Clinical/Scientific Notes
Christian Schneider, MD Tobias D. Henning, MD Gereon R. Fink, MD Michael Schroeter, MD Helmar C. Lehmann, MD
PRIMARY INTRACRANIAL PLASMA CELL GRANULOMA RESPONSIVE TO RITUXIMAB
Plasma cell granuloma (PCG) is a sporadically occurring tumor-like mass that is histologically characterized by a non-neoplastic proliferation of inflammatory cells. The predominant cell types in PCG are polyclonal plasma cells and their precursors, including a substantial amount of mature B cells. PCGs can manifest in different organs and occur most commonly in the lung.1 Primary intracranial PCG is rare and its treatment poses an interdisciplinary challenge.2 Surgical resection is considered to be first-line treatment in PCG. Patients with nonresectable PCG are usually treated by radiotherapy or maintenance therapy with corticosteroids. However, those treatments have significant side effects and often fall short in reducing the tumor mass. In addition, recurrence is frequently observed, especially in cases of subtotal excision, which emphasizes the need for more specific long-term therapies with fewer adverse effects.3 This is a single observational study without controls, providing Class IV evidence. Case report. A 66-year old woman presented in 2006 with cephalgia, vomiting, dizziness, unsteady gait, and fatigue that progressed over several weeks. On neurologic examination, the patient demonstrated left-sided hemiataxia and unsteady gait with a tendency to fall to the left side. MRI showed a tumor mass of the left cerebellar hemisphere. A biopsy combined with subtotal resection and subsequent pathologic examination revealed a duraadherent PCG. Immunohistochemical analysis confirmed the presence of plasma cells and a marked number of CD20-positive B cells. As there was no light chain restriction, plasmacytoma could be excluded. After initial clinical improvement subsequent to the surgery, the patient’s symptoms relapsed and progressed continuously over the following years, despite treatment with radiotherapy as well as maintenance plus pulsed corticosteroid treatment. Radiation was done of the extended tumor region by 4-field isocentric technique (5 3 2 Gy per
week, cumulative 30 Gy) followed by low-volume radiation of the main (macroscopic) tumor region (5 3 2 Gy per week) to a total dose of 50 Gy. In 2012, the patient was essentially restricted to a wheelchair and also developed a homonymous hemianopia to the right. MRI at this point revealed local tumor progress with contralateral cerebellar and left occipital involvement. Since the inoperable tumor mass was refractory to corticosteroid treatment but contained a remarkable number of CD20-positive B cells, treatment with rituximab (375 mg/m2), a chimeric monoclonal antibody directed against CD20, was initiated. After 4 cycles of weekly administration, the patient was treated over the following 12 months monthly with the same dose of rituximab. During this treatment, the patient showed remarkable clinical improvement, with complete remission of hemianopia and marked gait stabilization. The patient was able to walk unaided beyond a distance of 50 meters. Repeated MRI scans confirmed a sustained response of the PCG to this treatment with considerable reduction of the tumor mass (figure). Discussion. Rituximab is a chimeric monoclonal antibody that binds to the surface protein CD20 expressed on B cells and occasionally on plasma cells. It is commonly used in the treatment of lymphoma and autoimmune diseases with a presumed autoantibody-mediated pathogenesis such as myasthenia gravis and neuromyelitis optica.4–6 Rituximab was previously reported to be effective in cases of extracranial (orbital) PCG,7 but to our knowledge, has never been applied with similar effectiveness to primary intracranial PCG. Our case report suggests that rituximab has a beneficial effect in primary intracranial PCG and may offer a therapeutic option for cases that are refractory to corticosteroid treatment or that are not accessible to complete surgical excision. Because the treatment efficiency of rituximab in individual cases will largely depend on the expression of CD20 on the surface of lymphocytes within the tumor mass, prior histopathologic evaluation with regard to the number of CD20-positive cells in PCG may help identify eligible patients.
