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Mantle cell lymphoma—a spectrum from indolent to aggressive disease

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Abstract

Mantle cell lymphoma (MCL) is a distinctive lymphoma type generally characterized by the presence of CCND1 translocation and overexpression of cyclin D1. MCL usually presents with advanced stage and rapid clinical progression. The diagnosis is in most instances uncomplicated but cases with variant morphologies or immunophenotypes, especially cyclin D1-negative cases, may cause diagnostic difficulties. During the mantle cell lymphoma (MCL) session at the European Association of Haematopathology/Society for Hematopathology workshop 2014 held in Istanbul, Turkey, submitted cases illustrated interesting features such as unusual morphology or immunophenotypes. In several submitted cases of cyclin D1-positive MCL, CCND1 rearrangement could not be detected by t(11;14)(q13;q32) dual-color dual-fusion FISH but was suggested by CCND1 break-apart probes, and advantages and disadvantages of different FISH probes were highlighted. Three cyclin D1-negative MCL cases were submitted. These were identified by SOX11 immunohistochemistry and found to carry CCND2 translocations and/or to express high levels of cyclin D2 mRNA. Features associated with aggressive clinical course were presented including high expression of p53 protein and MYC aberrations. The need to integrate histological, immunophenotypic, genetic, and clinical data to arrive at the correct diagnosis was emphasized.

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References

  1. Morton LM, Sampson JN, Cerhan JR, Turner JJ, Vajdic CM, Wang SS, Smedby KE, de Sanjose S, Monnereau A, Benavente Y, Bracci PM, Chiu BC, Skibola CF, Zhang Y, Mbulaiteye SM, Spriggs M, Robinson D, Norman AD, Kane EV, Spinelli JJ, Kelly JL, La Vecchia C, Dal Maso L, Maynadie M, Kadin ME, Cocco P, Costantini AS, Clarke CA, Roman E, Miligi L, Colt JS, Berndt SI, Mannetje A, de Roos AJ, Kricker A, Nieters A, Franceschi S, Melbye M, Boffetta P, Clavel J, Linet MS, Weisenburger DD, Slager SL (2014) Rationale and design of the international lymphoma epidemiology consortium (InterLymph) non-Hodgkin lymphoma subtypes project. J Natl Cancer Inst Monogr 2014(48):1–14. doi:10.1093/jncimonographs/lgu005

    Article  PubMed  PubMed Central  Google Scholar 

  2. Swerdlow S, Campo E, Harris NE, Jaffe ES, Pileri SA, Stein H, Thiele J, Vardiman JW (2008) WHO classification of tumours of haematopoietic and lymphoid tissues. IARC press, Lyon

    Google Scholar 

  3. Reya T, O’Riordan M, Okamura R, Devaney E, Willert K, Nusse R, Grosschedl R (2000) Wnt signaling regulates B lymphocyte proliferation through a LEF-1 dependent mechanism. Immunity 13(1):15–24

    Article  CAS  PubMed  Google Scholar 

  4. Tandon B, Peterson L, Gao J, Nelson B, Ma S, Rosen S, Chen YH (2011) Nuclear overexpression of lymphoid-enhancer-binding factor 1 identifies chronic lymphocytic leukemia/small lymphocytic lymphoma in small B-cell lymphomas. Mod Pathol 24(11):1433–1443. doi:10.1038/modpathol.2011.103

    Article  CAS  PubMed  Google Scholar 

  5. Menter T, Dirnhofer S, Tzankov A (2015) LEF1: a highly specific marker for the diagnosis of chronic lymphocytic B cell leukaemia/small lymphocytic B cell lymphoma. J Clin Pathol. doi:10.1136/jclinpath-2015-202862

    PubMed  Google Scholar 

  6. Walther N, Ulrich A, Vockerodt M, von Bonin F, Klapper W, Meyer K, Eberth S, Pukrop T, Spang R, Trumper L, Kube D (2013) Aberrant lymphocyte enhancer-binding factor 1 expression is characteristic for sporadic Burkitt’s lymphoma. Am J Pathol 182(4):1092–1098. doi:10.1016/j.ajpath.2012.12.013

    Article  CAS  PubMed  Google Scholar 

  7. Lord M, Wasik AM, Christensson B, Sander B (2015) Utility of mRNA analysis in defining SOX11 expression levels in mantle cell lymphoma and reactive lymph nodes. Haematologica. doi:10.3324/haematol.2015.123885

    PubMed  PubMed Central  Google Scholar 

  8. Ek S, Dictor M, Jerkeman M, Jirstrom K, Borrebaeck CA (2008) Nuclear expression of the non B-cell lineage Sox11 transcription factor identifies mantle cell lymphoma. Blood 111(2):800–805. doi:10.1182/blood-2007-06-093401

