Hyperactivated STAT3 in ALK-positive diffuse large B-cell lymphoma with clathrin-ALK fusion.

Anaplastic lymphoma kinase (ALK)-positive large B-cell lymphoma is a rare subtype of diffuse large B-cell lymphoma (DLBCL). Although a few cases of ALK-positive large B-cell lymphoma harbor nucleophosmin-ALK chromosomal translocation similar to ALK-positive anaplastic large cell lymphoma, most reported cases are characterized by t(2;17)(p23;q23) involving the clathrin gene. Here, we report 2 cases of ALK-positive DLBCL. The 2 cases presented similar morphologic features and immunohistochemical characteristics, that is, positivity for ALK, IgA, CD138, and MUM1; weak positivity for CD30 and CD79a; and negativity for CD20. The clathrin-ALK transcript was identified by reverse transcription-polymerase chain reaction, and the sequence was determined by direct sequencing. Recently, the essential role of STAT3 activation as well as STAT 5 activation in nucleophosmin-ALK fusion protein-mediated lymphomagenesis was reported. However, differential effects of ALK-fusion variant proteins on proliferation, transformation, and invasion properties were reported. Thus, we evaluated the phosphorylation status of STAT 3 and STAT 5, and found highly hyperphosphorylated STAT 3 on tyrosine 705 but not STAT 5 in our 2 cases of ALK-positive DLBCL with clathrin-ALK fusion. Furthermore, STAT 5A expression was not detected in either of the ALK-positive DLBCL cases, although 11 of the 36 ALK-negative DLBCL cases revealed STAT 5A expression. Expression of the antiapoptotic proteins survivin and BCL-X(L), which were believed to be the targets of STAT 3, was investigated. However, there were no significant associations between expression of survivin or BCL-X(L) and ALK positivity among the diffuse large B-cell lymphomas. In summary, similar signaling transduction mechanism involving STAT proteins seems to underlie DLBCL harboring the clathrin-ALK or nucleophosmin-ALK fusion gene.

Extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) arising in the small intestine with monoclonal cryoglobulinemia.

A case of small intestinal extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) with monoclonal cryoglobulinemia is described. The patient was a woman in her mid-sixties with purpura of the bilateral lower legs and abdominal pain. An immunoserological investigation showed expression of IgM-kappa type monoclonal cryoglobulin. A renal biopsy specimen revealed proliferative glomerulonephritis with cryoglobulin deposition. Physical examination disclosed a stenosis, edematous changes and ascariasis in the small intestine. In aspiration cytology of the ascites, proliferation of the atypical lymphoid cells with plasmacytoid differentiation was observed. These cells were positive for B-lineage antigens in immunocytochemistry, and showed an immunoglobulin heavy-chain gene rearrangement in Southern blotting and chromosomal alteration in G-banded karyotype analysis. Although medicinal treatment was used, the patient died of general prostration. The diagnosis of intestinal MALT lymphoma was made at autopsy. Expression of API2-MALT1 fusion transcripts was detected by reverse transcription-polymerase chain reaction analysis using formalin-fixed, paraffin-embedded tissue. Intestinal MALT lymphomas with API2-MALT1 expression have distinctive forms of infiltration compared with those without translocation. Therefore, detection of API2-MALT1 fusion transcripts is useful for evaluating the prognosis and clinical behavior of the disease.