Advertisement

Lymphomas

  • Serge Weis
  • Michael Sonnberger
  • Andreas Dunzinger
  • Eva Voglmayr
  • Martin Aichholzer
  • Raimund Kleiser
  • Peter Strasser
Chapter
  • 368 Downloads

Abstract

The most frequently encountered hematopoietic neoplasms of the brain encompass primary CNS lymphoma, intravascular lymphoma, post-transplant T-cell lymphoproliferation, intraocular lymphoma, neurolymphomatosis, and plasmacytoma.

Primary CNS lymphoma (PCNSL) is a diffuse large B-cell lymphoma confined to the CNS at presentation. It occurs in inherited or acquired immunodeficiency. There is an association with Epstein-Barr virus (EBV) infection in immunocompromised patients. Molecular changes include alterations and translocations in copy number of 9p.24/PD-L1/PD-L2, neurotropic factors, JAK/STAT signaling pathway, dysregulation in B cell receptor signaling pathway, in NF-κB pathway, in Toll-like receptor signaling pathway, mutations in PIM1, TBL1XR1, TRDM1, BTG2, PRDM1, protein-changing mutations, and chromosomal translocations involving oncogenes. Treatment in immunocompetent PCNSL consists in the administration of glucocorticoids, radiation therapy, and hemotherapy (CHOP: cyclophosphamide, doxorubicin, vincristine, prednisone). In AIDS-related PCNSL, high-dose intravenous methotrexate is given. 5-year survival is 29.3%. Molecular predictive markers for adverse prognosis or favorable outcome have been published.

Intravascular lymphoma is characterized by exclusively intravascular growth. It is sought to be derived from immunoglobulin gene rearrangement accompanied by altered expression of adhesion molecules, i.e., CD44, ß-1 integrin. Treatment consists in a combination of chemotherapy (combination of MTX-based intrathecal chemotherapy and R-CHOP), intrathecal therapy with cytarabine, prednisolone, intravascular use of unfractionated heparin, and bone marrow transplantation. Because of its aggressive behavior, survival ranges between 14 months and 2 years.

Post-transplant lymphoproliferative disorders (PTLDs) are lymphoid or plasmacytic proliferations that develop as a consequence of immunosuppression in a recipient of a solid organ or stem cell allograft. Surgical resection, reduction in immunosuppression, steroids, radiotherapy, high-dose methotrexate, and immunotherapy make up the treatment armamentarium. Prognosis is poor with a median survival of 13 weeks and a mortality rate of 60–90%.

Plasmacytoma is composed of mature-appearing neoplastic plasma cells. The neoplastic cells originate from postgerminal center. Clonal rearrangement of the IgL- and IgH-chain genes was described. Treatment includes surgical resection followed by radiation therapy. Clinical outcome is variable. 66% of cases progress within 3 years to generalized myeloma.

