Primary CNS Lymphoma

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BIOPATOLOGIA DEI LINFOMI PRIMITIVI CEREBRALI
Felice Giangaspero
Mediterranean School of Oncology Burning
questions on lymphoproliferative diseases Rieti
27-29 ottobre 2006
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Primary CNS Lymphoma (PCNSL) Epidemiology

• Incidence has risen dramatically in past few
  decades, as PCNSL now accounts for 4-7 of all
  newly diagnosed primary brain tumors
• Incidence has decreased in the HIV/immunocompromis
  ed (HAART)
• Median age of onset 55 years in immunocompetent,
  incidence rises with age
• Greatest rise has occurred among the elderly

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Sites of Disease Involvement

• Brain parenchyma is usual location (gt90)
• Usually solitary lesion (75), can be multifocal
• Mainly occur in supratentorial sites (75), but
  may also be infratentorial
• Tend to be periventricular in location

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Imaging Other considerations

• Features of mass lesion in brain that are
  suggestive of CNS lymphoma
• Periventricular distribution
• Multiple lesions
• Less edema than expected for brain met or glioma
• Steroids can significantly alter appearance on
  imaging by decreasing tumor size, edema, and
  enhancement and preferably should be held prior
  to Dx if CNS lymphoma suspected

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Sites of Disease Involvement

• Ocular only involvement in 10
• Leptomeningeal disease may occur, but usually not
  without brain involvement
• Primary spinal disease is rare (lt1 PCNSL)

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• Clinical History
• Focal neurologic deficit (i.e. hemiparesis,
  aphasia) present in gt50 of all patients with
  PCNSL
• Altered mental status (memory loss, confusion,
  etc.) found in 33 - may be insidious onset
• Headache, nausea (from increased ICP) in 33
• May present with new-onset seizure in lt10
• Blurred vision if ocular lymphoma is present

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PCNSL Tissue diagnosis

• Stereotactic biopsy is usually preferred
• Goal of surgery is to obtain a tissue diagnosis
  with minimal morbidity, without formal attempt at
  surgical resection
• Steroids can cause false negative biopsy results
  due to cytolytic effects, and should be held if
  suspected PCNSL on imaging

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PCNSL Pathology
More than 95 of primary CNS lymphomas are
diffuse large B cell (DLBCL).
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Are DLCBL of CNS a distinct entity?

• Short duration of response to combined therapy
• Growth limited to CNS
• Angiotropism
• High responsiveness to methotrexate

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Rubenstein, J. L. et al. Blood 20061073716-3723
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IL-4
Target gene
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IL-4 EXPRESSION IN PCNSL
Rubenstein, J. L. et al. Blood 20061073716-3723
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Are DLCBL of CNS a distinct entity?
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Primary CNS Lymphoma Pathology

• DIFFUSE LARGE B CELL LYMPHOMA
• T-CELL LYMPHOMAS
• INTRAVASCULAR LYMPHOMA
• MALT/MARGINAL ZONE B CELL LYMPHOMA
• LYMPHOPLASMACYTIC LYMPHOMA
• PLASMOCYTOMA
• BURKITT LYMPHOMA
• PRECURSOR B-CELL LYMPHOBLASTIC LYMPHOMA
• ANAPLASTIC LARGE-CELL LYMPHOMA
• NK/T CELL LYMPHOMA
• HODGKIN DISEASE

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INTRAVASCULAR LYMPHOMA

• ACCUMULATIONS OF LARGE B-CELLS, WITHIN SMALL AND
  MEDIUM VESSELS
• EXCEPTIONALLY T-CELLS, NK CELLS OR HISTIOCYTIC
  CELLS,
• AFFECTS MULTIPLE ORGAN SYSTEMS.
• THE CNS, INCLUDING THE ENTIRE NEURAXIS, IS
  INVOLVED IN MORE THAN 30 OF CASES.
• ALTERED MENTAL STATUS (MEMORY LOSS, CONFUSION)

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INTRAVASCULAR LYMPHOMA
ACCUMULATIONS OF LARGE B-CELLS, WITHIN SMALL AND
MEDIUM VESSELS LEAD TO VASCULAR OCCLUSION AND
DISSEMINATED SMALL INFARCTS
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INTRAVASCULAR LYMPHOMA
Diffusion weighted image Areas of ischemia
Baehring, J M et al. J Neurol Neurosurg
Psychiatry 200576540-544
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INTRACRANIAL MALT TYPE LYMPHOMA
THE MOST COMMON PRIMARY LOW-GRADE INTRACRANIAL
LYMPHOMA
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INTRACRANIAL MALT TYPE LYMPHOMA

• N15 12 F(80) FM 41
• Age 55 yrs, 29-70 yrs (mean, range)
• All but 1 presented with a dural based masses
  mimicking meningioma
• All tumor resection Radiation (6) and/or chemo
  (3)
• Follow-up available in 10 patients
• Complete remission
• FU length 11 mo to 7.9 yrs

Tu et al. J Clin Oncol 2005 235718
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INTRACRANIAL MALT TYPE LYMPHOMA
DIFFUSE THICKENING OF DURA
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CD20
CD3
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kappa
lambda
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MALT of the Dura genetic alterations (FISH)
Trisomy chr 3 in 50 of cases
No traslocations
J Clin Oncol 2005 235718
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Primary CNS Lymphoma (PCNSL) Histogenesis

• B-CELLS MAY BE TRANSFORMED AT A SITE ELSEWHERE IN
  THE BODY AND THEN DEVELOP ADHESION MOLECULES
  SPECIFIC FOR CEREBRAL ENDOTHELIA.
• LYMPHOMA CELLS MAY BE SYSTEMATICALLY ERADICATED
  BY AN INTACT IMMUNE SYSTEM BUT MAY ESCAPE THE
  IMMUNE SYSTEM WITHIN THE CNS.
• A POLYCLONAL INTRACEREBRAL INFLAMMATORY LESION
  MAY EXPAND CLONALLY WITHIN THE BRAIN AND PROGRESS
  TO THE MONOCLONAL NEOPLASTIC STATE.