- Email: [email protected]
Unusual patterns of recurrence in low grade gliomas
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Case Reports / Journal of Clinical Neuroscience 21 (2014) 360–363
8. Raghunath A, Adamus G, Bodurka DC, et al. Cancer-associated retinopathy in neuroendocrine carcinoma of the fallopian tube. J Neuroophthalmol 2010;30:252–4. 9. Braithwaite T, Vugler A, Tufail A. Autoimmune retinopathy. Ophthalmologica 2012;228:131–42. 10. Eltabbakh GH, Hoogerland DL, Kay MC. Paraneoplastic retinopathy associated with uterine sarcoma. Gynecol Oncol 1995;58:120–3. 11. Adamus G, Amundson D, MacKay C, et al. Long-term persistence of antirecoverin antibodies in endometrial cancer-associated retinopathy. Arch Ophthalmol 1998;116:251–3. 12. Peek R, Verbraak F, Coevoet HM, et al. Muller cell-specific autoantibodies in a patient with progressive loss of vision. Invest Ophthalmol Vis Sci 1998;39:1976–9. 13. Salgia R, Hedges TR, Rizk M, et al. Cancer-associated retinopathy in a patient with non-small-cell lung carcinoma. Lung Cancer 1998;22:149–52. 14. Harmon JP, Purvin VA, Guy J, et al. Cancer-associated retinopathy in a patient with advanced epithelial ovarian carcinoma. Gynecol Oncol 1999;73: 430–2. 15. Kashiwabara K, Nakamura H, Kishi K, et al. Cancer-associated retinopathy during treatment for small-cell lung carcinoma. Intern Med 1999;38:597–601. 16. Yoon YH, Cho EH, Sohn J, et al. An unusual type of cancer-associated retinopathy in a patient with ovarian cancer. Korean J Ophthalmol 1999;13:43–8. 17. Katsuta H, Okada M, Nakauchi T, et al. Cancer-associated retinopathy associated with invasive thymoma. Am J Ophthalmol 2002;134:383–9. 18. Yamada G, Ohguro H, Aketa K, et al. Invasive thymoma with paraneoplastic retinopathy. Hum Pathol 2003;34:717–9. 19. Ohguro H, Odagiri H, Miyagawa Y, et al. Clinicopathological features of gastric cancer cases and aberrantly expressed recoverin. Tohoku J Exp Med 2004;202:213–9.
20. Hayashi M, Hatsukawa Y, Yasui M, et al. Cancer-associated retinopathy in a child with Langerhans cell histiocytosis. Jpn J Ophthalmol 2007;51:393–6. 21. Ejma M, Misiuk-Hojlo M, Gorczyca WA, et al. Antibodies to 46-kDa retinal antigen in a patient with breast carcinoma and cancer-associated retinopathy. Breast Cancer Res Treat 2008;110:269–71. 22. Kim SJ, Toma HS, Thirkill CE, et al. Cancer-associated retinopathy with retinal periphlebitis in a patient with ovarian cancer. Ocul Immunol Inflamm 2010;18:107–9. 23. Tanaka A, Takase H, Adamus G, et al. Cancer-associated retinopathy caused by benign thymoma. Br J Ophthalmol 2010;94:526–8. 24. Sakamori Y, Kim YH, Okuda C, et al. Two cases of cancer-associated retinopathy combined with small-cell lung cancer. Jpn J Clin Oncol 2011;41:669–73. 25. Ohguro H, Yokoi Y, Ohguro I, et al. Clinical and immunologic aspects of cancerassociated retinopathy. Am J Ophthalmol 2004;137:1117–9. 26. Weleber RG, Watzke RC, Shults WT, et al. Clinical and electrophysiologic characterization of paraneoplastic and autoimmune retinopathies associated with antienolase antibodies. Am J Ophthalmol 2005;139:780–94. 27. Adamus G. Autoantibody targets and their cancer relationship in the pathogenicity of paraneoplastic retinopathy. Autoimmun Rev 2009;8:410–4. 28. Adamus G, Aptsiauri N, Guy J, et al. The occurrence of serum autoantibodies against enolase in cancer-associated retinopathy. Clin Immunol Immunopathol 1996;78:120–9. 29. Ferreyra HA, Jayasundera T, Khan NW, et al. Management of autoimmune retinopathies with immunosuppression. Arch Ophthalmol 2009;127:390–7. 30. Whitcup SM, Vistica BP, Milam AH, et al. Recoverin-associated retinopathy: a clinically and immunologically distinctive disease. Am J Ophthalmol 1998;126:230–7. 31. Murphy MA, Thirkill CE, Hart Jr WM. Paraneoplastic retinopathy: a novel autoantibody reaction associated with small-cell lung carcinoma. J Neuroophthalmol 1997;17:77–83.