Selected References

  1. Adachi K, Yamaguchi F, Node Y, Kobayashi S, Takagi R, Teramoto A (2013) Neuroimaging of primary central nervous system lymphoma in immunocompetent patients: comparison of recent and previous findings. J Nippon Med Sch 80(3):174–183Google Scholar
  2. Agarwal A (2014) Neuroimaging of plasmacytoma. A pictorial review. Neuroradiol J 27(4):431–437.  https://doi.org/10.15274/nrj-2014-10078Google Scholar
  3. Anastasi J (2009) Another great medical mimic: intravascular lymphoma. Leuk Lymphoma 50(11):1742–1743.  https://doi.org/10.3109/10428190903350439Google Scholar
  4. Baehring JM, Henchcliffe C, Ledezma CJ, Fulbright R, Hochberg FH (2005) Intravascular lymphoma: magnetic resonance imaging correlates of disease dynamics within the central nervous system. J Neurol Neurosurg Psychiatry 76(4):540–544.  https://doi.org/10.1136/jnnp.2003.033662Google Scholar
  5. Batchelor TT (2016) Primary central nervous system lymphoma. Hematology Am Soc Hematol Educ Program 2016(1):379–385.  https://doi.org/10.1182/asheducation-2016.1.379Google Scholar
  6. Bierman PJ (2014) Surgery for primary central nervous system lymphoma: is it time for reevaluation? Oncology 28(7):632–637Google Scholar
  7. Brandao LA, Castillo M (2016a) Lymphomas-Part 1. Neuroimaging Clin N Am 26(4):511–536.  https://doi.org/10.1016/j.nic.2016.06.004Google Scholar
  8. Brandao LA, Castillo M (2016b) Lymphomas-part 2. Neuroimaging Clin N Am 26(4):537–565.  https://doi.org/10.1016/j.nic.2016.06.005Google Scholar
  9. Brennan KC, Lowe LH, Yeaney GA (2005) Pediatric central nervous system posttransplant lymphoproliferative disorder. Am J Neuroradiol 26(7):1695–1697Google Scholar
  10. Carnevale J, Rubenstein JL (2016) The challenge of primary central nervous system lymphoma. Hematol Oncol Clin North Am 30(6):1293–1316.  https://doi.org/10.1016/j.hoc.2016.07.013Google Scholar
  11. Cerase A, Tarantino A, Gozzetti A, Muccio CF, Gennari P, Monti L, Di Blasi A, Venturi C (2008) Intracranial involvement in plasmacytomas and multiple myeloma: a pictorial essay. Neuroradiology 50(8):665–674.  https://doi.org/10.1007/s00234-008-0390-xGoogle Scholar
  12. Citterio G, Reni M, Ferreri AJ (2015) Present and future treatment options for primary CNS lymphoma. Expert Opin Pharmacother 16(17):2569–2579.  https://doi.org/10.1517/14656566.2015.1088828Google Scholar
  13. Citterio G, Reni M, Gatta G, Ferreri AJM (2017) Primary central nervous system lymphoma. Crit Rev Oncol Hematol 113:97–110.  https://doi.org/10.1016/j.critrevonc.2017.03.019Google Scholar
  14. Clarke JL, Deangelis LM (2012) Primary central nervous system lymphoma. Handb Clin Neurol 105:517–527.  https://doi.org/10.1016/b978-0-444-53502-3.00006-9Google Scholar
  15. Daras M, DeAngelis LM (2013) Management of elderly patients with primary central nervous system lymphoma. Curr Neurol Neurosci Rep 13(5):344.  https://doi.org/10.1007/s11910-013-0344-5Google Scholar
  16. DeAngelis LM (2014) Whither whole brain radiotherapy for primary CNS lymphoma? Neuro Oncol 16(8):1032–1034.  https://doi.org/10.1093/neuonc/nou122Google Scholar
  17. Deckert M, Paulus W (2007) Malignant lymphomas. In: Louis DN, Ohgaki H, Wiestler OD, Cavenee WK (eds) WHO Classification of Tumours of the Central Nervous System, 4th edn. International Agency for Research on Cancer, Lyon, pp 188–192Google Scholar
  18. Deckert M, Brunn A, Montesinos-Rongen M, Terreni MR, Ponzoni M (2014) Primary lymphoma of the central nervous system—a diagnostic challenge. Hematol Oncol 32(2):57–67.  https://doi.org/10.1002/hon.2087Google Scholar
  19. Deckert M, Paulus W, Kluin PM, Ferry JA (2016) Lymphomas. In: Louis DN, Ohgaki H, Wiestler OD, Cavenee WK (eds) WHO classification of tumours of the central nervous system, Revised 4th edn. IARC, Lyon, pp 272–277Google Scholar
