- Email: [email protected]
Autoimmune retinopathy associated with carcinoid tumour of the small bowel
358
Case Reports / Journal of Clinical Neuroscience 21 (2014) 358–360
3. Schulz H, Pels H, Schmidt-Wolf I, et al. Intraventricular treatment of relapsed central nervous system lymphoma with the anti-CD20 antibody rituximab. Haematologica 2004;89:753–4. 4. Rubenstein JL, Fridlyand J, Abrey L, et al. Phase I study of intraventricular administration of rituximab in patients with recurrent CNS and intraocular lymphoma. J Clin Oncol 2007;25:1350–6. 5. Rubinstein JL, Li J, Chen L, et al. Multicenter phase 1 trial of intraventricular immunochemotherapy in recurrent CNS lymphoma. Blood 2013;121:745–51.
6. Pels H, Schmidt-Wolf IG, Glasmacher A, et al. Primary central nervous system lymphoma: results of a pilot and phase II study of systemic and intraventricular chemotherapy with deferred radiotherapy. J Clin Oncol 2003;21:4489–95. 7. Soussain C, Hoang-Xuan K, Taillandier L, et al. Intensive chemotherapy followed by hematopoietic stem-cell rescue for refractory and recurrent primary CNS and intraocular lymphoma: Societe Francaise de Greffe de Moelle Osseuse-Therapie Cellulaire. J Clin Oncol 2008;26:2512–8.
doi:http://dx.doi.org/10.1016/j.jocn.2013.07.002
Autoimmune retinopathy associated with carcinoid tumour of the small bowel Siddharth Ogra ⇑, Dianne Sharp, Helen Danesh-Meyer Department of Ophthalmology, Faculty of Medical and Health Sciences, The University of Auckland, Private Bag 92019, Auckland, New Zealand
a r t i c l e
i n f o
Article history: Received 28 June 2013 Accepted 14 July 2013
Keywords: Alpha enolase Autoimmune retinopathy Cancer associated retinopathy Carbonic anhydrase Neuroendocrine tumour Paraneoplastic syndromes (ocular)
a b s t r a c t Cancer associated retinopathy (CAR) is an immune mediated paraneoplastic condition associated with vision loss. It has been associated with a variety of systemic malignancies. The primary clinical presentation is rapid, progressive vision loss. Rod and cone dysfunction can cause other associated symptoms, such as nyctalopia. Electrophysiological testing and detection of anti-retinal antibodies are used to confirm the diagnosis. To our knowledge we describe the first patient with CAR associated with a carcinoid tumour of the gastrointestinal system. Auto-antibodies against alpha enolase and carbonic anhydrase II were detected with western blotting. Electroretinogram findings were consistent with rod and cone dysfunction. Ó 2013 Elsevier Ltd. All rights reserved.
1. Introduction Cancer associated retinopathy (CAR) is an immune mediated paraneoplastic condition associated with vision loss.1–9 Certain systemic malignancies trigger auto-antibody formation leading to immune mediated retinal damage, possibly through a caspase led apoptotic process4 although this is not fully understood. Typically associated with small cell or non-small cell lung cancer, cases have been reported secondary to invasive thymoma, breast and uterine carcinoma, lymphoma, endometrial carcinoma, Langerhans cell histiocytosis and more.2,7,8,10–24 The primary clinical presentation of CAR is rapid onset, progressive vision loss. Both rods and cones within the retina are affected, leading to a variety of symptoms. Rod dysfunction typically presents with nyctalopia, reduction of peripheral vision, prolonged dark adaptation and abnormal electroretinogram (ERG) response. Cone dysfunction can lead to reduced visual acuity, colour vision disturbance, central scotoma and an abnormal cone-mediated ERG response.2,9,25,26 Ophthalmological examination may show attenuated retinal arteriole calibre, optic disc pallor and retinal pigment changes.25,26 The fundus frequently appears normal.26 2. Case report A 66-year-old man presented after experiencing progressive blurring of vision and nyctalopia over 4 months. There was no past ocular history of note. Medical history included a known carcinoid tumour of small bowel origin (45 54 53 mm) surrounding and ⇑ Corresponding author. Tel.: +64 9 373 7599x86712; fax: +64 9 367 7173. E-mail address: [email protected] (S. Ogra).
