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Splenic marginal zone lymphoma: from genetics to management

Luca Arcaini, Davide Rossi and Marco Paulli

Article Figures & Data

Figures

  • Figure 1

    Histopathology of SMZL. In this typical case, (A) a nodular lymphoid proliferation with a biphasic appearance effaces the white pulp, infiltrates the wall of a great vessel (arrow) (hematoxylin and eosin [H&E] stain; magnification ×20) and extends to (B) the red pulp in a patchy distribution (CD79a; magnification ×100). (C) Morphologic pictures show medium sized, monocytoid lymphocytes with only scattered large cells (H&E stain; magnification ×400) and (D) a variable degree of plasmacytic differentiation (Giemsa stain; magnification ×400). (E) Anti-CD23 immunostain (magnification ×100) depicts the CD23+ marginal zone cells as well as the residual dendritic meshwork within the colonized follicles highlighted by (F) Mib/Ki-67 (magnification ×100), which confers a targetoid appearance. (G) A prototypical BM biopsy shows a small to medium size lymphoid population (Giemsa stain; magnification ×400) with (H) a nodular and sinusoidal distribution (CD20; magnification ×400). (G) Note the megaloblastoid features within the erythroblastic lineage, a common finding in cases associated with paraproteinemia and anemia.

  • Figure 2

    Key molecular alterations in SMZL. Schematic representation of genes and pathways that are molecularly deregulated in SMZL. The prevalence of molecular alterations in SMZL is shown as a percentage beside each gene or pathway.

Tables

  • Table 1

    Flow cytometry features of SMZL and other leukemic B-cell lymphoproliferative disorders

    SMZLCLLMCLHCLHCL-v
    sIgStrongWeakStrongStrongStrong
    CD5+++++++
    CD23++++
    FMC7+++++++++++++
    CD11c++++++++
    CD103+++++
    CD123+++
    CD25++++
    CD27++++++++++
    CD200++++++
    • −, <10% of cases positive; +, 11%-35% positive cases; ++, 36%-75% positive cases; +++, >75% positive cases.

    • CLL, chronic lymphocytic leukemia; MCL, mantle cell lymphoma; sIg, superficial immunoglobulin expression.

  • Table 2

    Immunohistochemistry features of SMZL and other small B-cell lymphomas

    SMZLLPLSDRPLHCL-vHCLEMZL/ NMZLCLLMCLFL
    CD20++++++−/+++
    CD79a+++++++++
    CD5−/+−/+−/+−/+++
    CD21−/+
    CD23−/+−/+−/++−/+
    BCL1−/+++
    DBA44+/−+++−/+
    Annexin A1+
    CD103+/−+
    CD123+
    IRTA1+/−
    IgM+++++++++
    IgD+/−−/+++−/++++
    CD10**+/−
    BCL6−/+−/++
    CD43−/+−/+++
    SOX11+
    LEF1+−/+
    • –, <25% of cases; –/+, 25%-50% of cases; +/–, 50%-75% of cases; +, >75% of cases.

    • FL, follicular lymphoma; NMZL, nodal marginal zone lymphoma; SDRPL, splenic diffuse red pulp lymphoma.

    • * Sporadic cases reported.

  • Table 3

    Series of SMZL patients treated with splenectomy

    ReferenceYearNResponseOSDeaths due to surgery
    ORR (%)Duration
    Mulligan et al6819912095Median DOR 4 yNR1
    Troussard et al5919962875NR71% at 5 y1
    Chacon et al6120026093.3Median FFS 40 mo65% at 5 yNR
    Thieblemont et al1200248100PFS 48% at 5 yNRNR
    Parry-Jones et al60200333NRNRLSS 95% at 10 yNR
    Iannitto et al6920042191Median DOR 4 yNRNR
    Tsimberidou et al7020061060FFS 80% at 3 y89% at 3 y0
    Olszewski et al712012652NRNR67.8% at 5 yNR
    Kalpadakis et al7320132785PFS 58% at 5 y77% at 5 y1
    Lenglet et al7201410097PFS 61% at 5 y84% at 5 y0
    Xing et al62201552§NRFFS 39% at 10 y61% at 10 y0
    Pata et al8920154190PFS 35% at 5 y75% at 5 y0
    • DOR, duration of response; FFS, failure-free survival; LSS, lymphoma-specific survival; NR, not reported; ORR, overall response rate; OS, overall survival; PFS, progression-free survival.

    • Splenectomy alone in 29 patients.

    • Splenectomy alone in 25 patients.

    • Survival of entire series of 1251 patients with no impact of splenectomy on OS.

    • § Splenectomy alone in 42 patients.

  • Table 4

    Series of SMZL patients treated with rituximab-based approach

    Response
    ReferenceYearStudy typeSchemePatient statusNORRDurationOS
    Rituximab monotherapy
     Bennett et al82,1022005RetrospectiveR monotherapyRR1191%PFS 60% at 5 y70% at 5 y
     Tsimberidou et al702006RetrospectiveR monotherapyFirst line2588%FFS 86% at 3 y95% at 3 y
     Kalpadakis et al83,962007RetrospectiveR monotherapyFirst line16100%PFS 92% at 2.4 y100% at 2.1 y
     Else et al1032012RetrospectiveR monotherapyFirst line and RR10100%DFS 89% at 3 yNR
     Kalpadakis et al732013RetrospectiveR monotherapyFirst line5895%PFS 73% at 5 y92% at 5 y
    Rituximab + chemotherapy
     Tsimberidou et al702006RetrospectiveR-chemoFirst line683%FFS 100% at 3 y100% at 3 y
     Cervetti et al85,862010RetrospectiveR-2CDAFirst line and RR47*87%PFS 80% at 5 y86% at 5 y
     Else et al1032012RetrospectiveR-chemoFirst line and RR33100%DFS 71% at 3 yNR
     Iannitto et al872015ProspectiveR-COMPFirst line5184%PFS 54% at 6 y72% at 6 y
    • 2CDA, 2-chlorodeoxyadenosine; chemo, chemotherapy; DFS, disease-free survival; R, rituximab; RR, relapsed/refractory.

    • * Rituximab in 32 patients.

  • Table 5

    Novel agents in MZLs

    AgentYearPhasePatient statusNo. of patientsMZLResponse
    ORRDuration
    Vorinostat10420111RR35922%Median PFS 18.8 mo
    Ibrutinib10520131RR56425%NR
    Idelalisib1062014*2RR1251547%Median PFS 6.6 mo
    Median DOR 18.4 mo
    Lenalidomide + Rituximab10720142First line1032789%Median PFS 53.8 mo
    • * Updated at the 56th American Society of Hematology Annual Meeting and Exposition, San Francisco, CA, December 6-9, 2014.