months with a tumor recurrence. Maiuri et al. [3] described a 29year-old female, with a vermian mass, who also presented with signs of raised ICT and ataxia, and the patient survived only 8 months after surgery. Similar to the two patients reported, our patient is also a female and presented with signs of raised ICT and ataxia. Table 1 summarizes all reported cases of ICMNST to date. Malignant intracerebellar nerve sheath tumor is an enigmatic entity. Theories about the origin of these tumors are filled with ambiguity. Arthur Purdy Stout (1885–1967) was a pioneering pathologist and has played a pivotal role in understanding the origin of nerve sheath tumors. He demonstrated that these tumors arise from Schwann cells [4]. Though this might be true for the benign counterparts arising from peripheral nerves, the origin of malignant intracerebral nerve sheath tumors is elusive. Histogenesis of these tumors is thought to occur from the perivascular nerve plexus of the brain [5] and the spinal cord [1]. Prakash et al. [6] stated that myelinated fibers with Schwann cells can be found in the brain substance as hamartomatous malformations. Considering the young age of the patient, a developmental origin has also been suggested. The possibility of these tumors originating from displaced neural crest cells [7] or differentiation of multipotent mesenchymal elements [8] cannot be ruled out. Immunohistochemistry plays a pivotal role in diagnosing these lesions. In our case, the absence of GFAP rules out gliomas and desmoplastic infantile ganglioglioma, and the absence of EMA, desmin, and CD34 excludes hemangiopericytoma and melanoma. As per Gupta and Maniker [9], malignant intracerebral nerve sheath tumors express S-100; interestingly, others [10] have found a loss of S-100 protein positivity in recurrent undifferentiated malignant schwannoma. A greater than 5 % cellular sharing with
MIB-1 proliferative markers indicates the presence of a highgrade tumor as in our case.
Conclusion ICMNST is an extremely rare tumor in childhood. The clinical course and the natural history of these tumors are largely unknown in childhood. Though their counterparts in adults have shown a dismal prognosis, children might have a better prognosis, as in our case. Awareness of this tumor, extensive surgical excision, thorough histological examination, and immunohistochemistry serve as essential components in diagnosis and management. Postoperative radiotherapy might help in preventing recurrences and increasing the disease-free interval. Further studies in this entity might shed some light into the histogenesis of intracerebral schwannomas.
References 1. Casadei GP, Komori T, Scheithauer BW, Miller GM, Parisi JE, Kelly PJ (1993) Intracranial parenchymal schwannoma. J Neurosurg 79: 217–222 2. Singh RV, Suys S, Campbell DA, Broome JC (1993) Malignant schwannoma of the cerebellum: case report. Surg Neurol 39:128–132 3. Maiuri F, Colella G, D’Acunzi G, De Caro Mdel B (2004) Malignant intracerebellar schwannoma. J Neuro-Oncol 66:191–195 4. Stout AP (1949) tumors of peripheral nervous system. In: Stout AP (ed) Atlas of tumor pathology. Armed Forces Institute of Pathology, Washington D.C. 5. MJ P (1972) The physiology of cerebral circulation. The physiology of cerebral circulation. Cambridge University Press, London, pp 44– 68 6. Prakash B, Roy S, Tandon PN (1980) Schwannoma of the brain stem. J Neurosurg 53:121–123 7. Frim DM, Ogilvy CS, Vonsattal JP, Chapman PH (1992) Is intracerebral schwannoma a developmental tumor of children and young adults? Pediatr Neurosurg 18:190–194 8. FEIGIN I, OGATA J (1971) Schwann cells and peripheral myelin within human central nervous tissues: the mesenchymal character of Schwann cells. J Neuropathol Exp Neurol 30:603–612 9. Gupta G, Maniker A (2007) Malignant peripheral nerve sheath tumors. Neurosurg Focus 22:1–8 10. Akimoto J, Ito H, Kudo M (2000) Primary intracranial malignant schwannoma of trigeminal nerve. A case report with review of the literature. Acta Neurochir 142:591–595