occluding the superior mesenteric vein. Originally diagnosed in May 2011 (22 months prior to presentation), this had been deemed inoperable due to its proximity to the superior mesenteric artery. There was no history of prior chemotherapy or radiotherapy. Immunohistochemistry of the tumour showed positivity for CK8/ 18, AE1/AE3, cytokeratin, chromogranin, synaptophysin and CD56. CK7 and CK20 were negative. Ki67 proliferation index was less than 3%. This was consistent with a low grade neuroendocrine neoplasm. Other significant history included polymyalgia rheumatica, for which the patient had been on a reducing regime of oral corticosteroid over the past few months. He had ceased the prednisone approximately 4 weeks prior to presentation. On examination, visual acuity was 6/9 oculus dexter and 6/12 oculus sinistra. Colour vision was 2/15 for Ishihara colour plates on the right and only the test plate on the left. Slit lamp examination was otherwise unremarkable with normal appearance of the fundus. Peripheral field defects were present bilaterally with standard automated perimetry (Humphrey field analyser, SITA-standard protocol, 24-2 threshold; Carl Zeiss Surgical, Oberkochen, Germany) (Fig. 1). Electrodiagnostic assessment revealed a poorly defined pattern ERG in each eye. There was no recordable rod-mediated function to dim flash, and the response to bright flash was reduced. Cone mediated function was reported as being 60% of normal. Flicker 30 Hz latency was slightly increased at 31 ms (normal 28 ms) and amplitude was 60 lV (normal >100 lV). Due to the high index of suspicion for CAR, anti-retinal antibody analysis was performed (Oregon Health and Science University, OR, USA). Western blotting was positive for anti-retinal antibodies against 30 kDa (carbonic anhydrase II), 45 and 46 kDa (alphaenolase) proteins. Immunohistochemistry was negative.
Case Reports / Journal of Clinical Neuroscience 21 (2014) 358–360
359
Fig. 1. Humphrey visual field (SITA-standard protocol, 24-2 threshold; Carl Zeiss Surgical, Oberkochen, Germany) showing the peripheral visual field loss. GHT = glaucoma hemifield test, MD = mean deviation, NEG = negative, POS = positive, PSD = pattern standard deviation, VFI = visual field index.
The patient was commenced on high dose oral corticosteroid. As there was no widely reported link between carcinoid tumours and CAR, further investigation was initiated to rule out any new malignancy. CT scans of the chest, abdomen and pelvis were negative for any new changes. Unfortunately the patient died 1 month following initial diagnosis of CAR from a small bowel obstruction.
immunosuppression during this time may have resulted in the manifestation of CAR. In conclusion, CAR is an immune mediated cause of rapid vision loss in those with various systemic malignancies. Any patients with symptoms such as rapidly reducing vision, peripheral field constriction, nyctalopia, reduced colour vision and ERG changes suggestive of rod or cone dysfunction should be investigated for possible malignancy. A variety of auto-antibodies may cause CAR, however clinical detection is the crucial step.
