Original Article
Primary Intracranial Atypical Teratoid/ Rhabdoid Tumors: A Clinicopathologic and Neuroradiologic Study
Journal of Child Neurology 1-7 ª The Author(s) 2014 Reprints and permission: sagepub.com/journalsPermissions.nav DOI: 10.1177/0883073814551795 jcn.sagepub.com
Rui-jiao Zhao, MM1, Kai-yan Wu, BM1, Jian-guo Zhang, MD2, Yi-hui Ma, MD3, and Ling-fei Kong, MM1
Abstract Atypical teratoid/rhabdoid tumors are rare malignant pediatric brain tumors. This study was performed to characterize the clinicopathologic and neuroradiologic characteristics of atypical teratoid/rhabdoid tumors from 8 patients, including 5 male and 3 female infants (median age, 67 months). Neuroimaging revealed bulky masses of heterogeneous intensity with inhomogeneous enhancement. Three cases were infratentorial and 5 were supratentorial. Histopathologically, the tumors were predominantly composed of rhabdoid cells and undifferentiated small cells, mixed with some spindle or epithelial components. The tumors displayed striking polyphenotypic immunoreactivity, including varying degrees of positivity for vimentin, epithelial membrane antigen, smooth-muscle actin, cytokeratin, glial fibrillary acidic protein, neurofilament protein, synaptophysin, and CD99, and immunonegativity for desmin, placental alkaline phosphatase, and INI-1. The median survival duration was 9.5 months (range, 1-15 months) despite aggressive therapy. These results suggest that atypical teratoid/rhabdoid tumors display distinct clinicopathologic characteristics and indicate a poor prognosis. Immunohistochemistry facilitates the appropriate diagnosis of these tumors. Keywords atypical teratoid/rhabdoid tumor, brain neoplasm, immunohistochemistry, Prognosis Received April 24, 2014. Received revised August 26, 2014. Accepted for publication August 26, 2014.
Atypical teratoid/rhabdoid tumors are highly aggressive brain tumors described as a distinct entity in the late 1980s. They usually occur during early childhood,1-3 although they have been reported in adults as well.4,5 They may arise anywhere within the central nervous system with a predilection for the posterior fossa.1-3 In the past, this lesion has been misdiagnosed as a primitive neuroectodermal tumor/medulloblastoma or choroid plexus carcinoma because of their similar histologic and radiologic features.1-3 Neuroimaging typically displays a bulky mass of heterogeneous intensity with inhomogeneous enhancement, intratumoral hemorrhage, and subarachnoid spread.6-8 Histopathologically, the tumor is primarily composed of rhabdoid cells and undifferentiated small cells, as well as some mesenchymal or epithelial components.1-3,9,10 Distinction between atypical teratoid/rhabdoid tumor and other lesion types can now be made by its histopathology and multilineage antigen expression in combination with loss of nuclear INI1 protein expression and/or inactivation of the INI1/hSNF5 tumor suppressor gene locus at 22q11.2 in tumor cells.1-3,5,9-13 Proper recognition of this entity is important because it typically presents with a remarkably aggressive course and has a poor prognosis despite aggressive surgical treatment and adjuvant radiochemotherapy.1-3,14,15
In this report, the authors retrospectively review the clinicopathologic and neuroradiologic characteristics and outcomes of 8 patients with an atypical teratoid/rhabdoid tumor to emphasize the process of diagnosis and treatment and to assess patient outcomes.
Materials and Methods Patient Group and Clinical Review The authors retrospectively reviewed the medical records of 8 patients with a primary intracranial atypical teratoid/rhabdoid tumor between
1
Department of Pathology, The People’s Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of China 2 Department of Neurosurgery, The People’s Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of China 3 Department of Pathology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of China Corresponding Author: Jian-guo Zhang, MD, Department of Neurosurgery, The People’s Hospital of Zhengzhou University, No. 7 Weiwu Road, Zhengzhou 450003, Henan, People’s Republic of China. Email: [email protected]
2
Journal of Child Neurology
Table 1. Clinical Information, Treatment, and Outcome of 8 Patients With an Atypical Teratoid/Rhabdoid Tumor. Patient (no.)
