CNS lymphoma

Case contributed by RMH Neuropathology

Presentation

4 months cognitive decline, on background 2 years Etanercept treatment (TNF inhibitor) for severe rheumatoid arthritis. CSF JC PCR negative, cytology negative, flow cytometry negative.

Patient Data

Age: 75 years
Gender: Male

MRI brain

Modality: MRI

T2-weighted scans demonstrate extensive abnormal signal continuously from medulla through pons and midbrain into the thalami and basal ganglia bilaterally. Patchy further areas of isolated abnormal signal extend to the subcortical region of both cerebral hemispheres. There is no positive mass effect associated with these changes. The underlying ventricles and cortical sulci are normal in size for a patient of this age. T1-weighted scans show small areas of minimally elevated signal corresponding with T2 abnormal signal is in the deep white matter of the left frontal lobe. 

Both diffusion restriction and amorphous contrast enhancement involves the inferior aspect of the right frontal lobe, extending as far inferiorly as gyrus rectus.

The predominant abnormality on both single voxel and chemical shift spectroscopy is slightly elevated choline to creatine ratio and reduced NAA. No significant lipid and lactate signal seen. No definite perfusion abnormality detected.

Conclusion:

Extensive, predominantly white matter abnormality in the absence of mass effect makes demyelination the most likely cause. Contrast enhancement has been described in progressive multifocal leucoencephalopathy (PML) induced by some immunosuppressants. Gray matter involvement has also been described in single episode acute disseminated encephalomyelitis.

The apparently complete lack of mass effect, limited contrast enhancement and only slight choline elevation on MRS makes lymphoma less likely.

CT brain and body - 2 weeks later, post biopsy

Modality: CT

Brain

Right frontal craniotomy has been performed. Deep to this site, there is a  focal region of high attenuation within the brain measuring approximately 9 mm in diameter. It is surrounded by ill-defined low attenuation. The appearances are those of focal haemorrhage at site of prior biopsy. Post- operative pneumocephalus is also noted deep to the right frontal bone. A 2 cm focal region of ill-defined low attenuation is seen in the deep white matter of the left frontal lobe, corresponding to MRI changes at this site. The ventricular system is of normal size and is midline in location.

Chest (not shown) and abdomen

Scans through the abdomen demonstrate left para-aortic lymphadenopathy measuring 2.4 centimetres transverse 1.7 centimetres AP and 5 cm craniocaudally. No further lymphadenopathy. 

Histology

Modality: Pathology

MICROSCOPIC DESCRIPTION: The sections contain cerebral cortex and white matter. There are atypical lymphoid cells surrounding some of the cerebral blood vessels. They are at least medium-sized.  They have enlarged hyperchromatic nuclei, angulated nuclear contour, focal conspicuous nucleoli and scanty cytoplasm. A few associated mitoses are noted. Small mature lymphocytes are also seen. The blood vessels show no fibrinoid necrosis or thrombosis. There are no  macrophages to suggest demyelination. No viral inclusions are seen.  There are no granulomas.  No spongioform change is present. 

The atypical lymphocytes are CD20, PAX-5, bcl-2, bcl-6 and MUM1 positive.  These atypical lymphoid cells are also seen in the parenchyma, as highlighted by the B-cell markers.  The Ki-67 index is more than 75%. They are CD3, CD10 and EBER-CISH (EBV) negative.  Immunostain for polyoma virus (SV40/BKV) is negative.  Beta-amyloid immunostain shows no amyloid plaques. 

The features are those of diffuse large B-cell lymphoma, with activated B-cell-like phenotype.

FINAL DIAGNOSIS: Diffuse large B-cell lymphoma.

US orbit - 1 week later

Modality: Ultrasound

The left globe demonstrates an unusual serpiginous sheet of avascular material within the posterior aspect of the vitreous and slight hyperdensity of the because anterior to this. This does not attach to the optic disc and there is normal enhancement of the choroidal layer beneath. Within the right globe, there is subtle increased linear echogenicity and some streaming but no discrete mass or veiling region as shown on the right. On discussion with the ophthalmology registrar, this correlates with what was seen at thalamus The and could be consistent with intraocular lymphoma. 

Conclusion: 

Right greater than left heterogeneous testicular echotexture without discrete mass. While this may be normal or related to chronic vascular disease, leukaemic/lymphomatous infiltration cannot be entirely excluded. No discrete testicular lesion to suggest other primary malignancy. Thin veiling lesion within the left vitreous with increased vitreous density anterior to it and minor right vitreous debris. This is again non-specific but could certainly be consistent with clinical impression of intraocular lymphoma.

Vitreous biopsy

Modality: Pathology

Specimen Type: Intraocular fluid

CLINICAL NOTES: Primary CNS lymphoma left eye vitreous biopsy + intraocular fluid from vitrectomy ?intraocular lymphoma.

MACROSCOPIC  DESCRIPTION: 

  1.  (L) Vitreous biopsy: 4ml clear colourless fluid.
  2. (L) Intraocular fluid: 90ml clear colourless fluid.

MICROSCOPIC  DESCRIPTION:

1. The smears are paucicelluar with scattered lymhpocytes, ciliated cells and apoptotic debris. The lymphoid cells are abnormal with increased size, irregular nuclear shape and irregular chromatin. However there is little material present for assessment.

2. The smears contain abnormal lymphoid cells with enlarged, irregular or indented nuclei and uneven chromatin. In the background there is abundant apoptotic debris and blood.

FINAL DIAGNOSIS:

Lymphoma.

MRI brain 4 weeks after first MRI

Modality: MRI

Multiplanar multi sequence MR imaging performed with comparison to recent CT brain done the previous MRI.

Extensive confluent T2 hyperintensity involving cerebral periventricular and deep white matter, basal ganglia, internal and external capsules, palmar, and extending through midbrain and pons into the middle cerebellar peduncles and medulla. The changes are almost symmetric, apart from more pronounced left than right thalamic and more pronounced right than left cerebellar peduncle involvement. The overall extent of signal change is similar to previous, possible slight increase in thalamic involvement.

Throughout the regions of signal abnormality there is patchy diffusion restriction. The enhancing focus in the right inferior frontal lobe has reduced in size from 11 x 16 mm to 9 x 12 mm. No new enhancing focus identified.

Right frontal biopsy track contains blood product. Small old lacuna in the left caudate head is again noted. No hydrocephalus.

Conclusion 

The right frontal enhancing focus has mildly reduced in size, but extensive cerebral, midbrain, brainstem and deep grey nuclei signal abnormality is similar in extent to previous. 

Case Discussion

MRI perfusion, MRS and histology pending

Frank

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Case Information

rID: 25275
Case created: 17th Oct 2013
Last edited: 14th Jan 2016
Inclusion in quiz mode: Included

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