3. Discussion This report presents the occurrence of CAR in a patient with histologically confirmed carcinoid tumour. Despite a thorough literature review, no patients with CAR associated with carcinoid tumour were identified at the time of writing. Anti-recoverin antibody was not identified in this patient, however other anti-retinal antibodies (carbonic anhydrase II, alpha enolase) were detected. Alpha enolase antibody is detected in approximately 30% of seropositive patients with CAR, and anti-carbonic anhydrase II antibody in 14%.27 Patients positive for antienolase antibodies usually demonstrate a slower deterioration compared to anti-recoverin associated retinopathy.26,28 This may explain the 4 month history of progression in our patient. There is currently no protocol for management of CAR. As it is an immune mediated condition, immunosuppression is usually targeted however there is no strong evidence base for this.9 One study showed five out of six patients with CAR improved with prolonged systemic immunosuppression.29 However, other case studies have shown mixed results with oral immunosuppression, as well as plasmapheresis and intravenous immunoglobulin administration.26,30,31 Our patient had been on reducing oral steroids preceding his onset of visual symptoms. We postulate that the reduction in
Conflict of interest/disclosure S.O. is supported by Optic Nerve Research Fellowship, funded by Allergan. The authors declare that they have no other financial or other conflicts of interest in relation to this research and its publication.
References 1. Thirkill CE, Roth AM, Keltner JL. Cancer-associated retinopathy. Arch Ophthalmol 1987;105:372–5. 2. Goldstein SM, Syed NA, Milam AH, et al. Cancer-associated retinopathy. Arch Ophthalmol 1999;117:1641–5. 3. Guy J, Aptsiauri N. Treatment of paraneoplastic visual loss with intravenous immunoglobulin: report of 3 cases. Arch Ophthalmol 1999;117:471–7. 4. Shiraga S, Adamus G. Mechanism of CAR syndrome: anti-recoverin antibodies are the inducers of retinal cell apoptotic death via the caspase 9- and caspase 3dependent pathway. J Neuroimmunol 2002;132:72–82. 5. Adamus G, Ren G, Weleber RG. Autoantibodies against retinal proteins in paraneoplastic and autoimmune retinopathy. BMC Ophthalmol 2004;4:5. 6. Magrys A, Anekonda T, Ren G, et al. The role of anti-alpha-enolase autoantibodies in pathogenicity of autoimmune-mediated retinopathy. J Clin Immunol 2007;27:181–92. 7. Misiuk-Hojlo M, Ejma M, Gorczyca WA, et al. Cancer-associated retinopathy in patients with breast carcinoma. Arch Immunol Ther Exp (Warsz) 2007;55:261–5.
360
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.2013.07.002
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) 358–360
3. Schulz H, Pels H, Schmidt-Wolf I, et al. Intraventricular treatment of relapsed central nervous system lymphoma with the anti-CD20 antibody rituximab. Haematologica 2004;89:753–4. 4. Rubenstein JL, Fridlyand J, Abrey L, et al. Phase I study of intraventricular administration of rituximab in patients with recurrent CNS and intraocular lymphoma. J Clin Oncol 2007;25:1350–6. 5. Rubinstein JL, Li J, Chen L, et al. Multicenter phase 1 trial of intraventricular immunochemotherapy in recurrent CNS lymphoma. Blood 2013;121:745–51.
6. Pels H, Schmidt-Wolf IG, Glasmacher A, et al. Primary central nervous system lymphoma: results of a pilot and phase II study of systemic and intraventricular chemotherapy with deferred radiotherapy. J Clin Oncol 2003;21:4489–95. 7. Soussain C, Hoang-Xuan K, Taillandier L, et al. Intensive chemotherapy followed by hematopoietic stem-cell rescue for refractory and recurrent primary CNS and intraocular lymphoma: Societe Francaise de Greffe de Moelle Osseuse-Therapie Cellulaire. J Clin Oncol 2008;26:2512–8.
