Which clinical history findings are characteristic of primary central nervous system lymphoma (PCNSL)?

Answer

The most typical presentation of PCNSL in an immunocompetent patient is progressive focal symptoms indicative of a mass lesion. Seizures may occur. Sometimes, nonspecific mental status change leads to the diagnosis. Several variant presentations of PCNSL are discussed in this section.

Patients with AIDS are more likely to present with an encephalopathy than other patients with PCNSL. This correlates with the more often multifocal, diffuse enhancement pattern seen on magnetic resonance imaging (MRI) scans. A history of concurrent infections is quite common, and the median CD4⁺ count is 20 cells/µL.

Much of the history taking should be devoted to establishing whether the patient may have immune deficiency. A careful sexual and drug abuse history is necessary. If the patient is a transplant recipient, the nature and duration of immune suppression must be clarified.

The diagnosis of PCNSL in immunocompetent and immunocompromised patients is particularly difficult if they present with one of the variant syndromes outlined here.

Isolated, ocular, or meningeal tumor may occur in the absence of any focal abnormalities on MRI. Such patients give a history of (1) blurred vision, (2) headache, (3) isolated cranial nerve dysfunction (eg, diplopia, dizziness, dysphagia, facial numbness, monocular visual loss), or (4) spinal nerve root symptoms (eg, pain, dysfunction localized to 1 dermatome, bowel or bladder problems).

Relapsing, remitting lesions may disappear for periods of as long as several months to a year or more. Administration of corticosteroids may cause prolonged remission of clinical and radiographic signs and symptoms, but remission also occurs spontaneously.

Progressive dementia or stupor with no focal signs and with little or no enhancement on MRI may be more common in patients with AIDS who have PCNSL.

Intravascular malignant lymphomatosis (previously called neoplastic angioendotheliosis) is a series of strokelike focal events, and the MRI may look like multiple large- and small-vessel ischemic strokes and at times single or multiple focal intracerebral hemorrhage. Parasitosis, malignant lymphoma, or metastatic brain tumor often enter the differential diagnosis. Diagnosis often moves away from stroke by the steady progressive clinical course and is often confirmed by brain biopsy and histology and immunochemical staining of the biopsy specimen.

Neurolymphomatosis is the only PCNSL syndrome that involves both the central and peripheral nervous systems at presentation. Cerebral lymphoma with focal mass lesions, as well as infiltration of peripheral nerves, is seen.

