t(1;14) and t(11;18) in the differential diagnosis of Waldenström's macroglobulinemia

University of Cambridge, Cambridge, England, United Kingdom
Modern Pathology (Impact Factor: 6.19). 10/2004; 17(9):1150-4. DOI: 10.1038/modpathol.3800164
Source: PubMed


Waldenström's macroglobulinemia is caused by several B-cell proliferative disorders including lymphoplasmacytic lymphoma, marginal zone B-cell lymphoma, B-cell chronic lymphocytic leukemia and multiple myeloma. Differential diagnosis between lymphoplasmacytic lymphoma and extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue is particularly difficult as there is a considerable overlap in histological presentation. We report a case of Waldenström's macroglobulinemia with involvement of the peripheral blood, bone marrow and stomach. Serum chemistry revealed an IgM of 5.4 g/dl, but Bence-Jones protein in urine was negative. Abnormal lymphoid cells were detected in both blood and the bone marrow. Flow cytometry of the bone marrow aspirate showed that majority of cells were CD20(+), CD38(+), expressing immunoglobulin lambda light chain, but CD5(-) and CD10(-). Gastric biopsies revealed infiltration of the gastric mucosa by small lymphoid cells showing plasmacytoid differentiation and occasional Dutcher bodies. Lymphoepithelial lesions and Helicobacter pylori were not seen. Thus, the differential diagnosis between lymphoplasmacytic lymphoma and mucosa-associated lymphoid tissue lymphoma was raised. To resolve this, we performed BCL10 immunohistochemistry and reverse transcriptional polymerase chain reaction (RT-PCR) for the API2-MALT1 fusion transcript of t(11;18)(q21;q21). Both bone marrow and gastric biopsies showed strong BCL10 nuclear staining, similar to that seen in t(1;14)(p22;q32) positive mucosa-associated lymphoid tissue lymphoma, but absence of the API2-MALT1 fusion transcript. To further ascertain whether the detection of t(1;14)(p22;q32) and t(11;18)(q21;q21) can be reliably used for the differential diagnosis between lymphoplasmacytic lymphoma and mucosa-associated lymphoid tissue lymphoma, we screened for these translocations by BCL10 immunohistochemistry in 58 lymphoplasmacytic lymphomas and RT-PCR for t(11;18)(q21;q21) in 40 lymphoplasmacytic lymphomas, respectively. None of the lymphoplasmacytic lymphomas studied harbored these translocations. Thus, detection of t(1;14)(p22;q32) and t(11;18)(q21;q21) is useful in the differential diagnosis between lymphoplasmacytic lymphoma and mucosa-associated lymphoid tissue lymphoma.

Download full-text


Available from: Hongtao Ye, Nov 17, 2014
  • [Show abstract] [Hide abstract]
    ABSTRACT: Waldenstrom's macroglobulinemia (WM) is characterized by lymphoplasmacytic infiltration of bone marrow and/or other tissues and by the presence of serum monoclonal immunoglobulin M ([IgM], without cutoff limit). Differential diagnosis from other B-cell disorders (BCDs) is usually easy based on clinical, morphologic, histopathologic, immunophenotypic, and genetic features. However, all BCDs potentially produce monoclonal IgM. In this study we reviewed the medical files of 130 patients with IgM-secreting BCDs. Eighty-four patients were diagnosed with WM, 5 with IgM-monoclonal gammopathy of undetermined significance (MGUS), and 41 with other BCDs (9 with B-cell chronic lymphocytic leukemia, 5 with small lymphocytic lymphoma, 14 with marginal zone lymphoma, 5 with mantle-cell lymphoma, 2 with follicular lymphoma, 2 with diffuse large B-cell lymphoma, 2 with cryoglobulinemia, and 2 with low-grade lymphoma not otherwise specified). Median IgM levels were 3215 mg/dL in WM, 840 mg/dL in IgM-MGUS, and 285 mg/dL in other BCDs (5 had IgM levels > 1500 mg/dL). In 10% of non-WM BCDs, monoclonal IgM was found only when more sensitive immunofixation methods were used. Forty-four percent of patients with BCDs (splenic marginal zone lymphoma or small lymphocytic lymphoma) had diagnoses that corresponded to that of WM. Careful diagnosis requires the concomitant evaluation of all parameters of BCDs together. Marginal zone lymphoma is the most frequently overlapping entity. Special attention should be given to mantle cell lymphoma in its atypical forms. Research in this field should continue to further clarify the disease entities that overlap with WM. New technology such as gene-expression profile techniques may contribute to this purpose.
    No preview · Article · Mar 2005 · Clinical lymphoma
  • [Show abstract] [Hide abstract]
    ABSTRACT: The concept of Waldenstrom macroglobulinemia has evolved from the original description of a clinical syndrome to its more recent designation as a distinct clinicopathologic entity, that is, lymphoplasmacytic lymphoma/Waldenstrom macroglobulinemia (LPL/WM), in the World Health Organization (WHO) classification and by the participants of consensus meetings on WM. The diagnosis of LPL/WM, however, remains a challenge in daily practice. Distinguishing LPL/WM from other B-cell lymphomas, especially marginal zone B-cell lymphomas, which share overlapping morphologic features, is difficult. The traditional practice of separating LPL/WM from other lymphomas by an arbitrary level of serum IgM is no longer considered valid. The characteristic immunophenotype described for LPL/WM by the WHO classification, that is, CD5(-)CD10(-)CD23-, is observed in 60-80% of neoplasms, but variations from this pattern of antigen expression are common, with CD23 being detected in up to 40% of cases. Lack of a distinct molecular genetic hallmark complicates the distinction of LPL/WM from other B-cell lymphomas. Although the t(9;14) is stated to be present in 50% of cases in the WHO classification, translocations involving the Ig heavy chain including the t(9;14) are actually rare in LPL/WM. Deletion of 6q21-q23, a nonspecific finding, is the most common aberration reported in 40-70% of patients. At the molecular level, the neoplastic clone in most cases has undergone Ig variable gene mutation, but not isotype switching, and the clone retains the capability of plasmacytic differentiation. Currently, the diagnosis of LPL/WM can only be established by incorporating clinical and pathologic findings and excluding alternative diagnoses. In some cases, in our opinion, distinguishing LPL/WM from marginal zone B-cell lymphomas seems arbitrary using currently recommended criteria.
    No preview · Article · Oct 2005 · Advances in Anatomic Pathology
  • [Show abstract] [Hide abstract]
    ABSTRACT: Lymphoma remains a fascinating disease with myriad presentations both in terms of anatomical localization and histopathological diversity. This chapter is complementary to the chapter in the previous edition in that it looks at this diversity from a pathological perspective and focuses on the rarer types of lymphoma. While providing a general overview, a few new and interesting biological correlates are included, and, where possible, therapeutic recommendations are included.
    No preview · Chapter · Jul 2006
Show more