doi:http://dx.doi.org/10.1016/j.jocn.2013.07.002
Autoimmune retinopathy associated with carcinoid tumour of the small bowel Siddharth Ogra ⇑, Dianne Sharp, Helen Danesh-Meyer Department of Ophthalmology, Faculty of Medical and Health Sciences, The University of Auckland, Private Bag 92019, Auckland, New Zealand
a r t i c l e
i n f o
Article history: Received 28 June 2013 Accepted 14 July 2013
Keywords: Alpha enolase Autoimmune retinopathy Cancer associated retinopathy Carbonic anhydrase Neuroendocrine tumour Paraneoplastic syndromes (ocular)
a b s t r a c t Cancer associated retinopathy (CAR) is an immune mediated paraneoplastic condition associated with vision loss. It has been associated with a variety of systemic malignancies. The primary clinical presentation is rapid, progressive vision loss. Rod and cone dysfunction can cause other associated symptoms, such as nyctalopia. Electrophysiological testing and detection of anti-retinal antibodies are used to confirm the diagnosis. To our knowledge we describe the first patient with CAR associated with a carcinoid tumour of the gastrointestinal system. Auto-antibodies against alpha enolase and carbonic anhydrase II were detected with western blotting. Electroretinogram findings were consistent with rod and cone dysfunction. Ó 2013 Elsevier Ltd. All rights reserved.
1. Introduction Cancer associated retinopathy (CAR) is an immune mediated paraneoplastic condition associated with vision loss.1–9 Certain systemic malignancies trigger auto-antibody formation leading to immune mediated retinal damage, possibly through a caspase led apoptotic process4 although this is not fully understood. Typically associated with small cell or non-small cell lung cancer, cases have been reported secondary to invasive thymoma, breast and uterine carcinoma, lymphoma, endometrial carcinoma, Langerhans cell histiocytosis and more.2,7,8,10–24 The primary clinical presentation of CAR is rapid onset, progressive vision loss. Both rods and cones within the retina are affected, leading to a variety of symptoms. Rod dysfunction typically presents with nyctalopia, reduction of peripheral vision, prolonged dark adaptation and abnormal electroretinogram (ERG) response. Cone dysfunction can lead to reduced visual acuity, colour vision disturbance, central scotoma and an abnormal cone-mediated ERG response.2,9,25,26 Ophthalmological examination may show attenuated retinal arteriole calibre, optic disc pallor and retinal pigment changes.25,26 The fundus frequently appears normal.26 2. Case report A 66-year-old man presented after experiencing progressive blurring of vision and nyctalopia over 4 months. There was no past ocular history of note. Medical history included a known carcinoid tumour of small bowel origin (45 54 53 mm) surrounding and ⇑ Corresponding author. Tel.: +64 9 373 7599x86712; fax: +64 9 367 7173. E-mail address: [email protected] (S. Ogra).
occluding the superior mesenteric vein. Originally diagnosed in May 2011 (22 months prior to presentation), this had been deemed inoperable due to its proximity to the superior mesenteric artery. There was no history of prior chemotherapy or radiotherapy. Immunohistochemistry of the tumour showed positivity for CK8/ 18, AE1/AE3, cytokeratin, chromogranin, synaptophysin and CD56. CK7 and CK20 were negative. Ki67 proliferation index was less than 3%. This was consistent with a low grade neuroendocrine neoplasm. Other significant history included polymyalgia rheumatica, for which the patient had been on a reducing regime of oral corticosteroid over the past few months. He had ceased the prednisone approximately 4 weeks prior to presentation. On examination, visual acuity was 6/9 oculus dexter and 6/12 oculus sinistra. Colour vision was 2/15 for Ishihara colour plates on the right and only the test plate on the left. Slit lamp examination was otherwise unremarkable with normal appearance of the fundus. Peripheral field defects were present bilaterally with standard automated perimetry (Humphrey field analyser, SITA-standard protocol, 24-2 threshold; Carl Zeiss Surgical, Oberkochen, Germany) (Fig. 1). Electrodiagnostic assessment revealed a poorly defined pattern ERG in each eye. There was no recordable rod-mediated function to dim flash, and the response to bright flash was reduced. Cone mediated function was reported as being 60% of normal. Flicker 30 Hz latency was slightly increased at 31 ms (normal 28 ms) and amplitude was 60 lV (normal >100 lV). Due to the high index of suspicion for CAR, anti-retinal antibody analysis was performed (Oregon Health and Science University, OR, USA). Western blotting was positive for anti-retinal antibodies against 30 kDa (carbonic anhydrase II), 45 and 46 kDa (alphaenolase) proteins. Immunohistochemistry was negative.
