J Neurosurg Pediatrics 13:29–32, 2014 ©AANS, 2014

Association of cerebellopontine angle atypical teratoid/rhabdoid tumors with acute facial nerve palsy in infants Report of 3 cases Alan Siu, M.D.,1 Michaela Lee, M.D.,1 Robert Rice, M.D., 2 and John S. Myseros, M.D.1,3 Department of Neurological Surgery, George Washington University; 2Department of Neurological Surgery, Georgetown University School of Medicine; and 3Department of Neurological Surgery, Children’s National Medical Center, Washington, DC 1

Atypical teratoid/rhabdoid tumors (AT/RTs) are highly malignant CNS tumors found almost exclusively in childhood. Although essentially universally fatal when incompletely resected, prompt diagnosis followed by early chemoradiation can improve outcomes. An AT/RT can occur extraaxially at the cerebellopontine angle (CPA) and cause acute cranial nerve deficits as the presenting sign. The authors report a series of 3 children who presented with isolated acute facial nerve palsies and in whom subsequent diagnosis of a CPA AT/RT was made. The authors propose that in young children whose presenting symptom is an acute facial nerve palsy with a CPA tumor, AT/RT should be highly suspected. (http://thejns.org/doi/abs/10.3171/2013.10.PEDS13292)

Key Words      •      cerebellopontine angle      •      atypical teratoid rhabdoid tumor      •      facial nerve palsy      •      oncology

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typical teratoid/rhabdoid tumors (AT/RTs) are rare intracranial embryonal cell tumors that occur in very young children. These tumors are highly malignant WHO Grade IV neoplasms that carry a poor prognosis. Aggressive resection or biopsy for prompt diagnosis followed by chemoradiation is the cornerstone of treatment, which can improve survival by up to 10 months in younger individuals.1,4,16 Cytoreductive surgery can decrease the tumor burden in AT/RT, but may be difficult to achieve in the cerebellopontine angle (CPA), a region that contains a diversity of critical structures with different cellular origins.3 Specifically, these highly vascular lesions often infiltrate into the porus acusticus in very small infants, thus eliminating the possibility for a safe and complete resection. Additionally, a more benign lesion (that is, schwannoma) may be assumed, which would invariably delay treatment. Thus, the identification of perioperative variables that differentiate these tumors can aid in the surgical planning and prognostication. We report a series of 3 patients with AT/RT at the CPA who

all initially presented with acute cranial nerve palsies, and propose that this association should raise the concern for AT/RT in the preoperative differential diagnosis.

Abbreviations used in this paper: AT/RT = atypical teratoid/ rhabdoid tumor; CPA = cerebellopontine angle; IAC = internal auditory canal.

This article contains some figures that are displayed in color on­line but in black-and-white in the print edition.

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Case 1

Case Reports

This 4-month-old girl presented with acute left facial hemiplegia, and was found on MRI to have a left CPA mass extending into the internal auditory canal (IAC), measuring 9 × 14 mm, and adjacent enhancement into the proximal aspect of the facial nerve (Fig. 1). There was no disease dissemination. She underwent a left suboccipital craniectomy to obtain a biopsy specimen of the lesion, without complication. Pathological investigation demonstrated a primitive malignant tumor composed of round blue cells with focal areas of rhabdoid cells that were positive for smooth-muscle actin and epithelial membrane antigen, with a loss of INI1 that was consistent with AT/ RT (Fig. 2). Also noted were positive staining for vimen-

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A. Siu et al. given its infiltration into the porus acusticus. Pathological findings were consistent with AT/RT. Considering the dissemination, a ventricular access device was placed for initiation of intrathecal and systemic chemotherapy in addition to proton beam radiation. Despite these treatments, his dissemination persisted, with a 6-month MRI study indicating new lesion in the left lateral ventricle and right choroidal fissure. He died 8 months after initial diagnosis. Case 3

