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Indolent and Pleomorphic Mantle Cell Lymphoma Variants: A Hematopathology Case Study

This case study presents a 54-year-old man with indolent and pleomorphic mantle cell lymphoma variants, detailing clinical history, diagnoses, observations, and key genetic findings. The text discusses morphologic variants, gene expression profiling, and important immunophenotypic characteristics, emphasizing the importance of further study in understanding these lymphomas.

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Indolent and Pleomorphic Mantle Cell Lymphoma Variants: A Hematopathology Case Study

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  1. Case Presentation #18Frontiers 2011 Lauren B. Smith, M.D. Hematopathology

  2. Clinical History: 54 year-old man 10/2001 Lymphocytosis Splenomegaly Adenopathy

  3. Femoral lymph node biopsy October 2001 (H&E, 20X magnification)

  4. Femoral lymph node biopsy October 2001 (H&E, 400X magnification)

  5. Peripheral blood smear October 2001 (1000X magnification)

  6. Peripheral blood flow cytometry, 2001

  7. Diagnosis • B-cell non-Hodgkin lymphoma of small cells

  8. Clinical History 10/2001 April 2009 Observation Lymphocytosis Splenomegaly Adenopathy Splenectomy 4625 g spleen

  9. Spleen, April 2009 (H&E, magnification 20X)

  10. Spleen, April 2009 (H&E, magnification 400X)

  11. Splenectomy specimen flow cytometry April 2009

  12. Cyclin D1 Spleen, April 2009 (magnification 20X)

  13. Repeat Cyclin D1 Femoral lymph node biopsy October 2001 (100X magnification)

  14. Clinical History 10/2001 April 2009 July 2009 Observation 7.5 years Lymphocytosis Splenomegaly Adenopathy Dyspnea/ Worsening Lymphadenopathy ARF, tumor lysis Splenectomy 4625 g spleen

  15. Peripheral blood smear July 2009; absolute lymphocyte count = 24500/μL

  16. IGH/CCND1 CCND1 IGH IGH/CCND1 Peripheral blood FISH (8/2009): nuc ish(IGHx3), (CCND1x3), (IGH con CCND1x2) [72/200]

  17. B-cell (IGH) Gene rearrangement Analysis by PCR on paraffin blocks Spleen sample (April 2009) Femoral lymph node (October 2001) clonal identity (122 base pair amplicon)

  18. Clinical History 10/2001 April 2009 July 2009 Dec 2009 Observation 7.5 years Lymphocytosis Splenomegaly Adenopathy Dyspnea/ Worsening Lymphadenopathy ARF, tumor lysis Splenectomy 4625 g spleen CNS dz

  19. Diagnosis • Indolent mantle cell lymphoma (2001) • Pleomorphic mantle cell lymphoma (2009)

  20. MCL Variants • Blastoid • Fine chromatin • High mitotic rate (20-30/10 hpf) • High proliferative fraction (Ki-67) • Pleomorphic • Large with oval to irregular nuclear contours • Prominent nucleoli, pale cytoplasm

  21. Indolent Mantle Cell • Typical MCL • Widespread disease at diagnosis • Survival 3-5 years with chemotherapy • Indolent MCL • Bone marrow/spleen/GI-based disease • Usually no lymphadenopathy • 7-10 year survival (often untreated)

  22. Indolent Populations • PB/Bone marrow only • Ondrejka et al (2011) • PB/Bone marrow, spleen, GI tract • Orchard et al (2003) • Fernandez et al (2010)

  23. Gene Expression Profiling • SOX11 (2p25.3) • Involved in neuronal development • Possibly a tumor-suppressor gene in MCL • Immunohistochemistry • Expressed in 78-93% of MCL cases • Expressed in many cyclin D1 negative cases • Expressed in B/T-LBL, Burkitt, T-PLL, Hairy cell • Negative expression in many indolent cases • Not present in CLL/SLL, marginal zone, FL, Myeloma with t(11;14)

  24. Immunophenotype

  25. Take Home Points: MCL • Clinical and morphologic variants exist • Recommend Cyclin D1 on CD5 negative splenectomy specimens • SOX11 may be helpful • Further study is needed

  26. AcknowledgementsCase Submission for the XVth Meeting of the European Association for Haematopathology – Lymphoma Workshop M. Chiselite, B. Schnitzer, D. Roulston and LB. Smith University of Michigan Department of Pathology, Ann Arbor, MI, USA

  27. References • Bosch F, Lopez-Guillermo A, Campo E, Ribera JM, Conde E, Piris MA, et al. Mantle cell lymphoma: Presenting features, response to therapy, and prognostic factors. Cancer 1998;101(2)302-310. • Fernandez V, Salamero O, Espinet B, Sole F, Royo C, Navarro A, et al. Genomic and gene expression profiling defines indolent forms of mantle cell lymphoma. Cancer Res 2010;70(4):1408-18. • Ondrejka SL, Lai R, Smith SD & His ED. Indolent mantle cell leukemia: a clinicopathological variant characterized by isolated lymphocytosis, interstitial bone marrow involvement, kappa light chain restriction, and good prognosis. Hematologica 2011;96(8): 1121-27. • Orchard J, Garand R, Davis Z, Babbage G, Sahota S, Matutes E, et al. A subset of t(11;14) lymphoma with mantle cell features displays mutated IgVH genes and includes patient with good prognosis, nonnodal disease. Blood. 2003;101(12):4975-81. • Wang X, Asplund AC, Porwit A, Flygare J, Smith CI, Christensson B, et al. The subcellular SOX11 distribution pattern identifies subsets of mantle cell lymphoma: Correlation to overall survival. Br J Hematol 2008;143(2):248-52. • Xu Wei & Jian-Yong Li. SOX11 expression in mantle cell lymphoma. Leuk & Lymph 2010;51(11): 1962-67.

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