European Journal of Medical Genetics 57 (2014) 312e313
Contents lists available at ScienceDirect
European Journal of Medical Genetics journal homepage: http://www.elsevier.com/locate/ejmg
Letter to the Editor
Brain tumors in Turner syndrome Keywords: Turner syndrome Pilocytic astrocytoma Children Cerebellum
Dear Editor, We read with great interest the recent article by Pier et al. on Turner syndrome and meningioma occurrence [Pier et al., 2014]. The authors report on a meningioma case in a woman with Turner syndrome and reviewed 10 other similar cases. FISH analysis in this patient revealed retention of the NF2 gene locus. The authors concluded that although neoplasia may be a rare associated medical problem in Turner syndrome, this should be considered since these patients require hormone replacement therapy and artificial reproductive technologies to conceive [Pier et al., 2014]. Recently, we encountered a pilocytic astrocytoma of the cerebellum in a girl with Turner syndrome. The patient was a 13-year-old girl who was investigated by brain magnetic resonance imaging (MRI) because of short stature and delayed sexual development. MRI revealed a cerebellar lesion (2.4 2.2 2.5 cm), hypointense on T1 and hyperintense on T2 weighted images that
enhanced after contrast administration (Fig. 1). Diffusion tensor imaging demonstrated decreased fractional anisotropy in the lesion and displacement of the white matter fiber tracts without infiltration. Spinal MRI revealed no tumor dissemination. The patient was operated on via a suboccipital approach and gross total excision was achieved. Microscopic examination showed a astrocytic neoplasm with moderate cellularity, a biphasic pattern with alternating areas composed of piloid cells and microcystic areas composed of protoplasmic astrocytes with mild nuclear atypia and rare mitotic figures [0-1/10HPF]. Characteristic features were the presence of Rosenthal fibers and eosinophilic granular bodies. Immunohistochemistry revealed a heterogenous GFAP expression in neoplastic cells, being increased in the perivascular areas. Tumor cells were negative for synaptophysin, neurofilaments 2F11 and EMA. The Ki-67/MIB-1 index was 2e3%, the p-53 expression was 5% and there was cytoplasmic expression of bcl-2 in 20% of the neoplastic cells. Reverse transcription-PCR revealed gene fusion between KIAA1549 exon 16 and BRAF exon 9. The final diagnosis was pilocytic astrocytoma, grade I. A karyotypic analysis was also performed revealing a XO karyotype, establishing the diagnosis of Turner syndrome. Turner’s syndrome occurs in 1 in 2500 to 1 in 3000 live-born girls and is characterised by complete or partial X-chromosome monosomy [Sybert and McCauley, 2004]. Turner’s syndrome is the most common cause of short stature in otherwise healthy girls [Schoemaker et al., 2008]. Growth hormone therapy is
Fig. 1. A. Axial T1-weighted MRI pre and post gadolinium administration (B) revealing a space occupying lesion in the cerebellum. The lesion enhanced after contrast administration. Differential diagnosis included mainly medulloblastoma, ependymoma and astrocytoma. http://dx.doi.org/10.1016/j.ejmg.2014.04.001 1769-7212/Ó 2014 Elsevier Masson SAS. All rights reserved.
Letter to the Editor / European Journal of Medical Genetics 57 (2014) 312e313
usually administered in order to attain a normal height as early as possible and progress through puberty at a normal age. Regarding cancer incidence, Schoemaker et al. found an increased risk of gonadoblastoma and also an increased risk for meningioma and childhood brain tumors [Schoemaker et al., 2008]. GH treatment has been associated previously with an increased risk of meningioma, nevertheless our patient had not received any treatment prior to diagnosis [Jostel et al., 2005]. To the best of our knowledge no previous case of cerebellar astrocytoma in Turner syndrome has been reported. Thus, our case adds another patient with Turner syndrome that harbored a brain tumor. Although this case might be incidental, clinicians should be aware of this potential association. References Jostel A, Mukherjee A, Hulse PA, Shalet SM. Adult growth hormone replacement therapy and neuroimaging surveillance in brain tumour survivors. Clin Endocrinol (Oxf) 2005;62:698e705. Pier DB, Nunes FP, Plotkin SR, Stemmer-Rachamimov AO, Kim JC, Shih HA, et al. Turner syndrome and meningioma: support for a possible increased risk of neoplasia in Turner syndrome. Eur J Med Genet; 2014 Mar 25. Schoemaker MJ, Swerdlow AJ, Higgins CD, Wright AF, Jacobs PA, UK Clinical Cytogenetics Group. Cancer incidence in women with Turner syndrome in Great Britain: a national cohort study. Lancet Oncol 2008;9:239e46. Sybert VP, McCauley E. Turner’s syndrome. N Engl J Med 2004;351:1227e38.
George A. Alexiou*, Maria Varela Department of Neurosurgery, Children’s Hospital “Agia Sofia”, Athens, Greece
313
Efthymios Dimitriadis Department of Genetics, Saint Savvas Hospital, Athens, Greece Amalia Patereli Department of Pathology, Children’s Hospital “Agia Sofia”, Athens, Greece Vassilios Papadakis Department of Pediatric Hematology-Oncology, Children’s Hospital “Agia Sofia”, Athens, Greece Kalliopi Stefanaki Department of Pathology, Children’s Hospital “Agia Sofia”, Athens, Greece George Sfakianos, Neofytos Prodromou Department of Neurosurgery, Children’s Hospital “Agia Sofia”, Athens, Greece * Corresponding author. Aetideon 52, Holargos, Attikis 11561, Greece. Tel.: þ30 210 6526507, þ30 6948 525134; fax: þ30 210 7467014. E-mail addresses: [email protected], [email protected] (G.A. Alexiou).
