Primary CNS lymphoma
Primary CNS lymphoma (PCNSL) are uncommon tumours, accounting for only 1% of malignant CNS tumours. By definition, there is no co-existing systemic disease at the time of diagnosis, distinguishing it from CNS involvement from systemic lymphoma (secondary CNS lymphoma).
On imaging, PCNSL characteristically is identified as a CT hyperdense enhancing supratentorial mass, with MRI T1 hypointense, T2 iso- to hyperintense, vivid homogeneous enhancement and restricted diffusion. Usually, there is no expressive associated vasogenic oedema. It is important to note that in immunocompromised appearances tend to be more heterogeneous.
Typically patients diagnosed with PCNSL are over the age of 50 with short duration of symptoms (at most a few months) 4. There is a male predominance of approximately 2:1 4. As there is a strong association with HIV/AIDS and other immunocompromised states, demographics in these patients reflects the underlying condition.
Predisposing factors include:
- HIV/AIDS: approximately 2-6% of patients with HIV will develop PCNSL 5
- prior EBV infection
- post transplantation (see: primary central nervous system post-transplant lymphoproliferative disorder)
- IgA deficiency
- Wiskott-Aldrich syndrome
Primary CNS lymphoma accounts for approximately 1% of all extranodal lymphoma, and ~1% of intracranial tumours. Recently there appears to be increasing incidence at least partially due to increasing rates of immunocompromised patients. An increase is however also seen in the non-immunocompromised population.
Patients with PCNS lymphoma present similarly to patients with other central nervous system masses; symptoms and signs of raised intracranial pressure, focal neurological disorders and seizures.
An important factor to be aware of is the transient but profound response of CNS lymphoma to the use of glucocorticoids (e.g. dexamethasone and prednisolone) which are routinely administered in patients with intracranial mass effect from tumour and oedema. Within a few days of administration of steroids, CNS lymphoma can shrink dramatically due to the combined effect of steroid as a cytotoxic agent (reducing the neoplastic B-cell population) and anti-oedema agent (resulting in decreased permeability of capillaries via variety of mechanisms)12.
PCNSL present as solitary or multiple, well-defined or infiltrating mass lesion/s that can arise in cortex, white matter or deep grey matter (more common in low-grade lesions 1). They may demonstrate areas of necrosis, especially in immunodeficient patients.
Origin of malignant cell is not well understood as intra-axial CNS does not have lymphatic system. The vast majority (>90%) of PCNSL are B cell in origin: diffuse large B-cell lymphoma and high-grade Burkitt-like B-cell lymphoma 1. Malignant cells tend to accumulate around blood vessels. There is high association with EBV in immunodeficient patients.
Low-grade tumours are more frequently T-cell in origin 1.
CSF examination demonstrates elevated protein and decreased glucose. Positive cytology is uncommon (~25%). Positive EBV DNA in CSF PCR is helpful for diagnosis of lymphoma particularly in HIV/AIDS patients.
The most helpful imaging pattern presents mainly in untreated non-immunocompromised patients is of a CT hyperdense avidly enhancing mass, with MRI T1 hypointense, T2 iso- to hyperintense, vivid homogeneous gadolinium-enhancing lesion/s with restricted diffusion, subependymal extension, and crossing of the corpus callosum. Unfortunately, this pattern is not always present (see below).
Typically PCNSL are supratentorial (75-85%) 5 and appear as a mass or multiple masses (11-50% 3) that are usually in contact with the subarachnoid/ependymal surfaces. Crossing the corpus callosum is not infrequently seen. Enhancement on both CT and MRI is pronounced and usually homogeneous. Even with larger lesions there is little mass effect for size, and limited surrounding vasogenic oedema.
Low grade tumours differ from the more common high-grade PCNSL in several ways 1:
- deep locations and spinal involvement is more common
- contrast enhancement is absent, irregular or only mild
Disseminated meningeal/intraventricular disease is uncommon, it is seen in ~5% (range 1-7%) of cases at presentation and usually in high grade cases 8.
