Info
primary CNS lymphoma
Definition
NHL involving the CNS, including the brain, leptomeninges, spinal cord, eye Epidemiology Rare subtype of NHL (1% of cases) Rare subtype of 1° CNS tumors (4% of cases) Age-adjusted incidence 0.47/100000 person-y In immunocompetent pts, median age at ↣ dx 60 y
Risk Factors
Congenital immunosuppression: Ataxia-telangiectasia, Wiskott-Aldrich syndrome, & sev. common & combined variable immunodeficiencies HIV infxn: CD4 count <500 cells/μL Iatrogenic immune suppression: Solid organ transplant or HSCT Autoimmune disorder: RA, SLE, Sjögren syndrome, MG, sarcoidosis, vasculitis Pathogenesis Pathogenesis is → incompletely understood EBV is → a causal link, but only in immunodeficient individuals
Histopathology
95% of PCNSLs are DLBCL Angiocentric neoplasm, typically w/ perivascular distribution Immunophenotype: Positive B-cell markers (CD19, CD20). Majority positive for BCL-6, MUM1, & BCL-2 while negative for CD10; >80% nongerminal center subtype T-cell PCNSL approximately 2% of cases Molecular testing: Positive for Ig heavy chain gene rearrangement
Clinical Subtypes
Overlap between subtypes w/ multifocal disease in >50% of cases: Intracranial parenchymal lesion: Solitary or multiple (>90% of cases) Leptomeningeal or periventricular lesions: Either w/ adjacent parenchymal disease or diffuse (30%) Ocular: Infiltration of vitreous humor, retina, choroid, optic nerve (10-20%) Intradural spinal cord lesion: Lower cervical & upper thoracic most common sites (rare) Neurolymphomatosis: Invasion of peripheral nerves, cranial nerves, spinal nerves, or ganglia (rare)
Clinical Presentation
Presenting s/s may vary depending on site of disease: Focal neurologic deficits (70%), mental status changes (43%), signs of elevated ICP (33%), seizures (14%), & visual sx (4%) (J Neurosurg 2000;92:261) Diagnosis and Initial Evaluation Contrast-enhanced brain MRI: Lesions are isointense to hypointense on T1-weighted images & enhances frequently. PCNSL presents as solitary intracranial lesion in 60-70% of cases, often located in hemispheres, basal ganglia, corpus callosum, & periventricular regions Contrast-enhanced head CT if MRI contraindicated Definitive pathologic dx required: Stereotactic needle bx of the brain indicated in most cases. In select cases, vitreous bx or CSF analysis may secure dx. W/ isolated neurolymphomatosis, nerve bx required Withhold steroids if possible until pathologic dx confirmed: PCNSL responds rapidly to steroid Rx & lesions can regress on radiographs, making bx more difficult. Unless evidence of mass effect/impending herniation, hold initial steroids until bx done Initial evaluation: Bilateral slit lamp eye examination, LP & CSF fluid analysis (if safe w/o evidence of elevated ICP), HIV, & CT CAP. In select cases, MRI spine if spinal sx, BM bx, testicular U/S, or FDG-PET scan
Poor Prognostic Factors of primary CNS lymphoma
Staging
Not applicable, typically disease is → limited to CNS (Ann Arbor stage IE) Evaluate to exclude systemic lymphoma & define extent of disease
Adequate Performance Status (>40%)
HD-MTX containing regimen: Recommended for all pts w/ goal of avoiding RT, especially for older pts. Combination regimens (MTX+ cytarabine, MTX + temozolomide, MTX+ procarbazine/vincristine) superior to single agent. Include rituximab unless CD20-negative or T-cell lymphoma HD-MTX + Rituximab vs. HD-MTX: PFS of 26.7 mos vs. 4.5 mos (Neurology 2014;83:235) Phase II trial of HD-MTX, temozolomide, rituximab w/ consolidation cytarabine/etoposide: 66% CR w/ induction & median PFS of 2.4 y (JCO 2013;31:3061)
HD-MTX: Optimal dose > or = 3.5 mg/m2 Low dose WBRT after CR used w/ efficacy & less neurotoxicity (JCO 2013;31:3971) Ocular irradiation: intraocular lymphoma Poor Performance Status (<40% Despite Steroid Therapy) HD MTX unless contraindicated (renal insufficiency, Cr Cl < 30 mL/min) WBRT: Rarely curative alone, a/w significant neurotoxicity, 25-35%, median survival 10-18 mos (J Neuro Oncol 1999;43:241) Non-MTX containing chemotherapy Investigational Rituximab: Has activity & has been combined w/ all upfront regimens Intrathecal/intraventricular chemotherapy: Unclear benefit HDC w/ ASCT: Low level of evidence but appears very promising HIV-Positive PCNSL HAART in conjunction HD-MTX vs. WBRT