3 April 2014 Available online 13 April 2014
Contents lists available at ScienceDirect
European Journal of Medical Genetics journal homepage: http://www.elsevier.com/locate/ejmg
Letter to the Editor
Brain tumors in Turner syndrome Keywords: Turner syndrome Pilocytic astrocytoma Children Cerebellum
Dear Editor, We read with great interest the recent article by Pier et al. on Turner syndrome and meningioma occurrence [Pier et al., 2014]. The authors report on a meningioma case in a woman with Turner syndrome and reviewed 10 other similar cases. FISH analysis in this patient revealed retention of the NF2 gene locus. The authors concluded that although neoplasia may be a rare associated medical problem in Turner syndrome, this should be considered since these patients require hormone replacement therapy and artificial reproductive technologies to conceive [Pier et al., 2014]. Recently, we encountered a pilocytic astrocytoma of the cerebellum in a girl with Turner syndrome. The patient was a 13-year-old girl who was investigated by brain magnetic resonance imaging (MRI) because of short stature and delayed sexual development. MRI revealed a cerebellar lesion (2.4 2.2 2.5 cm), hypointense on T1 and hyperintense on T2 weighted images that
enhanced after contrast administration (Fig. 1). Diffusion tensor imaging demonstrated decreased fractional anisotropy in the lesion and displacement of the white matter fiber tracts without infiltration. Spinal MRI revealed no tumor dissemination. The patient was operated on via a suboccipital approach and gross total excision was achieved. Microscopic examination showed a astrocytic neoplasm with moderate cellularity, a biphasic pattern with alternating areas composed of piloid cells and microcystic areas composed of protoplasmic astrocytes with mild nuclear atypia and rare mitotic figures [0-1/10HPF]. Characteristic features were the presence of Rosenthal fibers and eosinophilic granular bodies. Immunohistochemistry revealed a heterogenous GFAP expression in neoplastic cells, being increased in the perivascular areas. Tumor cells were negative for synaptophysin, neurofilaments 2F11 and EMA. The Ki-67/MIB-1 index was 2e3%, the p-53 expression was 5% and there was cytoplasmic expression of bcl-2 in 20% of the neoplastic cells. Reverse transcription-PCR revealed gene fusion between KIAA1549 exon 16 and BRAF exon 9. The final diagnosis was pilocytic astrocytoma, grade I. A karyotypic analysis was also performed revealing a XO karyotype, establishing the diagnosis of Turner syndrome. Turner’s syndrome occurs in 1 in 2500 to 1 in 3000 live-born girls and is characterised by complete or partial X-chromosome monosomy [Sybert and McCauley, 2004]. Turner’s syndrome is the most common cause of short stature in otherwise healthy girls [Schoemaker et al., 2008]. Growth hormone therapy is
Fig. 1. A. Axial T1-weighted MRI pre and post gadolinium administration (B) revealing a space occupying lesion in the cerebellum. The lesion enhanced after contrast administration. Differential diagnosis included mainly medulloblastoma, ependymoma and astrocytoma. http://dx.doi.org/10.1016/j.ejmg.2014.04.001 1769-7212/Ó 2014 Elsevier Masson SAS. All rights reserved.
Letter to the Editor / European Journal of Medical Genetics 57 (2014) 312e313
usually administered in order to attain a normal height as early as possible and progress through puberty at a normal age. Regarding cancer incidence, Schoemaker et al. found an increased risk of gonadoblastoma and also an increased risk for meningioma and childhood brain tumors [Schoemaker et al., 2008]. GH treatment has been associated previously with an increased risk of meningioma, nevertheless our patient had not received any treatment prior to diagnosis [Jostel et al., 2005]. To the best of our knowledge no previous case of cerebellar astrocytoma in Turner syndrome has been reported. Thus, our case adds another patient with Turner syndrome that harbored a brain tumor. Although this case might be incidental, clinicians should be aware of this potential association. References Jostel A, Mukherjee A, Hulse PA, Shalet SM. Adult growth hormone replacement therapy and neuroimaging surveillance in brain tumour survivors. Clin Endocrinol (Oxf) 2005;62:698e705. Pier DB, Nunes FP, Plotkin SR, Stemmer-Rachamimov AO, Kim JC, Shih HA, et al. Turner syndrome and meningioma: support for a possible increased risk of neoplasia in Turner syndrome. Eur J Med Genet; 2014 Mar 25. Schoemaker MJ, Swerdlow AJ, Higgins CD, Wright AF, Jacobs PA, UK Clinical Cytogenetics Group. Cancer incidence in women with Turner syndrome in Great Britain: a national cohort study. Lancet Oncol 2008;9:239e46. Sybert VP, McCauley E. Turner’s syndrome. N Engl J Med 2004;351:1227e38.
George A. Alexiou*, Maria Varela Department of Neurosurgery, Children’s Hospital “Agia Sofia”, Athens, Greece
313
Efthymios Dimitriadis Department of Genetics, Saint Savvas Hospital, Athens, Greece Amalia Patereli Department of Pathology, Children’s Hospital “Agia Sofia”, Athens, Greece Vassilios Papadakis Department of Pediatric Hematology-Oncology, Children’s Hospital “Agia Sofia”, Athens, Greece Kalliopi Stefanaki Department of Pathology, Children’s Hospital “Agia Sofia”, Athens, Greece George Sfakianos, Neofytos Prodromou Department of Neurosurgery, Children’s Hospital “Agia Sofia”, Athens, Greece * Corresponding author. Aetideon 52, Holargos, Attikis 11561, Greece. Tel.: þ30 210 6526507, þ30 6948 525134; fax: þ30 210 7467014. E-mail addresses: [email protected], [email protected] (G.A. Alexiou).
3 April 2014 Available online 13 April 2014
