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

Abstract

Waldenströ m'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 Waldenströ m'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 þ , CD38 þ , expressing immunoglobulin lambda light chain, but CD5 À and CD10 À . 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.

A Case of Mucosa-Associated Lymphoid Tissue Lymphoma (MALToma) That Developed From Lungs and Stomach

“…As for t(11;18)(q21;q21), it is detected in 18% -53% cases of MALToma which develop from all loci [10,11]. Some MALTomas are accompanied by macroglobulinemia [12], and for many cases of gastric MALToma, antibiotic therapy for HP is ineffective [10]. The present case was in agreement with earlier reports on both these points.…”

Nuclear BCL-10 expression is common in lymphoplasmacytic lymphoma/Waldenström macroglobulinemia and does not correlate with p65 NF-κB activation

“…20,31,32 In addition, other B-cell lymphoproliferative disorders have been reported to express BCL-10 in a nuclear pattern although the staining is of moderate or weak intensity. 17,27 These findings are controversial, however, as other studies using immunohistochemistry or fluorescence in situ hybridization have failed to confirm BCL-10 nuclear expression in non-MALT lymphomas. [27][28][29] In this study, we were interested in assessing BCL-10 expression in LPL/WM, a neoplasm that has been rarely studied for BCL-10 expression in the past, most likely because these neoplasms are rare and primarily involve the BM.…”

“…17,27 These findings are controversial, however, as other studies using immunohistochemistry or fluorescence in situ hybridization have failed to confirm BCL-10 nuclear expression in non-MALT lymphomas. [27][28][29] In this study, we were interested in assessing BCL-10 expression in LPL/WM, a neoplasm that has been rarely studied for BCL-10 expression in the past, most likely because these neoplasms are rare and primarily involve the BM. We identified aberrant nuclear expression of BCL-10 in more than half of the specimens.…”

“…In fact, some investigators have used the pattern of BCL-10 immunostaining as a surrogate marker for the presence of these chromosomal translocations in MALT-lymphomas. 19,27 Currently, the mechanism underlying this aberrant expression pattern is not understood, but BCL-10 gene mutation seems an unlikely cause. [27][28][29][30] Moderate nuclear BCL-10 expression, however, has been observed in some cases of MALT lymphoma without the t (11;18).…”

“…19,27 Currently, the mechanism underlying this aberrant expression pattern is not understood, but BCL-10 gene mutation seems an unlikely cause. [27][28][29][30] Moderate nuclear BCL-10 expression, however, has been observed in some cases of MALT lymphoma without the t (11;18). 20,31,32 In addition, other B-cell lymphoproliferative disorders have been reported to express BCL-10 in a nuclear pattern although the staining is of moderate or weak intensity.…”