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. 2019 Aug 28;7(3):219–221. doi: 10.4103/sjmms.sjmms_103_19

Primary Central Nervous System Lymphoma: Saudi Lymphoma Group's Clinical Practice Guidelines for Diagnosis, Management and Follow-up

Ahmed Sagheir 1, Ayman Alhejazi 1, Mubarak Al-Mansour 2,3,✉, Hani Alhashmi 4, Magdy Kandil 5,6, Ibraheem Motabi 7, Musa Alzahrani 8, Reyad Dada 9,10
PMCID: PMC6734741  PMID: 31543748

INTRODUCTION

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

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. PATHOLOGIC DIAGNOSIS

    • 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. DIAGNOSIS AND WORKUP

    • 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. MANAGEMENT

    • 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. FOLLOW-UP

    • 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

Nil.

Conflicts of interest

There are no conflicts of interest.

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