  20. Di Micco P, Di Micco B (2005) Up-date on solitary plasmacytoma and its main differences with multiple myeloma. Exp Oncol 27(1):7–12Google Scholar
  21. Fonkem E, Dayawansa S, Stroberg E, Lok E, Bricker PC, Kirmani B, Wong ET, Huang JH (2016) Neurological presentations of intravascular lymphoma (IVL): meta-analysis of 654 patients. BMC Neurol 16:9.  https://doi.org/10.1186/s12883-015-0509-8Google Scholar
  22. Fraser E, Gruenberg K, Rubenstein JL (2015) New approaches in primary central nervous system lymphoma. Chin Clin Oncol 4(1):11.  https://doi.org/10.3978/j.issn.2304-3865.2015.02.01Google Scholar
  23. Gan LP, Ooi WS, Lee HY, Ng WH (2013) A case of large B-cell intravascular lymphoma in the brain. Surg Neurol Int 4:99.  https://doi.org/10.4103/2152-7806.115709
  24. Giannini C, Dogan A, Salomao DR (2014) CNS lymphoma: a practical diagnostic approach. J Neuropathol Exp Neurol 73(6):478–494.  https://doi.org/10.1097/nen.0000000000000076Google Scholar
  25. Haldorsen IS, Espeland A, Larsson EM (2011) Central nervous system lymphoma: characteristic findings on traditional and advanced imaging. Am J Neuroradiol 32(6):984–992.  https://doi.org/10.3174/ajnr.A2171Google Scholar
  26. Hottinger AF, Alentorn A, Hoang-Xuan K (2015) Recent developments and controversies in primary central nervous system lymphoma. Curr Opin Oncol 27(6):496–501.  https://doi.org/10.1097/cco.0000000000000233Google Scholar
  27. Illerhaus G (2015) III. Current concepts in primary central nervous lymphoma. Hematol Oncol 33(Suppl 1):25–28.  https://doi.org/10.1002/hon.2211Google Scholar
  28. Kageyama T, Yamanaka H, Nakamura F, Suenaga T (2017) Persistent lesion hyperintensity on brain diffusion-weighted MRI is an early sign of intravascular lymphoma. BMJ Case Rep 2017.  https://doi.org/10.1136/bcr-2017-220099
  29. Kerbauy MN, Moraes FY, Lok BH, Ma J, Kerbauy LN, Spratt DE, Santos FP, Perini GF, Berlin A, Chung C, Hamerschlak N, Yahalom J (2017) Challenges and opportunities in primary CNS lymphoma: a systematic review. Radiother Oncol 122(3):352–361.  https://doi.org/10.1016/j.radonc.2016.12.033Google Scholar
  30. Kleihues P, Burger PC, Scheithauer BW (1993) Histological typing of tumours of the central nervous system, 2nd edn. Springer-Verlag, BerlinGoogle Scholar
  31. Kloc G, Budziak M, Wieckiewicz A, Plesniak M, Bartosik-Psujek H (2016) Intravascular lymphoma mimicking multiple sclerosis. Neurol Neurochir Pol 50(4):313–317.  https://doi.org/10.1016/j.pjnns.2016.04.007Google Scholar
  32. Ko CC, Tai MH, Li CF, Chen TY, Chen JH, Shu G, Kuo YT, Lee YC (2016) Differentiation between glioblastoma multiforme and primary cerebral lymphoma: additional benefits of quantitative diffusion-weighted MR imaging. PLoS One 11(9):e0162565.  https://doi.org/10.1371/journal.pone.0162565Google Scholar
  33. Korfel A, Schlegel U (2013) Diagnosis and treatment of primary CNS lymphoma. Nat Rev Neurol 9(6):317–327.  https://doi.org/10.1038/nrneurol.2013.83Google Scholar
  34. Nabavizadeh SA, Vossough A, Hajmomenian M, Assadsangabi R, Mohan S (2016) Neuroimaging in central nervous system lymphoma. Hematol Oncol Clin North Am 30(4):799–821.  https://doi.org/10.1016/j.hoc.2016.03.005Google Scholar
  35. Nayak L, Pentsova E, Batchelor TT (2015) Primary CNS lymphoma and neurologic complications of hematologic malignancies. Continuum 21(2 Neuro-oncology):355–372.  https://doi.org/10.1212/01.CON.0000464175.96311.0aGoogle Scholar
  36. Nizamutdinov D, Patel NP, Huang JH, Fonkem E (2017) Intravascular lymphoma in the CNS: options for treatment. Curr Treat Options Neurol 19(10):35.  https://doi.org/10.1007/s11940-017-0471-4Google Scholar