Fig. 1.  Admission MRI obtained with contrast in a 4-month-old girl who presented with acute left facial hemiplegia. Imaging shows a left CPA mass that extends into an enlarged IAC, probably involving the 7th and 8th cranial nerves. Pathological findings were consistent with AT/RT.

tin, synaptophysin, and glial fibrillary acidic protein (data not shown). She was subsequently treated with high-dose chemotherapy with peripheral stem cell rescue. She then received focal radiation therapy followed by 6 months of metronomic maintenance chemotherapy. Follow-up MRI at 5 years indicated no residual enhancement. She continued to have a left facial palsy. Case 2

This 6-month-old boy presented with acute left facial weakness. Admission MRI studies demonstrated an 8-mm enhancing, lobulated, extraaxial tumor in the left CPA that filled the left IAC (Fig. 3). Results of a hearing test were normal, and a lumbar puncture revealed tumor cells without a clear pathological type. He was thus taken to the operating room for biopsy sampling of this probably malignant tumor. Complete resection was not possible

This 12-month-old girl presented with facial weakness consistent with a facial nerve palsy, in addition to head tilt and vomiting that on ophthalmological examination confirmed a right fourth and sixth cranial nerve palsy. Admission MRI demonstrated a 26 × 15–mm right CPA heterogeneously enhancing cystic mass, consistent with a high-grade lesion (Fig. 4). Lumbar puncture demonstrated dissemination. She was taken to the operating room to drain the cyst and obtain a biopsy specimen of the lesion, which was well tolerated. Pathological findings were consistent with AT/RT. Subsequently, she received high-dose chemotherapy with stem cell rescue, and proton beam therapy. At 2 months postradiation, she developed progressive lethargy, with an MRI study that was significant for new infiltration into the pons and midbrain, which was of concern for tumor progression or treatment-related change. As she continued to decline, the family elected to withdraw care. She died 8 months after the initial diagnosis. At autopsy, she was found to have multifocal necrotizing leukoencephalopathy, a known complication of aggressive treatment for AT/RT.7

Discussion

Cerebellopontine angle tumors in children are rare,

Fig. 2.  Case 1. Immunohistochemical staining of pathological specimen showing AT/RT. Frozen sections showing small round blue cells (A), focal rhabdoid areas (B), smooth-muscle actin (C), epithelial membrane antigen (D), and loss of INI1 staining (E), all consistent with AT/RT. Original magnification ×40 (A and B) and ×20 (C–E).

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Facial nerve palsy in CPA atypical teratoid/rhabdoid tumors

Fig. 3.  Admission MRI obtained with contrast in a 6-month-old boy with an acute left facial weakness. Imaging shows a left CPA mass and an enlarged IAC. Pathological findings were consistent with AT/RT.

accounting for a minority of lesions, representing approximately 1%–3% of pediatric brain tumors.8,18 Likewise AT/RTs themselves are also rare, comprising 1%–2% of all pediatric CNS tumors, although this number can rise as high as 20% in patients younger than 3 years.15 Case studies vary regarding the predominant tumor type, ranging from benign tumors17,18 to more malignant phenotypes.13 Additionally, there is a paucity of data correlating the timing of the presenting symptoms with the diagnosis. One study observed that pediatric CPA tumors frequently caused cranial nerve palsies, but made no mention of duration. Another series showed cranial nerve palsies in 46% of patients with AT/RT as a presenting symptom. 5 We have observed in our cohort a correlation between acute facial nerve deficits and CPA AT/RT, and suggest that in children in whom acute facial palsies and a CPA tumor develop, AT/RT should be highly suspected. Other variables that may assist with differentiating a high-grade lesion are MRI findings of signal voids, vascular encasement, widening of the lateral recess, cerebellar edema, hydrocephalus, and seeding of the neuraxis.13 The nature of AT/RT as it relates to cranial nerves, specifically the facial nerve, is unknown. As a distinct tumor entity that was once misdiagnosed as a primitive neuroectodermal tumor,14 it is very likely that it carries

