Intraventricular rhabdoid tumor
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《美国医学杂志》
1 Departments of Neurosurgery, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India
2 Departments of Neuroradiology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India
3 Departments of Neuropathology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India
Abstract
Malignant rhabdoid tumor (MRT) most commonly occurs in kidney. In the central nervous system, cerebellum is the most common site of occurrence. CNS rhabdoid tumors typically occur in small children, do not respond favorably to treatment and are usually fatal within 1-year. Here is reported a 4-year-old child who presented with features of raised intracranial pressure. Apart from papillodema, there were no neurological signs. Imaging revealed a left lateral ventricular heterogeneous mass abutting the foramen of monro, with mild irregular contrast enhancement and hydrocephalus. The child underwent right ventriculo-peritoneal shunt followed by craniotomy and gross total tumor resection. He was discharged 10-days after surgery without any neurological deficits. Histopathology revealed features compatible with rhabdoid tumor. Despite radiotherapy and chemotherapy, the child died of progressive disease 10-months after surgery. The highly malignant nature of this tumor makes early diagnosis essential for aggressive management and prognostication.
Keywords: Rhabdoid tumor; Brain; Lateral ventricle; CNS
Malignant rhabdoid tumor (MRT) is a rare aggressive childhood neoplasm, predominantly of renal origin. Beckwith and Palmer described a group of renal neoplasms with unique histological features while reviewing a large number of Wilms' tumors for the Children's cancer study group in 1978. They considered it a type of Wilms' tumor with rhabdomyosarcomatoid features because of abundant eosinophilic cytoplasm and virulent biological behavior.[1] However, neither immunohistochemical nor electron microscopic features of the tumor supported this diagnosis and they were named malignant rhabdoid tumor of the kidney by Haas et al in 1981.[2] It has been reported at several extra-renal sites, including the brain. They most frequently involve the posterior fossa but have been documented in the supratentorial compartment as well.[3],[4] Clinical features are non specific and depend upon the site of occurrence. MRT of brain occurs usually in children and carries a poor prognosis with frequent local recurrences and dissemination through CSF pathways.[5],[6] However no established protocol is available for treatment of rhabdoid tumor patients as yet.
Primary intraventricular MRT is extremely rare with only a handful of reported cases.[5],[7],[8],[9],[10] A rare case of a lateral ventricular MRT in a 4-year-old child is reported.
Case Report
A 4-year-old male child presented with one year history of headache and vomiting. The frequency of vomiting had increased in the last ten days and he had one episode of generalized seizure one day prior to admission. On examination, his vision was normal though he had bilateral gross papillodema. There was no motor, sensory or cranial nerve deficit. His chest X-ray, ultrasound of abdomen and urine routine and microscopic examination were within normal limits.
Contrast enhanced CT scan showed a well defined heterogeneous mass in the left lateral ventricle with hydrocephalus. Magnetic resonance imaging (MRI) revealed a large heterogeneous mass in the central part of the body of the left lateral ventricle, abutting the foramen of monro, with dilatation of the right lateral ventricle. The tumor was isointense on T1 and hyperintense on T2-W images, with cystic areas. Mild heterogeneous enhancement was seen on contrast administration Figure1A and B.
The child underwent right ventriculo-peritoneal shunt on second day of admission, followed by left fronto-parietal craniotomy and gross total excision of the tumor through transcallosal approach, five days later. The tumor was highly vascular, grayish pink, firm and suckable with Cavitron Ultrasonic aspirator (CUSA) with a softer central necrotic area. Post-operative CT scan showed decompressed ventricles with operative changes. There was no evidence of residual tumor or hematoma. Post-operative meningitis responded to antimeningitic treatment. There was no headache or neurologic deficit at discharge ten days after surgery.
Histopathology revealed sheets of typical rhabdoid cells with abundant cytoplasm and eccentric vesicular nuclei with prominent nucleoli Figure2A & B. Immunohistochemistry revealed tumor cells to be strongly positive for vimentin (VIM), epithelial membrane antigen (EMA), smooth muscle actin (SMA), focal positivity for glial fibrillary acid protein (GFAP) and synaptophysin Figure2C to F, thus confirming the diagnosis. Electron microscopy showed perinuclear aggregates of intermediate filaments. The child underwent radiotherapy and chemotherapy in post-operative period. However, he developed a recurrence ten months after surgery and died of progressive disease.
