- Department of Neurosurgery, David Geffen School of Medicine at UCLA, University of California at Los Angeles, Los Angeles, CA 90095, USA
- Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, University of California at Los Angeles, Los Angeles, CA 90095, USA
- Department of Neurology, David Geffen School of Medicine at UCLA, University of California at Los Angeles, Los Angeles, CA 90095, USA
Department of Neurosurgery, David Geffen School of Medicine at UCLA, University of California at Los Angeles, Los Angeles, CA 90095, USA
DOI:10.4103/2152-7806.85471Copyright: © 2011 Chou AP. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
How to cite this article: Chou AP, Lalezari S, Fong BM, Dye J, Pham T, Vinters HV, Pouratian N. Post-transplantation primary central nervous system lymphoma: A case report and review of the literature. Surg Neurol Int 27-Sep-2011;2:130
How to cite this URL: Chou AP, Lalezari S, Fong BM, Dye J, Pham T, Vinters HV, Pouratian N. Post-transplantation primary central nervous system lymphoma: A case report and review of the literature. Surg Neurol Int 27-Sep-2011;2:130. Available from: http://sni.wpengine.com/surgicalint_articles/post-transplantation-primary-central-nervous-system-lymphoma-a-case-report-and-review-of-the-literature/
Background:Post-transplantation primary central nervous system lymphoma (PT-PCNSL) is a rare neoplasm that can develop within months to years after transplantation, and imaging often reveals multiple lesions with homogeneous or ring enhancement. The clinical and imaging presentation of PT-PCNSL can often be nonspecific and present a diagnostic challenge.
Case Description:A 56-year-old woman presented to a tertiary university emergency room with altered mental status 15 months after undergoing renal transplantation. On brain MRI, she was found to have three rim-enhancing mass lesions, and biopsy revealed PT-PCNSL.
Conclusion:There has been a steady increase in the number of patients living following organ transplantation in the United States and an increasing likelihood that PT-PCNSL will increasingly be encountered in neurosurgical practice. We present here a case of PT-PCNSL and a brief review of the relevant clinical characteristics, treatment options, and prognosis of PT-PCNSL.
Keywords: Primary central nervous system lymphoma, transplantation
Primary central nervous system lymphoma (PCNSL) is a type of non-Hodgkin's lymphoma confined to the brain and spinal cord which represents approximately 3% of all primary intracranial neoplasms.[
An otherwise healthy female patient initially presented with hypertension at the age of 53 and was found to have bilaterally atrophic kidneys. She was later diagnosed with end-stage renal disease of unknown etiology and considered a good candidate for renal transplantation. She subsequently underwent living-related renal transplantation in April 2009 at the age of 56. She underwent induction immunosuppression with alemtuzumab, methylprednisolone, and intravenous immunoglobulin. She tolerated the transplantation without complications and postoperatively was placed on mycophenolate 500 mg twice a day, tacrolimus 2 mg every morning and 1 mg every night, and prednisone for the maintenance of immunosuppression.
She was well until she presented to the emergency room in July 2010 with 5 days of headaches, 2 days of lethargy, and 1 day of nausea and vomiting. On physical examination, she was found to be slightly somnolent but otherwise neurologically intact. A noncontrast head CT demonstrated left frontal hypodensities with 10 mm of a left-to-right shift. An MRI with contrast demonstrated three rim-enhancing lesions in the left frontal and parietal lobes with significant perilesional edema [
Pre-operative (a) T2, and (b,c) contrast-enhanced T1- weighted MRI demonstrating three ring-enhancing lesions with significant perilesional edema. (d) Postoperative contrast-enhanced T1-weighted MRI demonstrating postoperative changes from biopsy of the left parietal-occipital and left frontal lesions
Intraoperatively, stereotactic needle biopsies of the left parietal-occipital and posterior frontal lesions were attempted but were nondiagnostic, consisting of necrotic tissue on frozen sections. There was no frank evidence of infection. In order to secure a diagnosis, a gross total excision of the left frontal lesion (the largest lesion and associated with the most perilesional edema) was carried out. The patient tolerated the procedure well with no new neurological deficits postoperatively.
Pathologic examination revealed a predominantly angiocentric lymphoproliferative lesion characterized by large atypical lymphocytes with prominent nucleoli and moderate amounts of cytoplasm. Numerous mitotic figures and apoptotic bodies were seen. Zones of necrosis were present in multiple areas [
Further workup showed that the patient had isolated CNS disease. CT of the chest, abdomen, and pelvis was negative for malignancy. A bone-marrow biopsy was performed which showed no evidence of lymphoproliferative disease. Serology was negative for human immunodeficiency virus (HIV), Epstein-Barr virus (EBV), and cryptococcus. Cytomegalovirus (CMV) IgG and IgM were positive, but CMV PCR was negative. Intraoperative cultures were negative for infection.