Case Reports / Journal of Clinical Neuroscience 21 (2014) 358–360
359
Fig. 1. Humphrey visual field (SITA-standard protocol, 24-2 threshold; Carl Zeiss Surgical, Oberkochen, Germany) showing the peripheral visual field loss. GHT = glaucoma hemifield test, MD = mean deviation, NEG = negative, POS = positive, PSD = pattern standard deviation, VFI = visual field index.
The patient was commenced on high dose oral corticosteroid. As there was no widely reported link between carcinoid tumours and CAR, further investigation was initiated to rule out any new malignancy. CT scans of the chest, abdomen and pelvis were negative for any new changes. Unfortunately the patient died 1 month following initial diagnosis of CAR from a small bowel obstruction.
immunosuppression during this time may have resulted in the manifestation of CAR. In conclusion, CAR is an immune mediated cause of rapid vision loss in those with various systemic malignancies. Any patients with symptoms such as rapidly reducing vision, peripheral field constriction, nyctalopia, reduced colour vision and ERG changes suggestive of rod or cone dysfunction should be investigated for possible malignancy. A variety of auto-antibodies may cause CAR, however clinical detection is the crucial step.
3. Discussion This report presents the occurrence of CAR in a patient with histologically confirmed carcinoid tumour. Despite a thorough literature review, no patients with CAR associated with carcinoid tumour were identified at the time of writing. Anti-recoverin antibody was not identified in this patient, however other anti-retinal antibodies (carbonic anhydrase II, alpha enolase) were detected. Alpha enolase antibody is detected in approximately 30% of seropositive patients with CAR, and anti-carbonic anhydrase II antibody in 14%.27 Patients positive for antienolase antibodies usually demonstrate a slower deterioration compared to anti-recoverin associated retinopathy.26,28 This may explain the 4 month history of progression in our patient. There is currently no protocol for management of CAR. As it is an immune mediated condition, immunosuppression is usually targeted however there is no strong evidence base for this.9 One study showed five out of six patients with CAR improved with prolonged systemic immunosuppression.29 However, other case studies have shown mixed results with oral immunosuppression, as well as plasmapheresis and intravenous immunoglobulin administration.26,30,31 Our patient had been on reducing oral steroids preceding his onset of visual symptoms. We postulate that the reduction in
Conflict of interest/disclosure S.O. is supported by Optic Nerve Research Fellowship, funded by Allergan. The authors declare that they have no other financial or other conflicts of interest in relation to this research and its publication.
References 1. Thirkill CE, Roth AM, Keltner JL. Cancer-associated retinopathy. Arch Ophthalmol 1987;105:372–5. 2. Goldstein SM, Syed NA, Milam AH, et al. Cancer-associated retinopathy. Arch Ophthalmol 1999;117:1641–5. 3. Guy J, Aptsiauri N. Treatment of paraneoplastic visual loss with intravenous immunoglobulin: report of 3 cases. Arch Ophthalmol 1999;117:471–7. 4. Shiraga S, Adamus G. Mechanism of CAR syndrome: anti-recoverin antibodies are the inducers of retinal cell apoptotic death via the caspase 9- and caspase 3dependent pathway. J Neuroimmunol 2002;132:72–82. 5. Adamus G, Ren G, Weleber RG. Autoantibodies against retinal proteins in paraneoplastic and autoimmune retinopathy. BMC Ophthalmol 2004;4:5. 6. Magrys A, Anekonda T, Ren G, et al. The role of anti-alpha-enolase autoantibodies in pathogenicity of autoimmune-mediated retinopathy. J Clin Immunol 2007;27:181–92. 7. Misiuk-Hojlo M, Ejma M, Gorczyca WA, et al. Cancer-associated retinopathy in patients with breast carcinoma. Arch Immunol Ther Exp (Warsz) 2007;55:261–5.
360
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.2013.07.002
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.