ALK-positive diffuse large B-cell lymphoma with ALK-Clathrin fusion belongs to the spectrum of pediatric lymphomas

ALK-positive diffuse large B-cell lymphoma: report of four cases and review of the literature

“…Cases with CLTC-ALK/t(2;17) rearrangement show a distinctly cytoplasmic and granular ALK staining pattern, whereas those cases with an NPM-ALK/t(2;5) rearrangement show both cytoplasmic and nuclear staining. [2][3][4][5][6][8][9][10][11]16 However, this correlation may be imperfect, as Onciu et al 5 reported one case of ALK-DLBCL with NPM-ALK fusion that showed cytoplasmic ALK staining only. Thus, ALK gene rearrangements, originally thought to be uniquely associated with T-/null cell ALCL, have now been convincingly shown to occur in rare cases of B-cell lymphoma.…”

“…Thus, ALK gene rearrangements, originally thought to be uniquely associated with T-/null cell ALCL, have now been convincingly shown to occur in rare cases of B-cell lymphoma. [2][3][4][5][6][7][8][9][10][11][12][13] Of note, prior to the initial series by Delsol et al, 1 Arber et al 17 in 1996 reported NPM/ALK fusion transcripts (by RT-PCR) in four of 33 cases of large B-cell lymphoma. Interestingly, and in contrast to the cases of ALK-DLBCL reported thus far, these four cases had a conventional B-cell immunophenotype (CD20 þ and CD79a þ ).…”

“…[2][3][4][5][6] The ALK gene located on chromosome 2p23 may be translocated to either the Clathrin (CLTC) gene locus on chromosome 17q23 or to the nucleophosmin (NPM) gene on chromosome 5q35, resulting in CLTC-ALK and NPM-ALK fusion products, respectively [2][3][4][5][6][8][9][10][11] (Table 4). Both of these genetic rearrangements were originally identified in classic ALK( þ ) ALCL, with NPM-ALK being distinctly more common (70-80% of cases).…”

“…1 Recently however, Clathrin/ALK (CLTC/ALK) and NPM/ALK gene rearrangements have been identified in 16 and three cases of ALK-DLBCL, respectively. [2][3][4][5][6][7][8][9][10][11][12][13] All of these cases display the morphologic and immunophenotypic features of ALK-DLBCL, as originally described by Delsol et al Importantly, ALK positivity and ALK gene rearrangements can be seen in B-cell lymphomas and are now no longer uniquely restricted to the T-cell lymphoma, ALCL. To our knowledge, only 29 cases of ALK-DLBCL have been reported thus far in the literature.…”

Novel clathrin activity: developments in health and disease

“…First, chromosomal translocation t(2;17)(p23;q23) fuses CHC17 with an intact trimerization domain (aa1-1634) to the C-terminus (aa1058-1620) of anaplastic lymphoma kinase (ALK) (40). The CHC-ALK fusion is often detected in non-Hodgkin's lymphomas and has been reported in anaplastic nul/T-cell lymphoma (41,42), large B-cell lymphoma (43)(44)(45)(46)(47)(48)(49)(50), and the rare inflammatory myofibroblastic tumor (51,52). To initiate ALKmediated lymphomagenesis, Stat3 must be activated (53).…”