primary central nervous system (CNS) lymphoma (PCNSL)
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Introduction
Lymphoma limited to CNS without systemic disease.
Etiology
- associated with immunodeficiency disorders
- HIV1 infection, Wiskott-Aldrich, renal transplantation)[1]
- occurs less frequently in elderly immunocompetent persons
Epidemiology
- overall incidence ~0.31 per 100,000 person years
- affects all ages with peak in 6th & 7th decades in immunocompetent patients
- formerly rare tumor, ~0.5% - 1.2% of intracranial neoplasms
- highest incidence in AIDS, ~1.9% - 6%, accounts for ~19% of AIDS non-Hodgkins lymphomas, ~30% of CNS lesions in patients with AIDS
Pathology
- more commonly B cell lymphomas
- diffuse large B-cell lymphoma
- diffuse large B-cell immunoblastic lymphoma
- centroblastic polymorphic lymphoma
- rapidly growing tumor
- often disseminated within CNS at time of diagnosis
- frontal lobe commonly involved
- tend to involve deep brain structures over cerebral cortex
- many lesions are perivascular & infiltrate surrounding brain parenchyma
- ~20% have ocular involvement (vitreous, retina) at diagnosis
- association of CSF EBV DNA seen by PCR with PCNSL
Clinical manifestations
- majority of patients have isolated disease
- some patients may present with systemic manifestations
- some patients may present with subtle changes in personality, behavior or cognition[1]
- some patients may present with space-occupying intracranial mass lesions
- focal findings on neurologic examination
- seizures
- cognitive impairment, memory loss
- confusion
- lethargy
- headache
- personality changes
- changes in level of alertness
- hypopituitarism with secondary adrenal insufficiency
Laboratory
- cerebrospinal fluid analysis (CSF analysis):
- lymphocytic pleocytosis/malignant lymphocytes
- low or normal CSF glucose
- elevated CSF protein
- PCR detecting EBV DNA together with increased uptake on T1 single photon emission CT -> high sensitivity
Diagnostic procedures
- lumbar puncture for CSF analysis
- slit lamp examination, vitreous fluid sampling [1]
- less invasive than brain biopsy
- brain biopsy vs vitreous fluid sampling
- may be required for diagnosis[1]
- rule out infection
- glucocorticoids should be avoided if possible before diagnosis (decreased sampling yield)[1]
Radiology
- computed tomography (CT) or magnetic resonance imaging (MRI)
- single or multiple lesions
- deep white matter, periventricular lesions
- minimal mass effect or edema, MKSAP19 contends mass effect[1]
- contrast enhancement in 90% of patients
- may be ring-enhancing - typical in AIDS patient, reflecting higher incidence of necrosis
- single or multiple lesions
- thallium single-photon emission computed tomography
- F18-fluorodeoxyglucose positron emission tomography
Differential diagnosis
- CNS infection
- cytomegalovirus (CMV)
- toxoplasmosis
- neither clinical nor MRI reliable distinguishes primary CNS lymphoma from toxoplasmosis
- progressive multifocal leukoencephalopathy
- non-enhancing, no mass effect[1]
Management
- refrain from administration of high-dose glucocorticoids (dexamethasone)
- can obscure results of brain biopsy
- sensitive to whole brain radiation & chemotherapy
- relapses are common
- immunocompetent patients
- methotrexate in combination with glucocorticoid
- high-dose systemic methotrexate, or
- intrathecal methetrexate. followed by whole brain radiation
- chemotherapy alone recommended for patients > 60 years of age because of excessive neurotoxity from radiation in older patients[1]
- response rates of 85%
- median survival of 17-44 months
- 5 year survival after combined therapy is 25-40%
- methotrexate in combination with glucocorticoid
- immunocompromised patients
- HIV1 infection: start vs continue antiretroviral therapy
- organ transplantation: stop immunosuppressive therapy
- radiation with adjunct chemotherapy of unclear benefit
- prognosis is poor -> 12-24 months
- AIDS patients with focal brain lesions
- in those with antitoxoplasmosis antibodies, empirical treatment with antitoxoplasmosis therapy first
- brain biopsy for those seronegative for antitoxoplasma antibodies or who fail treatment
- surgical resection not indicated
- may worsen outcomes[1]
- prognosis
More general terms
More specific terms
References
- ↑ 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 Medical Knowledge Self Assessment Program (MKSAP) 11, 14, 15, 16, 17, 18, 19. American College of Physicians, Philadelphia 1998, 2006, 2009, 2012, 2015, 2018, 2021.
Medical Knowledge Self Assessment Program (MKSAP) 19 Board Basics. An Enhancement to MKSAP19. American College of Physicians, Philadelphia 2022 - ↑ Cancer, Principles and Practice of Oncology; 6th ed. deVita et al (eds); Lippincott, Williams & Wilkins, 2001, pg 2330-2, 2587
- ↑ Batchelor TT, Chen YB, Rapalino O, Cobos I. CASE RECORDS of the MASSACHUSETTS GENERAL HOSPITAL. Case 23-2015. A 51-Year-Old Woman with Headache, Cognitive Impairment, and Weakness. N Engl J Med. 2015 Jul 23;373(4):367-77. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/26200983 <Internet> http://www.nejm.org/doi/full/10.1056/NEJMcpc1406415
- ↑ Hoang-Xuan K, Bessell E, Bromberg J et al Diagnosis and treatment of primary CNS lymphoma in immunocompetent patients: guidelines from the European Association for Neuro-Oncology. Lancet Oncol. 2015 Jul;16(7):e322-32. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/26149884 Free Article
- ↑ Primary CNS Lymphoma (PDQ): Treatment http://www.nci.nih.gov/cancertopics/pdq/treatment/primary-CNS-lymphoma/HealthProfessional