doi:http://dx.doi.org/10.1016/j.jocn.2013.05.013
Unusual patterns of recurrence in low grade gliomas Jonathan R. Ellenbogen ⇑, Peter Davies, Paul R. Eldridge, Michael D. Jenkinson Department of Neurosurgery, The Walton Centre for Neurology & Neurosurgery, Lower Lane, Fazakerley, Liverpool L9 7LJ, UK
a r t i c l e
i n f o
Article history: Received 11 November 2012 Accepted 15 May 2013
Keywords: Low grade glioma Metastasis Recurrence
a b s t r a c t Some of the more unusual patterns of recurrence in previously treated low grade gliomas are demonstrated. As treatment choices develop and life expectancy is prolonged, patterns of tumour recurrence are likely to change within such a heterogeneous group of tumours, including metastatic spread via cerebrospinal fluid pathways. Ó 2013 Elsevier Ltd. All rights reserved.
1. Introduction
2. Case reports
Diffuse grade II gliomas are slow growing, highly infiltrative, have a propensity to migrate along white matter tracts and almost inevitably undergo malignant transformation. Even with gross total resection surgical cure is not possible and infiltrative tumour cells appear to be particularly resistant to adjuvant cytotoxic therapy.1,2 Although tumour recurrence typically occurs within the resection margins or treatment fields, here three patients are reported to illustrate more atypical patterns of recurrence in these tumours.
2.1. Patient 1
⇑ Corresponding author. Tel.: +44 78 0114 1619. E-mail address: [email protected] (J.R. Ellenbogen).
A 36-year-old man with a right frontotemporal grade II oligodendroglioma underwent biopsy and adjuvant radiotherapy in 1998 (Fig. 1a). Annual MRI revealed local recurrence in 2006, and a biopsy confirmed recurrence but not malignant transformation (Fig. 1b). He received procarbazine, lomustine and vincristine (PCV) chemotherapy and showed a partial response on MRI (Fig. 1c). In 2009 he presented with acute paraplegia and MRI revealed tumour recurrence in the spine (Fig. 1d) without evidence of recurrent intracranial disease. Due to his poor performance status, a tissue diagnosis was not obtained and he died 5 months later.
Case Reports / Journal of Clinical Neuroscience 21 (2014) 360–363
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Fig. 1. Patient 1. Axial (a,c) T1-weighted MRI with (b,d) gadolinium (GAD) contrast demonstrating (a) right frontotemporal tumour, (b) local recurrence following radiotherapy treatment, (c) partial response to chemotherapy, and (d) spinal recurrence on sagittal view.
2.2. Patient 2 A 26-year-old woman with a left frontal grade II oligoastrocytoma underwent resection in Australia in 2005. She did not receive any adjuvant therapy. In 2008 MRI demonstrated local recurrence and further surgical resection in Australia revealed histological progression to a World Health Organization grade IV glioblastoma. She returned to the United Kingdom and received adjuvant chemoradiotherapy and the tumour showed a complete response (Fig. 2a). In 2010 she presented with acute paraperesis, paraesthesia of both hands and intractable leg pain. MRI demonstrated intramedullary recurrence with intrathecal ‘‘droplet’’ metastasis throughout her spine without cranial recurrence (Fig. 2b,c). Biopsy of spinal lesions revealed high grade glioma consistent with at
least a grade III anaplastic astrocytoma. She was given palliative chemoradiotherapy. She was discharged to the palliative care team and died 1 month later. 2.3. Patient 3 A 28-year-old woman presented with a seizure secondary to a right posterior frontal tumour in 1996. Biopsy revealed a grade II oligodendroglioma. She did not receive any adjuvant therapy and was placed on active surveillance. In 1998 she presented with a progressive left hemiparesis and underwent tumour resection of the grade II oligodendroglioma. She received adjuvant radiotherapy and chemotherapy. Continued MRI surveillance showed stable disease with no evidence of recurrence (Fig. 3a). In 2009, 1 month
Fig. 2. Patient 2. T1-weighted (a) axial MRI demonstrating complete response of tumour. (b) Axial brain and (c) sagittal spine MRI showing spinal recurrence without evidence of cranial recurrence.
