Neuroradiological Findings in Atypical Teratoid/ Rhabdoid Tumor of the Central Nervous System
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1 cta Radiologica ISSN: (Print) (Online) Journal homepage: Neuroradiological Findings in typical Teratoid/ Rhabdoid Tumor of the entral Nervous System Y.. heng, J. F. Lirng, F.. hang, W. Y. Guo, M. M. H. Teng,. Y. hang, T. T. Wong & D. M. T. Ho To cite this article: Y.. heng, J. F. Lirng, F.. hang, W. Y. Guo, M. M. H. Teng,. Y. hang, T. T. Wong & D. M. T. Ho (2005) Neuroradiological Findings in typical Teratoid/Rhabdoid Tumor of the entral Nervous System, cta Radiologica, 46:1, To link to this article: Published online: 09 Jul Submit your article to this journal rticle views: 150 Full Terms & onditions of access and use can be found at
2 ORIGINL RTILE T RDIOLOGI Neuroradiological Findings in typical Teratoid/Rhabdoid Tumor of the entral Nervous System Y.-. HENG, J.-F. LIRNG, F.-. HNG, W.-Y. GUO, M. M.-H. TENG,.-Y. HNG, T.-T. WONG & D. M.-T. HO Department of Radiology, I-Lan Hospital, Department of Health, The Executive Yuan, I-Lan, Taiwan, R.O..; National Yang-Ming University, School of Medicine, Taipei, Taiwan; Department of Radiology, Taipei Veterans General Hospital, Taipei, Taiwan, R.O..; National Yang-Ming University, School of Medicine, Taipei, Taiwan; Section of Pediatric Neurosurgery, Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan, R.O..; Department of Pathology, Taipei Veterans General Hospital, Taipei, Taiwan, R.O.. heng Y-, Lirng J-F, hang F-, Guo W-Y, Teng MM-H, hang -Y, Wong T-T, Ho DM-T. Neuroradiological findings in atypical teratoid/rhabdoid tumor of the central nervous system. cta Radiol 2005;46: Purpose: To evaluate the computed tomography (T) and magnetic resonance imaging (MRI) findings of atypical teratoid tumor/rhabdoid tumor (T/RT) of the central nervous system (NS). Material and methods: Twenty cases of NS T/RT have been found over the past 23 years in our hospital; these involving 11 boys and 9 girls whose mean age at diagnosis was 5.5 years. Their clinical data, the T, and MRI findings were reviewed retrospectively. Results: T/RT was located in the cerebellum in 15 cases. Four cases arose from the supratentorial region, while only one occurred primarily in the lumbar spinal cord. lmost all cases revealed heterogeneous intensity and heterogeneous enhancement. Peripheral cystic components were common. Survival time ranged from 2 months to 3 years, with a mean survival of 11.6 months. onclusion: Most cases of T/RT are located in the cerebellum. The radiologic manifestations are non-specific. The diagnosis mainly depends on the pathologic findings. However, T/RT should still remain in the differential diagnosis of brain tumors in young children, especially those located in the cerebellar hemisphere and with eccentric cysts. Key words: rain neoplasm; computed tomography; magnetic resonance imaging J.-F. Lirng, Department of Radiology, Taipei Veterans General Hospital, 201, Sec. 2, Shih- Pai Rd Taipei 112, Taiwan, R.O.., National Yang-Ming University, School of Medicine, Taipei, Taiwan (fax , . jflirng@vghtpe.gov.tw) ccepted for publication 20 ugust 2004 typical teratoid tumor/rhabdoid tumor (T/RT) of the central nervous system (NS), first described by LEFKOWITZ et al. in 1987 (13), is a highly malignant neoplasm in infants and young children. Two-thirds of the cases arise infratentorially, with the cerebellum being the predominant site; however, the tumors may arise in any site in the NS (2). pproximately one-third of the patients were found to have intracranial dissemination and cerebrospinal fluid (SF) spread (14). The tumors do not respond to standard chemotherapy and are usually fatal within 1 year (2). The main differential diagnosis includes primitive neuroectodermal tumor/medulloblastoma (PNET/ M) of the NS, both predominantly located in the posterior fossa of the brain. hildren with PNET/ M have clinical symptoms and imaging findings similar to those of children with T/RT. The definite diagnosis depends on the result of the histopathological examinations, namely, the presence of large rhabdoid cells. Many cases of T/RT were diagnosed as PNET/M in the past and had a much poorer prognosis than that of PNET/M despite standard chemotherapy. Our purpose was to investigate the T and MRI findings of NS T/ RT since few reports have previously been published about this entity. Material and Methods In total, 20 cases of NS T/RT have been collected over the past 23 years (from 1979 to DOI / # 2005 Taylor & Francis