    Article  CAS  PubMed  Google Scholar 

  9. Mozos A, Royo C, Hartmann E, De Jong D, Baro C, Valera A, Fu K, Weisenburger DD, Delabie J, Chuang SS, Jaffe ES, Ruiz-Marcellan C, Dave S, Rimsza L, Braziel R, Gascoyne RD, Sole F, Lopez-Guillermo A, Colomer D, Staudt LM, Rosenwald A, Ott G, Jares P, Campo E (2009) SOX11 expression is highly specific for mantle cell lymphoma and identifies the cyclin D1-negative subtype. Haematologica 94(11):1555–1562. doi:10.3324/haematol.2009.010264

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Gradowski JF, Sargent RL, Craig FE, Cieply K, Fuhrer K, Sherer C, Swerdlow SH (2012) Chronic lymphocytic leukemia/small lymphocytic lymphoma with cyclin D1 positive proliferation centers do not have CCND1 translocations or gains and lack SOX11 expression. Am J Clin Pathol 138(1):132–139. doi:10.1309/AJCPIVKZRMPF93ET

    Article  PubMed  PubMed Central  Google Scholar 

  11. Soldini D, Valera A, Sole C, Palomero J, Amador V, Martin-Subero JI, Ribera-Cortada I, Royo C, Salaverria I, Bea S, Gonzalvo E, Johannesson H, Herrera M, Colomo L, Martinez A, Campo E (2014) Assessment of SOX11 expression in routine lymphoma tissue sections: characterization of new monoclonal antibodies for diagnosis of mantle cell lymphoma. Am J Surg Pathol 38(1):86–93. doi:10.1097/PAS.0b013e3182a43996

    Article  PubMed  Google Scholar 

  12. Wasik AM, Priebe V, Lord M, Jeppsson-Ahlberg A, Christensson B, Sander B (2014) Flow cytometric analysis of SOX11: a new diagnostic method for distinguishing B-cell chronic lymphocytic leukemia/small lymphocytic lymphoma from mantle cell lymphoma. Leuk Lymphoma 1–7. doi:10.3109/10428194.2014.953147

  13. Nakashima MO, Durkin L, Bodo J, Lin J, Quintanilla-Martinez L, Fu K, Hsi ED (2014) Utility and diagnostic pitfalls of SOX11 monoclonal antibodies in mantle cell lymphoma and other lymphoproliferative disorders. Appl Immunohistochem Mol Morphol AIMM/Off Publ Soc Appl Immunohistochem 22(10):720–727. doi:10.1097/PAI.0000000000000067

    Article  CAS  Google Scholar 

  14. Swerdlow SH, Zukerberg LR, Yang WI, Harris NL, Williams ME (1996) The morphologic spectrum of non-Hodgkin’s lymphomas with BCL1/cyclin D1 gene rearrangements. Am J Surg Pathol 20(5):627–640

    Article  CAS  PubMed  Google Scholar 

  15. Akhter A, Mahe E, Street L, Pournazari P, Perizzolo M, Shabani-Rad MT, Stewart DA, Mansoor A (2015) CD10-positive mantle cell lymphoma: biologically distinct entity or an aberrant immunophenotype? Insight, through gene expression profile in a unique case series. J Clin Pathol. doi:10.1136/jclinpath-2015-202955

    PubMed  Google Scholar 

  16. Avet-Loiseau H, Garand R, Gaillard F, Daviet A, Mellerin MP, Robillard N, Bouyge I, Arcot S, Batzer M, Talmant P, Harousseau JL, Milpied N, Bataille R (1998) Detection of t(11;14) using interphase molecular cytogenetics in mantle cell lymphoma and atypical chronic lymphocytic leukemia. Genes Chromosomes Cancer 23(2):175–182

    Article  CAS  PubMed  Google Scholar 

  17. Li JY, Gaillard F, Moreau A, Harousseau JL, Laboisse C, Milpied N, Bataille R, Avet-Loiseau H (1999) Detection of translocation t(11;14)(q13;q32) in mantle cell lymphoma by fluorescence in situ hybridization. Am J Pathol 154(5):1449–1452. doi:10.1016/S0002-9440(10)65399-0

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Delas A, Sophie D, Brousset P, Laurent C (2013) Unusual concomitant rearrangements of cyclin D1 and MYC genes in blastoid variant of mantle cell lymphoma: case report and review of literature. Pathol Res Pract 209(2):115–119. doi:10.1016/j.prp.2012.12.001