Discussion
Malignant rhabdoid tumor (MRT) is a rare and highly malignant childhood neoplasm. Several cases of primary intracranial MRT have been reported since its recognition as a separate entity in 1978.[1] The term "rhabdoid" was used due to its similarity with rhabdomyosarcoma under the light microscope. The exact pathogenesis of MRT is unknown, although a possible neuroectodermal origin for renal MRT has been proposed.[2] The cerebellum is the most common location for primary intracerebral MRT. Biggs et al were first to report a primary intracranial MRT.[6] A case of primary renal and brain MRT occurring concomitantly has also been reported.[3] Its highly invasive nature may in part be explained by the over expression of type-IV collagenases relative to tissue inhibitors of metalloproteases (TIMPs).[11]
The average age of presentation of primary MRT of brain is two years (with a range of one month to twelve years) with 1.9:1 male predominance.[12] However such tumors have also been described in the adults.[13]
Though the tumors were located in supratentorial compartment among 6 out of 11 patients reviewed from literature by Kumar R[14], most of the authors agree that posterior fossa is the most common site of occurrence.[7],[8],[10],[12],[13],[15],[16],[17]
Clinical features depend upon the location of the tumor, though features of raised intracranial pressure are common. Lethargy, ataxia, vomiting, headache, squint, seizures and irritability are common presenting features.[14] MRT has a marked tendency for subarachnoid dissemination,[10] which may be due its spread along Virchow-Robin spaces[3] and one-third of tumors already have CNS dissemination at presentation.[12] Pathologically, all tumors have rhabdoid cells with abundant eosinophilic cytoplasm, well defined round nuclei and prominent nucleolus. There are abundant mitosis and foci of necrosis are common. Reactive inflammatory cells are present in the background. Two-third of such tumors contain areas that, taken in isolation, would be classical primitive neuroectodermal tumors. The most common chromosomal abnormality involves chromosome 22.[12]
The imaging features usually are non-specific, showing zones of iso or slight hyperdensity alternating with cystic and necrotic hypodense areas, together with the occasional hyperdensity because of presence of calcification or hemorrhage. Contrast administration causes irregular enhancement pattern, which probably parallels the varied cellular composition of these neoplasms. On Magnetic resonance imaging, they are hypointense on T1WI and iso-to-hyper intense on T2WI, with inhomogeneous enhancement on contrast administration. Its heterogeneous appearance is because of presence of cystic and necrotic areas with occasional hemorrhagic changes and moderate to marked surrounding edema. Obstruction of CSF pathways can lead to hydrocephalus. The differential diagnosis must include ependymoma, choroid plexus papilloma, teratoma and especially PNET/medulloblastoma.[15] The earlier age of onset, larger size and polymorphic appearance help in differentiating MRT with PNETs.[16]
Prognosis for MRT is very poor despite surgical excision, irradiation and extensive chemotherapy. Median survival is six months.[12] However, aggressive multimodality treatment including radical surgery, multiagent chemotherapy, radiotherapy, intrathecal chemotherapy and stem cell rescue has prolonged the natural history in a subset of children.[18],[19]
The authors conclude that the possibility of primary intracranial MRT should be kept in the differential diagnosis of large malignant intracranial childhood neoplasms, especially if they have non-specific imaging findings and are present in the posterior fossa. Final diagnosis can only be made pathologically. The tumor has a particularly poor prognosis and is largely considered incurable at present, though few cases of long term survival with aggressive multimodality treatment have been reported. As compared to primitive neuroectodermal tumors, MRT has earlier age of onset, large size at presentation, varying density pattern and inhomogeneous enhancement on imaging and poorer prognosis.
References
1. Beckwith JB, Palmer NF. Histopathology and prognosis of Wilm's tumor: Results from First National Wilm's tumor study. Cancer 1978; 41: 1937-1948.
2. Haas JE, Palmer NF, Weinberg AG et al. Ultrastructure of the malignant rhabdoid tumor of the kidney. A distinctive renal tumor of the children. Hum Pathol 1981; 14: 107-115.
3. Caldemeyer KS, Smith RR, Azzarelli B et al. Primary central nervous system malignant rhabdoid tumor: CT and MR appearances simulates a primitive neuroectodermal tumor. Pediatr Neurosurg 1994; 21(4): 232-236.
