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Deniz Gur, David C Park.

Aggressive B-Cell Lymphoma Arising From Lymphoplasmacytic Lymphoma with a Distinct Genomic Profile. Deniz Gur, David C Park. Department of Hematopathology, Memorial Sloan- Kettering Cancer Center, New York, NY, USA. Clinical History.

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Deniz Gur, David C Park.

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  1. Aggressive B-Cell Lymphoma Arising From Lymphoplasmacytic Lymphoma with a Distinct Genomic Profile Deniz Gur, David C Park. Department of Hematopathology, Memorial Sloan- Kettering Cancer Center, New York, NY, USA

  2. Clinical History • 64-year-old man with severe atrial fibrillation • April 2009 (work up for radiofrequency ablation treatment): Hb: 9 g/dL IgM: 3.6 g/dL IgA: 1.0 g/dL IgG: 1.1 g/dL • Bone marrow biopsy (April 2009): Lymphoplasmacytic lymphoma (LPL) with 40-50% involvement

  3. Clinical History 03/ 2013 07/ 2015 04/ 2009 08/ 2010 12/2013 09/ 2015 Good Response No response Persistent disease with progression At the Time of Dx

  4. Clinical History Cytogenetics: Bone marrow aspirate (4/21/2010): 46, XY [20]; Normal male karyotype Molecular Studies: Mutations identified by comprehensive genomic profiling are as follows: • ARID1A Q2037* • CXCR4 H341fs*1+ • MYD88 L265P • TP53 G245D, R249T, S241F – subclonal

  5. Bone Marrow Biopsy (07/23/2015) Extensive involvement by LPL Necrotic area

  6. Bone Marrow Biopsy (07/23/2015) CD79a

  7. Bone Marrow Biopsy (07/23/2015) MUM1 MYC LPL, more than 95% involvement with extensive tumor necrosis highly concerning for transformation to diffuse large B cell lymphoma

  8. Bone Marrow Biopsy and Aspirate (09/04/2015)

  9. Bone Marrow Biopsy (09/04/2015) CD138 PAX5

  10. Bone Marrow Biopsy (09/04/2015) P53 MYC MUM1

  11. Bone Marrow Biopsy (09/04/2015) Ki67 Aggressive B cell lymphoma consistent with large cell transformation of lymphoplasmacytic lymphoma

  12. Interesting Features • Compared to CLL/SLL, the risk of LPL/WM to transform into an aggressive B cell lymphoma is much lower and has been reported as isolated case reports or small series • Risk factors for adverse prognosis in LPL/WM patients: • cytopenias • heavy tumor burden • complex karyotype • poor response to therapy • Our patient had most of the risk factors (cytopenias, high tumor burden and poor response to therapy), however he had a normal karyotype

  13. Interesting Features • Comprehensive genomic profiling detected 6 genomic mutation in 4 genes • ARID1A Q2037* • CXCR4 H341fs*1+ • MYD88 L265P • TP53 G245D, R249T, S241F – subclonal • Concurrent mutations may explain the adverse outcome and aggressive transformation in our patient • Patients with both ARID1A and MYD88 mutations have a greater involvement of bone marrow, lower hematocrit and platelet counts • ARID1A and p53 mutations promote tumor development in a co-dependent fashion • CXCR4 mutations are also shown to be associated with increased disease activity

  14. Summary • Large cell transformation in LPL/WM cases is not well studied and the underlying molecular mechanisms are not known • This is a rare case of LPL/WM with distinct genomic profile, transformed into an aggressive large B cell lymphoma • Studying these cases may help identifying LPL/WM patients with a high risk of transformation and also help tailoring optimal chemotherapeutic intervention

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