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Case Reports / Journal of Clinical Neuroscience 21 (2014) 360–363
Fig. 3. Patient 3. T1-weighted axial MRI demonstrating (a) stable disease, and (b) tumour recurrence through both frontal lobes.
after a routine follow-up MRI showed no evidence of tumour recurrence, she developed rapid onset personality change and a further MRI demonstrated widespread tumour recurrence of both hemispheres (Fig. 3b). Biopsy confirmed tumour progression to a grade III anaplastic oligodendroglioma. No adjuvant therapy was offered due to her poor performance status and she died 1 month after biopsy.
3. Discussion The median survival for a grade II astrocytoma and oligodendroglioma is 4.7 and 7.1 years, respectively. Despite advances in therapy the prognosis has not significantly changed and death often results from local recurrence and/or malignant transformation. The presented patients were all longer-term survivors, which may reflect the atypical pattern of tumour recurrence. Gliomagenesis is thought to be driven by several biological events, such as activated growth factor receptor signaling pathways, down-regulation of many apoptotic mechanisms and unbalance among angiogenic and antiangiogenic factors. The ‘‘apex cell’’, the cell of origin, in the subsets of gliomas remains a source of debate but there may well be a multitude of different cell types that develop into the same disease. Initial theories postulated dedifferentiation of normal astrocytes and oligodendrocytes.3 Alternative theories propose that gliomas have monoclonal origin, as regions of differing histology within the same tumour have been shown to have an identical genotype, and regions of differing histological subtype could not be distinguished by differing genetic markers alone.4,5 A possible theory is that a low grade glioma starts with a single abnormal cell that undergoes clonal expansion, forming the solid tumour, as well as disseminating abnormal cells throughout the central nervous system leading to recurrence at low grade following removal, or progression to high-grade. Reservoirs of neural stem cells in the subventricular zone, the subgranular zone of the dentate gyrus, and possibly other small stem-cell bays throughout the brain may be the pool from which gliomas originate. In addition there are also reports that glial progenitor cells are widely distributed throughout the adult brain, so although the subventricular zone contains the highest density of neuroglial precursor cells, glioma might also arise from precursors in other areas of the brain.3,6 This raises the question as to whether progression is a single cellular event, in that tumours are monoclonal in
origin with heterogeneous genetic changes arising during clonal expansion, or whether it is a consequence of several lines arising at several points in time. Clues to this would be in the timing of dissemination. The patients we present suggest periods of stability followed by relatively sudden widespread involvement, indicating the possibility of a single clonal line origin to progression. If this is so then the trend towards more aggressive cyto-reductive surgery for low grade gliomas can be backed up by a mechanistic argument as once all tumour cells are removed no cell can progress. Surgical series have demonstrated that maximising the extent of resection as objectively measured on post-operative MRI demonstrates increased overall survival by delayed malignant transformation7,8 Duffau has postulated that achieving surgical resection based upon functional rather than oncological boundaries will allow further maximal resection and therefore improved survival.9–12 This together with the use of PCV chemotherapy and temozolomide could extend the survival of some patients.13 As demonstrated by the reported patients, there is no single pattern of glioma recurrence, and clinicians should be alert to signs suggesting tumour recurrence throughout the neuroaxis.