4. Guessoum M, Christtmann D, Pimelli A et al. Rhabdoid tumor of central nervous system: US, CT scan nad MRI results in a male infant. J Neuroradiol 1977; 24: 60-64.
5. Agranovich AL, Ang LC, Griebel RW et al. Malignant rhabdoid tumor of the central nervous system with subarachnoid dissemination. Surg Neurol 1992; 37(5): 410-414.
6. Biggs PJ, Garen PD, Powers JM, Garvin AJ, Malignant rhabdoid tumor of the central nervous system. Hum Pathol 1987; 18(4): 332-337.
7. Bergmann M, Spaar JH, Ebhard G et al. Primary malignant rhabdoid tumors of the central nervous system: an immunohistochemical and ultrastructural study. Acta Neurochir (Wien) 1997; 139(10): 961-968.
8. Hanna SL, Langston JW, Parham DM et al. Primary malignant rhabdoid tumor of the brain: clinical imaging and pathological findings. Am J Neuroradiol 1993; 14(1): 107-115.
9. Briner J, Bannwart F, Kleihues P et al. Malignant small cell tumor of the brain with intermediate filaments - a case of primary cerebral rhabdoid tumor. Pediatr Pathol 1985; 3: 117-178.
10. Reinhardt D, Behnke-Mursch J, Christen H-J et al. Rhabdoid tumors of the central nervous system. Chilld's Nerv Syst 2000; 16: 228-234.
11. Muller M, Hubbard SL, Fukuyama K et al. Characterization of a pineal region malignant rhabdoid tumor: Towards understanding brain tumor cell invasion. Pediatr Neurosurg 1995; 22: 204-209.
12. Rorke LB, Packer R. Biegel J. Central nervous system atypical teratoid/rhabdoid tumors of infancy and childhood. Journal of Neuro-oncology 1995; 24: 21-28.
13. Arrazola J, Pedrosa I, Mendez R et al. Primary malignant rhabdoid tumor of the brain in an adult. Neuroradiol 2000; 42(5): 363-367.
14. Kumar R. Primary malignant rhabdoid tumours of brain, clinicoradiological findings of two cases. Neurol India 1999; 47: 314-317.(Ahmad Faiz Uddin, Suri As)
2 Departments of Neuroradiology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India
3 Departments of Neuropathology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India
Abstract
Malignant rhabdoid tumor (MRT) most commonly occurs in kidney. In the central nervous system, cerebellum is the most common site of occurrence. CNS rhabdoid tumors typically occur in small children, do not respond favorably to treatment and are usually fatal within 1-year. Here is reported a 4-year-old child who presented with features of raised intracranial pressure. Apart from papillodema, there were no neurological signs. Imaging revealed a left lateral ventricular heterogeneous mass abutting the foramen of monro, with mild irregular contrast enhancement and hydrocephalus. The child underwent right ventriculo-peritoneal shunt followed by craniotomy and gross total tumor resection. He was discharged 10-days after surgery without any neurological deficits. Histopathology revealed features compatible with rhabdoid tumor. Despite radiotherapy and chemotherapy, the child died of progressive disease 10-months after surgery. The highly malignant nature of this tumor makes early diagnosis essential for aggressive management and prognostication.
Keywords: Rhabdoid tumor; Brain; Lateral ventricle; CNS
Malignant rhabdoid tumor (MRT) is a rare aggressive childhood neoplasm, predominantly of renal origin. Beckwith and Palmer described a group of renal neoplasms with unique histological features while reviewing a large number of Wilms' tumors for the Children's cancer study group in 1978. They considered it a type of Wilms' tumor with rhabdomyosarcomatoid features because of abundant eosinophilic cytoplasm and virulent biological behavior.[1] However, neither immunohistochemical nor electron microscopic features of the tumor supported this diagnosis and they were named malignant rhabdoid tumor of the kidney by Haas et al in 1981.[2] It has been reported at several extra-renal sites, including the brain. They most frequently involve the posterior fossa but have been documented in the supratentorial compartment as well.[3],[4] Clinical features are non specific and depend upon the site of occurrence. MRT of brain occurs usually in children and carries a poor prognosis with frequent local recurrences and dissemination through CSF pathways.[5],[6] However no established protocol is available for treatment of rhabdoid tumor patients as yet.
