1% of all NHL, 3% of all brain tumours


Clinical Presentation

Varied – Behavioural change, memory or language impairment, focal motor deficits, seizures, raised intracranial pressure, neuropsychiatric symptoms

Uveitis – 20% of patients have intraocular involvement resembling chronic uveitis 




Biopsy – intra-operative rapid cytology may avoid extensive surgery

Effect of steroids prior to biopsy – up to 1/3 of biopsies non-diagnostic after <1 week of steroids

CSF – 3-10ml for protein, cytology and immunophenotyping (Alternative: PCR for IGHV rearrangement)

MRI – imaging modality of choice but appearances not to be confused with neurosarcoidosis, multiple sclerosis, glioblastoma and vasculitis which may all share similar features

PET-CT – to look for systemic involvement (CT if PET unavailable)

Testicular USS – PET-CT may not detect testicular involement

Bone marrow biopsy? – not essential if FBC normal & no paraprotein detected

LDH – forms part of prognostic scores

Mini Mental State Examination (MMSE) +/- more detailed neuropsychological assessments

Ophthalmology review – Slit Lamp examination

Other – U&E, LFT, Creatinine Clearance, HIV & Hep B/C prior to chemotherapy

MDT – review of the above at lymphoma MDT




General Considerations


Fitness for treatment

  • Assess physiological fitness over chronological age

  • High dose methotrexate requires adequate renal, liver and cardiac function for safe delivery

  • Performance Status likely to be impaired at diagnosis, may improve with initial treatment


Offer clinical trial where available


Remission Induction


Combination chemotherapy regimen that includes high dose methotrexate (HD-MTX)



  • HD-MTX, Cytarabine, Thiotepa & Rituximab

  • 69% 2 year OS in IELSG32 (International Extranodal Lymphoma Study Group) trial

  • 4-7% treatment-related mortality (TRM), mostly in first cycle


MATRix preferred in UK, but other available regimens include:

  • MT-R – HD-MTX, Temozolimide & Rituximab

  • R-MPV – Rituximab, HD-MTX, Procarbazine & Vincristine

  • R-MBPV – Rituximab, HD-MTX, Carmustine, Etoposide, Prednisolone


Less Fit Patients:

  • Patients considered not fit for MATRix but still able to receive HD-MTX

  • Several regimens available, most combing HD-MTX with oral alkylating agents


Palliative therapy

  • Patients unfit to receive HD-MTX have a very poor prognosis

  • Whole brain radiotherapy, steroids and oral chemotherapy are all options




Chemotherapy Consolidation

  • i.e. Autologous Stem Cell Transplant

  • 70-80% 3-5 year OS in prospective trials, only a minority of patients also received WBRT

  • PRECIS Trial – 2-year PFS 86% Autograft vs 63% WBRT, no difference in OS


Whole Brain Radiotherapy (WBRT)

  • 30-45Gy

  • Causes irreversible, potentially debilitating, neurocognitive dysfunction. Esp. if >60 y.o.

  • Some evidence to suggest of less benefit with modern induction regimens

  • Decision to use requires MDT discussion including neuroradiology




MRI 1-2 months after completion of consolidation


MRI Surveillance?

  • Consider 3-4 monthly MRI for 2 years is patient would be fit for salvage chemotherapy

  • Rationale: Higher OS rates when patients salvaged for asymptomatic relapse


Relapsed/Refractory Disease


Median survival – 3.5 months


Offer clinical trial wherever possible



  • Ifofomide-based regimens: R-ICE (Rituximab, Ifosfomide, Carboplatin, Etoposide)

  • Re-treatment with HD-MTX if good first remission

  • Novel agents: Ibrutinib, Nivolumab, Lenlidomide


primary intraocular lymphoma (piol)


Variant of PCNSL

High rate of CNS relapse post treatment and CNS lymphoma is primary cause of death in PIOL

Drugs that cross blood-brain barrier also cross blood-ocular barrier

Fit Rx: MATRix or similar, followed by ocular radiotherapy +/- WBRT or Autograft

Unfit Rx: Intravitreal methotrexate