Neurology 83
September 16, 2014
1119
Figure
MRI of plasma cell granuloma before and after rituximab therapy
(A–F) Coronal and axial MRI of a patient with histopathologically confirmed plasma cell granuloma. (A–C) MRI before rituximab treatment shows a dural-based left cerebellar tumor with contralateral and left occipital involvement. (D–F) MRI 12 months after treatment with rituximab shows considerable reduction of tumor mass, with nearly complete remission of occipital involvement. (A, D) Coronal T1-weighted gadolinium-enhanced MRI. (B, E) Axial T1-weighted gadolinium-enhanced MRI. (C, F) Axial T2-weighted MRI.
2. From the University Hospital of Cologne (C.S., T.D.H., G.R.F., M.S., H.C.L.); and the Institute of Neuroscience and Medicine (INM-3) (G.R.F.), Research Center Jülich, Germany. Author contributions: Dr. Schneider: medical care of patient, analysis of data. Dr. Henning: analysis of data with special focus on neuroimaging. Dr. Fink: medical care of patient, analysis of data. Dr. Schroeter: medical care of patient, analysis of data. Dr. Lehmann: medical care of patient, analysis of data. Study funding: No targeted funding reported. Disclosure: The authors report no disclosures relevant to the manuscript. Go to Neurology.org for full disclosures. Received January 31, 2014. Accepted in final form May 7, 2014.
3.
4.
5.
Correspondence to Dr. Lehmann: [email protected] © 2014 American Academy of Neurology 1.
1120
Coffin CM, Watterson J, Priest JR, Dehner LP. Extrapulmonary inflammatory myofibroblastic tumor (inflammatory pseudotumor): a clinicopathologic and immunohistochemical study of 84 cases. Am J Surg Pathol 1995; 19:859–872.
Neurology 83
September 16, 2014
6.
7.
Buccoliero AM, Caldarella A, Santucci M, et al. Plasma cell granuloma: an enigmatic lesion: description of an extensive intracranial case and review of the literature. Arch Pathol Lab Med 2003;127:220–223. Flannery T, Al-Sabah F, Bhangu J, Alderazi Y, Brett F, Pidgeon C. Treatment of subtotally resected intracranial plasma cell granuloma with steroids: a case report. Br J Neurosurg 2007;21:501–503. Plosker GL, Figgitt DP. Rituximab: a review of its use in non-Hodgkin’s lymphoma and chronic lymphocytic leukaemia. Drugs 2003;63:803–843. Díaz-Manera J, Martínez-Hernández E, Querol L, et al. Long-lasting treatment effect of rituximab in MuSK myasthenia. Neurology 2012;78:189–193. Jacob A, Weinshenker BG, Violich I, et al. Treatment of neuromyelitis optica with rituximab: retrospective analysis of 25 patients. Arch Neurol 2008;65:1443–1448. Garcia BA, Tinsley S, Schellenberger T, Bobustuc GC. Recurrent inflammatory pseudotumor of the jaw with perineural intracranial invasion demonstrating sustained response to rituximab. Med Oncol 2012;29:2452–2455.
Primary intracranial plasma cell granuloma responsive to rituximab Christian Schneider, Tobias D. Henning, Gereon R. Fink, et al. Neurology 2014;83;1119-1120 Published Online before print August 8, 2014 DOI 10.1212/WNL.0000000000000799 This information is current as of August 8, 2014 Updated Information & Services
including high resolution figures, can be found at: http://www.neurology.org/content/83/12/1119.full.html
References
This article cites 7 articles, 1 of which you can access for free at: http://www.neurology.org/content/83/12/1119.full.html##ref-list-1
Subspecialty Collections
This article, along with others on similar topics, appears in the following collection(s): Gait disorders/ataxia http://www.neurology.org//cgi/collection/gait_disorders_ataxia MRI http://www.neurology.org//cgi/collection/mri Primary brain tumor http://www.neurology.org//cgi/collection/primary_brain_tumor Visual fields http://www.neurology.org//cgi/collection/visual_fields
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Information about reproducing this article in parts (figures,tables) or in its entirety can be found online at: http://www.neurology.org/misc/about.xhtml#permissions
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Information about ordering reprints can be found online: http://www.neurology.org/misc/addir.xhtml#reprintsus
Neurology ® is the official journal of the American Academy of Neurology. Published continuously since 1951, it is now a weekly with 48 issues per year. Copyright © 2014 American Academy of Neurology. All rights reserved. Print ISSN: 0028-3878. Online ISSN: 1526-632X.
