Clinicopathologic characterization of diffuse-large-B-cell lymphoma with an associated serum monoclonal IgM component.
Recently, diffuse-large-B-cell lymphoma (DLBCL) associated with serum IgM monoclonal component (MC) has been shown to be a very poor prognostic subset although, detailed pathological and molecular data are still lacking. In the present study, the clinicopathological features and survival of IgM-secreting DLBCL were analyzed and compared to non-secreting cases in a series of 151 conventional DLBCL treated with R-CHOP. IgM MC was detected in 19 (12.5%) out of 151 patients at disease onset. In 17 of these cases secretion was likely due to the neoplastic clone, as suggested by the expression of heavy chain IgM protein in the cytoplasm of tumor cells. In IgM-secreting cases immunoblastic features (p<.0001), non-GCB-type (p = .002) stage III-IV(p = .003), ≥ 2 extra nodal sites (p<.0001), bone-marrow (p = .002), central-nervous-system (CNS) involvement at disease onset or relapse (p<.0001), IPI-score 3-5 (p = .009) and failure to achieve complete remission (p = .005), were significantly more frequent. FISH analyses for BCL2, BCL6 and MYC gene rearrangements detected only two cases harboring BCL2 gene translocation and in one case a concomitant BCL6 gene translocation was also observed. None of the IgM-secreting DLBCL was found to have L265P mutation of MYD88 gene. Thirty-six month event-free (11.8% vs 66.4% p<.0001), progression-free (23.5% vs 75.7%, p<.0001) and overall (47.1% vs 74.8%, p<.0001) survivals were significantly worse in the IgM-secreting group. In multivariate analysis IgM-secreting (p = .005, expB = 0.339, CI = 0.160-0.716) and IPI-score 3-5 (p = .010, expB = 0.274, CI = 0.102-0.737) were the only significant factors for progression-free-survival. Notably, four relapsed patients, who were treated with salvage immunochemotherapy combined with bortezomib or lenalidomide, achieved lasting remission. Our data suggests that IgM-secreting cases are a distinct subset of DLBCL, originating from activated-B-cells with terminally differentiated features, prevalent extra nodal dissemination and at high risk of CNS involvement.
Hematology Unit, Sant'Andrea Hospital, Department of Clinical and Molecular Medicine La Sapienza University, Rome, Italy.
M Christina
MC
Cox
Pathology Unit, Department of Clinical and Molecular Medicine, Sant'Andrea Hospital, La Sapienza University, Rome, Italy.
Arianna
A
Di Napoli
Pathology Unit, Department of Clinical and Molecular Medicine, Sant'Andrea Hospital, La Sapienza University, Rome, Italy.
Stefania
S
Scarpino
Clinical Pathology Unit, Department of Clinical and Molecular Medicine Sant'Andrea Hospital, La Sapienza University, Rome, Italy.
Gerardo
G
Salerno
Hematology Unit, Sant'Andrea Hospital, Department of Clinical and Molecular Medicine La Sapienza University, Rome, Italy.
Caterina
C
Tatarelli
Pathology Unit, Department of Clinical and Molecular Medicine, Sant'Andrea Hospital, La Sapienza University, Rome, Italy.
Caterina
C
Talerico
Pathology Unit, Department of Clinical and Molecular Medicine, Sant'Andrea Hospital, La Sapienza University, Rome, Italy.
Mariangela
M
Lombardi
Hematology Unit, Sant'Andrea Hospital, Department of Clinical and Molecular Medicine La Sapienza University, Rome, Italy.
Bruno
B
Monarca
Hematology Department, Tor Vergata University, Rome, Italy.
Sergio
S
Amadori
Pathology Unit, Department of Clinical and Molecular Medicine, Sant'Andrea Hospital, La Sapienza University, Rome, Italy.
Luigi
L
Ruco
D000911:Antibodies, Monoclonal / Q000276:immunology*; D058846:Antibodies, Monoclonal, Murine-Derived / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D003520:Cyclophosphamide / Q000627:therapeutic use; D004268:DNA-Binding Proteins / Q000378:metabolism; D004317:Doxorubicin / Q000627:therapeutic use; D006801:Humans; D007075:Immunoglobulin M / Q000276:immunology*; D017404:In Situ Hybridization, Fluorescence; D007558:Italy; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology*; D011241:Prednisone / Q000627:therapeutic use; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051560:Proto-Oncogene Proteins c-bcl-6; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D012189:Retrospective Studies; D000069283:Rituximab; D016019:Survival Analysis; D014750:Vincristine / Q000627:therapeutic use
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; C084103:BCL6 protein, human; D004268:DNA-Binding Proteins; D007075:Immunoglobulin M; C489427:MYC protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D051560:Proto-Oncogene Proteins c-bcl-6; D016271:Proto-Oncogene Proteins c-myc; C571759:R-CHOP protocol; D000069283:Rituximab; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone