CNS lymphoma and demyelination

Case contributed by RMH Neuropathology

Presentation

5 months headaches and visual changes, following a febrile illness while overseas. Previously well.

Patient Data

Age: 25 years
Gender: Female
MRI

MRI brain


Multiple (*20) bilateral ovoid, periventricular and callososeptal T2 hyperintense, T1 hypointense lesions are demonstrated. The lesions are perpendicularly orientated to the ventricles. A right frontal juxtacortical
lesion is also seen. There is moderate surrounding adjacent FLAIR / T2 high signal. Some of these are T1 hypointense. Several, however not all of these lesions demonstrate contrast enhancement. 

A moderate to large area of right parietal cortical abnormality is seen, with oedema / T2 high signal and associated vasogenic oedema involving  cortex and underlying white matter. There is vivid contrast enhancement within this region along with diffusion restriction (correspondingly low on  ADC map) that mainly involves cortex. There is minimal mass effect for the degree of signal abnormality.

While some of the periventricular lesions have well-defined ovoid lesions surrounded by a more ill-defined confluent T2 "halo", these lesions do not  demonstrate definite concentric ring pattern characteristic of Balo's type MS.  Some small brainstem T2 hyperintense lesions may also be present. 

No hemorrhage on EPI (not shown). No venous sinus thrombosis seen in non dedicated imaging. MRA has no findings suspicious for vasculitis. Regions of high  signal corresponding to the areas of T2 FLAIR parenchymal hyperintensity and not with corresponding T1 hyperintensity are present, unusual but thought  most likely to be related to magnetization transfer effect. No increase in cerebral blood volume. 

MR Spectroscopy demonstrates elevated creatine:choline and lactate in the right parietal signal abnormality. Voxels placed in bilateral periventricular T2 hyperintense foci demonstrate elevated creatine:choline and mildly elevated lactate. 

Conclusion: 

Overall MRI finding favour demyelination with a tumefactive plaque in the right parietal region and multiple smaller active plaques elsewhere-- particularly consider ADEM or MS variants (such as Marburg's). CNS lymphoma or cerebral vasculitis are differentials. Dual pathology (e.g. subacute infarct of the occipital lobe) not excluded. 

Pathology

The patient went on to have a stereotactic biopsy from the frontal lobe. 

Histology

Paraffin sections show cores of cerebral white matter. These show prominent perivascular cuffs of small lymphoid cells which are a mixture of CD3+ T lymphocytes and CD20+ B lymphocytes. Smaller numbers of CD68+ monocyte-macrophages are also present in these perivascular aggregates. Vessel walls are intact. There is expansion of perivascular spaces. In one of the cores in specimen 2 there is a well-demarcated area of demyelination.  Many monocyte-macrophages containing cytoplasmic myelin debris are seen in this area. There is activation of microglial cells. The overall features strongly favour inflammatory demyelination.  Immunostaining for SV-40/JC/BKV is negative. No organisms are identified and there is no evidence of tumour.

DIAGNOSIS:

Stereotactic brain biopsies: Features strongly suggestive of inflammatory demyelination; no evidence of tumour seen.

Clinical progress

The patient was treated with 3 x methyl prednisolone for the diagnosis of ADEM. Clinically had a relapsing / remitting symptoms with two additional MRI scans (2 and 3 months later) demonstrating relatively stable features, but continued enhancement of the occipital lesion. Increasing headaches and confusion prompted a further MRI scan. 

MRI

MRI brain - 4 months later

The periventricular burden of FLAIR signal abnormality has progressed. The left frontal biopsy tract is noted with residual haemosiderin staining evident. The periventricular enhancement is again demonstrated and largely stable. The right occipital lesion has shown a discrete change in morphological appearance with increasing mass effect and prominent thickening of the occipital cortex. 

The surrounding FLAIR signal abnormality remains largely unchanged, however the gyriform pattern of enhancement is far more intense. Extensive restricted diffusion. The MR spectroscopy trace demonstrates a marked elevation in choline and lactate peak. 

The remainder of the brain is within normal limits, with no intra or extraaxial collection, mass or region of abnormal contrast enhancement. 

Conclusion: 

The evolution of the right occipital lesion is difficult to reconcile with demyelination, or evolving infarction and an alternative diagnosis should be sought. The possibility of all these changes representing CNS lymphoma should be entertained.

Pathology

The patient went on to have a biopsy of the occipital lobe. 

MICROSCOPIC DESCRIPTION:

Paraffin sections show a densely hypercellular tumour. Tumour cells have features of atypical large lymphoid cells with large round and oval vesicular nuclei many with conspicuous nucleoli and a narrow rim of pale cytoplasm. These are arranged in diffuse sheets in a vascular stroma. Frequent mitotic figures and apoptoses are identified. Tumour appears to completely replace brain parenchyma.

IMMUNOHISTOCHEMISTRY:

Atypical lymphoid cells show strong membrane staining for CD20, strong nuclear staining for bcl-6 and MUM-1 and strong perinuclear staining for bcl-2.  Moderate numbers of small CD3+ T lymphocytes are scattered among the large atypical cells. No staining for CD5, CD23 or cyclin D1 is seen in the large atypical cels.

The features are of non Hodgkin lymphoma - diffuse large B cell type.

EBER-CISH is NEGATIVE

DIAGNOSIS: non Hodgkin diffuse large B cell lymphoma.

Case Discussion

The diagnosis of lymphoma is not always straight forward, and in this case it remains difficult to know whether the two processes were  coincidental or more likely related to each other. Demyelination preceding a CNS lymphoma is a recognised phenomenon, and is likely the case in this instance. 

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Case information

rID: 25592
Case created: 31st Oct 2013
Last edited: 3rd Mar 2016
Inclusion in quiz mode: Included

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