IgM Expression on Paraffin Sections Distinguishes Primary Cutaneous Large B-cell Lymphoma, Leg Type From Primary Cutaneous Follicle Center Lymphoma

Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands.
The American journal of surgical pathology (Impact Factor: 5.15). 07/2010; 34(7):1043-8. DOI: 10.1097/PAS.0b013e3181e5060a
Source: PubMed


In the World Health Organization (WHO) 2008 classification 2 main types of primary cutaneous large B-cell lymphomas (PCLBCLs) are distinguished: primary cutaneous follicle center lymphoma (PCFCL) and primary cutaneous large B-cell lymphoma, leg type (PCBCL-LT). PCFCL has a 5-year overall survival rate of 95%, and PCBCL-LT of approximately 50%. Expression profiling studies have shown higher RNA expression of the IgM heavy chain in PCBCL-LT compared with PCFCL. To find out whether this difference could also be demonstrated at the protein level, we performed immunohistochemical staining for B-cell receptor heavy and light chains on skin biopsies from 53 patients with PCFCL and 40 patients with PCBCL-LT. All 40 cases of PCBCL-LT consistently showed cytoplasmic staining for IgM, in 18 of them with coexpression of IgD. In contrast, only 5 of the PCFCL cases showed cytoplasmic staining for IgM and/or IgD, including all 3 PCFCLs presenting on the leg. Hence, staining for IgM on paraffin-embedded sections seems to be an additional tool for differentiating between the 2 entities in clinical pathology practice. Analogous to other nodal and extranodal large B-cell lymphomas, expression of IgM in PCLBCL seems to be related to an activated B cell-like phenotype. Finally, the expression of IgM (and IgD) in this type of lymphoma might imply defective class switch recombination.

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Available from: Lianne Koens, Feb 06, 2015
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    • "Widely used and inexpensive routine analysis could easily detect serum monoclonal IgM component. Further confirmation by immunohistochemistry or by other molecular detection assays of IgM expression by tumor cells [43], [54] would allow to identify IgM-secreting DLBCL. We believe that IgM-secreting capability represents a very robust prognostic marker, since it is related to a defined biological characteristic of DLBCL derived from terminally differentiated B-lymphocytes. "
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    ABSTRACT: 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 immmunochemotherapy 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.
    Full-text · Article · Apr 2014 · PLoS ONE
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    • ". Differing from Koens et al. in our series, none of the cases of PCFCL had the expression of IgM, even those located on the legs [7]. Although there was one case of PCFCL with staining of bcl-6, bcl-2 and IRF4/MUM-1 at the same time, it was also negative for IgM. "

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