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 Table of Contents  
Year : 2019  |  Volume : 7  |  Issue : 3  |  Page : 219-221

Primary central nervous system lymphoma: Saudi Lymphoma Group's clinical practice guidelines for diagnosis, management and follow-up

1 Oncology Institute, Johns Hopkins Aramco Healthcare, Dhahran, Kingdom of Saudi Arabia
2 Department of Oncology, King Abdulaziz Medical City, Ministry of National Guard Health Affairs-Central Region, Riyadh, Kingdom of Saudi Arabia
3 College of Medicine, King Saud Bin Abdulaziz University for Health Sciences; Princess Noorah Oncology Center, King Abdulaziz Medical City, Ministry of National Guard Health Affairs-Western Region, Jeddah, Kingdom of Saudi Arabia
4 Adult Hematology and Stem Cell Transplantation Department, King Fahad Specialist Hospital, Dammam, Kingdom of Saudi Arabia
5 Oncology Department, Prince Sultan Military Medical City, Riyadh, Kingdom of Saudi Arabia; Department of Clinical Oncology, Cairo University, Giza, Egypt
6 Department of Adult Hematology and BMT, Comprehensive Cancer Center, King Fahad Medical City, Riyadh, Kingdom of Saudi Arabia
7 Department of Medicine, College of Medicine, King Saud University, Riyadh, Kingdom of Saudi Arabia
8 Department of Oncology, King Faisal Specialist Hospital and Research Centre; College of Medicine, Alfaisal University, Jeddah, Kingdom of Saudi Arabia

Date of Submission25-Mar-2019
Date of Decision06-May-2019
Date of Acceptance24-Jul-2019
Date of Web Publication28-Aug-2019

Correspondence Address:
Dr. Mubarak Al-Mansour
Adult Medical Oncology, Princess Noorah Oncology Center, King Abdulaziz Medical City, Ministry of National Guard Health Affairs-Western Region, PO Box 9515, Jeddah 21423
Kingdom of Saudi Arabia
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DOI: 10.4103/sjmms.sjmms_103_19

PMID: 31543748

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How to cite this article:
Sagheir A, Alhejazi A, Al-Mansour M, Alhashmi H, Kandil M, Motabi I, Alzahrani M, Dada R. Primary central nervous system lymphoma: Saudi Lymphoma Group's clinical practice guidelines for diagnosis, management and follow-up. Saudi J Med Med Sci 2019;7:219-21

How to cite this URL:
Sagheir A, Alhejazi A, Al-Mansour M, Alhashmi H, Kandil M, Motabi I, Alzahrani M, Dada R. Primary central nervous system lymphoma: Saudi Lymphoma Group's clinical practice guidelines for diagnosis, management and follow-up. Saudi J Med Med Sci [serial online] 2019 [cited 2022 Jan 28];7:219-21. Available from: https://www.sjmms.net/text.asp?2019/7/3/219/265637

  Introduction Top

Primary central nervous system lymphoma (PCNSL) is a rare variant of the aggressive extranodal non-Hodgkin lymphoma of the diffuse large B-cell type. It accounts for about 1% of all lymphomas, 4%–6% of all extranodal lymphomas and 3% of all central nervous system (CNS) tumors.[1] The risk of developing PCNSL is highly associated with having congenital or acquired immunodeficiencies such as human immunodeficiency virus (HIV) infection. The incidence is highest in patients aged >65 years, who represent the largest proportion of immunocompetent patients.[2],[3],[4] Few population studies about PCNSL have been published in Saudi Arabia; however, recent studies have shown a slight female predominance, and the mean age at diagnosis has been found to be 50.4 years (range: 20 to ≥60 years).[5],[6]

  Methods Top

A committee comprising experts in hematology and medical oncology was established under the supervision of the Saudi Lymphoma Group and in collaboration with the Saudi Oncology Society. For collecting evidence, a literature search was carried out with relevant keywords using online database search engines such as PubMed/Medline, Web of Science and Scopus. In addition, an expert's opinion was considered when necessary. The levels of evidence used in developing this guideline were as follows:

  • Evidence level (EL)-1 (highest), evidence from Phase III randomized trials or meta-analyses
  • EL-2 (intermediate), evidence from well-designed Phase II trials or Phase III trials with limitations
  • EL-3 (low), evidence from retrospective or observational studies/reports and/or expert opinion.