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Malani R, Bhatia A, Wolfe J, Grommes C. Staging identifies non-CNS malignancies in a large cohort with newly diagnosed lymphomatous brain lesions. Leuk Lymphoma. 2019 Sep. 60 (9):2278-2282. [Medline].
Jahnke K, Thiel E, Martus P, Herrlinger U, Weller M, Fischer L, et al. Relapse of primary central nervous system lymphoma: clinical features, outcome and prognostic factors. J Neurooncol. 2006 Nov. 80 (2):159-65. [Medline].
Villano JL, Koshy M, Shaikh H, Dolecek TA, McCarthy BJ. Age, gender, and racial differences in incidence and survival in primary CNS lymphoma. Br J Cancer. 2011 Oct 25. 105 (9):1414-8. [Medline].
Camilleri-Broët S, Martin A, Moreau A, Angonin R, Hénin D, Gontier MF, et al. Primary central nervous system lymphomas in 72 immunocompetent patients: pathologic findings and clinical correlations. Groupe Ouest Est d'étude des Leucénies et Autres Maladies du Sang (GOELAMS). Am J Clin Pathol. 1998 Nov. 110 (5):607-12. [Medline].
Chihara D, Fowler NH, Oki Y, Fanale MA, Nastoupil LJ, Westin JR, et al. Impact of histologic subtypes and treatment modality among patients with primary central nervous system lymphoma: a SEER database analysis. Oncotarget. 2018 Jun 22. 9 (48):28897-28902. [Medline].
Weller M. Glucocorticoid treatment of primary CNS lymphoma. J Neurooncol. 1999 Jul. 43 (3):237-9. [Medline].
Önder E, Arıkök AT, Önder S, Han Ü, Sorar M, Kertmen H, et al. Corticosteroid pre-treated primary CNS lymphoma: a detailed analysis of stereotactic biopsy findings and consideration of interobserver variability. Int J Clin Exp Pathol. 2015. 8 (7):7798-808. [Medline].
Brandsma D, Bromberg JEC. Primary CNS lymphoma in HIV infection. Handb Clin Neurol. 2018. 152:177-186. [Medline].
Ding Y, Xing Z, Liu B, Lin X, Cao D. Differentiation of primary central nervous system lymphoma from high-grade glioma and brain metastases using susceptibility-weighted imaging. Brain Behav. 2014 Oct 10. [Medline]. [Full Text].
Sugita Y, Tokunaga O, Nakashima A, Shigemori M. SHP-1 expression in primary central nervous system B-cell lymphomas in immunocompetent patients reflects maturation stage of normal B cell counterparts. Pathol Int. 2004 Sep. 54(9):659-66. [Medline].
Nayyar N, White MD, Gill CM, Lastrapes M, Bertalan M, et al. MYD88 L265P mutation and CDKN2A loss are early mutational events in primary central nervous system diffuse large B-cell lymphomas. Blood Adv. 2019 Feb 12. 3 (3):375-383. [Medline].
Pulczynski EJ, Kuittinen O, Erlanson M, Hagberg H, Fosså A, Eriksson M, et al. Successful change of treatment strategy in elderly patients with primary central nervous system lymphoma by de-escalating induction and introducing temozolomide maintenance: results from a phase 2 study by The Nordic Lymphoma Group. Haematologica. 2014 Dec 5. [Medline].
Kranick SM, Goncalves PH, Stetler-Stevenson M, Aleman K, Polizzotto MN, Little RF, et al. Paradoxical central nervous system immune reconstitution syndrome in acquired immunodeficiency syndrome-related primary central nervous system lymphoma. Haematologica. 2014 Oct 10. [Medline].
Corboy JR, Garl PJ, Kleinschmidt-DeMasters BK. Human herpesvirus 8 DNA in CNS lymphomas from patients with and without AIDS. Neurology. 1998 Feb. 50(2):335-40. [Medline].
Gomez-Brouchet A, Delisle MB, Vital A, Brousset P. Immunohistochemical assessment of human herpesvirus 8 infection in primary central nervous system large B cell lymphomas. J Clin Pathol. 2001 Aug. 54(8):617-8. [Medline].
Evens AM, Choquet S, Kroll-Desrosiers AR, Jagadeesh D, Smith SM, Morschhauser F, et al. Primary CNS posttransplant lymphoproliferative disease (PTLD): an international report of 84 cases in the modern era. Am J Transplant. 2013 Jun. 13 (6):1512-22. [Medline].
Crane GM, Powell H, Kostadinov R, Rocafort PT, Rifkin DE, Burger PC, et al. Primary CNS lymphoproliferative disease, mycophenolate and calcineurin inhibitor usage. Oncotarget. 2015 Oct 20. 6 (32):33849-66. [Medline].
Dandachi D, Ostrom QT, Chong I, Serpa JA, Giordano TP, Kruchko C, et al. Primary central nervous system lymphoma in patients with and without HIV infection: a multicenter study and comparison with U.S national data. Cancer Causes Control. 2019 May. 30 (5):477-488. [Medline].
Bataille B, Delwail V, Menet E, Vandermarcq P, Ingrand P, Wager M, et al. Primary intracerebral malignant lymphoma: report of 248 cases. J Neurosurg. 2000 Feb. 92 (2):261-6. [Medline].
Sagoo MS, Mehta H, Swampillai AJ, Cohen VM, Amin SZ, Plowman PN, et al. Primary intraocular lymphoma. Surv Ophthalmol. 2014 Sep-Oct. 59 (5):503-16. [Medline].
Savage KJ. Secondary CNS relapse in diffuse large B-cell lymphoma: defining high-risk patients and optimization of prophylaxis strategies. Hematology Am Soc Hematol Educ Program. 2017 Dec 8. 2017 (1):578-586. [Medline].