3 90 Y.-. heng et al. 2002) at Taipei Veterans General Hospital; 15 were cerebellar tumors (9 in the cerebellar vermis and 6 in the cerebellar hemisphere), 4 suptatentorial tumors (1 located in the right lateral ventricle), and 1 spinal tumor. Six cases were primarily diagnosed as PNET/ M but revised as T/RT (9) in 2000 (includes 2 cases before 1987). Imaging studies (T/MRI) were performed in 11 of the 20 patients (11 boys and 9 girls aged from 7 months to 25 years, mean 5.5 years). MRI was performed on 1.5T units (Signa 5X; G.E. Medical Systems, Milwaukee, Wisc., US) with a standard quadrature head coil; pulse sequences included non-enhanced axial T1-weighted and T2-weighted images, gadolinium-enhanced axial, sagittal and fat-saturation coronal T1- weighted images. Three patients were imaged with T and MR, 4 with only T, and 4 with only MR studies. In total, 7 T and 7 MR examinations were available for evaluation. ll patients underwent surgery, and histopathologic studies confirmed NS T/RT. Results The clinical data and available preoperative imaging appearances in 11 T and/or MRI examined patients are summarized in Table 1. Most cases demonstrated heterogeneous or high attenuation on non-enhanced T images, with heterogeneous contrast enhancement. On MR images, heterogeneous iso-signal intensity was shown on T1-weighted images, while a heterogeneous isointense signal was present on T2-weighted images with variable enhancement (heterogeneous, peripheral nodular enhancement, intense, and mild). ystic components were common and present in approximately half (6/11), almost all cysts were peripherally located. alcifications were uncommon and only 2 of our 11 cases (18%) had calcifications. None of the cases had perifocal edema. Sixteen patients (80%) had leptomeningeal spread, which included intracranial dissemination and SF spread, as proved with malignant cells in SF. In addition, one patient developed liver metastasis and neck lymphadenopathy during the course of the disease. Patients survival time ranged from 2 months to 3 years, with mean survival of 11.6 months. Only one patient survived more than 3 years. Figs. 1 5 summarize the findings of the tumor when located in different sites of the NS, including the cerebellar vermis (Fig. 1), the left cerebellar hemisphere (Fig. 2), the right cerebral hemisphere (Fig. 3), the lumbar spinal cord (Fig. 4), and the right lateral ventricle (Fig. 5). Discussion In 1987, LEFKOWITZ et al. (13) first described a distinctive brain tumor arising in young children. This tumor contained neuroepithelial, peripheral epithelial, and mesenchymal elements, but lacked divergent tissue differentiation characteristic of malignant teratomas. It was originally designated as atypical teratoid tumor, but because of the prominent rhabdoid component the tumor designation was modified to atypical teratoid/rhabdoid tumors (T/RT) of infancy and childhood (2). ecause T/RT often contained PNET-like regions (small cells), the diagnosis of T/RT was mainly based on the presence of large rhabdoid cells on light microscopy and specific immunohistochemistry findings (4). ytogenetic analysis enabled the distinction of T/RT from PNET/M 22q11.2 chromosomal deletions are common in T/RT (75 77%) and not associated with PNET/M (3, 6). Table 1. Eleven cases of NS atypical teratoid tumor/rhabdoid tumor with preoperative imaging findings No. ge/sex Location T Pre-contrast Post-contrast MR T1WI T2WI Post-Gd 1 6 y/f erebellar vermis Hetero HD Well EN None y/f LT frontoparietal Hetero ID Hetero EN None y/m RT cerebellum None Low Hetero iso-si Hetero EN y/m erebellar vermis None Hetero iso-si Hetero iso-si Intense EN y/f LT cerebellum None Hetero iso-si Hetero iso-si Hetero EN y/m LT cerebellum Homo ID Mild EN Homo low SI Homo high SI Mild EN y/m erebellar vermis Hetero HD Well EN None y/m erebellar vermis Hetero HD Well EN None y/f RT temporal Hetero ID Mild EN Hetero iso-si Hetero iso-si Hetero EN y/f L-spinal cord None Hetero iso-si Hetero iso-si Hetero EN y/f RT lateral ventricle Hetero HD Mild EN Hetero iso-si Hetero iso-si Hetero EN ystic parts L LM seeding L: calcification; EN: enhancement; F: female; HD: high density; Hetero: heterogeneous; Homo: homogeneous; ID: isodense to cerebral parenchyma; iso-si: isointensity to gray matter; LM: leptomeningeal; LT: left; M: male; MR: magnetic resonance; None: not done; Post-Gd: post-gadolinium; RT: right; SI: signal intensity; T1WI: T1-weighted images; T2WI: T2-weighted images; y: years old.