  37. Panda AK, Malik S (2014) CNS intravascular lymphoma: an underappreciated cause of rapidly progressive dementia. BMJ Case Rep 2014.  https://doi.org/10.1136/bcr-2014-203772
  38. Patrick LB, Mohile NA (2015) Advances in primary central nervous system lymphoma. Curr Oncol Rep 17(12):60.  https://doi.org/10.1007/s11912-015-0483-8Google Scholar
  39. Paulus W, Jellinger K, Morgello S, Deckert-Schlüter M (2000) Malignant lymphomas. In: Kleihues P, Cavenee WK (eds) Pathology and genetics of tumours of the nervous system, 3rd edn. IARC, Lyon, pp 198–203Google Scholar
  40. Paydas S (2017) Primary central nervous system lymphoma: essential points in diagnosis and management. Med Oncol 34(4):61.  https://doi.org/10.1007/s12032-017-0920-7Google Scholar
  41. Phillips EH, Fox CP, Cwynarski K (2014) Primary CNS lymphoma. Curr Hematol Malig Rep 9(3):243–253.  https://doi.org/10.1007/s11899-014-0217-2Google Scholar
  42. Prayson RA (2016) Intravascular lymphoma mimicking vasculitis. J Clin Neurosci 34:224–225.  https://doi.org/10.1016/j.jocn.2016.06.010Google Scholar
  43. Roohi F (2013) Diagnosis of intravascular lymphoma. JAMA Neurol 70(7):941.  https://doi.org/10.1001/jamaneurol.2013.307Google Scholar
  44. Roth P, Korfel A, Martus P, Weller M (2012) Pathogenesis and management of primary CNS lymphoma. Expert Rev Anticancer Ther 12(5):623–633.  https://doi.org/10.1586/era.12.36Google Scholar
  45. Schaafsma JD, Hui F, Wisco D, Staugaitis SM, Uchino K, Kouzmitcheva E, Jaigobin C, Hazrati LN, Mikulis DJ, Mandell DM (2017) High-resolution vessel wall MRI: appearance of intravascular lymphoma mimics central nervous system vasculitis. Clin Neuroradiol 27(1):105–108.  https://doi.org/10.1007/s00062-016-0529-9Google Scholar
  46. Schafer N, Glas M, Herrlinger U (2012) Primary CNS lymphoma: a clinician’s guide. Expert Rev Neurother 12(10):1197–1206.  https://doi.org/10.1586/ern.12.120Google Scholar
  47. Slone HW, Blake JJ, Shah R, Guttikonda S, Bourekas EC (2005) CT and MRI findings of intracranial lymphoma. Am J Roentgenol 184(5):1679–1685.  https://doi.org/10.2214/ajr.184.5.01841679Google Scholar
  48. Sugiyama A, Kobayashi M, Daizo A, Suzuki M, Kawashima H, Kagami SI, Tanaka H, Suzuki Y, Matsunaga T, Kuwabara S (2017) Diffuse cerebral vasoconstriction in a intravascular lymphoma patient with a high serum MPO-ANCA level. Intern Med 56(13):1715–1718.  https://doi.org/10.2169/internalmedicine.56.8051Google Scholar
  49. Sureka B, Bansal K, Arora A (2015) Intravascular lymphoma. Am J Roentgenol 205(3):W387.  https://doi.org/10.2214/ajr.15.14741Google Scholar
  50. Swerdlow SH, Webber SA, Chadburn A, Ferry JA (2008) Post-transplant lymphoproliferative disorders. In: Swerdlow SH, Campo E, Harris NL et al (eds) WHO classification of tumours of haematopoietic and lymphoid tissues. IARC, Lyon, pp 343–349Google Scholar
  51. Swerdlow SH, Campo E, Pileri SA, Harris NL, Stein H, Siebert R, Advani R, Ghielmini M, Salles GA (2016) The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood 127(20):2375–2390.  https://doi.org/10.1182/blood-2016-01-643569Google Scholar
  52. Swerdlow SE, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Arber DA, Hasserjian RP, Le Beau MM, Orazi A, Siebert R (2017a) WHO classification of tumours of haematopoietic and lymphoid tissues. IARC, LyonGoogle Scholar
  53. Swerdlow SH, Webber SA, Chadburn A, Ferry JA (2017b) Post-translplant lymphoproliferative disorders. In: Swerdlow SE, Campo E, Harris NL et al (eds) WHO classification of tumours of haematopoietic and lymphoid tissues. IARC, Lyon, pp 453–462Google Scholar
