原發性中樞神經淋巴瘤

Buzzwords → Dx

Diagnostic Criteria

• Aggressive B-cell lymphoma (almost always DLBCL) confined to brain, leptomeninges, eyes, or spinal cord (no systemic involvement at diagnosis).
• Confirm with biopsy (stereotactic) OR CSF cytology/flow/PCR if accessible / amenable.
• Avoid steroids before biopsy — they cause rapid lymphocyte apoptosis and can render biopsy non-diagnostic for weeks.
• Workup for systemic disease to confirm CNS-only (CT chest/abdomen/pelvis, marrow, testicular US in men) — secondary CNS involvement of systemic DLBCL is treated differently.

Workup

• MRI brain with contrast + spinal MRI if symptoms.
• Slit-lamp + dilated fundus exam (vitreoretinal involvement).
• CSF analysis (cytology + flow + IgH PCR + EBV PCR) — can avoid biopsy if positive.
• Stereotactic brain biopsy if CSF unrevealing — full IHC + MYD88 testing.
• HIV testing mandatory.
• Bone marrow + CT C/A/P + testicular US (in men) to rule out systemic DLBCL with CNS involvement.
• CrCl + cardiac assessment before HD-MTX (excretion + fluid load).
• Hold steroids until biopsy unless herniation imminent — and then minimum dose.

Treatment Algorithm

flowchart TD
  A[Suspected PCNSL] --> B[MRI + slit-lamp<br>+ HIV test + CSF analysis]
  B --> C{Steroids urgent?}
  C -- no --> D[Stereotactic biopsy first<br>OR CSF/vitreous if positive]
  C -- yes mass effect --> E[Lowest-dose dex<br>biopsy ASAP]
  D --> F[Confirm B-NHL DLBCL]
  E --> F
  F --> G{Fit for HD-MTX?}
  G -- yes --> H[MATRix: HD-MTX + Ara-C + Thiotepa + Rituximab × 4<br>or HD-MTX + R based regimen]
  G -- frail --> I[HD-MTX monotherapy<br>or temozolomide / palliative WBRT]
  H --> J{CR / VGPR?}
  J -- yes, fit --> K[Auto-HCT consolidation<br>BCNU/thiotepa preferred over WBRT for long-term neurocog]
  J -- yes, frail --> L[Reduced-dose WBRT 23.4 Gy<br>or maintenance temozolomide / lenalidomide]
  J -- partial --> M[Continue HD-MTX or salvage]
  K --> N{Relapse?}
  L --> N
  M --> N
  N -- yes --> O[Salvage HD-MTX rechallenge<br>or temozolomide<br>or ibrutinib (penetrates CNS)<br>or R/R clinical trial]

Pearls / Pitfalls

• AVOID STEROIDS BEFORE BIOPSY. They cause rapid lymphocyte apoptosis (cytoreductive effect) → biopsy can be non-diagnostic for weeks. If herniation/mass-effect demands urgent dex, give the lowest dose and biopsy ASAP.
• HD-MTX (≥3–3.5 g/m²) is the backbone. Ensure CrCl >50, urinary alkalinization (pH >7), aggressive hydration, leucovorin rescue. Monitor MTX levels q24h.
• MATRix regimen (Ferreri, Lancet Haematol 2016) — HD-MTX + Ara-C + thiotepa + rituximab — superior CR rates, with auto-HCT consolidation = best long-term outcomes in fit pts.
• WBRT consolidation causes severe long-term neurocognitive decline, especially in pts >60 yo. Auto-HCT (BCNU/thiotepa) is preferred for fit pts.
• Ibrutinib penetrates CNS and has activity in R/R PCNSL (MYD88-mutated subtype responsive). Consider for unfit/relapsed.
• HIV-associated PCNSL: treat HIV with ART; consider EBV-targeted approaches; outcomes improving in modern era.
• Vitreoretinal lymphoma often coexists — ophth eval + intravitreal MTX/rituximab if isolated. Systemic HD-MTX still recommended as it crosses blood-retinal barrier.
• Toxoplasmosis vs PCNSL in HIV+: thallium-201 or amino-acid PET favors lymphoma; empirical toxo trial × 2 wk → if no response, biopsy/treat as PCNSL.
• Secondary CNS lymphoma (SCNSL) of systemic DLBCL is a different entity — different workflow (systemic R-chemo + CNS-penetrating drugs).

Cross-references

• Drug Regimens — HD-MTX, MATRix, ibrutinib
• DLBCL — secondary CNS lymphoma
• Auto-HCT — BCNU/thiotepa consolidation
• Infection ppx — HD-MTX immunosuppression

相關題目

• Q-055 — PCNSL — pre-biopsy steroid timing
• Q-056 — PCNSL — induction backbone (MATRix vs WBRT)
• Q-057 — PCNSL vs toxoplasmosis in HIV+ patient

Sources