Conflict of interest/disclosure The authors declare that they have no financial or other conflicts of interest in relation to this research and its publication. References 1. Massey V, Wallner KE. Patterns of second recurrence of malignant astrocytomas. Int J Radiat Oncol Biol Phys 1990;18:395–8. 2. Shaw E, Berkey B, Coons S, et al. Recurrence following neurosurgeondetermined gross-total resection of adult supratentorial low-grade glioma: results of a prospective clinical trial. J Neurosurg 2008;109:835–41. 3. Maher E, Furnari FB, Bachoo RM, et al. Malignant glioma: genetics and biology of a grave matter. Genes Dev 2001;15:1311–33. 4. Quiñones-Hinojosa A, Chaichana K. The human subventricular zone: a source of new cells and a potential source of brain tumors. Exp Neurol 2007;205: 313–24. 5. Walker C, Du Plessis DG, Joyce KA, et al. Phenotype versus genotype in gliomas displaying inter- or intratumoral histological heterogeneity. Clin Cancer Res 2003;9:4841–51. 6. Westphal M, Lamszus K. The neurobiology of gliomas: from cell biology to the development of therapeutic approaches. Nat Rev Neurosci 2011;12:495–508. 7. Smith JS, Chang EF, Lamborn KR, et al. Role of extent of resection in the longterm outcome of low-grade hemispheric gliomas. J Clin Oncol 2008;26:1338–45.
Case Reports / Journal of Clinical Neuroscience 21 (2014) 360–363 8. Duffau H. Surgery of low-grade gliomas: towards a ‘‘functional neurooncology’’. Curr Opin Oncol 2009;21:543–9. 9. Robles SG, Gatignol P, Lehéricy S, et al. Long-term brain plasticity allowing a multistage surgical approach to World Health Organization Grade II gliomas in eloquent areas. J Neurosurg 2008;109:615–24. 10. Duffau H, Mandonnet E. The ‘‘onco-functional balance’’ in surgery for diffuse low-grade glioma: integrating the extent of resection with quality of life. Acta neurochirurgica 2013;155:951–7.
doi:http://dx.doi.org/10.1016/j.jocn.2013.05.013
363
11. Duffau H. Lessons from brain mapping in surgery for low-grade glioma: insights into associations between tumour and brain plasticity. Lancet Neurol 2005;4:476–86. 12. Duffau H. The challenge to remove diffuse low-grade gliomas while preserving brain functions. Acta Neurochir 2012;154:569–74. 13. Blonski M, Taillandier L, Herbet G, et al. Combination of neoadjuvant chemotherapy followed by surgical resection as a new strategy for WHO grade II gliomas: a study of cognitive status and quality of life. J Neurooncol 2012;106:353–66.
Case Reports / Journal of Clinical Neuroscience 21 (2014) 360–363
8. Raghunath A, Adamus G, Bodurka DC, et al. Cancer-associated retinopathy in neuroendocrine carcinoma of the fallopian tube. J Neuroophthalmol 2010;30:252–4. 9. Braithwaite T, Vugler A, Tufail A. Autoimmune retinopathy. Ophthalmologica 2012;228:131–42. 10. Eltabbakh GH, Hoogerland DL, Kay MC. Paraneoplastic retinopathy associated with uterine sarcoma. Gynecol Oncol 1995;58:120–3. 11. Adamus G, Amundson D, MacKay C, et al. Long-term persistence of antirecoverin antibodies in endometrial cancer-associated retinopathy. Arch Ophthalmol 1998;116:251–3. 12. Peek R, Verbraak F, Coevoet HM, et al. Muller cell-specific autoantibodies in a patient with progressive loss of vision. Invest Ophthalmol Vis Sci 1998;39:1976–9. 13. Salgia R, Hedges TR, Rizk M, et al. Cancer-associated retinopathy in a patient with non-small-cell lung carcinoma. Lung Cancer 1998;22:149–52. 14. Harmon JP, Purvin VA, Guy J, et al. Cancer-associated retinopathy in a patient with advanced epithelial ovarian carcinoma. Gynecol Oncol 1999;73: 430–2. 15. Kashiwabara K, Nakamura H, Kishi K, et al. Cancer-associated retinopathy during treatment for small-cell lung carcinoma. Intern Med 1999;38:597–601. 16. Yoon YH, Cho EH, Sohn J, et al. An unusual type of cancer-associated retinopathy in a patient with ovarian cancer. Korean J Ophthalmol 1999;13:43–8. 17. Katsuta H, Okada M, Nakauchi T, et al. Cancer-associated retinopathy associated with invasive thymoma. Am J Ophthalmol 2002;134:383–9. 18. Yamada G, Ohguro H, Aketa K, et al. Invasive thymoma with paraneoplastic retinopathy. Hum Pathol 2003;34:717–9. 19. Ohguro H, Odagiri H, Miyagawa Y, et al. Clinicopathological features of gastric cancer cases and aberrantly expressed recoverin. Tohoku J Exp Med 2004;202:213–9.
