Brain metastasis of Wilms tumor with diffuse anaplasia and complex cytogenetic phenotype in a child with neurofibromatosis Type 1

Case report

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The authors report the first case of a Wilms tumor (WT) with diffuse anaplasia metastatic to the brain in a 13-year-old girl with a history of neurofibromatosis Type 1. At presentation, the metastatic tumor had radiological features that suggested a meningioma. Histologically it was characterized by striking anaplasia and features similar to the patient's previously resected WT with diffuse anaplasia.

Abbreviations used in this paper: AE1/AE3 = low- and high-molecular-weight cytokeratin; NF1 = neurofibromatosis Type 1; WT = Wilms tumor.

Article Information

Address correspondence to: Marianna Shvartsbeyn, M.D., Department of Pathology, New York University, 522 First Avenue, Smilow, 301C, New York, New York 10016. email:

© AANS, except where prohibited by US copyright law.



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    Axial T2-weighted FLAIR MR imaging study revealing a homogeneously enhancing dural-based mass along the lateral aspect of the left middle cranial fossa; meningioma was suspected.

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    Photomicrographs of histological sections demonstrating an undifferentiated blastemal component in the primary renal tumor (A) and in the brain metastasis (B). Photomicrographs of the original WT showing focally myxoid stroma with abundant neoplastic cells (C), some forming primitive tubules (D), highlighted by AE1/AE3 (inset). H & E. Original magnification × 20 (A–C, inset) and × 40 (D).

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    Photomicrographs of tumor sections showing cytological features, which included severe anaplasia with numerous hyperchromatic, bizarre cells and scattered multipolar mitotic figures in the renal tumor (A and B) and in the metastatic neoplasm (C and D). H & E. Original magnification × 40 (A–C) and × 60 (D).



Bardeesy NFalkoff DPetruzzi MJNowak NZabel BAdam M: Anaplastic Wilms' tumour, a subtype displaying poor prognosis, harbours p53 gene mutations. Nat Genet 7:91971994


Basta-Jovanović GRadonjic VStolic INenadovic MBrasanac DJovanovic D: Significance of proto-oncogene Bcl-X(S/L) expression in Wilms tumor. Ren Fail 27:13182005


Betts DRKoesters RPlüss HJNiggli FK: Routine karyotyping in Wilms tumor. Cancer Genet Cytogenet 96:1511561997


Bouffet EDoumi NThiesse PMottolese CJouvet ALacroze M: Brain metastases in children with solid tumors. Cancer 79:4034101997


Coppes MJPerlman ETremblay C: Intracranial metastases from Wilms' tumor. A report from the National Wilms Tumor Study Group (NWTSG). Med Ped Onc 267:185a2000


Fukuzawa RHeathcott RWSano MMorison IMYun KReeve AE: Myogenesis in Wilms' tumors is associated with mutations of the WT1 gene and activation of Bcl-2 and the Wnt signaling pathway. Pediatr Dev Pathol 7:1251372004


Goutagny SKalamarides M: Meningiomas and neurofibromatosis. J Neurooncol 99:3413472010


Gow KWMurphy JJ: Cytogenetic and histologic findings in Wilms' tumor. J Pediatr Surg 37:8238272002


Graus FWalker RWAllen JC: Brain metastases in children. J Pediatr 103:5585611983


Haber DAEnglert CMaheswaran S: Functional properties of WT1. Med Pediatr Oncol 27:4534551996


Hansson CMBuckley PGGrigelioniene GPiotrowski AHellström ARMantripragada K: Comprehensive genetic and epigenetic analysis of sporadic meningioma for macromutations on 22q and micro-mutations within the NF2 locus. BMC Genomics 8:162007


Kebudi RAyan IGörgün OAğaoğlu FYVural SDarendeliler E: Brain metastasis in pediatric extracranial solid tumors: survey and literature review. J Neurooncol 71:43482005


Louis DNOhgaki HWiestler ODCavenee WKBurger PCJouvet A: The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol 114:971092007


Lowis SPFoot AGerrard MPCharles AImeson JMiddleton H: Central nervous system metastasis in Wilms' tumor: a review of three consecutive United Kingdom trials. Cancer 83:202320291998


MacRae RGrimard LHsu ENizalik EHalton JM: Brain metastases in Wilms' tumor: case report and literature review. J Pediatr Hematol Oncol 24:1491532002


McDonald OGRodriguez RBergner AArgani P: Metanephric stromal tumor arising in a patient with the neurofibromatosis type 1 syndrome. Int J Surg Pathol [epub ahead of print]2009


Morrison DJEnglish MALicht JD: WT1 induces apoptosis through transcriptional regulation of the proapoptotic Bcl-2 family member Bak. Cancer Res 65:817481822005


Murphy WMBeckwith JBFarrow GM: Nephroblastoma (Wilms' Tumor). ed 4Washington, DCArmed Forces Institute of Pathology2004. 1037


Perilongo GFelix CAMeadows ATNowell PBiegel JLange BJ: Sequential development of Wilms tumor, T-cell acute lymphoblastic leukemia, medulloblastoma and myeloid leukemia in a child with type 1 neurofibromatosis: a clinical and cytogenetic case report. Leukemia 7:9129151993


Shao LHill DAPerlman EJ: Expression of WT-1, Bcl-2, and CD34 by primary renal spindle cell tumors in children. Pediatr Dev Pathol 7:5775822004


Simon MBoström JPHartmann C: Molecular genetics of meningiomas: from basic research to potential clinical applications. Neurosurgery 60:7877982007


Stay EJVawter G: The relationship between nephroblastoma and neurofibromatosis (Von Recklinghausen's disease). Cancer 39:255025551977


Wiemels JWrensch MClaus EB: Epidemiology and etiology of meningioma. J Neurooncol 99:3073142010




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