Primary intraventricular MRT is extremely rare with only a handful of reported cases.[5],[7],[8],[9],[10] A rare case of a lateral ventricular MRT in a 4-year-old child is reported.
Case Report
A 4-year-old male child presented with one year history of headache and vomiting. The frequency of vomiting had increased in the last ten days and he had one episode of generalized seizure one day prior to admission. On examination, his vision was normal though he had bilateral gross papillodema. There was no motor, sensory or cranial nerve deficit. His chest X-ray, ultrasound of abdomen and urine routine and microscopic examination were within normal limits.
Contrast enhanced CT scan showed a well defined heterogeneous mass in the left lateral ventricle with hydrocephalus. Magnetic resonance imaging (MRI) revealed a large heterogeneous mass in the central part of the body of the left lateral ventricle, abutting the foramen of monro, with dilatation of the right lateral ventricle. The tumor was isointense on T1 and hyperintense on T2-W images, with cystic areas. Mild heterogeneous enhancement was seen on contrast administration Figure1A and B.
The child underwent right ventriculo-peritoneal shunt on second day of admission, followed by left fronto-parietal craniotomy and gross total excision of the tumor through transcallosal approach, five days later. The tumor was highly vascular, grayish pink, firm and suckable with Cavitron Ultrasonic aspirator (CUSA) with a softer central necrotic area. Post-operative CT scan showed decompressed ventricles with operative changes. There was no evidence of residual tumor or hematoma. Post-operative meningitis responded to antimeningitic treatment. There was no headache or neurologic deficit at discharge ten days after surgery.
Histopathology revealed sheets of typical rhabdoid cells with abundant cytoplasm and eccentric vesicular nuclei with prominent nucleoli Figure2A & B. Immunohistochemistry revealed tumor cells to be strongly positive for vimentin (VIM), epithelial membrane antigen (EMA), smooth muscle actin (SMA), focal positivity for glial fibrillary acid protein (GFAP) and synaptophysin Figure2C to F, thus confirming the diagnosis. Electron microscopy showed perinuclear aggregates of intermediate filaments. The child underwent radiotherapy and chemotherapy in post-operative period. However, he developed a recurrence ten months after surgery and died of progressive disease.
Discussion
Malignant rhabdoid tumor (MRT) is a rare and highly malignant childhood neoplasm. Several cases of primary intracranial MRT have been reported since its recognition as a separate entity in 1978.[1] The term "rhabdoid" was used due to its similarity with rhabdomyosarcoma under the light microscope. The exact pathogenesis of MRT is unknown, although a possible neuroectodermal origin for renal MRT has been proposed.[2] The cerebellum is the most common location for primary intracerebral MRT. Biggs et al were first to report a primary intracranial MRT.[6] A case of primary renal and brain MRT occurring concomitantly has also been reported.[3] Its highly invasive nature may in part be explained by the over expression of type-IV collagenases relative to tissue inhibitors of metalloproteases (TIMPs).[11]
The average age of presentation of primary MRT of brain is two years (with a range of one month to twelve years) with 1.9:1 male predominance.[12] However such tumors have also been described in the adults.[13]
Though the tumors were located in supratentorial compartment among 6 out of 11 patients reviewed from literature by Kumar R[14], most of the authors agree that posterior fossa is the most common site of occurrence.[7],[8],[10],[12],[13],[15],[16],[17]
Clinical features depend upon the location of the tumor, though features of raised intracranial pressure are common. Lethargy, ataxia, vomiting, headache, squint, seizures and irritability are common presenting features.[14] MRT has a marked tendency for subarachnoid dissemination,[10] which may be due its spread along Virchow-Robin spaces[3] and one-third of tumors already have CNS dissemination at presentation.[12] Pathologically, all tumors have rhabdoid cells with abundant eosinophilic cytoplasm, well defined round nuclei and prominent nucleolus. There are abundant mitosis and foci of necrosis are common. Reactive inflammatory cells are present in the background. Two-third of such tumors contain areas that, taken in isolation, would be classical primitive neuroectodermal tumors. The most common chromosomal abnormality involves chromosome 22.[12]
