Case presentation 21 September 2012

1. Case presentation21 September 2012 Flip Otto Dept. of Clinical Imaging Sciences UFS

2. Clinical information • 15 year old girl from Kimberly Problem list: • Burkitts lymphoma/leukemia (bonemarrow biopsy confirmed Burkitt type blasts on immunophenotyping) • Thrombocytopaenia, anaemia • Subdural collection with mass effect on presentation • HIV positive, on ARV’s since June 2012, latest CD4 count 501 • Infective endocarditis of mitral valve • DVT • On empirical TB treatment • Presented with sudden loss of vision on 19 August 2012

3. Clinical information (cont) • Management • Subdural collection drained on 14 June 2012 • Intrathecal chemotherapy started (flow cytometry negative) • First cycle of chemo started on 26 June, complicated by neutropenic sepsis • ICU admission on 13 July for respiratory failure • Transferred to ward on 10 August • Patient discharged to Kimberley for further palliative management

4. Imaging findings • Initial uncontrasted CT brain on 13 June 2012: • Left subdural collection (20HU) 9mm deep • Left frontal dural-based density 3mm deep • 9mm midline shift to the right • Follow up uncontrasted CT on 28 June 2012: • Left parietal burrhole • Left subdural collection decreased in size with decreased mass effect

5. Imaging findings cont. • CT brain pre and post-contrast on 19 August 2012: • Hyperdensesubdurally based lesions with contrast enhancement, left frontoparietal and left occipital regions • Leptomeningeal/cortical hyperdense lesions, with contrast enhancement, in the right occipital and left frontal lobes, with underlying subcortical white matter hypodensity

6. Imaging findings cont. • MRI of the brain on 22 August 2012: • Subdurally based lesions left frontoparietal and occipital appear iso-intense to grey-matter on T1, T2, T2* and T2 FLAIR, with intense contrast enhancement • Uniform, intense dural enhancement in the left hemisphere • Leptomeningeal lesions left frontal and right occipital are hyperintense on T1, with contrast enhancement • Underlying subcortical white matter show high signal on T2 and T2 FLAIR

7. Diagnosis • Dural metastases of Burkitts lymphoma/leukemia • Differential diagnosis of right occipital and left frontal leptomeningeal enhancement and underlying white matter lesions includes subacute ischaemic infarctions with luxury perfusion, laminar necrosis and/or haemorrhagic transformation and leptomeningealmetatsases. • Leukemic cells subsequently confirmed in CSF

8. Differential diagnosis of Dural Metastases • Usually hematogenously disseminated en plaque lesions from extracranial primary tumours • Lung, breast and prostate cancer, as well as melanoma, known to cause dural metastases • Breast carcinoma most commonly associated with purely dural metastases • Dural lymphoma may be the primary focus of neoplasm • Dural plasmacytoma nearly identical to dural lymphoma • In children dural metastases are commonly associated with leukemia and neuroblastomas • Inflammatory lesions that may simulate dural metastases include granulomatous infections, sarcoidosis, Erdheim-Chester disease and Langerhans cell histiocytosis

9. Discussion: Burkitt’s lymphoma • Burkitt’s lymphoma/Burkitt cell leukemia: • Clinically most aggressive lymphoid leukemia, of B-cell origin. • Association with EBV in a variable proportion of cases • <1% of NHL but 30% of childhood NHL in USA • Leukemia presents with widespread involvement of the bone marrow and peripheral blood. • Lymphoma used for proliferations arising as discrete masses • Distinction between lymphoma and leukemia often blurred

10. Pathology • Cells homogeneous in size and shape with a very high proliferative fraction • Pathologists sometimes have difficulty distinguishing between Burkitt’s lymphoma and diffuse large B cell lymphoma • Distinction can sometimes be made based on the extremely high proliferative fraction in Burkitt’s lymphoma • Most rapidly progressive human tumour, with a propensity to metastasize to the CNS

11. Burkitt’s lymphoma:“Starry sky” appearance at low power light microscopy

12. High power microscopy showing multiple small nucleoli and high mitotic index

13. Burkitt’s lymphoma: Clinical presentation • Three distinct clinical forms: • Endemic (African) type • Sporadic (nonendemic) • Immunodeficiency-associated (in HIV infection) • Extranodal disease common and all three variants are at risk for CNS disease • Endemic form involves jaws and orbits in 50% of cases (floating tooth sign on plain radiography) • Sporadic form has predilection for ileocecalregion • Ovaries, kidneys and breast may be involved in both • Retroperitoneal and paraspinal disease causing paraplegia is a presenting feature in up to15% of cases • Leptomeningeal disease can be seen at presentation and is a site of relapse

14. Diagnostic and staging work-up • Once diagnosis of BL suspected, diagnosis and staging evaluation should be prompt • Since it is the most rapidly progressing human tumour, delay in starting therapy can be detrimental to the prognosis • Initial examination should always include CSF analysis to rule out metastases, in addition to standard staging investigations for NHL

15. Treatment and Prognosis • Treatment should commence within 48hrs of diagnosis • Intensive chemotherapy regimens including high doses cyclophosphamide are used • Prophylactic therapy to the CNS is mandatory • One of the first cancers cured by chemotherapy • Cure in high percentage of young patients treated effectively, but salvage therapy following relapse generally ineffective, with poor prognosis

16. References • Armitage JO, Longo DL: Malignancies of Lymphoid cells, in Harrison’s Principles of Internal Medicine, 16thed, DL Kasper et al (eds.). New York, McGraw-Hill, 2005, Chap 97 • Aster JC: Disease of the White Blood Cells, Lymph Nodes, Spleen and Thymus, in Robbins and Cotran Pathological Basis of Disease, 7thed, V Kumar et al (eds.). Philadelphia, Elsevier Saunders, 2005, Chap 14 • Vinnicombe SJ, Reznek RH: Reticuloedothelial Disorders: Lymphoma, in Grainger & Allison’s Diagnostic Radiology, 5thed, A Adam et al (eds.). Churchill-Livingstone, 2008, Chap 72 • Yousem DM, Grossman RI. Neuroradiology: The Requisites, 3rd ed. Philadelphia, Mosby, 2010, p.65-67