Elavarasi A, Dash D, Warrier AR, Bhatia R, Kumar L, Jain D, et al. Spinal cord involvement in primary CNS lymphoma. J Clin Neurosci. 2018 Jan. 47:145-148. [Medline].
Ferreri AJM, Calimeri T, Lopedote P, Francaviglia I, Daverio R, et al. MYD88 L265P mutation and interleukin-10 detection in cerebrospinal fluid are highly specific discriminating markers in patients with primary central nervous system lymphoma: results from a prospective study. Br J Haematol. 2021 May. 193 (3):497-505. [Medline].
Fischer L, Martus P, Weller M, Klasen HA, Rohden B, Röth A, et al. Meningeal dissemination in primary CNS lymphoma: prospective evaluation of 282 patients. Neurology. 2008 Sep 30. 71(14):1102-8. [Medline].
Barajas RF, Politi LS, Anzalone N, Schöder H, Fox CP, Boxerman JL, et al. Consensus recommendations for MRI and PET imaging of primary central nervous system lymphoma: guideline statement from the International Primary CNS Lymphoma Collaborative Group (IPCG). Neuro Oncol. 2021 Jul 1. 23 (7):1056-1071. [Medline].
Goyal P, Kumar Y, Gupta N, Malhotra A, Gupta S, Gupta S, et al. Usefulness of enhancement-perfusion mismatch in differentiation of CNS lymphomas from other enhancing malignant tumors of the brain. Quant Imaging Med Surg. 2017 Oct. 7 (5):511-519. [Medline].
Ferreri AJ, Reni M, Foppoli M, Martelli M, Pangalis GA, et al. High-dose cytarabine plus high-dose methotrexate versus high-dose methotrexate alone in patients with primary CNS lymphoma: a randomised phase 2 trial. Lancet. 2009 Oct 31. 374 (9700):1512-20. [Medline].
Thiel E, Korfel A, Martus P, Kanz L, Griesinger F, Rauch M, et al. High-dose methotrexate with or without whole brain radiotherapy for primary CNS lymphoma (G-PCNSL-SG-1): a phase 3, randomised, non-inferiority trial. Lancet Oncol. 2010 Nov. 11 (11):1036-47. [Medline].
Hoang-Xuan K, Bessell E, Bromberg J, Hottinger AF, Preusser M, et al. Diagnosis and treatment of primary CNS lymphoma in immunocompetent patients: guidelines from the European Association for Neuro-Oncology. Lancet Oncol. 2015 Jul. 16 (7):e322-32. [Medline].
Morris PG, Correa DD, Yahalom J, Raizer JJ, Schiff D, Grant B, et al. Rituximab, methotrexate, procarbazine, and vincristine followed by consolidation reduced-dose whole-brain radiotherapy and cytarabine in newly diagnosed primary CNS lymphoma: final results and long-term outcome. J Clin Oncol. 2013 Nov 1. 31 (31):3971-9. [Medline].
Nayak L, Iwamoto FM, LaCasce A, Mukundan S, Roemer MGM, Chapuy B, et al. PD-1 blockade with nivolumab in relapsed/refractory primary central nervous system and testicular lymphoma. Blood. 2017 Jun 8. 129 (23):3071-3073. [Medline].
Ney DE, Reiner AS, Panageas KS, Brown HS, DeAngelis LM, Abrey LE. Characteristics and outcomes of elderly patients with primary central nervous system lymphoma: the Memorial Sloan-Kettering Cancer Center experience. Cancer. 2010 Oct 1. 116 (19):4605-12. [Medline].
Roth P, Martus P, Kiewe P, Möhle R, Klasen H, Rauch M, et al. Outcome of elderly patients with primary CNS lymphoma in the G-PCNSL-SG-1 trial. Neurology. 2012 Aug 28. 79(9):890-6. [Medline].
Ferreri AJ, Blay JY, Reni M, Pasini F, Spina M, Ambrosetti A, et al. Prognostic scoring system for primary CNS lymphomas: the International Extranodal Lymphoma Study Group experience. J Clin Oncol. 2003 Jan 15. 21 (2):266-72. [Medline].
Abrey LE, Ben-Porat L, Panageas KS, Yahalom J, Berkey B, Curran W, et al. Primary central nervous system lymphoma: the Memorial Sloan-Kettering Cancer Center prognostic model. J Clin Oncol. 2006 Dec 20. 24 (36):5711-5. [Medline].
Bayraktar S, Bayraktar UD, Ramos JC, Stefanovic A, Lossos IS. Primary CNS lymphoma in HIV positive and negative patients: comparison of clinical characteristics, outcome and prognostic factors. J Neurooncol. 2011 Jan. 101 (2):257-65. [Medline].
Hottinger AF, Iwamoto FM, Karimi S, et al. YKL-40 and MMP-9 as serum markers for patients with primary central nervous system lymphoma. Annals of Neurology. January 10, 2011.
Linnebank M, Schmidt S, Kolsch H, et al. The methionine synthase polymorphism D919G alters susceptibility to primary central nervous system lymphoma. Br J Cancer. 2004 May 17. 90(10):1969-71. [Medline].
Ponzoni M, Campo E, Nakamura S. Intravascular large B-cell lymphoma: a chameleon with multiple faces and many masks. Blood. 2018 Oct 11. 132 (15):1561-1567. [Medline].
Grommes C, Nayak L, Tun HW, Batchelor TT. Introduction of novel agents in the treatment of primary CNS lymphoma. Neuro Oncol. 2019 Feb 19. 21 (3):306-313. [Medline].
Gupta NK, Nolan A, Omuro A, Reid EG, Wang CC, Mannis G, et al. Long-term survival in AIDS-related primary central nervous system lymphoma. Neuro Oncol. 2017 Jan. 19 (1):99-108. [Medline].
Moulignier A, Lamirel C, Picard H, Lebrette MG, Amiel C, Hamidi M, et al. Long-term AIDS-related PCNSL outcomes with HD-MTX and combined antiretroviral therapy. Neurology. 2017 Aug 22. 89 (8):796-804. [Medline].