    Article  CAS  PubMed  Google Scholar 

  19. Rocha CK, Praulich I, Gehrke I, Hallek M, Kreuzer KA (2011) A rare case of t(11;22) in a mantle cell lymphoma like B-cell neoplasia resulting in a fusion of IGL and CCND1: case report. Mol Cytogenet 4(1):8. doi:10.1186/1755-8166-4-8

    Article  PubMed  PubMed Central  Google Scholar 

  20. Komatsu H, Iida S, Yamamoto K, Mikuni C, Nitta M, Takahashi T, Ueda R, Seto M (1994) A variant chromosome translocation at 11q13 identifying PRAD1/cyclin D1 as the BCL-1 gene. Blood 84(4):1226–1231

    CAS  PubMed  Google Scholar 

  21. Espinet B, Salaverria I, Bea S, Ruiz-Xiville N, Balague O, Salido M, Costa D, Carreras J, Rodriguez-Vicente AE, Luis Garcia J, Hernandez-Rivas JM, Calasanz MJ, Siebert R, Ferrer A, Salar A, Carrio A, Polo N, Garcia-Marco JA, Domingo A, Gonzalez-Barca E, Romagosa V, Marugan I, Lopez-Guillermo A, Milla F, Luis Mate J, Luno E, Sanzo C, Collado R, Oliver I, Monzo S, Palacin A, Gonzalez T, Sant F, Salinas R, Ardanaz MT, Font L, Escoda L, Florensa L, Serrano S, Campo E, Sole F (2010) Incidence and prognostic impact of secondary cytogenetic aberrations in a series of 145 patients with mantle cell lymphoma. Genes Chromosomes Cancer 49(5):439–451. doi:10.1002/gcc.20754

    CAS  PubMed  Google Scholar 

  22. Wlodarska I, Meeus P, Stul M, Thienpont L, Wouters E, Marcelis L, Demuynck H, Rummens JL, Madoe V, Hagemeijer A (2004) Variant t(2;11)(p11;q13) associated with the IgK-CCND1 rearrangement is a recurrent translocation in leukemic small-cell B-non-Hodgkin lymphoma. Leukemia 18(10):1705–1710. doi:10.1038/sj.leu.2403459

    Article  CAS  PubMed  Google Scholar 

  23. Woroniecka R, Grygalewicz B, Pienkowska-Grela B, Rymkiewicz G, Konecki R, Swoboda P, Janik P (2007) Variant t(2;11)(p11.2;q13) without IGK involvement in a case of mantle cell lymphoma. Cancer Genet Cytogenet 175(2):154–158. doi:10.1016/j.cancergencyto.2007.02.012

    Article  CAS  PubMed  Google Scholar 

  24. Belaud-Rotureau MA, Parrens M, Dubus P, Garroste JC, de Mascarel A, Merlio JP (2002) A comparative analysis of FISH, RT-PCR, PCR, and immunohistochemistry for the diagnosis of mantle cell lymphomas. Mod Pathol 15(5):517–525

    Article  PubMed  Google Scholar 

  25. Ventura RA, Martin-Subero JI, Jones M, McParland J, Gesk S, Mason DY, Siebert R (2006) FISH analysis for the detection of lymphoma-associated chromosomal abnormalities in routine paraffin-embedded tissue. J Mol Diagn JMD 8(2):141–151. doi:10.2353/jmoldx.2006.050083

    Article  CAS  PubMed  Google Scholar 

  26. Greisman HA, Lu Z, Tsai AG, Greiner TC, Yi HS, Lieber MR (2012) IgH partner breakpoint sequences provide evidence that AID initiates t(11;14) and t(8;14) chromosomal breaks in mantle cell and Burkitt lymphomas. Blood 120(14):2864–2867. doi:10.1182/blood-2012-02-412791

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Fu K, Weisenburger DD, Greiner TC, Dave S, Wright G, Rosenwald A, Chiorazzi M, Iqbal J, Gesk S, Siebert R, De Jong D, Jaffe ES, Wilson WH, Delabie J, Ott G, Dave BJ, Sanger WG, Smith LM, Rimsza L, Braziel RM, Muller-Hermelink HK, Campo E, Gascoyne RD, Staudt LM, Chan WC (2005) Cyclin D1-negative mantle cell lymphoma: a clinicopathologic study based on gene expression profiling. Blood 106(13):4315–4321. doi:10.1182/blood-2005-04-1753

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Salaverria I, Zettl A, Bea S, Moreno V, Valls J, Hartmann E, Ott G, Wright G, Lopez-Guillermo A, Chan WC, Weisenburger DD, Gascoyne RD, Grogan TM, Delabie J, Jaffe ES, Montserrat E, Muller-Hermelink HK, Staudt LM, Rosenwald A, Campo E (2007) Specific secondary genetic alterations in mantle cell lymphoma provide prognostic information independent of the gene expression-based proliferation signature. J Clin Oncol 25(10):1216–1222. doi:10.1200/JCO.2006.08.4251