It should be noted that in patients who are immunocompromised (typically HIV/AIDS or post-transplant) appearances are more heterogeneous, including central non-enhancement / necrosis and haemorrhage, although the latter is still uncommon 8.
- most lesions are hyperattenuating (70%) 3
- shows enhancement
- haemorrhage is distinctly uncommon 8
- there are often multiple lesions in patients with HIV/AIDS
Reported signal characteristics include:
- T1: typically hypointense to white matter
T1 C+ (Gd)
- typical high grade tumours show intense homogeneous enhancement while low-grade tumours have absent to moderate enhancement 1
- peripheral ring enhancement may be seen in immunocompromised patients (HIV/AIDS)
- majority are iso to hypointense
- isointense: 33% 9
- hypointense: 20% 9
- hyperintense: 15-47%, more common in tumours with necrosis 1,9
- majority are iso to hypointense
- restricted diffusion with ADC values lower than normal brain, typically between 400 and 600 x 10-6 mm2/s (lower than high-grade gliomas and metastases 8, 13)
- a number of studies have suggested that the lower the ADC values of the tumour the poorer the response to tumour and higher likelihood of recurrence 13
- ADC is particularly useful in assessing response to chemotherapy, with increases in ADC values to above those of normal brain predictive of complete response 13
- large choline peak
- reversed choline/creatinine ratio
- markedly decreased NAA
- lactate peak may also be seen 7
- only modest if any increase in rCBV (much less marked than in high-grade gliomas, where angiogenesis is a prominent feature 11)
- shows increased uptake
C11 Methionine PET
- shows increased uptake
Treatment and prognosis
Treatment is predominantly with steroids (which can dramatically shrink the tumour due to combined anti-oedema and cytotoxic effects) and methotrexate based chemotherapy 4,13. Whole brain irradiation can also be added, particular in patients with high grade tumours, or recurrence 4,13.
If the tumour is low grade (uncommon: see above), then local treatment with surgical resection and radiotherapy may be effective 1 and long-term survival is possible.
The tumours are often high grade and despite treatment have a poor prognosis. If only surgical resection is performed, then death occurs within a few months. With high dose chemotherapy the tumour can be significantly reduced in size; however, recurrence is common, with a median survival of around 30 months 1. Those who are immunocompromised (e.g. HIV positive) do worse.
For general imaging appearances on CT and MRI consider:
- secondary CNS lymphoma: indistinguishable on imaging, however it tends to involve more leptomeninges (~2/3 of cases) 8
cerebral toxoplasmosis: see toxoplasmosis vs. lymphoma
- toxoplasmosis does not exhibit subependymal spread
- more likely to lie in basal ganglia, corticomedullary junction
- CNS lymphoma is thallium/PET avid, whereas toxoplasmosis is not
- more commonly centrally necrotic
- more commonly demonstrates evidence of haemorrhage
- tumefactive MS/ADEM
- peripheral enhancement of PCNSL is thicker 3
- central restricted diffusion
- neurosarcoidosis 4
- overview of lymphoma
WHO classification of tumours of haematopoietic and lymphoid tissues
- Hodgkin lymphoma
mature B-cell lymphoma
- Burkitt lymphoma
- follicular lymphoma
- lymphoplasmacytic lymphoma (Waldenström's macroglobulinaemia)
- lymphomatoid granulomatosis
- mantle cell lymphoma
- mature T-cell and NK-cell lymphoma
- post-transplant lymphoproliferative/lymphoproliferation disorders
- mature B-cell lymphoma
- location-specific lymphomas
- central nervous system
- head and neck lymphoma
- thoracic lymphoma
- gastrointestinal lymphoma
- hepatobiliary lymphoma
- genitourinary lymphoma
- musculoskeletal lymphoma
- cutaneous lymphoma
- lymphoma staging
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