01_05_JNS.2
12/15/04
2:37 PM
Page 167
J Neurosurg 102:167–168, 2005
Multiple meningiomas in a patient with Rubinstein–Taybi syndrome Case report MARCO J. T. VERSTEGEN, M.D., PEPIJN VAN DEN MUNCKHOF, M.D., M.SC., DIRK TROOST, M.D., PH.D., AND GERRIT J. BOUMA, M.D., PH.D. Departments of Neurosurgery and Neuropathology, Academic Medical Center, University of Amsterdam, The Netherlands √ The authors report a case of multiple meningiomas in a 37-year-old woman with Rubinstein–Taybi syndrome. The patient harbored a bifrontal ossifying meningioma and multiple intracranial meningiomas. She underwent surgery for the frontal ossifying meningioma and a right frontoparietal meningioma.
KEY WORDS • meningioma • Rubinstein–Taybi syndrome • tumor UBINSTEIN–TAYBI syndrome is a congenital malformation disease characterized by facial anomalies, broad thumbs, big toes, short stature, and mental retardation.6 It is inherited in an autosomal-dominant manner, and recently chromosomal rearrangements, microdeletions, and point mutations in one copy of the gene encoding the CREBBP were shown to be the underlying causes of RTS.5 The CREBBP plays a role as coactivator in the regulation of gene transcription.3 Approximately 5% of patients with RTS harbor neural or developmental neoplasms, especially those of the head.4 Among the reported tumors in the central nervous system were two oligodendrogliomas, two medulloblastomas, and two meningiomas. In the present case we report on multiple meningiomas in a patient with RTS.
R
Case Report First Admission. This 37-year-old woman with previous-
ly diagnosed RTS presented with a progressive bonelike swelling of the forehead. Computerized tomography scanning revealed bifrontal hyperostosis of the skull (Fig. 1), with no other intracranial lesion. A biopsy specimen of the lesion showed an ossifying meningioma. The swelling gradually increased during the next year and the lesion was partially resected for cosmetic reasons. Subsequently, the patient underwent adjuvant local radiotherapy. Preoperative magnetic resonance imaging results had demonstrated multiple de novo Gd-enhanced intracranial masses with the aspect of meningiomas (Fig. 2). These studies were expectantly followed with serial CT scanning Second Admission. Four years later the patient exhibited a change in her character, progressive bradyphrenia, proptoAbbreviations used in this paper: CREBBP = cyclic adenosine monophosphate response element-binding protein binding protein; CT = computerized tomography; RTS = Rubinstein–Taybi syndrome.
J. Neurosurg. / Volume 102 / January, 2005
FIG. 1. Three-dimensional reconstructed CT scan (right-sided view) demonstrating bifrontal hyperostosis of the skull.
sis, and a mild left-sided hemiparesis. A CT scan revealed significant enlargement of the right frontoparietal mass together with peritumoral edema, compression of the lateral ventricle, and midline shift (Fig. 3). She underwent decompressive surgery. Intraoperatively, the tumor had a clear cutting plane with the cortex and could be resected relatively easily, although the most frontal portion turned out to be continuous with an en plaque growing, meningiomalike sphenoid wing tumor. Histological analysis showed chordoid-type meningioma (Fig. 4). Postoperatively, the patient suffered slowly progressive intubation-related laryngeal swelling and died of respiratory complications 6 weeks later. Discussion There are two previously reported cases of solitary meningioma in a patient with RTS.1,7 These cases involved two adult women 39 and 41 years old. To our knowledge, the present case is the first report of multiple meningiomas in a patient with RTS. 167
01_05_JNS.2
12/15/04
2:37 PM
Page 168
M. J. T. Verstegen, et al.
FIG. 4. Photomicrograph of tumor tissue obtained from the right frontoparietal mass, displaying trabeculae of eosinophilic, vacuolated cells in a myxoid background. The diagnosis was meningioma, chordoid subtype. H & E, original magnification 3 100.
FIG. 2. A coronal T1-weighted Gd-enhanced magnetic resonance image demonstrating multiple homogeneously enhancing masses closely related with the dura mater and the falx cerebri.
At the molecular level, RTS is caused by disruption of one copy of the CREBBP gene.5 Note that CREBBP is an essential coactivator of many transcription factors. In addition, it has the ability to acetylate histones, which is also re-
garded as an important step in the regulation of gene transcription.2 Genetic disturbances in the regulation of gene transcription often result in developmental disorders and uncontrolled cell growth. Indeed, chromosomal translocations affecting the CREBBP gene have been found in hematological malignancies.2 Given that patients with RTS are haploinsufficient for CREBBP, it is tempting to hypothesize that functional allelic loss puts them at risk for tumorigenesis. Thus far, the role of CREBBP in the origin of meningiomas has not been analyzed. In addition, it remains to be elucidated why RTS mutations of this ubiquitously expressed gene preferentially cause developmental and neural tumors of the head. References 1. Hennekam RC: References on Rubinstein-Taybi syndrome. Am J Med Genet Suppl 6:77–83, 1990 2. Janknecht R: The versatile functions of the transcriptional coactivators p300 and CBP and their roles in disease. Histol Histopathol 17:657–668, 2002 3. Kwok RP, Lundblad JR, Chrivia JC, Richards JP, Bachinger HP, Brennan RG, et al: Nuclear protein CBP is a coactivator for the transcription factor CREB. Nature 370:223–226, 1994 4. Miller RW, Rubinstein JH: Tumors in Rubinstein-Taybi syndrome. Am J Med Genet 56:112–115, 1995 5. Murata T, Kurokawa R, Krones A, Tatsumi K, Ishii M, Taki T, et al: Defect of histone acetyltransferase activity of the nuclear transcriptional coactivator CBP in Rubinstein-Taybi syndrome. Hum Mol Genet 10:1071–1076, 2001 6. Rubinstein JH, Taybi H: Broad thumbs and toes and facial abnormalities. A possible mental retardation syndrome. Am J Dis Child 105:588–608, 1963 7. Siraganian PA, Rubinstein JH, Miller RW: Keloids and neoplasms in the Rubinstein-Taybi syndrome. Med Pediatr Oncol 17: 485–491, 1989
FIG. 3. Axial enhanced CT scan exhibiting the enlarged right frontoparietal mass with peritumoral edema, compression of the lateral ventricle, and midline shift.
168
Manuscript received June 14, 2004. Accepted in final form September 8, 2004. Drs. Verstegen and Van den Munckhof contributed equally to this work. Address reprint requests to: Marco J. T. Verstegen, M.D., Department of Neurosurgery H2-225, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. email: M.J.
[email protected].
J. Neurosurg. / Volume 102 / January, 2005