20. Hayashi M, Hatsukawa Y, Yasui M, et al. Cancer-associated retinopathy in a child with Langerhans cell histiocytosis. Jpn J Ophthalmol 2007;51:393–6. 21. Ejma M, Misiuk-Hojlo M, Gorczyca WA, et al. Antibodies to 46-kDa retinal antigen in a patient with breast carcinoma and cancer-associated retinopathy. Breast Cancer Res Treat 2008;110:269–71. 22. Kim SJ, Toma HS, Thirkill CE, et al. Cancer-associated retinopathy with retinal periphlebitis in a patient with ovarian cancer. Ocul Immunol Inflamm 2010;18:107–9. 23. Tanaka A, Takase H, Adamus G, et al. Cancer-associated retinopathy caused by benign thymoma. Br J Ophthalmol 2010;94:526–8. 24. Sakamori Y, Kim YH, Okuda C, et al. Two cases of cancer-associated retinopathy combined with small-cell lung cancer. Jpn J Clin Oncol 2011;41:669–73. 25. Ohguro H, Yokoi Y, Ohguro I, et al. Clinical and immunologic aspects of cancerassociated retinopathy. Am J Ophthalmol 2004;137:1117–9. 26. Weleber RG, Watzke RC, Shults WT, et al. Clinical and electrophysiologic characterization of paraneoplastic and autoimmune retinopathies associated with antienolase antibodies. Am J Ophthalmol 2005;139:780–94. 27. Adamus G. Autoantibody targets and their cancer relationship in the pathogenicity of paraneoplastic retinopathy. Autoimmun Rev 2009;8:410–4. 28. Adamus G, Aptsiauri N, Guy J, et al. The occurrence of serum autoantibodies against enolase in cancer-associated retinopathy. Clin Immunol Immunopathol 1996;78:120–9. 29. Ferreyra HA, Jayasundera T, Khan NW, et al. Management of autoimmune retinopathies with immunosuppression. Arch Ophthalmol 2009;127:390–7. 30. Whitcup SM, Vistica BP, Milam AH, et al. Recoverin-associated retinopathy: a clinically and immunologically distinctive disease. Am J Ophthalmol 1998;126:230–7. 31. Murphy MA, Thirkill CE, Hart Jr WM. Paraneoplastic retinopathy: a novel autoantibody reaction associated with small-cell lung carcinoma. J Neuroophthalmol 1997;17:77–83.
doi:http://dx.doi.org/10.1016/j.jocn.2013.05.013
Unusual patterns of recurrence in low grade gliomas Jonathan R. Ellenbogen ⇑, Peter Davies, Paul R. Eldridge, Michael D. Jenkinson Department of Neurosurgery, The Walton Centre for Neurology & Neurosurgery, Lower Lane, Fazakerley, Liverpool L9 7LJ, UK
a r t i c l e
i n f o
Article history: Received 11 November 2012 Accepted 15 May 2013
Keywords: Low grade glioma Metastasis Recurrence
a b s t r a c t Some of the more unusual patterns of recurrence in previously treated low grade gliomas are demonstrated. As treatment choices develop and life expectancy is prolonged, patterns of tumour recurrence are likely to change within such a heterogeneous group of tumours, including metastatic spread via cerebrospinal fluid pathways. Ó 2013 Elsevier Ltd. All rights reserved.
1. Introduction
2. Case reports
Diffuse grade II gliomas are slow growing, highly infiltrative, have a propensity to migrate along white matter tracts and almost inevitably undergo malignant transformation. Even with gross total resection surgical cure is not possible and infiltrative tumour cells appear to be particularly resistant to adjuvant cytotoxic therapy.1,2 Although tumour recurrence typically occurs within the resection margins or treatment fields, here three patients are reported to illustrate more atypical patterns of recurrence in these tumours.
2.1. Patient 1
⇑ Corresponding author. Tel.: +44 78 0114 1619. E-mail address: [email protected] (J.R. Ellenbogen).