Christian Schneider, MD Tobias D. Henning, MD Gereon R. Fink, MD Michael Schroeter, MD Helmar C. Lehmann, MD
PRIMARY INTRACRANIAL PLASMA CELL GRANULOMA RESPONSIVE TO RITUXIMAB
Plasma cell granuloma (PCG) is a sporadically occurring tumor-like mass that is histologically characterized by a non-neoplastic proliferation of inflammatory cells. The predominant cell types in PCG are polyclonal plasma cells and their precursors, including a substantial amount of mature B cells. PCGs can manifest in different organs and occur most commonly in the lung.1 Primary intracranial PCG is rare and its treatment poses an interdisciplinary challenge.2 Surgical resection is considered to be first-line treatment in PCG. Patients with nonresectable PCG are usually treated by radiotherapy or maintenance therapy with corticosteroids. However, those treatments have significant side effects and often fall short in reducing the tumor mass. In addition, recurrence is frequently observed, especially in cases of subtotal excision, which emphasizes the need for more specific long-term therapies with fewer adverse effects.3 This is a single observational study without controls, providing Class IV evidence. Case report. A 66-year old woman presented in 2006 with cephalgia, vomiting, dizziness, unsteady gait, and fatigue that progressed over several weeks. On neurologic examination, the patient demonstrated left-sided hemiataxia and unsteady gait with a tendency to fall to the left side. MRI showed a tumor mass of the left cerebellar hemisphere. A biopsy combined with subtotal resection and subsequent pathologic examination revealed a duraadherent PCG. Immunohistochemical analysis confirmed the presence of plasma cells and a marked number of CD20-positive B cells. As there was no light chain restriction, plasmacytoma could be excluded. After initial clinical improvement subsequent to the surgery, the patient’s symptoms relapsed and progressed continuously over the following years, despite treatment with radiotherapy as well as maintenance plus pulsed corticosteroid treatment. Radiation was done of the extended tumor region by 4-field isocentric technique (5 3 2 Gy per
week, cumulative 30 Gy) followed by low-volume radiation of the main (macroscopic) tumor region (5 3 2 Gy per week) to a total dose of 50 Gy. In 2012, the patient was essentially restricted to a wheelchair and also developed a homonymous hemianopia to the right. MRI at this point revealed local tumor progress with contralateral cerebellar and left occipital involvement. Since the inoperable tumor mass was refractory to corticosteroid treatment but contained a remarkable number of CD20-positive B cells, treatment with rituximab (375 mg/m2), a chimeric monoclonal antibody directed against CD20, was initiated. After 4 cycles of weekly administration, the patient was treated over the following 12 months monthly with the same dose of rituximab. During this treatment, the patient showed remarkable clinical improvement, with complete remission of hemianopia and marked gait stabilization. The patient was able to walk unaided beyond a distance of 50 meters. Repeated MRI scans confirmed a sustained response of the PCG to this treatment with considerable reduction of the tumor mass (figure). Discussion. Rituximab is a chimeric monoclonal antibody that binds to the surface protein CD20 expressed on B cells and occasionally on plasma cells. It is commonly used in the treatment of lymphoma and autoimmune diseases with a presumed autoantibody-mediated pathogenesis such as myasthenia gravis and neuromyelitis optica.4–6 Rituximab was previously reported to be effective in cases of extracranial (orbital) PCG,7 but to our knowledge, has never been applied with similar effectiveness to primary intracranial PCG. Our case report suggests that rituximab has a beneficial effect in primary intracranial PCG and may offer a therapeutic option for cases that are refractory to corticosteroid treatment or that are not accessible to complete surgical excision. Because the treatment efficiency of rituximab in individual cases will largely depend on the expression of CD20 on the surface of lymphocytes within the tumor mass, prior histopathologic evaluation with regard to the number of CD20-positive cells in PCG may help identify eligible patients.
Neurology 83
September 16, 2014
1119
Figure
MRI of plasma cell granuloma before and after rituximab therapy
(A–F) Coronal and axial MRI of a patient with histopathologically confirmed plasma cell granuloma. (A–C) MRI before rituximab treatment shows a dural-based left cerebellar tumor with contralateral and left occipital involvement. (D–F) MRI 12 months after treatment with rituximab shows considerable reduction of tumor mass, with nearly complete remission of occipital involvement. (A, D) Coronal T1-weighted gadolinium-enhanced MRI. (B, E) Axial T1-weighted gadolinium-enhanced MRI. (C, F) Axial T2-weighted MRI.