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Hartmann EM, Campo E, Wright G, Lenz G, Salaverria I, Jares P, Xiao W, Braziel RM, Rimsza LM, Chan WC, Weisenburger DD, Delabie J, Jaffe ES, Gascoyne RD, Dave SS, Mueller-Hermelink HK, Staudt LM, Ott G, Bea S, Rosenwald A (2010) Pathway discovery in mantle cell lymphoma by integrated analysis of high-resolution gene expression and copy number profiling. Blood 116(6):953–961. doi:10.1182/blood-2010-01-263806

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Salaverria I, Royo C, Carvajal-Cuenca A, Clot G, Navarro A, Valera A, Song JY, Woroniecka R, Rymkiewicz G, Klapper W, Hartmann EM, Sujobert P, Wlodarska I, Ferry JA, Gaulard P, Ott G, Rosenwald A, Lopez-Guillermo A, Quintanilla-Martinez L, Harris NL, Jaffe ES, Siebert R, Campo E, Bea S (2013) CCND2 rearrangements are the most frequent genetic events in cyclin D1(−) mantle cell lymphoma. Blood 121(8):1394–1402. doi:10.1182/blood-2012-08-452284

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Gesk S, Klapper W, Martin-Subero JI, Nagel I, Harder L, Fu K, Bernd HW, Weisenburger DD, Parwaresch R, Siebert R (2006) A chromosomal translocation in cyclin D1-negative/cyclin D2-positive mantle cell lymphoma fuses the CCND2 gene to the IGK locus. Blood 108(3):1109–1110. doi:10.1182/blood-2006-01-0015

    Article  CAS  PubMed  Google Scholar 

  32. Shiller SM, Zieske A, Holmes H 3rd, Feldman AL, Law ME, Saad R (2011) CD5-positive, cyclin D1-negative mantle cell lymphoma with a translocation involving the CCND2 gene and the IGL locus. Cancer Genet 204(3):162–164. doi:10.1016/j.cancergencyto.2010.08.016

    Article  PubMed  Google Scholar 

  33. Herens C, Lambert F, Quintanilla-Martinez L, Bisig B, Deusings C, de Leval L (2008) Cyclin D1-negative mantle cell lymphoma with cryptic t(12;14)(p13;q32) and cyclin D2 overexpression. Blood 111(3):1745–1746. doi:10.1182/blood-2007-10-120824

    Article  CAS  PubMed  Google Scholar 

  34. Quintanilla-Martinez L, Slotta-Huspenina J, Koch I, Klier M, Hsi ED, de Leval L, Klapper W, Gesk S, Siebert R, Fend F (2009) Differential diagnosis of cyclin D2+ mantle cell lymphoma based on fluorescence in situ hybridization and quantitative real-time-PCR. Haematologica 94(11):1595–1598. doi:10.3324/haematol.2009.010173

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Wlodarska I, Dierickx D, Vanhentenrijk V, Van Roosbroeck K, Pospisilova H, Minnei F, Verhoef G, Thomas J, Vandenberghe P, De Wolf-Peeters C (2008) Translocations targeting CCND2, CCND3, and MYCN do occur in t(11;14)-negative mantle cell lymphomas. Blood 111(12):5683–5690. doi:10.1182/blood-2007-10-118794

    Article  CAS  PubMed  Google Scholar 

  36. Martin P, Chadburn A, Christos P, Weil K, Furman RR, Ruan J, Elstrom R, Niesvizky R, Ely S, Diliberto M, Melnick A, Knowles DM, Chen-Kiang S, Coleman M, Leonard JP (2009) Outcome of deferred initial therapy in mantle-cell lymphoma. J Clin Oncol 27(8):1209–1213. doi:10.1200/JCO.2008.19.6121

    Article  PubMed  Google Scholar 

  37. Nygren L, Baumgartner Wennerholm S, Klimkowska M, Christensson B, Kimby E, Sander B (2012) Prognostic role of SOX11 in a population-based cohort of mantle cell lymphoma. Blood 119(18):4215–4223. doi:10.1182/blood-2011-12-400580

    Article  CAS  PubMed  Google Scholar 

  38. Eve HE, Furtado MV, Hamon MD, Rule SA (2009) Time to treatment does not influence overall survival in newly diagnosed mantle-cell lymphoma. J Clin Oncol Off J Am Soc Clin Oncol 27(32):e189–e190. doi:10.1200/JCO.2009.23.9731, author reply e191

