Indolent Mantle Cell Lymphoma With Nodal Involvement and Mutated Immunoglobulin Heavy Chain Genes

Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States
Human Pathlogy (Impact Factor: 2.77). 11/2003; 34(10):1030-4. DOI: 10.1053/S0046-8177(03)00410-6
Source: PubMed


Mantle cell lymphoma (MCL) is typically considered an aggressive but incurable neoplasm composed of cyclin D1+ monoclonal B-cells with a t(11;14)(q13;q32) and usually unmutated immunoglobulin (Ig) genes. Although it has been suggested that a more indolent leukemic disorder exists with the same phenotype and genotype but with mutated Ig genes, others have considered these cases to be variants of chronic lymphocytic leukemia. We present a case of an indolent MCL that was documented with cyclin D1 expression in a lymph node biopsy performed more than 12 years ago. The patient has peripheral blood involvement with a lymphocyte count in the reference range, variable thrombocytopenia, and minimal adenopathy but is otherwise well, never having received any antineoplastic therapy. Study of peripheral blood samples from 2002 revealed a CD5-variable B-cell monoclonal proliferation with a t(11;14)(q13;q32) plus other karyotypic abnormalities, positive fluorescence in situ hybridization studies for the CCND1/IgH translocation, and clonal Ig gene rearrangement with mutated Ig genes (95.7% homology to VH 4-31). The subtle but diagnostic lymph node biopsy in this case helps to further support that an indolent t(11;14) monoclonal lymphocytosis with mutated Ig genes can represent an MCL variant rather than chronic lymphocytic leukemia.

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    • "Indolent MCL has been recently described in the literature as patients who experience a long delay between the time from diagnosis to when intensive treatment is needed. Some studies have tried to identify these patients with more precision (Nodit et al., 2003; Fernandez et al., 2010; Ondrejka et al., 2011; Carvajal-Cuenca et al., 2011; Furtado and Rule, 2011; Nygren et al., 2012; Royo et al., 2012), but no clear clinical or biological characteristics have emerged to identify these patients at the time of diagnosis. Currently , there is controversy and contradictory evidence regarding the use of the biological marker SOX11 (Wang et al., 2008; Nygren et al., 2012; Navarro et al., 2012; Jares et al., 2012). "
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    ABSTRACT: Mantle cell lymphoma (MCL) is usually an aggressive disease. However, a few patients do have an "indolent" evolution (iMCL) defined by a long survival time without intensive therapy. Many studies highlight the prognostic role of additional genetic abnormalities, but these abnormalities are not routinely tested for and do not yet influence the treatment decision. We aimed to evaluate the prognostic impact of these additional abnormalities detected by conventional cytogenetic testing, as well as their relationships with the clinical characteristics and their value in identifying iMCL. All consecutive MCL cases diagnosed between 1995 and 2011 at four institutions were retrospectively selected on the basis of an informative karyotype with a t(11;14) translocation at the time of diagnosis. A total of 125 patients were included and followed for an actual median time of 35 months. The median overall survival (OS) and survival without treatment (TFS) were 73.7 and 1.3 months, respectively. In multivariable Cox models, a high mantle cell lymphoma international prognostic index score, a complex karyotype, and blastoid morphology were independently associated with a shortened OS. Spleen enlargement, nodal presentation, extra-hematological involvement, and complex karyotypes were associated with shorter TFS. A score based on these factors allowed for the identification of "indolent" patients (median TFS 107 months) from other patients (median TFS: 1 month). In conclusion, in this multicentric cohort of MCL patients, a complex karyotype was associated with a shorter survival time and allowed for the identification of iMCL at the time of diagnosis. © 2013 Wiley Periodicals, Inc.
    Genes Chromosomes and Cancer 01/2014; 53(1):106-16. DOI:10.1002/gcc.22123 · 4.04 Impact Factor
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    • "In contrast, it is recognized that a proportion of cases (10–30%) may present with more indolent disease (Eve et al, 2009a; Martin et al, 2009). These patients usually present with splenomegaly and a peripheral blood lymphocytosis , and lack significant nodal disease (Nodit et al, 2003; Orchard et al, 2003). Survival is in the order of 5–12 years. "
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    ABSTRACT: Historically, MCL was grouped with low-grade lymphomas in clinical studies and treated with regimens including CVP (cyclophosphamide, vincristine, prednisone) (Meusers et al, 1989; Teodorovic et al, 1995; Unterhalt et al, 1996), fludarabine-based regimens (Cohen et al, 2001), and CHOP (cyclophosphamide, vincristine, doxorubicin, and prednisone) (Meusers et al, 1989; Lenz et al, 2005; Nickenig et al, 2006). Most of the studies had small numbers but the general pattern was of reasonable overall response rates (ORR, 60–88%), but short PFS (7–21 months) and poor OS of 40–85% at 2 years. No particular combination appears superior in terms of OS. In particular, addition of an anthracycline in the only randomized controlled trial (RCT) performed (Meusers et al, 1989) did not confer a survival benefit. This has been confirmed in large retrospective analyses. The Nebraska Lymphoma Study Group demonstrated that, although 79% of patients were treated with anthracycline-containing regimens, no survival benefit of anthracycline could be demonstrated (Weisenburger et al, 2000). Similarly, the Barcelona experience showed an ORR of 61% in patients receiving anthracycline-containing regimens, and 66% in those treated without anthracyclines (Bosch et al, 1998). In those not fit for the more intensive induction regimens discussed below, there is no evidence that adding anthracycline confers any advantage. However, despite the lack of robust evidence, R-CHOP (CHOP + rituximab) remains a widely used combination chemotherapy regimen in this disease and forms the control arm in many randomized studies. For this reason, we have included it as a treatment option.
    British Journal of Haematology 09/2012; 159(4). DOI:10.1111/bjh.12046 · 4.71 Impact Factor
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    • "The histologic pattern of MCL may be diffuse, nodular, or mantle zone or a combination of the three patterns of growth. Infrequent cases may show involvement almost exclusively restricted to the inner mantle zones or to narrow mantles ( " in situ " MCL) [8] [9]. Mantle zone pattern and in situ MCL are different concepts. "
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    ABSTRACT: Synchronous occurrence of pulmonary squamous cell carcinoma and malignant lymphoma of the lymph node is not reported in the literature. We report a case of pulmonary squamous cell carcinoma coexisting with a mantle cell lymphoma involving cervical and mediastinal lymph node. It is important to recognize this synchronous occurrence histopathologically and to be aware of the existence of "in situ" MCL.
    07/2011; 2011:945181. DOI:10.1155/2011/945181
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