Age (mo)
Initial Gender symptoms
Tumor location
Male
Right cerebellopontine angle Left frontal lobe Vermis and the fourth ventricle Left occipital lobe Left occipital lobe
1
24
2 3
26 18
Deviation of the mouth and the eyes Female Right limbs weakness Female Vomiting
4 5
108 264
Male Male
6 7
24 144
8 144 Median 67 Range 18-264
Headache, vomiting Headache, vomiting, visual disturbances Male Nausea, vomiting, seizures Female Headache, vomiting, gait disturbance Male Headache, seizures
Tumor Surgical Postoperative size (cm) resection treatment
Left lateral ventricle Right cerebellar hemisphere Right temporal lobe
2003 and 2012 at The People’s Hospital of Zhengzhou University or The First Affiliated Hospital of Zhengzhou University. The diagnoses were based on the pathologic and immunohistochemical findings according to the World Health Organization (WHO) classification criteria of tumors of the central nervous system.13 The clinical characteristics of the patients were documented, including sex, age at diagnosis, initial symptoms, tumor location, tumor size, extent of surgical resection, postoperative adjuvant chemotherapy and/or radiotherapy, and outcome. All patients underwent maximal possible surgical resection of the primary lesion consistent with preservation of neurologic function. The extent of surgical resection was defined as partial (60%-90% of tumor removal), subtotal (>90% of tumor removal), or gross total resection (no distinct residual tumor) based on the operative reports and immediate (
Primary Intracranial Atypical Teratoid/ Rhabdoid Tumors: A Clinicopathologic and Neuroradiologic Study
Journal of Child Neurology 1-7 ª The Author(s) 2014 Reprints and permission: sagepub.com/journalsPermissions.nav DOI: 10.1177/0883073814551795 jcn.sagepub.com
Rui-jiao Zhao, MM1, Kai-yan Wu, BM1, Jian-guo Zhang, MD2, Yi-hui Ma, MD3, and Ling-fei Kong, MM1
Abstract Atypical teratoid/rhabdoid tumors are rare malignant pediatric brain tumors. This study was performed to characterize the clinicopathologic and neuroradiologic characteristics of atypical teratoid/rhabdoid tumors from 8 patients, including 5 male and 3 female infants (median age, 67 months). Neuroimaging revealed bulky masses of heterogeneous intensity with inhomogeneous enhancement. Three cases were infratentorial and 5 were supratentorial. Histopathologically, the tumors were predominantly composed of rhabdoid cells and undifferentiated small cells, mixed with some spindle or epithelial components. The tumors displayed striking polyphenotypic immunoreactivity, including varying degrees of positivity for vimentin, epithelial membrane antigen, smooth-muscle actin, cytokeratin, glial fibrillary acidic protein, neurofilament protein, synaptophysin, and CD99, and immunonegativity for desmin, placental alkaline phosphatase, and INI-1. The median survival duration was 9.5 months (range, 1-15 months) despite aggressive therapy. These results suggest that atypical teratoid/rhabdoid tumors display distinct clinicopathologic characteristics and indicate a poor prognosis. Immunohistochemistry facilitates the appropriate diagnosis of these tumors. Keywords atypical teratoid/rhabdoid tumor, brain neoplasm, immunohistochemistry, Prognosis Received April 24, 2014. Received revised August 26, 2014. Accepted for publication August 26, 2014.
Atypical teratoid/rhabdoid tumors are highly aggressive brain tumors described as a distinct entity in the late 1980s. They usually occur during early childhood,1-3 although they have been reported in adults as well.4,5 They may arise anywhere within the central nervous system with a predilection for the posterior fossa.1-3 In the past, this lesion has been misdiagnosed as a primitive neuroectodermal tumor/medulloblastoma or choroid plexus carcinoma because of their similar histologic and radiologic features.1-3 Neuroimaging typically displays a bulky mass of heterogeneous intensity with inhomogeneous enhancement, intratumoral hemorrhage, and subarachnoid spread.6-8 Histopathologically, the tumor is primarily composed of rhabdoid cells and undifferentiated small cells, as well as some mesenchymal or epithelial components.1-3,9,10 Distinction between atypical teratoid/rhabdoid tumor and other lesion types can now be made by its histopathology and multilineage antigen expression in combination with loss of nuclear INI1 protein expression and/or inactivation of the INI1/hSNF5 tumor suppressor gene locus at 22q11.2 in tumor cells.1-3,5,9-13 Proper recognition of this entity is important because it typically presents with a remarkably aggressive course and has a poor prognosis despite aggressive surgical treatment and adjuvant radiochemotherapy.1-3,14,15
In this report, the authors retrospectively review the clinicopathologic and neuroradiologic characteristics and outcomes of 8 patients with an atypical teratoid/rhabdoid tumor to emphasize the process of diagnosis and treatment and to assess patient outcomes.
Materials and Methods Patient Group and Clinical Review The authors retrospectively reviewed the medical records of 8 patients with a primary intracranial atypical teratoid/rhabdoid tumor between
1
Department of Pathology, The People’s Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of China 2 Department of Neurosurgery, The People’s Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of China 3 Department of Pathology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of China Corresponding Author: Jian-guo Zhang, MD, Department of Neurosurgery, The People’s Hospital of Zhengzhou University, No. 7 Weiwu Road, Zhengzhou 450003, Henan, People’s Republic of China. Email: [email protected]
2
Journal of Child Neurology
Table 1. Clinical Information, Treatment, and Outcome of 8 Patients With an Atypical Teratoid/Rhabdoid Tumor. Patient (no.)
Age (mo)
Initial Gender symptoms
Tumor location
Male
Right cerebellopontine angle Left frontal lobe Vermis and the fourth ventricle Left occipital lobe Left occipital lobe
1
24
2 3
26 18
Deviation of the mouth and the eyes Female Right limbs weakness Female Vomiting
4 5
108 264
Male Male
6 7
24 144
8 144 Median 67 Range 18-264
Headache, vomiting Headache, vomiting, visual disturbances Male Nausea, vomiting, seizures Female Headache, vomiting, gait disturbance Male Headache, seizures
Tumor Surgical Postoperative size (cm) resection treatment
Left lateral ventricle Right cerebellar hemisphere Right temporal lobe
2003 and 2012 at The People’s Hospital of Zhengzhou University or The First Affiliated Hospital of Zhengzhou University. The diagnoses were based on the pathologic and immunohistochemical findings according to the World Health Organization (WHO) classification criteria of tumors of the central nervous system.13 The clinical characteristics of the patients were documented, including sex, age at diagnosis, initial symptoms, tumor location, tumor size, extent of surgical resection, postoperative adjuvant chemotherapy and/or radiotherapy, and outcome. All patients underwent maximal possible surgical resection of the primary lesion consistent with preservation of neurologic function. The extent of surgical resection was defined as partial (60%-90% of tumor removal), subtotal (>90% of tumor removal), or gross total resection (no distinct residual tumor) based on the operative reports and immediate (