The imaging features usually are non-specific, showing zones of iso or slight hyperdensity alternating with cystic and necrotic hypodense areas, together with the occasional hyperdensity because of presence of calcification or hemorrhage. Contrast administration causes irregular enhancement pattern, which probably parallels the varied cellular composition of these neoplasms. On Magnetic resonance imaging, they are hypointense on T1WI and iso-to-hyper intense on T2WI, with inhomogeneous enhancement on contrast administration. Its heterogeneous appearance is because of presence of cystic and necrotic areas with occasional hemorrhagic changes and moderate to marked surrounding edema. Obstruction of CSF pathways can lead to hydrocephalus. The differential diagnosis must include ependymoma, choroid plexus papilloma, teratoma and especially PNET/medulloblastoma.[15] The earlier age of onset, larger size and polymorphic appearance help in differentiating MRT with PNETs.[16]
Prognosis for MRT is very poor despite surgical excision, irradiation and extensive chemotherapy. Median survival is six months.[12] However, aggressive multimodality treatment including radical surgery, multiagent chemotherapy, radiotherapy, intrathecal chemotherapy and stem cell rescue has prolonged the natural history in a subset of children.[18],[19]
The authors conclude that the possibility of primary intracranial MRT should be kept in the differential diagnosis of large malignant intracranial childhood neoplasms, especially if they have non-specific imaging findings and are present in the posterior fossa. Final diagnosis can only be made pathologically. The tumor has a particularly poor prognosis and is largely considered incurable at present, though few cases of long term survival with aggressive multimodality treatment have been reported. As compared to primitive neuroectodermal tumors, MRT has earlier age of onset, large size at presentation, varying density pattern and inhomogeneous enhancement on imaging and poorer prognosis.
References
1. Beckwith JB, Palmer NF. Histopathology and prognosis of Wilm's tumor: Results from First National Wilm's tumor study. Cancer 1978; 41: 1937-1948.
2. Haas JE, Palmer NF, Weinberg AG et al. Ultrastructure of the malignant rhabdoid tumor of the kidney. A distinctive renal tumor of the children. Hum Pathol 1981; 14: 107-115.
3. Caldemeyer KS, Smith RR, Azzarelli B et al. Primary central nervous system malignant rhabdoid tumor: CT and MR appearances simulates a primitive neuroectodermal tumor. Pediatr Neurosurg 1994; 21(4): 232-236.
4. Guessoum M, Christtmann D, Pimelli A et al. Rhabdoid tumor of central nervous system: US, CT scan nad MRI results in a male infant. J Neuroradiol 1977; 24: 60-64.
5. Agranovich AL, Ang LC, Griebel RW et al. Malignant rhabdoid tumor of the central nervous system with subarachnoid dissemination. Surg Neurol 1992; 37(5): 410-414.
6. Biggs PJ, Garen PD, Powers JM, Garvin AJ, Malignant rhabdoid tumor of the central nervous system. Hum Pathol 1987; 18(4): 332-337.
7. Bergmann M, Spaar JH, Ebhard G et al. Primary malignant rhabdoid tumors of the central nervous system: an immunohistochemical and ultrastructural study. Acta Neurochir (Wien) 1997; 139(10): 961-968.
8. Hanna SL, Langston JW, Parham DM et al. Primary malignant rhabdoid tumor of the brain: clinical imaging and pathological findings. Am J Neuroradiol 1993; 14(1): 107-115.
9. Briner J, Bannwart F, Kleihues P et al. Malignant small cell tumor of the brain with intermediate filaments - a case of primary cerebral rhabdoid tumor. Pediatr Pathol 1985; 3: 117-178.
10. Reinhardt D, Behnke-Mursch J, Christen H-J et al. Rhabdoid tumors of the central nervous system. Chilld's Nerv Syst 2000; 16: 228-234.
11. Muller M, Hubbard SL, Fukuyama K et al. Characterization of a pineal region malignant rhabdoid tumor: Towards understanding brain tumor cell invasion. Pediatr Neurosurg 1995; 22: 204-209.
12. Rorke LB, Packer R. Biegel J. Central nervous system atypical teratoid/rhabdoid tumors of infancy and childhood. Journal of Neuro-oncology 1995; 24: 21-28.
13. Arrazola J, Pedrosa I, Mendez R et al. Primary malignant rhabdoid tumor of the brain in an adult. Neuroradiol 2000; 42(5): 363-367.
14. Kumar R. Primary malignant rhabdoid tumours of brain, clinicoradiological findings of two cases. Neurol India 1999; 47: 314-317.(Ahmad Faiz Uddin, Suri As)