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Lymphoma Case, presented in Surgical Neurology International (

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  • Stem cells are “non-specialized” cells that have the potential to form into other types of specific cells, such as blood, muscles or nerves. They are unlike 'differentiated' cells which have already become whatever organ or structure they are in the body. Stem cells are present throughout our body, but more abundant in a fetus.
    Medical researchers and scientists believe that stem cell therapy will, in the near future, advance medicine dramatically and change the course of disease treatment. This is because stem cells have the ability to grow into any kind of cell and, if transplanted into the body, will relocate to the damaged tissue, replacing it. For example, neural cells in the spinal cord, brain, optic nerves, or other parts of the central nervous system that have been injured can be replaced by injected stem cells. Various stem cell therapies are already practiced, a popular one being bone marrow transplants that are used to treat leukemia. In theory and in fact, lifeless cells anywhere in the body, no matter what the cause of the disease or injury, can be replaced with vigorous new cells because of the remarkable plasticity of stem cells. Biomed companies predict that with all of the research activity in stem cell therapy currently being directed toward the technology, a wider range of disease types including cancer, diabetes, spinal cord injury, and even multiple sclerosis will be effectively treated in the future. Recently announced trials are now underway to study both safety and efficacy of autologous stem cell transplantation in MS patients because of promising early results from previous trials.
    Research into stem cells grew out of the findings of two Canadian researchers, Dr’s James Till and Ernest McCulloch at the University of Toronto in 1961. They were the first to publish their experimental results into the existence of stem cells in a scientific journal. Till and McCulloch documented the way in which embryonic stem cells differentiate themselves to become mature cell tissue. Their discovery opened the door for others to develop the first medical use of stem cells in bone marrow transplantation for leukemia. Over the next 50 years their early work has led to our current state of medical practice where modern science believes that new treatments for chronic diseases including MS, diabetes, spinal cord injuries and many more disease conditions are just around the corner.
    There are a number of sources of stem cells, namely, adult cells generally extracted from bone marrow, cord cells, extracted during pregnancy and cryogenically stored, and embryonic cells, extracted from an embryo before the cells start to differentiate. As to source and method of acquiring stem cells, harvesting autologous adult cells entails the least risk and controversy.
    Autologous stem cells are obtained from the patient’s own body; and since they are the patient’s own, autologous cells are better than both cord and embryonic sources as they perfectly match the patient’s own DNA, meaning that they will never be rejected by the patient’s immune system. Autologous transplantation is now happening therapeutically at several major sites world-wide and more studies on both safety and efficacy are finally being announced. With so many unrealized expectations of stem cell therapy, results to date have been both significant and hopeful, if taking longer than anticipated.
    What’s been the Holdup?
    Up until recently, there have been intense ethical debates about stem cells and even the studies that researchers have been allowed to do. This is because research methodology was primarily concerned with embryonic stem cells, which until recently required an aborted fetus as a source of stem cells. The topic became very much a moral dilemma and research was held up for many years in the US and Canada while political debates turned into restrictive legislation. Other countries were not as inflexible and many important research studies have been taking place elsewhere. Thankfully embryonic stem cells no longer have to be used as much more advanced and preferred methods have superseded the older technologies. While the length of time that promising research has been on hold has led many to wonder if stem cell therapy will ever be a reality for many disease types, the disputes have led to a number of important improvements in the medical technology that in the end, have satisfied both sides of the ethical issue.
    CCSVI Clinic
    CCSVI Clinic has been on the leading edge of MS treatment for the past several years. We are the only group facilitating the treatment of MS patients requiring a 10-day patient aftercare protocol following neck venous angioplasty that includes daily ultrasonography and other significant therapeutic features for the period including follow-up surgeries if indicated. There is a strict safety protocol, the results of which are the subject of an approved IRB study. The goal is to derive best practice standards from the data. With the addition of ASC transplantation, our research group has now preparing application for member status in International Cellular Medicine Society (ICMS), the globally-active non-profit organization dedicated to the improvement of cell-based medical therapies through education of physicians and researchers, patient safety, and creating universal standards. For more information please visit
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  1. 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. 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. 3. Imaging: CT Brain CT: Subtle hypodensity in the L medial thalamus and midbrain with mild expansion or prominence of the left midbrain
  4. 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. 5. Imaging: MRI Axial Post-Gadolinium T1WIs: Avid enhancement in areas corresponding to abnormal FLAIR signal (previous slide)
  6. 6. Imaging: MRI Coronal Post-Gadolinium T1WIs: Avid enhancement in the left posterior limb of the internal capsule, thalamus, midbrain and pons
  7. 7. Imaging: MRI Sagital Post-Gadolinium T1WIs: Avid enhancement in the thalamus, midbrain and pons
  8. 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. 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. 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. 11. DDX: GBM, Lymphoma, Metastatic disease
  12. 12. Operative Management: Stereotactic needle biopsy of the L thalamic lesion
  13. 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. 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. 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. 16. Pathology Lamda Light Chain IHC Kappa Light Chain IHC Tumor cells do not express immunoreactivity Tumor cells express positivity
  17. 17. Pathology MIB-1 IHC Proliferation index is 50-60%
  18. 18. Diagnosis: Diffuse Large B-Cell Lymphoma
  19. 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. 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. 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.