Lymphoma Case, presented in Surgical Neurology International (surgicalneurologyint.com)

1. Harbor-UCLA Neuro-Radiology Case Conference December, 2010 Sahar Farzin, M.D. Department of Radiology, Harbor-UCLA Medical Center Peter Abasolo, M.D. Department of Pathology, Harbor-UCLA Medical Center

2. History: 67 year old male presents with a 10-day history of headache, right facial weakness, right upper and lower extremity weakness, and dysarthria

3. Imaging: CT Brain CT: Subtle hypodensity in the L medial thalamus and midbrain with mild expansion or prominence of the left midbrain

4. Imaging: MRI Axial FLAIR: Abnormal bright signal in the left posterior limb of the internal capsule, left thalamus, midbrain, pons, cerebellar peduncle and left cerebellar vermis adjacent to the 4 th ventricle. There is tumor-like expansion or enlargement of these structures

5. Imaging: MRI Axial Post-Gadolinium T1WIs: Avid enhancement in areas corresponding to abnormal FLAIR signal (previous slide)

6. Imaging: MRI Coronal Post-Gadolinium T1WIs: Avid enhancement in the left posterior limb of the internal capsule, thalamus, midbrain and pons

7. Imaging: MRI Sagital Post-Gadolinium T1WIs: Avid enhancement in the thalamus, midbrain and pons

8. Imaging: MRI Axial Diffusion Weighted Imaging (DWI): Heterogeneous restricted diffusion in the left thalamus, posterior limb of internal capsule, midbrain, pons, and vermis

9. Imaging: MR Spectroscopy Left image: Single voxel placed over region of interest (ROI), left thalamus Right image: Spectroscopic tracing of ROI showing elevated choline:creatine ratio, diminished NAA peak and elevated lactate Cho Cr NAA Lactate

10. Imaging: 201 Thalium Scan 4-hour delayed axial SPECT images of a 201 Thalium scan shows abnormal increased activity in the left thalamus and brainstem

11. DDX: GBM, Lymphoma, Metastatic disease

12. Operative Management: Stereotactic needle biopsy of the L thalamic lesion

13. Pathology Hematoxylin-Eosin, 20x The neoplasm displays a starry sky pattern in some areas due to the presence of numerous tingible body macrophages

14. Pathology Hematoxylin-Eosin, 40x Hematoxylin-Eosin, 60x There is a mixture of small and large lymphocytes with large cells in predominance. These large neoplastic lymphocytes have round or slightly oval vesicular nuclei, one or more nucleoli, and a moderate amount of amphophilic cytoplasm The tumor cells have large nuclei, open chromatin, and prominent nucleoli. Mitotic figures are frequently seen

15. Pathology CD3 IHC CD20 IHC Tumor cells do not express immunoreactivity Neoplastic cells express positivity CD79a IHC Neoplastic cells express positivity GFAP IHC Tumor cells do not express immunoreactivity

16. Pathology Lamda Light Chain IHC Kappa Light Chain IHC Tumor cells do not express immunoreactivity Tumor cells express positivity

17. Pathology MIB-1 IHC Proliferation index is 50-60%

18. Diagnosis: Diffuse Large B-Cell Lymphoma

19. Discussion CNS Lymphoma may be primary or secondarily associated with systemic involvement. Although primary CNS lymphoma (PCNSL) was previously thought to be a rare disease, there is a well-documented increase in its incidence in recent years. This increase has occurred in both immunocompetent as well as immunocompromised patients. The majority of PCNSLs are B-cell, non-Hodgkins lymphomas. Intracranial metastases from systemic lymphoma most commonly involve the leptomeninges and/or dura, with or without a parenchymal mass. In contrast, the most common presentation of PCNSL is a focal intracranial mass or masses. Compared with systemic lymphomas, PCNSL is still relatively uncommon comprising 1% of all lymphomas, and 1-7% of primary brain tumors.

20. Discussion CNS lymphoma may present as a solitary mass or multiple lesions and can be well-circumscribed or poorly-marginated/infiltrative. Leptomeningeal and/or dural involvement is more common in secondary or metastatic lymphoma. 90% of focal mass lesions are supratentorial, and common locations include the frontal and parietal white matter, basal ganglia, periventricular white matter, and extension along the ependymal surfaces and along the corpus callosum. In immunocompetent patients lesions demonstrate relatively strong contrast enhancement, versus in immunocompromised patients where peripheral, ring-like enhancement is more common with areas of central necrosis and heterogeneity. Lesions typically demonstrate restricted diffusion on DWI with corresponding dark signal on ADC map. MR Spectroscopy shows diminished NAA and elevated Choline peaks. Lipid and lactate peaks have also been reported. A nuclear medicine Thallium-201 SPECT study may be helpful in delineating hypermetabolic lesions that support the diagnosis of lymphoma (vs. Toxoplasmosis for example, in an AIDS patient).

21. Discussion Our Case study patient was also found to have peri-renal soft tissue masses, which were biopsy-proven to be Large B-Cell Lymphoma as well. No significant lymphadenopathy was appreciated on physical exam or on further body imaging. Thus the findings in this case may represent secondary metastasis in a case of systemic lymphoma; however, as discussed above, the CNS imaging findings for secondary or metastatic lymphoma usually also include leptomeningeal involvement, which was not appreciated on this patient’s MRI. Perhaps, the leptomeningeal involvement is present on a microscopic level but cannot be visualized on imaging. A different diagnostic possibility is that the brain lesions represent primary CNS lymphoma, without evidence of leptomeningeal involvement. However, it would be highly unusual for PCNSL to present with peri-renal metastasis. Yet another diagnostic possibility is that of two synchronous lymphomatous lesions occurring in the CNS and the peri-renal space.