    Article  Google Scholar 

  39. Adam P, Schiefer AI, Prill S, Henopp T, Quintanilla-Martinez L, Bosmuller HC, Chott A, Fend F (2012) Incidence of preclinical manifestations of mantle cell lymphoma and mantle cell lymphoma in situ in reactive lymphoid tissues. Mod Pathol 25(12):1629–1636. doi:10.1038/modpathol.2012.117

    Article  CAS  PubMed  Google Scholar 

  40. Carvajal-Cuenca A, Sua LF, Silva NM, Pittaluga S, Royo C, Song JY, Sargent RL, Espinet B, Climent F, Jacobs SA, Delabie J, Naresh KN, Bagg A, Brousset P, Warnke RA, Serrano S, Harris NL, Swerdlow SH, Jaffe ES, Campo E (2012) In situ mantle cell lymphoma: clinical implications of an incidental finding with indolent clinical behavior. Haematologica 97(2):270–278. doi:10.3324/haematol.2011.052621

    Article  PubMed  PubMed Central  Google Scholar 

  41. Fend F, Cabecadas J, Gaulard P, Jaffe ES, Kluin P, Kuzu I, Peterson L, Wotherspoon A, Sundstrom C (2012) Early lesions in lymphoid neoplasia: conclusions based on the Workshop of the XV. Meeting of the European Association of Hematopathology and the Society of Hematopathology, in Uppsala, Sweden. J Hematop 5(3):169–199. doi:10.1007/s12308-012-0148-6

    Article  Google Scholar 

  42. Karube K, Scarfo L, Campo E, Ghia P (2014) Monoclonal B cell lymphocytosis and “in situ” lymphoma. Semin Cancer Biol 24:3–14. doi:10.1016/j.semcancer.2013.08.003

    Article  CAS  PubMed  Google Scholar 

  43. Lecluse Y, Lebailly P, Roulland S, Gac AC, Nadel B, Gauduchon P (2009) t(11;14)-positive clones can persist over a long period of time in the peripheral blood of healthy individuals. Leukemia 23(6):1190–1193. doi:10.1038/leu.2009.31

    Article  CAS  PubMed  Google Scholar 

  44. Hirt C, Schuler F, Dolken L, Schmidt CA, Dolken G (2004) Low prevalence of circulating t(11;14)(q13;q32)-positive cells in the peripheral blood of healthy individuals as detected by real-time quantitative PCR. Blood 104(3):904–905. doi:10.1182/blood-2004-02-0738

    Article  CAS  PubMed  Google Scholar 

  45. Espinet B, Ferrer A, Bellosillo B, Nonell L, Salar A, Fernandez-Rodriguez C, Puigdecanet E, Gimeno J, Garcia-Garcia M, Vela MC, Luno E, Collado R, Navarro JT, de la Banda E, Abrisqueta P, Arenillas L, Serrano C, Lloreta J, Minana B, Cerutti A, Florensa L, Orfao A, Sanz F, Sole F, Dominguez-Sola D, Serrano S (2014) Distinction between asymptomatic monoclonal B-cell lymphocytosis with cyclin D1 overexpression and mantle cell lymphoma: from molecular profiling to flow cytometry. Clin Cancer Res. doi:10.1158/1078-0432.CCR-13-1077

    PubMed  PubMed Central  Google Scholar 

  46. Espinet B, Sole F, Pedro C, Garcia M, Bellosillo B, Salido M, Florensa L, Camacho FI, Baro T, Lloreta J, Serrano S (2005) Clonal proliferation of cyclin D1-positive mantle lymphocytes in an asymptomatic patient: an early-stage event in the development or an indolent form of a mantle cell lymphoma? Hum Pathol 36(11):1232–1237. doi:10.1016/j.humpath.2005.08.021

    Article  CAS  PubMed  Google Scholar 

  47. Fernandez V, Salamero O, Espinet B, Sole F, Royo C, Navarro A, Camacho F, Bea S, Hartmann E, Amador V, Hernandez L, Agostinelli C, Sargent RL, Rozman M, Aymerich M, Colomer D, Villamor N, Swerdlow SH, Pileri SA, Bosch F, Piris MA, Montserrat E, Ott G, Rosenwald A, Lopez-Guillermo A, Jares P, Serrano S, Campo E (2010) Genomic and gene expression profiling defines indolent forms of mantle cell lymphoma. Cancer Res 70(4):1408–1418. doi:10.1158/0008-5472.CAN-09-3419

    Article  CAS  PubMed  Google Scholar 

  48. Racke F, Simpson S, Christian B, Blum KA, Hasserjian R, Zhao W (2010) Evidence of long latency periods prior to development of mantle cell lymphoma. Blood Abstract 116:323