A 36-year-old man with a right frontotemporal grade II oligodendroglioma underwent biopsy and adjuvant radiotherapy in 1998 (Fig. 1a). Annual MRI revealed local recurrence in 2006, and a biopsy confirmed recurrence but not malignant transformation (Fig. 1b). He received procarbazine, lomustine and vincristine (PCV) chemotherapy and showed a partial response on MRI (Fig. 1c). In 2009 he presented with acute paraplegia and MRI revealed tumour recurrence in the spine (Fig. 1d) without evidence of recurrent intracranial disease. Due to his poor performance status, a tissue diagnosis was not obtained and he died 5 months later.
Case Reports / Journal of Clinical Neuroscience 21 (2014) 360–363
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Fig. 1. Patient 1. Axial (a,c) T1-weighted MRI with (b,d) gadolinium (GAD) contrast demonstrating (a) right frontotemporal tumour, (b) local recurrence following radiotherapy treatment, (c) partial response to chemotherapy, and (d) spinal recurrence on sagittal view.
2.2. Patient 2 A 26-year-old woman with a left frontal grade II oligoastrocytoma underwent resection in Australia in 2005. She did not receive any adjuvant therapy. In 2008 MRI demonstrated local recurrence and further surgical resection in Australia revealed histological progression to a World Health Organization grade IV glioblastoma. She returned to the United Kingdom and received adjuvant chemoradiotherapy and the tumour showed a complete response (Fig. 2a). In 2010 she presented with acute paraperesis, paraesthesia of both hands and intractable leg pain. MRI demonstrated intramedullary recurrence with intrathecal ‘‘droplet’’ metastasis throughout her spine without cranial recurrence (Fig. 2b,c). Biopsy of spinal lesions revealed high grade glioma consistent with at
least a grade III anaplastic astrocytoma. She was given palliative chemoradiotherapy. She was discharged to the palliative care team and died 1 month later. 2.3. Patient 3 A 28-year-old woman presented with a seizure secondary to a right posterior frontal tumour in 1996. Biopsy revealed a grade II oligodendroglioma. She did not receive any adjuvant therapy and was placed on active surveillance. In 1998 she presented with a progressive left hemiparesis and underwent tumour resection of the grade II oligodendroglioma. She received adjuvant radiotherapy and chemotherapy. Continued MRI surveillance showed stable disease with no evidence of recurrence (Fig. 3a). In 2009, 1 month
Fig. 2. Patient 2. T1-weighted (a) axial MRI demonstrating complete response of tumour. (b) Axial brain and (c) sagittal spine MRI showing spinal recurrence without evidence of cranial recurrence.
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Case Reports / Journal of Clinical Neuroscience 21 (2014) 360–363
Fig. 3. Patient 3. T1-weighted axial MRI demonstrating (a) stable disease, and (b) tumour recurrence through both frontal lobes.
after a routine follow-up MRI showed no evidence of tumour recurrence, she developed rapid onset personality change and a further MRI demonstrated widespread tumour recurrence of both hemispheres (Fig. 3b). Biopsy confirmed tumour progression to a grade III anaplastic oligodendroglioma. No adjuvant therapy was offered due to her poor performance status and she died 1 month after biopsy.