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Caroline T Goldin, MD Fellow in Neuro-oncology, Department of Neurology, University of Colorado School of Medicine

Disclosure: Nothing to disclose.

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Douglas E Ney, MD Associate Professor of Neurology and Neurosurgery, Director of Neurology Residency Program, University of Colorado School of Medicine

Douglas E Ney, MD is a member of the following medical societies: American Academy of Neurology, American Society of Clinical Oncology, Society for Neuro-Oncology

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Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Jorge C Kattah, MD Head, Associate Program Director, Professor, Department of Neurology, University of Illinois College of Medicine at Peoria

Jorge C Kattah, MD is a member of the following medical societies: American Academy of Neurology, American Neurological Association, New York Academy of Sciences

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Chief Editor

Stephen A Berman, MD, PhD, MBA Professor of Neurology, University of Central Florida College of Medicine

Stephen A Berman, MD, PhD, MBA is a member of the following medical societies: Alpha Omega Alpha, American Academy of Neurology, Phi Beta Kappa

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Additional Contributors

Frederick M Vincent, Sr, MD Clinical Professor, Department of Neurology and Ophthalmology, Michigan State University Colleges of Human and Osteopathic Medicine

Frederick M Vincent, Sr, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Neurology, American Association of Neuromuscular and Electrodiagnostic Medicine, American College of Forensic Examiners Institute, American College of Legal Medicine, American College of Physicians

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Tarakad S Ramachandran, MBBS, MBA, MPH, FAAN, FACP, FAHA, FRCP, FRCPC, FRS, LRCP, MRCP, MRCS † Professor Emeritus of Neurology and Psychiatry, Clinical Professor of Medicine, Clinical Professor of Family Medicine, Clinical Professor of Neurosurgery, State University of New York Upstate Medical University; Neuroscience Director, Department of Neurology, Crouse Irving Memorial Hospital

Tarakad S Ramachandran, MBBS, MBA, MPH, FAAN, FACP, FAHA, FRCP, FRCPC, FRS, LRCP, MRCP, MRCS is a member of the following medical societies: American Academy of Neurology, American Academy of Pain Medicine, American College of Forensic Examiners Institute, American College of International Physicians, American College of Physicians, American Heart Association, American Stroke Association, National Association of Managed Care Physicians, Royal College of Physicians, Royal College of Physicians and Surgeons of Canada, Royal College of Surgeons of England, Royal Society of Medicine

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Which clinical history findings are characteristic of primary central nervous system lymphoma (PCNSL)?

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