    Google Scholar 

  49. Edlefsen KL, Greisman HA, Yi HS, Mantei KM, Fromm JR (2011) Early lymph node involvement by mantle cell lymphoma limited to the germinal center: report of a case with a novel “follicular in situ” growth pattern. Am J Clin Pathol 136(2):276–281. doi:10.1309/AJCP6KFFGTC8PLVR

    Article  PubMed  Google Scholar 

  50. Christian B, Zhao W, Hamadani M, Sotomayor EM, Navarro W, Devine SM, Racke F, Blum KA (2010) Mantle cell lymphoma 12 years after allogeneic bone marrow transplantation occurring simultaneously in recipient and donor. J Clin Oncol 28(31):e629–e632. doi:10.1200/JCO.2010.29.8992

    Article  CAS  PubMed  Google Scholar 

  51. Majlis A, Pugh WC, Rodriguez MA, Benedict WF, Cabanillas F (1997) Mantle cell lymphoma: correlation of clinical outcome and biologic features with three histologic variants. J Clin Oncol 15(4):1664–1671

    CAS  PubMed  Google Scholar 

  52. Tiemann M, Schrader C, Klapper W, Dreyling MH, Campo E, Norton A, Berger F, Kluin P, Ott G, Pileri S, Pedrinis E, Feller AC, Merz H, Janssen D, Hansmann ML, Krieken H, Moller P, Stein H, Unterhalt M, Hiddemann W, Parwaresch R (2005) Histopathology, cell proliferation indices and clinical outcome in 304 patients with mantle cell lymphoma (MCL): a clinicopathological study from the European MCL Network. Br J Haematol 131(1):29–38

    Article  PubMed  Google Scholar 

  53. Leitch HA, Gascoyne RD, Chhanabhai M, Voss NJ, Klasa R, Connors JM (2003) Limited-stage mantle-cell lymphoma. Ann Oncol 14(10):1555–1561

    Article  CAS  PubMed  Google Scholar 

  54. Nygren L, Wasik AM, Baumgartner-Wennerholm S, Jeppsson-Ahlberg A, Klimkowska M, Andersson P, Buhrkuhl D, Christensson B, Kimby E, Wahlin BE, Sander B (2014) T-cell levels are prognostic in mantle cell lymphoma. Clin Cancer Res. doi:10.1158/1078-0432.CCR-14-0889

    PubMed  Google Scholar 

  55. Hoster E, Dreyling M, Klapper W, Gisselbrecht C, van Hoof A, Kluin-Nelemans HC, Pfreundschuh M, Reiser M, Metzner B, Einsele H, Peter N, Jung W, Wormann B, Ludwig WD, Duhrsen U, Eimermacher H, Wandt H, Hasford J, Hiddemann W, Unterhalt M (2008) A new prognostic index (MIPI) for patients with advanced-stage mantle cell lymphoma. Blood 111(2):558–565. doi:10.1182/blood-2007-06-095331

    Article  CAS  PubMed  Google Scholar 

  56. Jares P, Colomer D, Campo E (2012) Molecular pathogenesis of mantle cell lymphoma. J Clin Invest 122(10):3416–3423. doi:10.1172/JCI61272

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Ondrejka SL, Lai R, Smith SD, Hsi ED (2011) Indolent mantle cell leukemia: a clinicopathological variant characterized by isolated lymphocytosis, interstitial bone marrow involvement, kappa light chain restriction, and good prognosis. Haematologica 96(8):1121–1127. doi:10.3324/haematol.2010.036277

    Article  PubMed  PubMed Central  Google Scholar 

  58. Royo C, Navarro A, Clot G, Salaverria I, Gine E, Jares P, Colomer D, Wiestner A, Wilson WH, Vegliante MC, Fernandez V, Hartmann EM, Trim N, Erber WN, Swerdlow SH, Klapper W, Dyer MJ, Vargas-Pabon M, Ott G, Rosenwald A, Siebert R, Lopez-Guillermo A, Campo E, Bea S (2012) Non-nodal type of mantle cell lymphoma is a specific biological and clinical subgroup of the disease. Leukemia 26(8):1895–1898. doi:10.1038/leu.2012.72

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Orchard J, Garand R, Davis Z, Babbage G, Sahota S, Matutes E, Catovsky D, Thomas PW, Avet-Loiseau H, Oscier D (2003) A subset of t(11;14) lymphoma with mantle cell features displays mutated IgVH genes and includes patients with good prognosis, nonnodal disease. Blood 101(12):4975–4981