3. Discussion The median survival for a grade II astrocytoma and oligodendroglioma is 4.7 and 7.1 years, respectively. Despite advances in therapy the prognosis has not significantly changed and death often results from local recurrence and/or malignant transformation. The presented patients were all longer-term survivors, which may reflect the atypical pattern of tumour recurrence. Gliomagenesis is thought to be driven by several biological events, such as activated growth factor receptor signaling pathways, down-regulation of many apoptotic mechanisms and unbalance among angiogenic and antiangiogenic factors. The ‘‘apex cell’’, the cell of origin, in the subsets of gliomas remains a source of debate but there may well be a multitude of different cell types that develop into the same disease. Initial theories postulated dedifferentiation of normal astrocytes and oligodendrocytes.3 Alternative theories propose that gliomas have monoclonal origin, as regions of differing histology within the same tumour have been shown to have an identical genotype, and regions of differing histological subtype could not be distinguished by differing genetic markers alone.4,5 A possible theory is that a low grade glioma starts with a single abnormal cell that undergoes clonal expansion, forming the solid tumour, as well as disseminating abnormal cells throughout the central nervous system leading to recurrence at low grade following removal, or progression to high-grade. Reservoirs of neural stem cells in the subventricular zone, the subgranular zone of the dentate gyrus, and possibly other small stem-cell bays throughout the brain may be the pool from which gliomas originate. In addition there are also reports that glial progenitor cells are widely distributed throughout the adult brain, so although the subventricular zone contains the highest density of neuroglial precursor cells, glioma might also arise from precursors in other areas of the brain.3,6 This raises the question as to whether progression is a single cellular event, in that tumours are monoclonal in
origin with heterogeneous genetic changes arising during clonal expansion, or whether it is a consequence of several lines arising at several points in time. Clues to this would be in the timing of dissemination. The patients we present suggest periods of stability followed by relatively sudden widespread involvement, indicating the possibility of a single clonal line origin to progression. If this is so then the trend towards more aggressive cyto-reductive surgery for low grade gliomas can be backed up by a mechanistic argument as once all tumour cells are removed no cell can progress. Surgical series have demonstrated that maximising the extent of resection as objectively measured on post-operative MRI demonstrates increased overall survival by delayed malignant transformation7,8 Duffau has postulated that achieving surgical resection based upon functional rather than oncological boundaries will allow further maximal resection and therefore improved survival.9–12 This together with the use of PCV chemotherapy and temozolomide could extend the survival of some patients.13 As demonstrated by the reported patients, there is no single pattern of glioma recurrence, and clinicians should be alert to signs suggesting tumour recurrence throughout the neuroaxis.
Conflict of interest/disclosure The authors declare that they have no financial or other conflicts of interest in relation to this research and its publication. References 1. Massey V, Wallner KE. Patterns of second recurrence of malignant astrocytomas. Int J Radiat Oncol Biol Phys 1990;18:395–8. 2. Shaw E, Berkey B, Coons S, et al. Recurrence following neurosurgeondetermined gross-total resection of adult supratentorial low-grade glioma: results of a prospective clinical trial. J Neurosurg 2008;109:835–41. 3. Maher E, Furnari FB, Bachoo RM, et al. Malignant glioma: genetics and biology of a grave matter. Genes Dev 2001;15:1311–33. 4. Quiñones-Hinojosa A, Chaichana K. The human subventricular zone: a source of new cells and a potential source of brain tumors. Exp Neurol 2007;205: 313–24. 5. Walker C, Du Plessis DG, Joyce KA, et al. Phenotype versus genotype in gliomas displaying inter- or intratumoral histological heterogeneity. Clin Cancer Res 2003;9:4841–51. 6. Westphal M, Lamszus K. The neurobiology of gliomas: from cell biology to the development of therapeutic approaches. Nat Rev Neurosci 2011;12:495–508. 7. Smith JS, Chang EF, Lamborn KR, et al. Role of extent of resection in the longterm outcome of low-grade hemispheric gliomas. J Clin Oncol 2008;26:1338–45.
Case Reports / Journal of Clinical Neuroscience 21 (2014) 360–363 8. Duffau H. Surgery of low-grade gliomas: towards a ‘‘functional neurooncology’’. Curr Opin Oncol 2009;21:543–9. 9. Robles SG, Gatignol P, Lehéricy S, et al. Long-term brain plasticity allowing a multistage surgical approach to World Health Organization Grade II gliomas in eloquent areas. J Neurosurg 2008;109:615–24. 10. Duffau H, Mandonnet E. The ‘‘onco-functional balance’’ in surgery for diffuse low-grade glioma: integrating the extent of resection with quality of life. Acta neurochirurgica 2013;155:951–7.
doi:http://dx.doi.org/10.1016/j.jocn.2013.05.013
363
11. Duffau H. Lessons from brain mapping in surgery for low-grade glioma: insights into associations between tumour and brain plasticity. Lancet Neurol 2005;4:476–86. 12. Duffau H. The challenge to remove diffuse low-grade gliomas while preserving brain functions. Acta Neurochir 2012;154:569–74. 13. Blonski M, Taillandier L, Herbet G, et al. Combination of neoadjuvant chemotherapy followed by surgical resection as a new strategy for WHO grade II gliomas: a study of cognitive status and quality of life. J Neurooncol 2012;106:353–66.