4 T/RT of the NS 91 D Fig. 1 D. ase 4, a 10-year-old boy with atypical teratoid tumor/rhabdoid tumor in cerebellar vermis, presented with vomiting for 2 months. He died within 1 year despite receiving multimodal intensified therapy.. Non-enhanced axial T1- and () T2-weighted images depict a tumor sized about cm with heterogeneously isointense signal in the cerebellar vermis. The images depict eccentric cystic parts in the posterior portion of the mass.. Gadolinium-enhanced coronal T1-weighted image demonstrates intense but heterogeneous enhancement of the tumor, which resulted in obstructive hydrocephalus. D. Gadolinium-enhanced sagittal T1-weighted image of the cervical and upper thoracic spine illustrates three enhancing nodules in the leptomeninges at the T1-2, T3-4, and T6 levels. These are indicative of SF dissemination, as proved with SF cytology.
5 92 Y.-. heng et al. Fig. 2. ase 5, an 8-year-old girl with atypical teratoid tumor/rhabdoid tumor in the left cerebellar hemisphere, suffering from dizziness and vomiting. s of this writing, she had survived for 3 years.. Non-enhanced axial T1- and () T2-weighted images depict an ill-defined heterogeneously isointense tumor sized about cm in the left cerebellar hemisphere and cerebellopontine cistern area. The images depict multiple cystic components especially in the posterior aspect of the tumor.. Gadolinium-enhanced axial T1-weighted image demonstrates heterogeneous enhancement of the tumor. The mass compresses the brainstem and the fourth ventricle. Most of the tumors arise infratentorially, with the cerebellum being the predominant site. However, the tumors may arise in any site of the NS. In the largest study of 52 infants and children with T/RT, RORKE et al. (18) found infratentorial involvement in 63% (56% in the cerebellum and 7% in the cerebellopontine angle), supratentorial involvement in 27% (19% in the cerebral hemisphere, 6% in the pineal region, and 2% in the suprasellar region), multiple sites in 8%, and intramedullary spinal cord involvement in 2%. In our study, 75% of the patients (45% in cerebellar vermis and 30% in hemisphere) had the lesions located infratentorially. The differential diagnosis of a posterior fossa tumor in children includes cerebellar astrocytoma, PNET/M, brainstem glioma, and ependymoma (17). T/RT should be added to the differential list of posterior fossa tumor in children. The major differential diagnosis of T/RT includes PNET/M because of their similar clinical symptoms and
6 T/RT of the NS 93 D Fig. 3 D. ase 9, a 3-year-old girl with atypical teratoid tumor/rhabdoid tumor in right temporal lobe, presented with headache for 2 months. When this article was written, she had been surviving for half a year.. Non-enhanced T scan depicts a huge heterogeneous tumor sized about cm in the right temporal region with mass effect causing a leftward shift of the brain parenchyma.. ontrast-enhanced T scan shows minimal enhancement in the medioanterior aspect of the tumor.. xial T2-weighted MR image depicts the heterogeneously high signal intensity of the tumor with large eccentric cystic parts in its posterior portion. D. Gadolinium-enhanced axial T1-weighted MR image demonstrates peripheral nodular enhancement. radiologic features. Signs and symptoms are those associated with mass effect in the NS, depending on the location of the tumor. The radiologic findings of T/RT are indistinguishable from those of PNET/M. To our knowledge, most studies have addressed the histopathologic characteristics, and the image findings have been presented in few case reports (1, 5, 10, 12, 19). Eccentric cystic
7 94 Y.-. heng et al. Fig. 4. ase 10, a 2-year-old girl with atypical teratoid tumor/ rhabdoid tumor in the lumbar spine suffering from low back pain and bilateral lower legs weakness. She died within 2 months despite undergoing multimodal intensified therapy.. xial T2-weighted image demonstrates an intradural tumor with heterogeneously high signal intensity at the L2 level.. Sagittal T2-weighted image depicts an intradural tumor with heterogeneously iso- to high signal intensity at the T12-S1 level, as well as eccentric cystic component in the inferior portion of the mass.. Gadolinium-enhanced sagittal T1-weighted image shows heterogeneous enhancement of the tumor. components in T/RT are common (1, 12) and were found in 55% of our patients. This may be helpful in differentiating T/RT