This easy-to-follow grading system is convenient for readers to understand and allows an accurate assessment of the guideline's applicability in individual patients.[7]


1.1. Magnetic resonance imaging (MRI) with contrast should be performed in all suspected cases of PCNSL to define the site and extent of disease

1.2. Fluid-attenuated inversion recovery and T1-weighted sequences before and after contrast injection are the methods of choice for diagnosis

1.3. The diagnosis of PNCSL should be confirmed pathologically according to the WHO classification (EL-1)[1]

1.4. Stereotactic needle brain biopsy is the optimal method to obtain a histopathological diagnosis; therefore, surgical reduction of PCNSL is not recommended (EL-3)[8]

1.5. Steroids should be withheld for at least 7–10 days prior to biopsy to minimize its lymphocytotoxic effect on histological diagnosis (EL-3)[9],[10]

1.6. The immunohistochemical markers for lymphoma cell characterization should include pan-B-cell antigens (i.e., CD19, CD20, CD22 and CD79a), BCL6, MUM1/IRF4, BCL2 and CD10 (EL-1)[1],[11],[12]

1.7. Other histologies for CNS lymphomas include Burkitt's lymphoma, lymphoblastic, indolent lymphoma (marginal zone lymphoma and small lymphocytic lymphoma) and T-cell lymphoma.


2.1. Pathology review is essential for all referral cases

2.2 Complete history should be documented (i.e., age, comorbidities, B-symptoms, Eastern Cooperative Oncology Group [ECOG] performance, neurological and neuropsychiatric symptoms, hepatitis or HIV risk factors, medications, allergy to contrast media or drugs as well as social and family history)

2.3. Physical examination should include

  1. Complete neurological examination, including the Mini-Mental State Examination (MMSE)
  2. Assessment of lymph nodes, Waldeyer's ring, spleen, liver and skin

2.4. Laboratory evaluations of all patients should include complete blood count with differential count, liver and renal function tests as well as routine blood chemistry including lactate dehydrogenase [LDH], electrolytes and calcium

2.5. Hepatitis serology tests (hepatitis B and C viruses) should be carried out

2.6. Screening test for HIV is required

2.7. Whole-brain MRI (contrast-enhanced) should be performed

2.8. Computed tomography scan of the neck and chest and abdomen and pelvis should be performed

2.9. Bone marrow biopsy is recommended for staging

2.10. Testicular ultrasonography is recommended in elderly patients

2.11. Cerebrospinal fluid (CSF) examination (lymphoma cell count, protein and glucose levels, cytology, flow cytometry and immunoglobulin heavy-chain variable region gene rearrangement studies)

2.12. To investigate ocular involvement, the slit-lamp examination should be carried out

2.13. Cardiac function (i.e., left ventricular function) should be assessed by echocardiogram before the treatment

2.14. Pregnancy test should be done for women of childbearing age

2.15. For prognosis, follow the International Prognostic Score for PCNSL:

  1. Age >60 years
  2. Eastern Cooperative Oncology Group Performance Status (ECOG PS) >1
  3. Elevated serum LDH
  4. Elevated CSF protein concentration
  5. Tumor localization within the deep regions of CNS.

2.16. Based on these predictors, the risk group classifications are as follows: 0–1 (low), 2–3 (intermediate) or 4–5 (high risk) (EL-3).[13]


3.1. The treatment of PCNSL is based on age and performance status [14],[15]

3.2. High-dose methotrexate (HDMTX) (≥3 g/m2) is the standard induction therapy to cross the blood–brain barrier and yield cytotoxic levels in the CSF. It should be delivered over 2–4 h (rapid infusion) through at least 4–6 injections at intervals of not >2–3 weeks (EL-1)[16],[17],[18]

3.3. HDMTX infusions require pre- and posthyperhydration, urine alkalinization, leucovorin rescue and MTX concentration monitoring

3.4. HDMTX in combination with temozolomide and rituximab improves the response rates compared with HDMTX alone

3.5. High-dose consolidation of cytarabine and etoposide following HDMTX-based polychemotherapy induction therapy is recommended (EL-2)[19]

3.6. Palliative whole-brain radiotherapy should be considered for patients deemed unsuitable to receive HDMTX owing to tolerability or relapse after treatment with HDMTX and CNS-penetrating chemotherapy or being unfit for further chemotherapy (EL-3).