    Article  CAS  PubMed  Google Scholar 

  60. Navarro A, Clot G, Royo C, Jares P, Hadzidimitriou A, Agathangelidis A, Bikos V, Darzentas N, Papadaki T, Salaverria I, Pinyol M, Puig X, Palomero J, Vegliante MC, Amador V, Martinez-Trillos A, Stefancikova L, Wiestner A, Wilson W, Pott C, Calasanz MJ, Trim N, Erber W, Sander B, Ott G, Rosenwald A, Colomer D, Gine E, Siebert R, Lopez-Guillermo A, Stamatopoulos K, Bea S, Campo E (2012) Molecular subsets of mantle cell lymphoma defined by the IGHV mutational status and SOX11 expression have distinct biologic and clinical features. Cancer Res 72(20):5307–5316. doi:10.1158/0008-5472.CAN-12-1615

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Chapman-Fredricks J, Sandoval-Sus J, Vega F, Lossos IS (2014) Progressive leukemic non-nodal mantle cell lymphoma associated with deletions of TP53, ATM, and/or 13q14. Ann Diagn Pathol 18(4):214–219. doi:10.1016/j.anndiagpath.2014.03.006

    Article  PubMed  Google Scholar 

  62. Parry-Jones N, Matutes E, Morilla R, Brito-Babapulle V, Wotherspoon A, Swansbury GJ, Catovsky D (2007) Cytogenetic abnormalities additional to t(11;14) correlate with clinical features in leukaemic presentation of mantle cell lymphoma, and may influence prognosis: a study of 60 cases by FISH. Br J Haematol 137(2):117–124. doi:10.1111/j.1365-2141.2007.06526.x

    Article  CAS  PubMed  Google Scholar 

  63. Nordstrom L, Sernbo S, Eden P, Gronbaek K, Kolstad A, Raty R, Karjalainen ML, Geisler C, Ralfkiaer E, Sundstrom C, Laurell A, Delabie J, Ehinger M, Jerkeman M, Ek S (2014) SOX11 and TP53 add prognostic information to MIPI in a homogenously treated cohort of mantle cell lymphoma—a Nordic Lymphoma Group study. Br J Haematol 166(1):98–108. doi:10.1111/bjh.12854

    Article  PubMed  PubMed Central  Google Scholar 

  64. Royo C, Salaverria I, Hartmann EM, Rosenwald A, Campo E, Bea S (2011) The complex landscape of genetic alterations in mantle cell lymphoma. Semin Cancer Biol 21(5):322–334. doi:10.1016/j.semcancer.2011.09.007

    Article  CAS  PubMed  Google Scholar 

  65. Klapper W, Hoster E, Determann O, Oschlies I, van der Laak J, Berger F, Bernd HW, Cabecadas J, Campo E, Cogliatti S, Hansmann ML, Kluin PM, Kodet R, Krivolapov YA, Loddenkemper C, Stein H, Moller P, Barth TE, Muller-Hermelink K, Rosenwald A, Ott G, Pileri S, Ralfkiaer E, Rymkiewicz G, van Krieken JH, Wacker HH, Unterhalt M, Hiddemann W, Dreyling M (2009) Ki-67 as a prognostic marker in mantle cell lymphoma-consensus guidelines of the pathology panel of the European MCL Network. J Hematop. doi:10.1007/s12308-009-0036-x

    PubMed  PubMed Central  Google Scholar 

  66. Hao S, Sanger W, Onciu M, Lai R, Schlette EJ, Medeiros LJ (2002) Mantle cell lymphoma with 8q24 chromosomal abnormalities: a report of 5 cases with blastoid features. Mod Pathol 15(12):1266–1272. doi:10.1097/01.MP.0000037310.82136.99

    Article  PubMed  Google Scholar 

  67. Michaux L, Wlodarska I, Theate I, Stul M, Scheiff JM, Deneys V, Ferrant A, Hagemeijer A (2004) Coexistence of BCL1/CCND1 and CMYC aberrations in blastoid mantle cell lymphoma: a rare finding associated with very poor outcome. Ann Hematol 83(9):578–583. doi:10.1007/s00277-004-0879-2

    Article  CAS  PubMed  Google Scholar 

  68. Aukema SM, Siebert R, Schuuring E, van Imhoff GW, Kluin-Nelemans HC, Boerma EJ, Kluin PM (2011) Double-hit B-cell lymphomas. Blood 117(8):2319–2331. doi:10.1182/blood-2010-09-297879

    Article  CAS  PubMed  Google Scholar 

  69. Pinyol M, Hernandez L, Cazorla M, Balbin M, Jares P, Fernandez PL, Montserrat E, Cardesa A, Lopez-Otin C, Campo E (1997) Deletions and loss of expression of p16INK4a and p21Waf1 genes are associated with aggressive variants of mantle cell lymphomas. Blood 89(1):272–280