from PNET/M, because PNET/M is usually homogeneous in young children, although marked heterogeneity and cystic changes are often seen in older children and adults. nother possible element in the diagnosis of these tumors is the location of the tumor. mong our 15 infratentorial cases, it seems that T/RT had a higher tendency to appear in the cerebellar hemisphere with a hemisphere-to-vermis ratio of about 6:9. In PNET/M, the most common localization is the cerebellar vermis, where this tumor is found in more than 90% of patients in the younger age group, but less commonly in the cerebellar hemisphere. The high attenuation of the tumor on non-enhanced T images (case 11, Fig. 5) is possibly due to the hypercellular nature of the tumor. High attenuation on non-enhanced T images may imply calcification or hemorrhage, but both were excluded on subsequent MRI and not found in histopathologic studies. alcifications are not common, neither in T/RT nor in PNET/M, and are not a useful finding in the differentiation between these two tumors. However, RSLNOGLU et al. (1) demonstrated calcifications in all their four cases. Hemorrhage was not observed in any of our 11 cases, and is seldom diagnosed in PNET/M. Paucity of perifocal edema was found in our T/ RT cases as well as PNET/M. The clinical characteristics of T/RT are slightly different from those of classic PNET/M. hildhood PNET/M tends to appear between ages 3 and 5 years, whereas T/RT is more likely to be diagnosed at an earlier age, with a median patient age of 16.5 months at diagnosis (4). The real incidence is difficult to determine, and is probably underestimated in children younger than 3 years of age. In the study of 11 cases of T/RT compared with 121 cases of PNET/M, HO et al. (9) reported that the frequency of T/RT, expressed as a ratio of T/RT to PNET/M, was 1:11 in the general population; but the frequency increased to 1:3.8 in patients younger than 3 years of age. The mean age of patients with T/RT was lower than that of patients with PNET/M. In a previously reported study, PNET/M had a male predominance with a male-to-female ratio of about 2:1, whereas T/RT had a female predominance with a male-to-female ratio of about 1:2 (4). Only two case reports demonstrate T/RT with extracranial metastasis: a 4-year-old girl with peritoneal metastasis via a ventriculoperitoneal shunt (11), and a 6-year-old-boy having lung metastasis without a cerebrospinal fluid shunt (7). Extracranial metastases of primary NS tumors are fairly rare, but can be seen relatively frequently in PNET/M, glioblastoma multiforme, malignant meningioma, and ependymoma, most frequently in the lungs, bones, liver, pleura, and kidneys (15). ervical lymph nodes are the most common sites of lymph node metastases (7). lthough extracranial metastasis of T/RT is rare, it should be keep in mind as in our case no. 10 with metastasis to the liver and lymph nodes of the neck. ecause most children with T/RT die within a year, it is important to distinguish this lesion from PNET/M so that aggressive therapy can be administered, because this seems to extend their survival (14, 16). Patients with T/RT are reported
8 T/RT of the NS 95 Fig. 5. ase 11, a 5-year-old girl with atypical teratoid tumor/rhabdoid tumor in the right lateral ventricle presented with headache and vomiting. Her condition has been stable for 3 months, as of this writing.. Non-enhanced T scan depicts a heterogeneously highattenuating mass sized about cm in the right lateral ventricle. The high attenuation of the tumor is due to its hypercellular nature. (High attenuation on non-enhanced T images may imply either hemorrhage or calcification, but both were excluded on subsequent MR images and not found in the histopathologic study).. xial T2-weighted MR image depicts a tumor with heterogeneously isointense signal in the right lateral ventricle.. Gadolinium-enhanced coronal T1-weighted MR image demonstrates heterogeneous enhancement of the mass. The tumor is located mainly in the right lateral ventricle with downward extension to the interventricular foramen of Monro. It causes obstructive hydrocephalus. The image shows no definite cystic component within the tumor. to have a shorter survival time than patients with PNET/M, with a median survival of 15.4 months versus months (9). In our cases, the survival time ranged from 2 months to 3 years, with a mean of about 11.6 months. Multimodal intensified therapy, including surgery, intensive chemotherapy, intrathecal chemotherapy, and radiation therapy, has recently been used in children with this disease, with improved outcome (8). However, effective treatment protocols have not been established yet. In conclusion, T/RT is not such a rare pediatric NS tumor, especially not in patients younger than