2. From the University Hospital of Cologne (C.S., T.D.H., G.R.F., M.S., H.C.L.); and the Institute of Neuroscience and Medicine (INM-3) (G.R.F.), Research Center Jülich, Germany. Author contributions: Dr. Schneider: medical care of patient, analysis of data. Dr. Henning: analysis of data with special focus on neuroimaging. Dr. Fink: medical care of patient, analysis of data. Dr. Schroeter: medical care of patient, analysis of data. Dr. Lehmann: medical care of patient, analysis of data. Study funding: No targeted funding reported. Disclosure: The authors report no disclosures relevant to the manuscript. Go to Neurology.org for full disclosures. Received January 31, 2014. Accepted in final form May 7, 2014.
3.
4.
5.
Correspondence to Dr. Lehmann: [email protected] © 2014 American Academy of Neurology 1.
1120
Coffin CM, Watterson J, Priest JR, Dehner LP. Extrapulmonary inflammatory myofibroblastic tumor (inflammatory pseudotumor): a clinicopathologic and immunohistochemical study of 84 cases. Am J Surg Pathol 1995; 19:859–872.
Neurology 83
September 16, 2014
6.
7.
Buccoliero AM, Caldarella A, Santucci M, et al. Plasma cell granuloma: an enigmatic lesion: description of an extensive intracranial case and review of the literature. Arch Pathol Lab Med 2003;127:220–223. Flannery T, Al-Sabah F, Bhangu J, Alderazi Y, Brett F, Pidgeon C. Treatment of subtotally resected intracranial plasma cell granuloma with steroids: a case report. Br J Neurosurg 2007;21:501–503. Plosker GL, Figgitt DP. Rituximab: a review of its use in non-Hodgkin’s lymphoma and chronic lymphocytic leukaemia. Drugs 2003;63:803–843. Díaz-Manera J, Martínez-Hernández E, Querol L, et al. Long-lasting treatment effect of rituximab in MuSK myasthenia. Neurology 2012;78:189–193. Jacob A, Weinshenker BG, Violich I, et al. Treatment of neuromyelitis optica with rituximab: retrospective analysis of 25 patients. Arch Neurol 2008;65:1443–1448. Garcia BA, Tinsley S, Schellenberger T, Bobustuc GC. Recurrent inflammatory pseudotumor of the jaw with perineural intracranial invasion demonstrating sustained response to rituximab. Med Oncol 2012;29:2452–2455.
Primary intracranial plasma cell granuloma responsive to rituximab Christian Schneider, Tobias D. Henning, Gereon R. Fink, et al. Neurology 2014;83;1119-1120 Published Online before print August 8, 2014 DOI 10.1212/WNL.0000000000000799 This information is current as of August 8, 2014 Updated Information & Services
including high resolution figures, can be found at: http://www.neurology.org/content/83/12/1119.full.html
References
This article cites 7 articles, 1 of which you can access for free at: http://www.neurology.org/content/83/12/1119.full.html##ref-list-1
Subspecialty Collections
This article, along with others on similar topics, appears in the following collection(s): Gait disorders/ataxia http://www.neurology.org//cgi/collection/gait_disorders_ataxia MRI http://www.neurology.org//cgi/collection/mri Primary brain tumor http://www.neurology.org//cgi/collection/primary_brain_tumor Visual fields http://www.neurology.org//cgi/collection/visual_fields
Permissions & Licensing
Information about reproducing this article in parts (figures,tables) or in its entirety can be found online at: http://www.neurology.org/misc/about.xhtml#permissions
Reprints
Information about ordering reprints can be found online: http://www.neurology.org/misc/addir.xhtml#reprintsus
Neurology ® is the official journal of the American Academy of Neurology. Published continuously since 1951, it is now a weekly with 48 issues per year. Copyright © 2014 American Academy of Neurology. All rights reserved. Print ISSN: 0028-3878. Online ISSN: 1526-632X.