  54. Szczepanek D, Wasik-Szczepanek E, Stoma F, Sokolowska B, Trojanowski T (2017) Primary central nervous system lymphoma as a neurosurgical problem. Neurol Neurochir Pol 51(4):319–323.  https://doi.org/10.1016/j.pjnns.2017.04.004Google Scholar
  55. Tahsili-Fahadan P, Rashidi A, Cimino PJ, Bucelli RC, Keyrouz SG (2016) Neurologic manifestations of intravascular large B-cell lymphoma. Neurol Clin Pract 6(1):55–60.  https://doi.org/10.1212/cpj.0000000000000185Google Scholar
  56. Toh CH, Castillo M, Wong AM, Wei KC, Wong HF, Ng SH, Wan YL (2008) Primary cerebral lymphoma and glioblastoma multiforme: differences in diffusion characteristics evaluated with diffusion tensor imaging. Am J Neuroradiol 29(3):471–475.  https://doi.org/10.3174/ajnr.A0872Google Scholar
  57. Usuda D, Arahata M, Temaru R, Iinuma Y, Kanda T, Hayashi S (2016) Autopsy-proven intravascular lymphoma presenting as rapidly recurrent strokes. Case Rep Oncol 9(1):148–153.  https://doi.org/10.1159/000444632Google Scholar
  58. Wavre A, Baur AS, Betz M, Muhlematter D, Jotterand M, Zaman K, Ketterer N (2007) Case study of intracerebral plasmacytoma as an initial presentation of multiple myeloma. Neuro Oncol 9(3):370–372.  https://doi.org/10.1215/15228517-2007-008Google Scholar
  59. Williams RL, Meltzer CC, Smirniotopoulos JG, Fukui MB, Inman M (1998) Cerebral MR imaging in intravascular lymphomatosis. Am J Neuroradiol 19(3):427–431Google Scholar
  60. Yang XL, Liu YB (2017) Advances in pathobiology of primary central nervous system lymphoma. Chin Med J (Engl) 130(16):1973–1979.  https://doi.org/10.4103/0366-6999.211879Google Scholar
  61. Yang M, Sun J, Bai HX, Tao Y, Tang X, States LJ, Zhang Z, Zhou J, Farwell MD, Zhang P, Xiao B, Yang L (2017) Diagnostic accuracy of SPECT, PET, and MRS for primary central nervous system lymphoma in HIV patients: a systematic review and meta-analysis. Medicine 96(19):e6676.  https://doi.org/10.1097/md.0000000000006676Google Scholar
  62. Yap KK, Sutherland T, Liew E, Tartaglia CJ, Pang M, Trost N (2012) Magnetic resonance features of primary central nervous system lymphoma in the immunocompetent patient: a pictorial essay. J Med Imaging Radiat Oncol 56(2):179–186.  https://doi.org/10.1111/j.1754-9485.2012.02345.xGoogle Scholar
  63. Zacharia TT, Law M, Naidich TP, Leeds NE (2008) Central nervous system lymphoma characterization by diffusion-weighted imaging and MR spectroscopy. J Neuroimaging 18(4):411–417.  https://doi.org/10.1111/j.1552-6569.2007.00231.xGoogle Scholar
  64. Zahid MF, Khan N, Hashmi SK, Kizilbash SH, Barta SK (2016) Central nervous system prophylaxis in diffuse large B-cell lymphoma. Eur J Haematol 97(2):108–120.  https://doi.org/10.1111/ejh.12763Google Scholar
  65. Zhang XM, Aguilera NS (2015) Lymph node. In: Lin F, Prichard J (eds) Handbook of practical immunohistochemistry. frequently asked questions, 2nd edn. Springer, Berlin, pp 591–628Google Scholar

Copyright information

© Springer-Verlag GmbH Austria, part of Springer Nature 2019

Authors and Affiliations

  • Serge Weis
    • 1
  • Michael Sonnberger
    • 2
  • Andreas Dunzinger
    • 3
  • Eva Voglmayr
    • 2
  • Martin Aichholzer
    • 4
  • Raimund Kleiser
    • 2
  • Peter Strasser
    • 5
  1. 1.Division of Neuropathology, Neuromed CampusKepler University Hospital, Johannes Kepler UniversityLinzAustria
  2. 2.Department of Neuroradiology, Neuromed CampusKepler University Hospital, Johannes Kepler UniversityLinzAustria
  3. 3.Department of Neuro-Nuclear Medicine, Neuromed CampusKepler University Hospital, Johannes Kepler UniversityLinzAustria
  4. 4.Department of Neurosurgery, Neuromed CampusKepler University Hospital, Johannes Kepler UniversityLinzAustria
  5. 5.PMU University Institute for Medical & Chemical Laboratory DiagnosticsSalzburgAustria

Personalised recommendations