9 96 Y.-. heng et al. 3 years of age. In cases involving young children with brain tumors located in the posterior fossa, both T/RT and PNET/M should be considered because both tumors have similar radiological features. In patients younger than 3 years of age with cerebellar hemispheric masses with eccentric cystic components, T/RT should be considered. However, the definitive diagnosis still depends on the histopathological examination. References 1. rslanoglu, ygun N, Tekhtani D, ronson L, ohen K, urger P, et al. Imaging findings of NS atypical teratoid/rhabdoid tumors. m J Neuroradiol 2004;25: hattacharjee M, Hicks J, Langford L, Dauser R, Strother D, hintagumpala M, et al. entral nervous system atypical teratoid/rhabdoid tumors of infancy and childhood. Ultrastruct Pathol 1997;21: ruch L, Hill D, ai DX, Levy K, Dehner LP, Perry. role for fluorescence in situ hybridization detection of chromosome 22q dosage in distinguishing atypical teratoid/rhabdoid tumors from medulloblastoma/central primitive neuroectodermal tumors. Hum Pathol 2001;32: urger P, Yu IT, Tihan T, Friedman HS, Strother DR, Kepner JL, et al. typical teratoid/rhabdoid tumor of the central nervous system: a highly malignant tumor of infancy and childhood frequently mistaken for medulloblastoma. pediatric oncology group study. m J Surg Pathol 1998;22: hang HK, Kim JH. lassical malignant tumor of central nervous system in a 9-year-old Korean. Yonsei Med J 2001;42: Fuller E, Pfeifer J, Humphrey P, ruch L, Dehner LP, Perry. hromosome 22q dosage in composite extrarenal rhabdoid tumors: clonal evolution or a phenotypic mimic? Hum Pathol 2001;32: Güler E, Varan, Söylemezoğlu F, ağlar K, Demirkazik F, üyükpamukcu M. Extraneural metastasis in a child with atypical teratoid rhabdoid tumor of the central nervous system. J Neurooncol 2001;54: Hilden JM, Watterson J, Longee D, Moertel L, Dunn ME, Kurtzberg J, et al. entral nervous system atypical teratoid tumor/rhabdoid tumor: response to intensive therapy and review of the literature. J Neurooncol 1998;40: Ho DMT, Hsu Y, Wong TT, Ting LT, hiang H. typical teratoid/rhabdoid tumor of the central nervous system: a comparative study with primitive neuroectodermal tumor/medulloblastoma. cta Neuropathol 2000;99: Howlett D, King P, Jarosz JM, Stewart R, al- Sarraj ST, ingham J, et al. Imaging and pathological features of primary malignant rhabdoid tumor of the brain and spine. Neuroradiology 1997;39: Korones DN, Meyers SP, Rubio, Torres, onstine LS. 4-year-old girl with a ventriculoperitoneal shunt metastasis of a central nervous system atypical teratoid/rhabdoid tumor. Med Pediatr Oncol 1999;32: Lee YK, hoi G, Lee JH. typical teradoid/rhabdoid tumor of the cerebellum: report of two infantile cases. m J Neuroradiol 2004;25: Lefkowitz I, Rorke L, Packer RJ, Sutton LN, Siegel KR, Katnick RJ. typical teratoid tumor of infancy: definition of an entity. nn Neurol 1987;22: Lu L, Wilkinson EJ, Yachnis T. SF cytology of atypical teratoid/rhabdoid tumor of the brain in a twoyear-old girl: a case report. Diagn ytopathol 2000;23: Nakamura K, Hawkin S, izawa M, Maekubo H, Kobayashi N, Ozasa T, et al. Extracranial metastases of brain tumors a case report and survey of patients with extracranial metastasis sampled from a report on pathological autopsy cases in Japan. Japanese J ancer lin 1986;32: Olson T, ayar E, Kosnik E, Hamoudi, Klopfenstein KJ, Pieters RS, et al. Successful treatment of disseminated central nervous system malignant rhabdoid tumor. J Pediatr Hematol Oncol 1995;17: Osborn G. rain tumors and tumorlike masses: classification and differential diagnosis. In: Patterson S, editor. Diagnostic neuroradiology. St Louis: Mosby; p Rorke L, Packer RJ, iegel J. entral nervous system atypical teratoid/rhabdoid tumors of infancy and childhood: definition of an entity. J Neurosurg 1996;85: Zuccoli G, Izzi G, acchini E, Tondelli MT, Ferrozzi F, ellomi M. entral nervous system atypical teratoid/ rhabdoid tumor of infancy: T and MR findings. lin Imag 1999;23:
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