a differential interaction with the tissue types in the CPA that is distinct from the classic medulloblastoma. This is in contrast to classic medulloblastoma in the CPA, which occurs in older patients, and often presents with multiple cranial nerve deficits over the course of months, with facial nerve weakness being uncommon and manifesting later.9 Although the cell of origin in AT/RT is unknown, some have postulated that the origin of this tumor is a primitive stem cell derived from the neural crest, because the histological studies of AT/RT can manifest neural, epithelial, and mesenchymal staining.2,12 In this regard, the typical immunohistochemical staining pattern includes epithelial membrane antigen, S100, and glial fibrillary acidic protein.10,12 Additionally, other studies have pointed to similar mutations in the SMARCB1/INI1 gene between familial schwannomas and malignant RTs.15 The observations of a relationship between the neural crest and AT/ RT suggest a propensity for cranial nerve invasion, resulting in acute cranial nerve disorders. The differential diagnosis in infants with CPA tumors can be quite broad, but in large case series these most commonly are medulloblastoma, schwannoma, ep­en­­dymo­ma, and astrocytoma.13,17,18 Although some of the patients with AT/RT may actually have been miscategorized as having medulloblastoma prior to 2006, facial nerve palsy was an uncommon finding for these tumors.17,18 A limitation, however, is that these studies did not correlate the specific symptoms with the pathological findings. In this report we highlight a key clinical finding that is highly associated with CPA AT/RT. Acute cranial neuropathies as the presenting symptom may serve as an adjunct that should raise the suspicion and concern for AT/RT in children with CPA lesions. This early consideration is important because the overall survival is quite poor, with a median of 10–17 months.6,11 Although the treatment course may not change with high-grade malignancies, earlier diagnosis could guide the treatment course when considering more malignant versus benign lesions, from directing the aggressiveness of resection to the prompt implementation of multimodal therapies, which can improve outcomes. Recent retrospective studies are in conflict in determining the prevalence of malignant versus benign CPA lesions in children.13 The presence and acuity of facial nerve deficits can serve as an authoritative variable to aid in the determination of the lesion’s pathological features, but we believe that it can define more malignant lesions, especially in very young patients. Future studies are needed to determine the specificity of facial nerve palsies in AT/RT compared with other malignant CPA lesions. Disclosure

Fig. 4.  Admission MRI obtained with contrast in a 12-month-old girl who presented with facial weakness and extraocular deficits. The MRI studies show a highly infiltrating right CPA mass with a cystic component that abuts the fourth ventricle.

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The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper. Author contributions to the study and manuscript preparation include the following. Conception and design: Myseros, Siu. Acquisition of data: Siu, Lee, Rice. Analysis and interpretation of data: Myseros, Siu. Drafting the article: Siu, Lee, Rice. Critically re­ vising the article: all authors. Reviewed submitted version of manuscript: all authors. Approved the final version of the manuscript on behalf of all authors: Myseros. Administrative/technical/material support: Siu. Study supervision: Siu.