Postoperatively, the patient was continued on dexamethasone and her antibiotics were discontinued. She was treated with a single cycle of high-dose methotrexate (4 g/m2) with leucovorin rescue. She tolerated the treatment well and was discharged on postoperative day 10. Her tacrolimus was subsequently transitioned to sirolimus. She is currently doing well 5 months after surgery and is on her seventh cycle of high-dose methotrexate (6 g/m2) and rituximab (375 mg/m2). Her brain MRI 2 months and PET-CT 4 months after surgery showed stable disease.
The increased incidence of solid organ transplantation in the United States has led to an increased need for neurosurgical intervention for post-transplantation lesions of the CNS. Systemic post-transplantation lymphoproliferative disorders (PTLD) occur in approximately 1% of renal transplant patients to as high as 20% of small bowel transplant recipients.[
The exact incidence of PT-PCNSL is unknown although it is likely to be rising in recent years from the increased number of transplant recipients. In the past decade, there has been an increase in the overall 1-year and 5-year survival for almost every type of organ transplantation.[
Multiple case series show renal transplantation to be the most frequent type of organ transplantation among PT-PCNSL patients, followed by liver and other solid organ transplantation types.[
The most common symptoms seen in PT-PCNSL are headache, hemiparesis, mental status changes, and gait disturbances.[
The presentation of PT-PCNSL on imaging can vary and a case series has suggested that MRI is more sensitive than CT for detecting lesions.[
The first step in the treatment of PT-PCNSL is to establish a definitive diagnosis, most commonly via a needle or excisional biopsy. PT-PCNSL lesions often have significant necrosis and a needle biopsy might not be diagnostic. In our case, our initial attempts at needle biopsy of both the parietal and frontal lesions were nondiagnostic. Although there has been one case series of PT-PCNSL suggesting a high risk of hemorrhage with four cases of hemorrhage in six patients who underwent stereotactic biopsy,[
Since PT-PCNSL is a rare disease that can vary in morphology, location, and subtype, a defined treatment protocol has not been established. Treatment of PT-PCNSL generally includes reducing immunosuppressive therapy, radiotherapy, and chemotherapy with the best 1-year survival resulting from the reduction of immunosuppression combined with either radiotherapy (80%) or radiotherapy plus chemotherapy (88%).[
A consensus on the best treatment of PT-PCNSL has not been established and further studies are ongoing. Surgery and reduction of immunosuppression, radiotherapy, and chemotherapy with agents such as methotrexate and rituximab seem to be the most promising. Despite treatment, the prognosis for PT-PCNSL remains poor. In the case series by Phan and co-workers, partly because of high perioperative mortality, median survival was only 13 weeks after diagnosis of PT-PCNSL.[
PT-PCNSL is a rare disease occurring in post-transplantation patients maintained on immunosuppression. It can develop within months to years after transplantation and most often presents with symptoms of mass effect or focal neurological deficits. PT-PCNSL can closely resemble brain abscesses in its clinical presentation and radiographic features. Unfortunately, no single diagnostic test has been shown to reliably distinguish between the various possible pathologies that might be encountered in a post-transplantation patient. Therefore, PT-PCNSL should be included in the differential diagnosis when contrast-enhancing lesions are observed in a post-transplant patient. Treatment options for PT-PCNSL include surgery, reduction of immunosuppression, radiotherapy, and chemotherapy when tolerated. Despite therapy, prognosis remains poor for PT-PCNSL and further studies are necessary to improve the management of this disease.