    CAS  PubMed  Google Scholar 

  70. Chisholm KM, Bangs CD, Bacchi CE, Molina-Kirsch H, Cherry A, Natkunam Y (2015) Expression profiles of MYC protein and MYC gene rearrangement in lymphomas. Am J Surg Pathol 39(3):294–303. doi:10.1097/PAS.0000000000000365

    Article  PubMed  Google Scholar 

  71. Oberley MJ, Rajguru SA, Zhang C, Kim K, Shaw GR, Grindle KM, Kahl BS, Kanugh C, Laffin J, Yang DT (2013) Immunohistochemical evaluation of MYC expression in mantle cell lymphoma. Histopathology 63(4):499–508. doi:10.1111/his.12207

    PubMed  PubMed Central  Google Scholar 

  72. Halldorsdottir AM, Lundin A, Murray F, Mansouri L, Knuutila S, Sundstrom C, Laurell A, Ehrencrona H, Sander B, Rosenquist R (2011) Impact of TP53 mutation and 17p deletion in mantle cell lymphoma. Leukemia 25(12):1904–1908. doi:10.1038/leu.2011.162

    Article  CAS  PubMed  Google Scholar 

  73. Slotta-Huspenina J, Koch I, de Leval L, Keller G, Klier M, Bink K, Kremer M, Raffeld M, Fend F, Quintanilla-Martinez L (2012) The impact of cyclin D1 mRNA isoforms, morphology and p53 in mantle cell lymphoma: p53 alterations and blastoid morphology are strong predictors of a high proliferation index. Haematologica 97(9):1422–1430. doi:10.3324/haematol.2011.055715

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Greiner TC, Moynihan MJ, Chan WC, Lytle DM, Pedersen A, Anderson JR, Weisenburger DD (1996) p53 mutations in mantle cell lymphoma are associated with variant cytology and predict a poor prognosis. Blood 87(10):4302–4310

    CAS  PubMed  Google Scholar 

  75. Hernandez L, Fest T, Cazorla M, Teruya-Feldstein J, Bosch F, Peinado MA, Piris MA, Montserrat E, Cardesa A, Jaffe ES, Campo E, Raffeld M (1996) p53 gene mutations and protein overexpression are associated with aggressive variants of mantle cell lymphomas. Blood 87(8):3351–3359

    CAS  PubMed  Google Scholar 

  76. Katzenberger T, Kienle D, Stilgenbauer S, Holler S, Schilling C, Mader U, Puppe B, Petzoldt C, Sander S, Bullinger L, Stocklein H, Kalla J, Hartmann E, Adam P, Ott MM, Muller-Hermelink HK, Rosenwald A, Ott G (2008) Delineation of distinct tumour profiles in mantle cell lymphoma by detailed cytogenetic, interphase genetic and morphological analysis. Br J Haematol 142(4):538–550. doi:10.1111/j.1365-2141.2008.07199.x

    Article  PubMed  Google Scholar 

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Acknowledgments

We thank all participants of the workshop for submitting their cases. The permission to use their images in this review is also gratefully acknowledged. The authors thank Dr. Irina Bonzheim from the Institute of Pathology, University of Tübingen, Germany, for performing the RT-PCR for cyclin D1 and cyclin D2 mRNA in several of the cases and Dr Itziar Salaverria from Insitut d’Investigació Biomèdica Augusti Pi i Sunyer (IDIBAPS) of Barcelona for performing FISH studies for CCND2.

Conflict of interest

We declare that we have no competing interests.

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Authors and Affiliations

  1. Department of Laboratory Medicine, Division of Pathology, Karolinska Institutet and Karolinska University Hospital Huddinge, SE 141 86, Stockholm, Sweden

    Birgitta Sander

  2. Institute of Pathology and Neuropathology, Eberhard Karls University of Tübingen and Comprehensive Cancer Center, University Hospital Tübingen, Tübingen, Germany

    Leticia Quintanilla-Martinez

  3. Department of Clinical Pathology, Robert-Bosch-Hospital and Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany

    German Ott

  4. Department of Bio-Pathology, Institut Paoli-Calmettes, Marseille, France

    Luc Xerri

  5. Department of Pathology, Ankara University School of Medicine, Sihhiye, Ankara, Turkey

    Isinsu Kuzu

  6. Queen Elizabeth Hospital, Hong Kong, SAR, China

    John K. C. Chan

  7. Division of Hematopathology, Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

    Steven H. Swerdlow

  8. Hospital Clinic, University of Barcelona, Barcelona, Spain

    Elias Campo

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  1. Birgitta Sander
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Correspondence to Birgitta Sander.

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Sander, B., Quintanilla-Martinez, L., Ott, G. et al. Mantle cell lymphoma—a spectrum from indolent to aggressive disease. Virchows Arch 468, 245–257 (2016). https://doi.org/10.1007/s00428-015-1840-6

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