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A. Siu et al. References   1.  Athale UH, Duckworth J, Odame I, Barr R: Childhood atypical teratoid rhabdoid tumor of the central nervous system: a metaanalysis of observational studies. J Pediatr Hematol Oncol 31:651–663, 2009  2. Biegel JA: Molecular genetics of atypical teratoid/rhabdoid tumor. Neurosurg Focus 20(1):E11, 2006   3.  Bonneville F, Sarrazin JL, Marsot-Dupuch K, Iffenecker C, Cordoliani YS, Doyon D, et al: Unusual lesions of the cerebellopontine angle: a segmental approach. Radiographics 21: 419–438, 2001   4.  Buscariollo DL, Park HS, Roberts KB, Yu JB: Survival outcomes in atypical teratoid rhabdoid tumor for patients undergoing radiotherapy in a Surveillance, Epidemiology, and End Results analysis. Cancer 118:4212–4219, 2012   5.  Chen ML, McComb JG, Krieger MD: Atypical teratoid/rhabdoid tumors of the central nervous system: management and outcomes. Neurosurg Focus 18(6a):E8, 2005   6.  Ginn KF, Gajjar A: Atypical teratoid rhabdoid tumor: current therapy and future directions. Front Oncol 2:114, 2012   7.  Hasan A, Palumbo M, Atkinson J, Carret AS, Farmer JP, Montes J, et al: Treatment-related morbidity in atypical teratoid/ rhabdoid tumor: multifocal necrotizing leukoencephalopathy. Pediatr Neurosurg 47:7–14, 2011  8. Izycka-Swieszewska E, Szurowska E, Kloc W, Rzepko R, Dubaniewicz-Wybieralska M, Skorek A, et al: Cerebellopontine angle tumours: radiologic-pathologic correlation and diagnostic difficulties. Folia Neuropathol 44:274–281, 2006   9.  Jaiswal AK, Mahapatra AK, Sharma MC: Cerebellopointine angle medulloblastoma. J Clin Neurosci 11:42–45, 2004 10.  Jóźwiak J, Bikowska B, Grajkowska W, Sontowska I, Roszkowski M, Galus R: Activation of Akt/mTOR pathway in a patient with atypical teratoid/rhabdoid tumor. Folia Neuropathol 48:185–189, 2010 11.  Morgenstern DA, Gibson S, Brown T, Sebire NJ, Anderson J: Clinical and pathological features of paediatric malignant rhabdoid tumours. Pediatr Blood Cancer 54:29–34, 2010

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12.  Parham DM, Weeks DA, Beckwith JB: The clinicopathologic spectrum of putative extrarenal rhabdoid tumors. An analysis of 42 cases studied with immunohistochemistry or electron microscopy. Am J Surg Pathol 18:1010–1029, 1994 13.  Phi JH, Wang KC, Kim IO, Cheon JE, Choi JW, Cho BK, et al: Tumors in the cerebellopontine angle in children: warning of a high probability of malignancy. J Neurooncol 112:383–391, 2013 14.  Rorke LB, Packer RJ, Biegel JA: Central nervous system atypical teratoid/rhabdoid tumors of infancy and childhood: definition of an entity. J Neurosurg 85:56–65, 1996 15.  Swensen JJ, Keyser J, Coffin CM, Biegel JA, Viskochil DH, Williams MS: Familial occurrence of schwannomas and malignant rhabdoid tumour associated with a duplication in SMARCB1. J Med Genet 46:68–72, 2009 16. Tekautz TM, Fuller CE, Blaney S, Fouladi M, Broniscer A, Merchant TE, et al: Atypical teratoid/rhabdoid tumors (ATRT): improved survival in children 3 years of age and older with radiation therapy and high-dose alkylator-based chemotherapy. J Clin Oncol 23:1491–1499, 2005 17.  Tsai MH, Wong AM, Jaing TH, Wang HS, Hsueh C, Wu CT: Treatment of cerebellopontine angle tumors in children: a single institution’s experience. J Pediatr Hematol Oncol 31: 832–834, 2009 18.  Zúccaro G, Sosa F: Cerebellopontine angle lesions in children. Childs Nerv Syst 23:177–183, 2007

Manuscript submitted June 15, 2013. Accepted October 8, 2013. Please include this information when citing this paper: published online November 15, 2013; DOI: 10.3171/2013.10.PEDS13292. Address correspondence to: John S. Myseros, M.D., Children’s National Medical Center, 111 Michigan Ave. NW, Washington, DC 20010-2970. email: [email protected].

J Neurosurg: Pediatrics / Volume 13 / January 2014

rhabdoid tumors with acute facial nerve palsy in infants.

Atypical teratoid/rhabdoid tumors (AT/RTs) are highly malignant CNS tumors found almost exclusively in childhood. Although essentially universally fat...
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