1. Caillard S, Dharnidharka V, Agodoa L, Bohen E, Abbott K. Posttransplant lymphoproliferative disorders after renal transplantation in the United States in era of modern immunosuppression. Transplantation. 2005. 80: 1233-43
2. Camilleri-Broet S, Martin A, Moreau A, Angonin R, Henin D, Gontier MF. Primary central nervous system lymphomas in 72 immunocompetent patients: Pathologic findings and clinical correlations. Groupe Ouest Est d’etude des Leucenies et Autres Maladies du Sang (GOELAMS). Am J Clin Pathol. 1998. 110: 607-12
3. Castellano-Sanchez AA, Li S, Qian J, Lagoo A, Weir E, Brat DJ. Primary central nervous system posttransplant lymphoproliferative disorders. Am J Clin Pathol. 2004. 121: 246-53
4. Cavaliere R, Petroni G, Lopes MB, Schiff D. Primary central nervous system post-transplantation lymphoproliferative disorder: An International Primary Central Nervous System Lymphoma Collaborative Group Report. Cancer. 2010. 116: 863-70
5. Cortese I, Nath A. Case 11: A young woman with ring-enhancing brain lesions. MedGenMed. 2006. 8: 3-
6. Fine HA, Mayer RJ. Primary central nervous system lymphoma. Ann Intern Med. 1993. 119: 1093-104
7. Gerstner ER, Batchelor TT. Primary central nervous system lymphoma. Arch Neurol. 2010. 67: 291-7
8. Kim M, Lee J, Kim W, Ko Y. Primary central nervous system lymphoma after liver transplantation treated by radiosurgery combined with fractionated radiotherapy. J Clin Neurosci. 2009. 16: 583-5
9. Knight J, Tsodikov A, Cibrik D, Ross C, Kaminski M, Blayney D. Lymphoma after solid organ transplantation: Risk, response to therapy, and survival at a transplantation center. J Clin Oncol. 2009. 27: 3354-62
10. Nabors LB, Palmer CA, Julian BA, Przekwas AM, Kew CE. Isolated central nervous system posttransplant lymphoproliferative disorder treated with high-dose intravenous methotrexate. Am J Transplant. 2009. 9: 1243-8
11. Opelz G, Daniel V, Naujokat C, Döhler B. Epidemiology of pretransplant EBV and CMV serostatus in relation to posttransplant Non-Hodkin lymphoma. Transplantation. 2009. 88: 962-7
12. Patrick A, Wee A, Hedderman A, Wilson D, Weiss J, Govani M. High-dose intravenous rituximab for multifocal, monomorphic primary central nervous system posttransplant lymphoproliferative disorder. J Neurooncol. 2011. 103: 739-43
13. Penn I, Porat G. Central nervous system lymphomas in organ allograft recipients. Transplantation. 1995. 59: 240-4
14. Peres E, Savasan S, Klein J, Abidi M, Dansey R, Abella E. High fatality rate of Epstein-Barr virus-associated lymphoproliferative disorder occurring after bone marrow transplantation with rabbit antithymocyte globulin conditioning regimens. J Clin Microbiol. 2005. 43: 3540-3
15. Phan TG, O’Neill BP, Kurtin PJ. Posttransplant primary CNS lymphoma. Neuro Oncol. 2000. 2: 229-38
16. Port FK, Merion RM, Roys EC, Wolfe RA. Trends in organ donation and transplantation in the United States, 1997-2006. Am J Transplant. 2008. 8: 911-21
17. Sacho RH, Kogels M, Plessis D, Jowitt S, Josan VA. Primary diffuse large B-cell central nervous system lymphoma presenting as an acute space-occupying subdural mass. J Neurosurg. 2010. 113: 384-7
18. Schabet M. Epidemiology of primary CNS lymphoma. J Neurooncol. 1999. 43: 199-201
19. Schneck SA, Penn I. Cerebral neoplasms associated with renal transplantation. Arch Neurol. 1970. 22: 226-33
20. Schwartz KM, Erickson BJ, Lucchinetti C. Pattern of T2 hypointensity associated with ring-enhancing brain lesions can help to differentiate pathology. Neuroradiology. 2006. 48: 143-9
21. Snanoudj R, Durrbach A, Leblond V, Caillard S, Hurault De Ligny B, Noel C. Primary brain lymphomas after kidney transplantation: presentation and outcome. Transplantation. 2003. 76: 930-7
22. Taylor AL, Marcus R, Bradley JA. Post-transplant lymphoproliferative disorders (PTLD) after solid organ transplantation. Crit Rev Oncol Hematol. 2005. 56: 155-67
23. Wolfe RA, Merion RM, Roys EC, Port FK. Trends in organ donation and transplantation in the United States, 1998-2007. Am J Transplant. 2009. 9: 869-78
24. Wolfe RA, Roys EC, Merion RM. Trends in organ donation and transplantation in the United States, 1999-2008. Am J Transplant. 2010. 10: 961-72
25. Xu QS, Ye S, Zhou YQ, Sheng JF, Ye K, Zheng SS. Posttransplantation lymphoproliferative disorder involving the central nervous system in liver transplant recipients. Hepatobiliary Pancreat Dis Int. 2008. 7: 551-4