4.1. Every 3 months for 2 years and then once every 6 months

4.2. History and physical examination should be documented in each visit

4.3. Cognitive evaluation, such as MMSE, should be conducted in every visit

4.4. Contrast-enhanced MRI of the brain must be performed in each visit

4.5. Ophthalmologic examination and CSF analysis should be carried out when clinically indicated (EL-3).

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, et al. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues (IARC WHO Classification of Tumours). Revised 4th Edition. Lyon: International Agency for Research on Cancer; 2017.  Back to cited text no. 1
Bessell EM, Dickinson P, Dickinson S, Salmon J. Increasing age at diagnosis and worsening renal function in patients with primary central nervous system lymphoma. J Neurooncol 2011;104:191-3.  Back to cited text no. 2
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;105:1414-8.  Back to cited text no. 3
O'Neill BP, Decker PA, Tieu C, Cerhan JR. The changing incidence of primary central nervous system lymphoma is driven primarily by the changing incidence in young and middle-aged men and differs from time trends in systemic diffuse large B-cell non-Hodgkin's lymphoma. Am J Hematol 2013;88:997-1000.  Back to cited text no. 4
Mufti ST, Baeesa SS, Al-Maghrabi JA. Primary intracranial lymphomas. Asian J Neurosurg 2016;11:232-9.  Back to cited text no. 5
  [Full text]  
Tailor IK, Hussain T, Shakweer W, Motabi IH, Murtaza G, Zaidi SZ, et al. Primary central nervous system lymphoma treatment outcomes-a decade's experience from a single centre in Riyadh, Saudi Arabia. Blood 2016;128:5416.  Back to cited text no. 6
Jazieh AR. Saudi lung cancer guidelines update 2012. J Infect Public Health 2012;5 Suppl 1:S11-3.  Back to cited text no. 7
Deckert M, Brunn A, Montesinos-Rongen M, Terreni MR, Ponzoni M. Primary lymphoma of the central nervous system – A diagnostic challenge. Hematol Oncol 2014;32:57-67.  Back to cited text no. 8
Pirotte B, Levivier M, Goldman S, Brucher JM, Brotchi J, Hildebrand J. Glucocorticoid-induced long-term remission in primary cerebral lymphoma: Case report and review of the literature. J Neurooncol 1997;32:63-9.  Back to cited text no. 9
Brück W, Brunn A, Klapper W, Kuhlmann T, Metz I, Paulus W, et al. Differential diagnosis of lymphoid infiltrates in the central nervous system: Experience of the network lymphomas and lymphomatoid lesions in the nervous system. Pathologe 2013;34:186-97.  Back to cited text no. 10
Giannini C, Dogan A, Salomão DR. CNS lymphoma: A practical diagnostic approach. J Neuropathol Exp Neurol 2014;73:478-94.  Back to cited text no. 11
Ferry JA, Pfannl R, Harris NL. Pathology of primary central nervous system lymphoma and related conditions. In: Batchelor T, DeAngelis LM, editors. Lymphoma and Leukemia of the Nervous System. 2nd ed. New York: Springer; 2012. p. 61-86.  Back to cited text no. 12
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;21:266-72.  Back to cited text no. 13
Abrey LE, Batchelor TT, Ferreri AJ, Gospodarowicz M, Pulczynski EJ, Zucca E, et al. Report of an international workshop to standardize baseline evaluation and response criteria for primary CNS lymphoma. J Clin Oncol 2005;23:5034-43.  Back to cited text no. 14
Corry J, Smith JG, Wirth A, Quong G, Liew KH. Primary central nervous system lymphoma: Age and performance status are more important than treatment modality. Int J Radiat Oncol Biol Phys 1998;41:615-20.  Back to cited text no. 15
Hiraga S, Arita N, Ohnishi T, Kohmura E, Yamamoto K, Oku Y, et al. Rapid infusion of high-dose methotrexate resulting in enhanced penetration into cerebrospinal fluid and intensified tumor response in primary central nervous system lymphomas. J Neurosurg 1999;91:221-30.  Back to cited text no. 16
Joerger M, Huitema AD, Illerhaus G, Ferreri AJ. Rational administration schedule for high-dose methotrexate in patients with primary central nervous system lymphoma. Leuk Lymphoma 2012;53:1867-75.  Back to cited text no. 17
Glass J, Gruber ML, Cher L, Hochberg FH. Preirradiation methotrexate chemotherapy of primary central nervous system lymphoma: Long-term outcome. J Neurosurg 1994;81:188-95.  Back to cited text no. 18
Rubenstein JL, Hsi ED, Johnson JL, Jung SH, Nakashima MO, Grant B, et al. Intensive chemotherapy and immunotherapy in patients with newly diagnosed primary CNS lymphoma: CALGB 50202 (Alliance 50202). J Clin Oncol 2013;31:3061-8.  Back to cited text no. 19


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